Comprehensive Textbook of Clinical Radiology Volume IV-Abdomen (May 15, 2023)_(B0C5WX2F7X)_(Elsevier India)

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COMPREHENSIVE TEXTBOOK OF

CLINICAL RADIOLOGY VOLUME IV: ABDOMEN EDITOR - IN-CHIEF:

AMARNATHC EDITOR:

HEMANT PATEL VOLUME EDITORS:

SHRINIVAS DESAI AVINASH NANIVADEKAR J DEVIMEENAL KARTHIK GANESAN KUSHALJIT SINGH SODHI

I I Sl \ II K

Comprehensive Textbook of Clinical Radiology VOLUME IV: ABDOMEN Editor-in-Chief

Amarnath C Professor and Head of Radiology, Stanley Medical College, Chennai, India Editor

Hemant Patel Consultant Radiologist & Director, Gujarat Imaging Center, Ahmedabad, India Assistant Editor

Gaurang Raval Consultant Radiologist, Wockhardt Hospital, Rajkot, India Volume Editors

Shrinivas Desai

(Sections: General Abdomen and Hepatobilliary System) Director, Department of Imaging and Interventional Radiology, Jaslok Hospital & Research Centre, Mumbai, India

Avinash Nanivadekar (Section: Urinary Tract Disease) Director Radiology, Ruby Hall Clinic, Pune, India

J Devimeenal (Section: Reproductive System) Professor & Head, Institute of Radiodiagnosis, Government Kilpauk Medical College, Chennai, India

Karthik Ganesan (Section: Gastrointestinal Tract) Clinical Director CT/MRI, Division Chief – Body and Head & Neck Imaging, Department of Radiology, Sir H.N. Reliance Foundation Hospital and Research Centre, Mumbai, India

Kushaljit Singh Sodhi (Section: Pediatric Radiology) Professor, Department of Radiodiagnosis, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India

Table of Contents Cover image Title page Copyright Foreword Foreword Foreword Preface Contributors SECTION 7. General Abdomen 7.1. Imaging techniques of abdomen and pelvis 7.1.1. UNDERSTANDING THE ADULT ABDOMINAL RADIOGRAPH: TECHNIQUES AND INTERPRETATION 7.1.2. OESOPHAGOGRAM 7.1.2.1. BARIUM UPPER GASTROINTESTINAL SERIES 7.1.2.2. BARIUM MEAL FOLLOW THROUGH (SMALL BOWEL SERIES) 7.1.2.3. SMALL BOWEL ENEMA: TIPS TO PERFORM AND INTERPRETATION 7.1.2.4. BARIUM ENEMA 7.1.2.5. FISTULOGRAM 7.1.2.6. HYSTEROSALPINGOGRAPHY

7.1.3. ULTRASOUND OF NORMAL ABDOMEN ANATOMY, TECHNIQUES, VARIATIONS, NOMOGRAMS AND SCANNING PROTOCOLS 7.1.4. NORMAL ANATOMY AND FLOW PATTERNS IN ABDOMINAL VESSELS 7.1.5. ULTRASOUND ASSESSMENT OF AORTA, ILIAC ARTERIES AND THE INFERIOR VENA CAVA 7.1.6. DOPPLER ASSESSMENT OF MESENTERIC ARTERIES 7.1.7. GENERAL PRINCIPLES OF ABDOMINAL IMAGING 7.1.7.1. PERIANAL FISTULAE AND ITS EVALUATION BY TRANSPERIANAL SONOGRAPHY AND MAGNETIC RESONANCE IMAGING 7.2. Normal anatomy and normal variant 7.2.1. CROSS SECTIONAL ANATOMY OF ABDOMEN 7.2.2. NORMAL ANATOMY OF ABDOMEN AND PELVIS 7.2.2.1. NORMAL VARIANTS: LIVER ANATOMY VARIANTS 7.3. Normograms of abdomen and gastrointestinal tract 7.4. Approach to radiological diagnosis 7.4.1. APPROACH TO HIGH INTESTINAL OBSTRUCTION IN A NEONATE 7.4.2. APPROACH TO PHARYNGEAL AND OESOPHAGEAL POUCHES AND DIVERTICULA 7.4.3. APPROACH TO OESOPHAGEAL DYSPHAGIA 7.4.4. APPROACH TO OESOPHAGEAL LUMINAL NARROWING 7.4.5. APPROACH TO GASTRIC FILLING DEFECTS

7.4.6. APPROACH TO WIDENING OF C LOOP OF DUODENUM 7.4.7. APPROACH TO MESENTERIC ISCHAEMIA 7.4.8. APPROACH TO MESENTERIC CYSTIC LESIONS 7.4.9. APPROACH TO SOLID MESENTERIC LESIONS 7.4.10. APPROACH TO MISTY MESENTERY 7.4.11. APPROACH TO COLITIS 7.4.12. APPROACH TO WIDENED RETRORECTAL SPACE 7.4.13. HEPATOBILIARY: APPROACH TO FOCAL LIVER MASS IN PAEDIATRICS 7.4.14. APPROACH TO LIVER LESIONS WITH A CENTRAL SCAR 7.4.15. APPROACH TO LIVER LESIONS CAUSING CAPSULAR RETRACTION 7.4.16. APPROACH TO CYSTIC LIVER LESIONS 7.4.17. APPROACH TO CYSTIC LESION OF PANCREAS 7.4.18. APPROACH TO CYSTIC LESION OF PANCREAS – MACROCYSTIC LESION 7.4.19. APPROACH TO OMENTAL PATHOLOGIES 7.5. Paediatric imaging techniques of abdomen and pelvis 7.5.1. MISCELLANEOUS PAEDIATRIC RADIOGRAPHY – TECHNIQUES AND INTERPRETATION: SKELETAL SURVEY 7.5.1.1. BABYGRAM 7.5.1.2. INVERTOGRAM 7.5.2. UPPER GASTROINTESTINAL SERIES 7.5.3. IMAGING MODALITIES IN PAEDIATRIC ABDOMEN

7.6. Anorectal malformations 7.7. Gastrointestinal masses in children 7.8. Neonatal gastrointestinal disorders 7.9. Upper gastrointestinal abnormalities (typically seen in infants and young children) 7.10. Imaging in paediatric mesentery disorders 7.11. Paediatric inflammatory bowel disease 7.12. Intussusception 7.13. Approach to acute abdomen 7.14. Imaging and interventions in abdominal trauma 7.15. Abdominal wall pathologies and hernias 7.16. Pelvic floor imaging 7.16.1. PELVIC FLOOR IMAGING – ANTERIOR AND MIDDLE COMPARTMENTS 7.16.2. MR DEFECOGRAPHY AND ITS ROLE IN PELVIC FLOOR IMAGING 7.17. Vascular interventions in gastrointestinal tract 7.18. Nonvascular interventions in the abdomen SECTION 8. Gastrointestinal Tract 8.1. Oesophagus 8.1.1. CLINICALLY RELEVANT EMBRYOLOGY OF OESOPHAGUS 8.1.2. IMAGING TECHNIQUES – OESOPHAGUS 8.1.3. ALGORITHMIC APPROACH TO A PATIENT WITH OESOPHAGEAL DYSPHAGIA 8.1.4. OESOPHAGEAL MOTILITY DISORDERS 8.1.5. APPROACH TO INDIGESTION, NAUSEA, VOMITING AND GASTRO-OESOPHAGEAL REFLUX 8.1.6. BENIGN NEOPLASMS OF OESOPHAGUS 8.1.7. CA OESOPHAGUS

8.2. Stomach 8.3. Small bowel 8.3.1. SMALL BOWEL IMAGING 8.3.2. INFLAMMATORY BOWEL DISEASE 8.3.3. IMAGING OF SMALL BOWEL ISCHAEMIA 8.3.4. SMALL BOWEL OBSTRUCTION 8.3.5. POSTOPERATIVE SMALL BOWEL IMAGING 8.4. Colon 8.4.1. EMBRIOLOGY AND ANATOMY OF COLON 8.4.2. IMAGING TECHNIQUES FOR COLON 8.4.3. IMAGING OF THE APPENDIX AND INTRAPERITONEAL FOCAL FAT INFARCTION 8.4.4. INFLAMMATORY BOWEL DISEASES OF COLON 8.4.5. DIVERTICULAR DISEASES OF COLON 8.4.6. ISCHAEMIC COLITIS 8.4.7. INFECTIOUS COLITIS 8.4.8. NEOPLASTIC DISEASE OF COLON 8.4.9. MISCELLANEOUS DISEASES OF COLON 8.5. Rectum 8.6. Peritoneum SECTION 9. Hepatobiliary System 9.1. Radiological techniques in hepatobiliary imaging 9.1.1. PLAIN RADIOGRAPHY FOR HEPATOBILIARY IMAGING 9.1.2. ULTRASOUND OF HEPATOBILIARY SYSTEM 9.1.3. DOPPLER OF PORTAL VEIN 9.1.4. INTRAOPERATIVE PANCREATIC AND HEPATIC ULTRASOUND

9.1.5. MULTIDETECTOR CT OF THE HEPATOBILIARY SYSTEM AND CHOLANGIOGRAPHY 9.1.6. CT ANGIOGRAPHY OF THE HEPATOBILIARY SYSTEM AND INTERVENTIONS IN HEPATOBILIARY SYSTEM 9.1.7. MRI LIVER TECHNIQUE, MRCP AND ERCP 9.1.8. LIVER FAT AND IRON ESTIMATION INCLUDING SPECTROSCOPY AND LIVER ELASTOGRAPHY 9.2. Normal anatomy and variants 9.3. Normogram and normal values 9.4. Approach to radiologic diagnosis 9.4.1. APPROACH TO CONGENITAL PANCREATIC ANOMALIES Introduction 9.4.2. APPROACH TO PANCREATIC CALCIFICATION 9.4.3. APPROACH TO PERIAMPULLARY LESIONS 9.5. Radiological signs – hepatobiliary system 9.6. Embroyology and congenital anomalies of the hepatobiliary system 9.7. Hepatobiliary system: Congenital anomalies 9.8. Paediatric hepatobiliary lesions 9.8.1. DIFFUSE PARENCHYMAL DISEASES OF THE LIVER 9.8.2. PEDIATRIC BENIGN HEPATIC MASSES (INCLUDING INFECTIONS) 9.8.3. IMAGING OF MALIGNANT PAEDIATRIC LIVER AND BILIARY TRACT LESIONS 9.8.4. VASCULAR ANOMALIES OF PEDIATRIC LIVER

9.8.5. DISEASES OF GALLBLADDER IN CHILDREN 9.8.6. LIVER TRANSPLANTATION IN CHILDREN 9.9. Imaging in portal hypertension and cirrhosis with emphasis on LI-RADS 9.10. Diffuse liver disease Abnormalities of attenuation 9.11. Focal liver lesions 9.12. Vascular pathologies of liver 9.13. Hepatic infections 9.14. Liver transplant imaging Posttransplant imaging 9.15. Imaging in biliary diseases 9.16. Paediatric pancreatic pathologies 9.17. Imaging in pancreatitis 9.18. Imaging in solid pancreatic masses 9.19. Cystic pancreatic masses 9.20. Role of imaging in pancreatic transplant 9.21. Paediatric splenic abnormalities 9.22. Imaging of spleen and splenic pathologies 9.22.1. CONGENITAL SPLENIC ABNORMALITIES 9.22.2. SPLENIC INFECTION AND ABSCESS 9.22.3. SPLENOMEGALY AND HYPERSPLENISM 9.22.4. SPLENIC INFARCTION 9.22.5. SPLENIC TRAUMA 9.22.6. BENIGN LESIONS OF THE SPLEEN 9.22.7. MALIGNANT LESIONS AND LYMPHOMA OF THE SPLEEN 9.22.8. SPLENIC INTERVENTIONS 9.23. Abdominal trauma

9.24. Biliary interventions 1. Percutaneous transhepatic biliary drainage 2. Biliary stenting 3. Percutaneous cholecystostomy 4. Biliary brush cytology and biopsy 5. Biliary radiofrequency ablation 6. Biliary internal radiotherapy 7. Benign biliary strictures and bile leaks 8. Other methods of biliary drainage 9.25. Transarterial therapy for liver tumours 9.26. Interventions in portal hypertension 9.27. Interventional management of Budd–Chiari syndrome 9.28. Portal vein embolization: Principle, technique and current status 9.29. Postliver transplant complications and interventions SECTION 10. Urinary Tract Disease 10.1. Imaging techniques: Plain radiograph, conventional imaging, fluoro–cine techniques, USG doppler, CT/MR 10.2. Anatomy, radiological anatomy, normal variants 10.3. Normograms for the urinary tract 10.4. Approach based algorithms 10.4.1. RENOVASCULAR HYPERTENSION 10.4.2. URINARY TRACT CALCIFICATIONS 10.4.3. RENAL MASS FOR EVALUATION 10.4.4. APPROACH TO HEMATURIA 10.4.5. ALGORITHMIC APPROACH TO A PATIENT WITH BLADDER LESIONS 10.5. Embryology of the urinary tract

10.6. Conventional paediatric uroradiology 10.7. Genitourinary anomalies 10.8. Urinary tract infections (including vesicoureteric reflux and neurogenic bladder) 10.9. Renal masses in children 10.10. Retroperitoneal masses in children (including adrenals) 10.11. Bladder and urethral abnormalities in children 10.12. Kidney 10.12.1. CYSTIC DISEASES OF KIDNEY 10.12.2. INFECTIONS 1. Acute bacterial pyelonephritis 2. Emphysematous pyelonephritis 3. Xanthogranulomatous pyelonephritis 4. Renal and perinephric abscess Pyonephrosis 5. Reflux nephropathy (RN) 6. Renal sinus lipomatosis Renal replacement lipomatosis (RRL) 7. Renal malakoplakia 8. Renal fungal disease: Includes candidiasis and mucormycosis 9. HIV-associated nephropathy 10. Opportunistic renal infections in HIV 11. Urogenital tuberculosis 12. Parasitic infestation in gut 10.12.3. RENAL FAILURE 1. Hydronephrosis and obstructive uropathy 2. Acute renal failure 3. Chronic renal failure

4. Glomerular diseases: An insight into imaging of nephritic and nephrotic pathologies 5. Differential diagnosis of bilateral large smooth kidneys 6. Approach to unilateral small kidney 10.12.4. RENAL METABOLIC DISORDERS 1. Nephrocalcinosis 2. Paroxysmal nocturnal haemoglobinuria 10.12.5. RENAL DISORDERS OF MIGRATION AND RENAL ANOMALIES Renal and genitourinary trauma 10.12.6. UROLITHIASIS 10.13. Bladder and urachus 10.14. Ureter 10.15. Urethra 10.15.1. URETHRAL DIVERTICULUM (URETHROCELES) 10.15.2. URETHRAL TRAUMA 10.15.3. URETHRAL TUMOURS 10.16. Adrenals 10.16.1. ADRENAL ANATOMY AND IMAGING TECHNIQUES 10.16.2. ADRENAL INCIDENTALOMA 10.16.3. ADENOMA 10.16.4. ROLE OF MULTIMODALITY IMAGING IN ADRENAL MALIGNANCIES 10.17. Retroperitoneum 10.17.1. CROSS-SECTIONAL IMAGING ANATOMY OF THE RETROPERITONEUM 10.17.2. IMAGING TECHNIQUES AND PROTOCOLS FOR THE RETROPERITONEUM

10.17.3. SOLID NONNEOPLASTIC LESIONS 10.17.4. IMAGE-GUIDED INTERVENTIONS OF RETROPERITONEAL MASSES AND IMAGING OF POSTPROCEDURAL COMPLICATIONS 10.17.5. IMAGING OF PRIMARY RETROPERITONEAL NEOPLASMS IN ADULTS 10.18. Renal vascular imaging 10.18.1. RENOVASCULAR DISEASE (RVD) 10.18.2. SPONTANEOUS PERIRENAL HAEMORRHAGE AND RENAL AV MALFORMATIONS 10.18.3. IMAGING IN ARTERIOVENOUS FISTULA FOR HAEMODIALYSIS ACCESS 10.19. Imaging in urological complications after renal transplantations 10.20. Endovascular management of renal artery stenosis 10.21. Other renal vascular interventions 10.21.1. NONVASCULAR RENAL INTERVENTION 10.21.2. POSTRENAL TRANSPLANT INTERVENTIONS 10.22. Surgical perspective 10.22.1. IMAGING IN RENAL TRANSPLANT – A VASCULAR SURGEON’S PERSPECTIVE 10.22.2. IMAGING FOR COMPLICATIONS AFTER BLADDER SURGERY 10.23. Recent advances 10.23.1. CONTRAST-ENHANCED ULTRASOUND IN ADULT GENITOURINARY IMAGING 10.23.2. DUAL-ENERGY AND SPECTRAL IMAGING IN GENITOURINARY SYSTEM 10.23.3. CT UROGRAPHY 10.23.4. MR UROGRAPHY

SECTION 11. Reproductive System 11.1. Radiological techniques in reproductive imaging 11.1.1. ULTRASOUND MALE PELVIS 11.1.2. ULTRASONOGRAPHY INGUINOSCROTAL REGION 11.1.3. TRANSRECTAL ULTRASOUND OF PROSTATE 11.1.4. USG FEMALE PELVIS 11.1.5. TRANSVAGINAL ULTRASOUND 11.1.6. 3D ULTRASOUND AND TOMOGRAPHIC ULTRASOUND IMGING (TUI) 11.1.7. HYSTEROSALPHINGOGRAPHY 11.1.8. SALINE INFUSION ‘SONOHYSTEROGRAPHY’ 11.1.9. MAGNETIC RESONANCE HYSTEROSALPINGOGRAPHY 11.1.10. COMPUTED TOMOGRAM OF PELVIS 11.1.11. MAGNETIC RESONANCE IMAGING OF THE FEMALE PELVIS 11.1.12. PET-CT IN UROLOGY AND GYNAECOLOGY 11.2. Anatomy and normal variants 11.2.1. IMAGING ANATOMY OF MALE REPRODUCTIVE SYSTEM 11.2.2. IMAGING ANATOMY OF FEMALE REPRODUCTIVE SYSTEM 11.2.3. IMAGING ANATOMY OF THE PERITONEAL SPACES 11.2.4. NORMAL VARIANTS OF PROSTRATE 11.2.5. NORMAL VARIANTS OF SCROTUM 11.2.6. NORMAL VARIANTS OF URETHRA 11.3. Nomogram (which plane, where, in tables)

11.4. Radiologic approach to lesions (a systematic approach to clinical scenarios/radiological abnormality) 11.4.1. OVARIAN CYST VERSUS BLADDER 11.4.2. UTERINE VERSUS EXTRAUTERINE MASS 11.4.3. BLADDER MASS VERSUS PROSTATE MASS 11.4.4. OVARIAN MASS VERSUS PARAOVARIAN MASS 11.4.5. OVARIAN CYST VERSUS HYDROSALPINX 11.4.6. TESTICULAR TORSION VERSUS EPIDIDYMITIS 11.4.7. OVARIAN TORSION VERSUS OHSS 11.4.8. GARTNER’S DUCT CYST VERSUS BARTHOLIN’S GLAND CYST 11.5. Signs in reproductive imaging 11.6. Embryology 11.7. Intersex disorders: Concepts, types and diagnostic approach 11.8. Testis 11.9. Epididymis 11.10. Seminal vesicles 11.11. Scrotum 11.11.1. FOURNIER GANGRENE (NECROTIZING FASCIITIS): AN INFREQUENT TISSUE EATING DISEASE 11.11.2. ABDOMINAL WALL HERNIA 11.11.3. TESTICULAR TRAUMA 11.11.4. VARICOCELE 11.12. Prostate 11.13. High-resolution ultrasound and colour doppler in penile pathologies and erectile dysfunction 11.14. Imaging of paediatric female reproductive tract Ü

11.14.1. MÜLLERIAN DUCT ANOMALIES 11.14.2. IMAGING OF FEMALE PELVIS IN CHILDREN 11.15. Uterus 11.15.1. ENDOMETRITIS 11.15.2. UTERINE ARTERIOVENOUS MALFORMATION 11.15.3. FIBROIDS 11.15.4. ADENOMYOSIS 11.15.5. ENDOMETRIAL POLYPS 11.15.6. ENDOMETRIAL HYPERPLASIA 11.15.7. NEOPLASM OF UTERUS 11.16. Ovaries 11.16.1. ADNEXAL (OVARIAN) TORSION 11.16.2. BENIGN OVARIAN LESIONS 11.16.3. TUBO-OVARIAN ABSCESS 11.16.4. IMAGING OF EPITHELIAL AND TUBAL OVARIAN TUMOURS 11.17. Fallopian tubes 11.17.1. SALPINGITIS 11.17.2. PELVIC INFLAMMATORY DISEASE 11.18. Cervix 11.18.1. CERVICITIS 11.18.2. CERVICAL STENOSIS 11.18.3. CERVICAL POLYPS 11.18.4. CERVICAL CARCINOMA 11.19. Vagina 11.19.1. VAGINAL CYSTS 11.19.2. VAGINAL MALIGNANCIES 11.19.3. ENDOMETRIOSIS

11.20. Imaging approach in infertility 11.20.1. FOLLICULAR STUDY 11.20.2. ROLE OF ULTRASOUND IN IVF PROCEDURES 11.21. Genital tuberculosis 11.22. Genitourinary interventions 11.23. Genitourinary nonvascular interventions 11.24. Recent advances in reproductive system 11.24.1. MULTIPARAMETRIC MRI OF THE PROSTRATE 11.24.2. MAGNETIC RESONANCE GUIDED FOCUSED ULTRASOUND SURGERY (MRgFUS) 11.25. Urogenital malignancies 11.25.1. IMAGING OF RENAL MALIGNANCIES IN ADULTS 11.25.2. ROLE OF MULTIMODALITY IMAGING IN TESTICULAR MALIGNANCIES 11.25.3. BLADDER CANCER

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Foreword My links with Indian medicine extend to my student days when I did my elective period at Kasturba Medical College in Mangalore. I was hugely impressed with the dedication, enthusiasm and thirst for knowledge of our fellow students, as well as by the erudition and clinical acumen of our teachers. In radiology, my many encounters with Indian colleagues in subsequent decades has confirmed those initial impressions. Radiology has advanced enormously since the 1970s, and Indian colleagues at home and abroad have contributed greatly to its progress. The Comprehensive Textbook of Clinical Radiology by the Indian Radiological and Imaging Association (IRIA) is very impressive in its scope and ambition, as it covers every aspect of modern imaging in its six volumes and the associated online content. With more than 500 contributors, mainly from India but from several countries abroad as well, it is a monumental work, involving huge effort. It aims to impart knowledge of every aspect of imaging, and also to guide those training in this specialty in methods of assessment that will stand them well in their careers. The online content will be an essential accompaniment to the printed volumes, because it will make possible continuous updating of the information as new knowledge becomes available. The excellent teamwork of the large number of experts involved in this project has demonstrated that even in the era of the internet there is a place for comprehensive traditional textbooks.

Andreas Adam CBE, FMedSci Professor Emeritus of Interventional Radiology King’s College London

Foreword It is a great honour to be invited to write the foreword to this remarkable Comprehensive Textbook of Clinical Radiology produced under the aegis of the IRIA (Indian Radiological and Imaging Association) by Prof Amarnath C, Dr Hemant Patel, Dr Gaurang Raval and their colleagues. And comprehensive it certainly is! The task of covering the entire spectrum of the fastchanging field of radiology is daunting enough; the task of persuading 500 leading radiologists from across the world to submit their expert contributions on time and then editing and collating them into this remarkable publication is even more daunting. Therefore, everyone involved in this production, including the editors, the authors and the publishers, should be congratulated on achieving this ambitious aim. It truly is a magnum opus. As the editors state, this textbook fulfils a muchneeded demand for a complete text in Radiodiagnosis and Interventional Radiology for residents and experienced practitioners alike. It covers far more than the requirements for passing the exit qualification for consultant radiologists in most countries (FRCR in the UK, DNB in India, Boards in the USA, EDiR in Europe), and thus it is an encyclopaedia worthy of a place in every radiological department worldwide. Although primarily aimed at helping the 20,000 plus radiologists in India – a lot of space is given to radiological manifestations of tuberculosis – I am sure that this book will become very popular among radiologists globally. It is pleasing to see the inclusion of some aspects of the history of Radiology, along with practical instructions about the main techniques currently used and recent

advances. Generic points such as medicolegal issues and communication skills are also covered. It is certainly right up to date – I learnt a lot while looking at the draft chapters. I am ashamed to say that I had not heard about the recent introduction of virtual organ computer-aided analysis (VOCAL) contrast-enhanced ultrasound assessment of ovaries, but on checking the PubMed I found that not only are there some publications related to voice changes with ovarian dysfunction but also the authors are actually discussing VOCAL to assess patients with polycystic/multifollicular ovaries, etc.! One limitation of large radiological textbooks is that they tend to go out of date quite quickly, given the rapidity of the technological advances. This aspect is overcome with the promise of annual online updates, presumably again under the aegis of the IRIA. It is excellent to see the two co-editors (both former presidents of the IRIA) taking this bold initiative and I wish them and the IRIA every success on a truly remarkable venture. Adrian K. Dixon MD, FRCR, FRCP, FRCS, FMedSci, FACR(Hon), FFRRCSI(Hon), FRANZCR(Hon), FHKCR(Hon) Emeritus Professor of Radiology, University of Cambridge, UK Emeritus Editor, European Radiology

Foreword This magnificent six-volume text encompassing the everburgeoning knowledge of imaging is a welcome addition to the pantheon of older published textbooks. Where previously these were largely of Anglo-AmericanGerman origin this new contribution is unique in that both the editors and authors are drawn almost, but not quite exclusively, from South Asia. This reflects the way that imagers and imaging have developed in leaps and bounds in that part of the world over the past generation. This book is a delight for those who like to gain knowledge available in conventional print as well as in digital format. This book is impressive in both scope and depth and organised in manageable sections allowing the enthusiastic reader to dip in and out of the text at will. The general radiologist will find it particularly helpful as a bench book available to refer to when facing a problem case during routine reporting duties. The six volumes are constructed in a conventional manner covering the differing imaging modalities from the conventional radiograph to the latest innovations with ample sections covering the various paediatric and adult body systems. The editors are to be congratulated on the outcome which I am confident will find a place in many imaging departments around the world over the next few years. Mark Davies Consultant Radiologist, Royal Orthopaedic Hospital, Birmingham, UK Former President European Society Skeletal Radiology and International Skeletal Society

Preface Radiology as a speciality holds the privilege of being the most expansive as well as the most advanced branch of modern medical science. The hyper pace of research and development in this speciality has blurred the lines of difference between a student and a consultant of radiology. Hence, the books which were touted to be ‘Textbooks of Radiology’ in the past have become insufficient to quench the thirst of a blooming radiologist. As a teacher, I could empathize with this confusion that a radiologist faces to become the ‘jack of all trades’ since the last 10–12 years. My guru, Prof T.S. Swaminathan, was constantly encouraging me to write a book on Radiology as a way to end this turmoil. The idea of this book came to me when I realized that there is a lack of single textbook for general radiology. Such a comprehensive textbook was one of the foremost demands of young and experienced radiologists across the country. Hence, I decided to publish under Indian Radiological and Imaging Association. Since the inception of the idea of this book in April 2019, my dear friend Dr Hemant Patel (Editor) and my student Dr Gaurang Raval (Assistant Editor) shared unmatched passion and enthusiasm to make this book the holy grail of radiology. This is our humble attempt to compile a single reference point, fully integrated and wellillustrated textbook of radiology as an end result of 2 years of hard work. In March 2020, the world was struck by the destructive COVID-19 infection. During the period of lockdown, I went into self-contemplation and understood two things: (1) A simple but deadly virus does not differentiate class, creed, religion, region −

things which differentiate us daily; and (2) any radiologist is a student for life. Taking these two thoughts, we ventured to start the biggest book on Radiology. The catch was not to make a textbook but to make a ‘standard comprehensive reference book’ on radiology which would cater to the students, consultants and superspecialists alike. COVID-19 lockdown turned to be a boon in disguise. Contributors made the apposite use of time at their disposal. The virus united us and the theme of the book became ‘One World, One Radiology, One Book’. Radiologists all over the world and in India showed unparalleled enthusiasm to give their best for the book. This book is a testament of unequalled unity and prodigious talent radiologists can show in times of great duress. Another hurdle we faced was that almost the entire team of editors and contributors (including myself) got infected with COVID-19 at some point. But even the infection could not bring down the spirit of teaching within each one of us. Many have worked while on a hospital bed or in a quarantine centre like crazy. This is a testimony of selflessness of a medical practitioner. Female editors and contributors are our biggest strength in this project. We are very proud that our book is probably the only work of this level with more than 40% of contribution by esteemed ladies. We are also proud that for the very first time a radiology textbook has a dedicated volume on women’s imaging – obstetrics and breast imaging. The contents of the book are very distinctive. Each system starts with the imaging techniques from X-ray to MRI to PET. Standard, reproducible and up-to-date protocols are enumerated. The second section is a detailed radiological anatomy of the given system. It is seen that a resident or a young consultant radiologist refers to radiological anatomy two to three times a day on an average. This section would be really helpful to them. Normal variants represent the extended spectrum of normal – knowledge of which is the prerequisite for

standard examination. This section deals in detail about the gamut of normal variants. Normograms and normal value section is made as a ready referral to accurately define pathologies across modalities. By mentioning the requisite cut-off values and their implication in the reporting, radiologists would be able to steer management and predict prognostication in each case. Embryology forms the basis of congenital diseases in an individual. Embryology in this book is described in detail as a precursor to the paediatric section. Our paediatric radiology section contributed by the best of the best radiologists across the globe make it one of the most anticipated sections in the book. The language is very lucid and reader friendly. The adult radiology section gets into the details of all pathologies. Section editors and contributors across systems have laboured to bring about each and every pathology on the reader’s platter. How and why imaging has a crucial role in each modality along with radiopathological correlation is beautifully explained throughout the book. The oncoimaging section is laden with the most advanced and contemporary information about the subspecialty. It deals in not only imaging but also posttreatment − surgery/chemo/radiation evaluation − a cornerstone in oncomanagement. The classifications and staging provided in the section are updated − up to the minute of publication. The field of radiology which has been in vogue since last few years is Intervention Radiology. There is hardly any disease where the intervention radiologist cannot help in healing the patient. The said section deals with vascular and nonvascular interventions in detail. Learning and mastering Intervention Radiology is truly the path ahead for radiologists in coming times. Radiology not only diagnoses the problems of clinicians but also helps saving life. One of the brightest examples of this adage is Emergency Radiology section that deals in detail with trauma and all emergencies encountered in the field of medicine.

Radiology has come a long way from 2D black and white images to interactive stuff. Hence, to serve today’s radiologists, the book is coming out with an interactive eversion. The total content of the book − print and eversions − comes close to 11,000 plus pages. Such a voluminous book would be with you − the reader always in your pocket − be it mobile or iPad. We hope that this book will serve as the primary reference for residents, superspecialist and consultant practicing radiologists in order to facilitate their education and particularly in clinical practice. We are most grateful to our editor, section editors, central associate editors, assistant editors and authors, for providing such lucid illustrative contents. We firmly believe that nothing is impossible for the person who has these six virtues – knowledge, logic, inclination towards science, strong memory, zeal to learn and skill. Happy reading! Dr. Amarnath C

Contributors Section 7: General Abdomen Abhishek Bairy, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Ajay Taranath, Women’s and Children’s Hospital, University of Adelaide, Adelaide, Australia Akriti Gujral, Med Student, American International College of Arts and Sciences – Antigua’s (AICASA), American University of Antigua (AUA), Antigua & Barbuda Amandeep Singh Professor, Department of Radiodiagnosis & Imaging, S.G.R.D. Institute of Medical Sciences & Research, Amritsar; Senior Consultant Radiologist & Managing Director, ACS Diagnostics, Amritsar, India Anit Parihar, King George’s Medical University, Lucknow, India Anju Garg, Department of Radiodiagnosis, Maulana Azad Medical College, New Delhi, India Annirudh Kohli, Head, Department of Radiology & Imaging, Breach Candy Hospital And Research Center, Mumbai, India Anu Epean, Professor, Department of Radiology, CMC, Vellore, India Archana Ahluwalia, Professor, Department of Radiodiagnosis & Imaging, Dayanand Medical College & Hospital, Ludhiana, India

Arul AS Babu, Consultant Interventional Radiologist, Dr Rela Institute Medical Centre, Chennai, India Arun Gupta, Department of Radiology, All India Institute of Medical Sciences, New Delhi, India Aswin Padmanabhan, Consultant Interventional Radiologist, Lisie Hospital, Cochin, India Avinash Parshuram Dhok, Professor & HOD, Department of Radiodiagnosis, NKP Salve Institute of Medical Sciences, Nagpur, India C.V. Kanimozhi, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India Chander Gupta, Director of Radiology, CGA Medical Imaging & Alberta Health Services zone 8, Calgary, Canada Chetana Ramesh Ratnaparkhi, Associate Professor, Department of Radiodiagnosis, All Indian Institute of Medical sciences, Nagpur, India Dasari Ravikiran, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Debraj Sen, Associate Professor, Armed Forces Medical College, Pune, India Deepa Korula, Assistant Professor, SRM Medical College Hospital & Research Centre, Kattankulathur, India Devasenathipathy Kandasamy, Professor, Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India Devinder Pal Singh Dhanota, Assistant Professor, Department of Radiodiagnosis & Imaging, Dayanand Medical College & Hospital, Ludhiana, India Eesha Rajput, Consultant Radiologist, INHS Dhanwantri, Port Blair, Andaman & Nicobar Islands, India

Gautham Shankar, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Geetika Khanna, Associate Division Director Pediatric Radiology, Acting Professor of Radiology and Pediatrics, Emory University School of Medicine, Atlanta, Georgia Gurdarshdeep Singh Madan, Department of Radiodiagnosis, Military Hospital, Chennai, India H.K. Karmalkar, Consultant Radiologist, Medicare Hospital, Indore, India K. Preetha, Consultant Radiologist, Star X diagnostic Centre, Agra, India Kavita Saggar, Professor & Head Radiodiagnosis and Imaging, Dayanand Medical College & Hospital, Ludhiana, India Krishnarjun M, Senior Resident Faculty, Department of Radiodiagnosis, Dr DY Patil Medical College, Hospital and Research Center, Pune, India Lino Piotto, Women’s and Children’s Hospital, University of Adelaide, Adelaide, Australia Maneesh Yadav K, Senior Consultant Vascular and Interventional Radiology, KIMS HEALTH Hospital, Trivandrum, India Manisha Jana, Professor, Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India Megha Nair, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Munawwar Ahmed, Professor, Department of Interventional Radiology, Christian Medical College, Vellore, India Namita Singh, Consultant Radiologist, Telerad Solutions, New Delhi, India Neera Kohli, King George’s Medical University, Lucknow, India

Padma V. Badhe, Professor, Department of Radiology, Seth GSMC and KEM Hospital, Mumbai, India Parveen Sulthana, Consultant Radiologist, Perth Radiological Clinic, WA, Australia Prashant Madhukar Onkar, Professor, Department of Radiodiagnosis, NKP Salve Institute of Medical Sciences, Nagpur, India Preeti Gupta, Associate Professor, Radiology Military Hospital, Hisar, India Priya Nakul Chandak, Consultant Radiologist, Chandak Radiology Center, Nagpur, India Rajagopal KV, Professor, Department of Radiodiagnosis, Kasturba Medical College, Manipal, India Rashmi Dixit, Maulana Azad Medical College, New Delhi, India Raveendran J., Assistant Professor, Institute of Child Health, Chennai, India Ravi Varma, Associate Professor, T.N.M.C & B.Y.L. Nair Hospital, Mumbai, India Revati Tekwani, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Roma Rai, Assistant Professor, INHS Patanjali, Karwar, India Rushit S. Shah, Clinical Associate, Department of Radiology, Jaslok Hospital and Research Centre, Mumbai, India S. Muralinath, Radiologist, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India Sandeep Anil Dhote Assistant Professor, Department of Radiodiagnosis, NKP Salve Institute of Medical Sciences, Nagpur; Consultant, Balaji Sonography Center, Nagpur, India

Santhosh Babu K.B., Senior Resident, Department of Interventional Radiology, Christian Medical College, Vellore, India Sarika Ashish Pongde (Kohar), Senior Resident, Department of Radiodiagnosis, NKP Salve Institute of Medical Sciences, Nagpur, India Satya Jha, Senior Resident, Department of Diagnostic & Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, India Sehajbir Kaur Pannu, Consultant Radiologist, Military Hospital, Patiala, India Shital Ajay Kurve, Senior Resident, Department of Radiodiagnosis, NKP Salve Institute of Medical Sciences, Nagpur, India Shweta Nagar, Director, Shweta Nagar’s Ultrasound Clinic, Indore, India Shyamkumar N. Keshava Professor and Head, Department of Interventional Radiology, Division of Clinical Radiology, Christian Medical College Hospital, Vellore; Editor, Journal of Clinical Interventional Radiology ISVIR; President, Tamil Nadu IRIA, India Soniya Patankar, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Sultan Moinuddin Shaukatali, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Tanvi Modi, Clinical Associate, Department of Radiology, Nanavati Superspeciality Hospital, Mumbai, India Vikash Jain, Consultant Interventional Radiologist, Wockhardt Hospital, Rajkot, India

Vikram Reddy, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Vineet Wadhwa, Consultant Radiologist, Vijaya Medical Center, Vishakhapatnam, India Wong Kang Min, Head & Senior Consultant, Diagnostic Radiology, Changi General Hospital, Singapore Yashant Aswani, Einstein Medical Center, Philadelphia, PA, United States Zillani Alam, Senior Resident, Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India Zunimol PKM, Consultant & Academic Coordinator, KIMS Hospital, Trivendrum, India Section 8: Gastrointestinal Tract Abhishek Jain, Ruby Hall Clinic, Pune, India Aditi Chaitanya Gujarathi-Saraf, Associate Consultant, Radiology, Deenanath Mangeshkar Hospital and Research Center, Pune, India Aditi Chandra, Consultant Radiologist, Department of Radiology and Imaging Sciences, Tata Medical Center, Kolkata, India Anisha Gehani, Consultant Radiologist, Department of Radiology and Imaging Sciences, Tata Medical Center, Kolkata, India Ankit Jain, Clinical Assistant, Department of Radiology, Sir H N Reliance Foundation Hospital, Mumbai, India Ankita Dhawan, Consultant Radiologist, Zydus Hospital, Ahmedabad, India Anuj Bahl, Consultant, Radiology, Sarvodaya Hospital and Research Centre, Faridabad, India Argha Chatterjee, Consultant Radiologist, Department of Radiology and Imaging Sciences, Tata Medical Center,

Kolkata, India Arvind Pandey, Senior Consultant, Medanta – The Medicity Multi-Speciality Hospital, Gurgaon, India Daksh Mehta, Chief Resident, Sir H N Reliance Foundation Hospital, Mumbai, India Disha Lokhandwala, Chief Resident, Department of Radiology, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Divya Kantesaria, Radiologist, Nathalal Parekh Cancer Institute, Rajkot, India Gaurav Goswami, Consultant Radiologist and Clinical Head, CT MR division, Zydus Hospital and Research Centre, Ahmedabad, Gujarat, India Gayathri Achuthan, Sahyadri Hospitals, Pune, India Gurdarshdeep Singh Madan, Head of Department, Department of Radiodiagnosis and Imaging, Military Hospital, Chennai, India Himanshu Gupta, GB Pant Institute of Medical Education and Research (GIPMER), Maulana Azad Medical College, New Delhi, India Komal Ninawe, Baxay Hospital, Vasai, Maharashtra Kulbir Ahlawat, Senior Director Radiology, Medanta – The Medicity Multi-Speciality Hospital, Gurgaon, India Mansi Jantre, Clinical Assistant, Department of Radiology, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Navni Garg, Director and Consultant Radiologist, Sanjeevani Ultrasound and Diagnostic Centre, Faridabad, India Poonam Narang, Director & Professor, GB Pant Institute of Medical Education and Research (GIPMER), Maulana Azad Medical College, New Delhi, India Priya Ghosh, Consultant Radiologist, Department of Radiology and Imaging Sciences, Tata Medical Center, Kolkata, India

Rajan Patel, Ruby Hall Clinic, Pune, India Ravi Chaudhary, Associate Director, Medanta – The Medicity Multi-Speciality Hospital, Gurgaon, India Richa Kothari, Radiologist, Narayana Health, Bengaluru, India Sanjay Desai, Deenanath Mangeshkar Hospital and Research Center, Pune, India Saugata Sen, Consultant Radiologist, Department of Radiology and Imaging Sciences, Tata Medical Center, Kolkata, India Shivsamb Jalkote, Associate Consultant Radiologist, Department of Radiology, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Slesha Bhalja, Clinical assistant, Department of Radiology, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Sonali Sharma, Consultant Radiologist, Park Hospital, Gurgaon, India Sonam Shah, Consultant Radiologist, Apollo Radiology International, Hyderabad, India Soumil Singhal, Associate Consultant, Department of Intervention Radiology, Medanta: The Medicity, Gurgaon, India Soumil Vyas, Consultant Hepato-Biliary-Pancreatic Surgery, Surgical Gastroenterology and Oncology/Liver Transplantation, Sir H N Reliance Foundation Hospital, Mumbai, India Sumit Mukhopadhyay, Senior Consultant, Department of Radiology and Imaging Sciences, Tata Medical Center, Kolkata, India Swarup Nellore, Consultant Radiologist, Department of Radiology, Sir H N Reliance Foundation Hospital and Research Centre, Mumbai, India Swati Mody, Parth Imaging Centre, Rajkot, India

Ujwal Bhure, Fellowship in PET/CT (Switzerland), Additional Director, Department of Nuclear Medicine and PET/CT, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Section 9: Hepatobiliary System Abdul Razik, Consultant Interventional Radiologist, Iqraa Hospital and Research Center, Calicut, India Ajay Jhaveri, Consultant, Gastroenterologist, Jaslok Hospital and Research Center, Mumbai, India Akshay Kumar Saxena, Department of Radiodiagnosis, PGIMER, Chandigarh, India Aman Snehil, Senior Resident, All India Institute of Medical Sciences, Bhopal, India Amar Mukund, Professor (Interventional Radiology), Controller of Examinations, Institute of Liver and Biliary Sciences, New Delhi, India Anirudh Kohli, Head, Department of Radiology & Imaging, Breach Candy Hospital and Research Center, Mumbai, India Anmol Bhatia, Department of Radiodiagnosis, PGIMER, Chandigarh, India Ashish Verma, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Ayushi Agarwal, Senior Resident, All India Institute of Medical Sciences, New Delhi Bhargavi Sovani, Resident, Radiology, Jaslok Hospital and Research Center, Mumbai, India Binit Sureka, Additional Professor, Department of Diagnostic & Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, India Chandan Jyoti Das, Additional Professor, Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India Chandresh Karnavat, Consultant Radiologist, Jaslok Hospital and Research Center, Mumbai, India

Deeksha Bhalla, Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India Deeksha Rastogi, Senior Consultant, Department of Radiology, Sir Ganga Ram Hospital, New Delhi, India Devasenathipathy Kandasamy, Professor, Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India Ishan Kumar, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Janani Baradwaj, Consultant Radiologist, Apollo Radiology International, Chennai, India Janani Kalyanraman, Consultant Radiologist, Gleneagles Global Hospital, Chennai, India Kajal Patel, Associate Professor, Department of Radiology, Smt. G. R. Doshi and Smt. K. M. Mehta Institute of Kidney Diseases and Research Center & Dr. H. L. Trivedi Insitute of Transplantation sciences, Ahmedabad, India Kalpana Bansal, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India Kumble Seetharama Madhusudhan, Additional Professor, Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India L. Murali Krishna, Head of Department & Lead Consultant, Department of Radiolgy and Imaging Sciences, Fortis Vadaplani, Chennai, India M.C. Uthappa, Director Interventional Radiology, Gleneagles Global Hospital, Bengaluru, India M.K. Mittal, Professor, Department of Radiology, VMMC & Safdarjung Hospital, New Delhi, India Mahmoud Al Heidous, Al-Wakra hospital, Hamad Medical Corporation, Doha, Qatar Mangal Subhash Mahajan, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical

College, Pune, India Manisha Jana, Professor, Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India Navjot Singh, Punjab Institute of Medical Sciences, Jalandhar, India Nilesh Doctor, Director, Surgical Gastroenterology, Jaslok Hospital and Research Center, Mumbai, India Nilesh P. Sable, Professor and Radiologist ‘F’, Officer in charge, Conventional Radiology and Regulatory Norms (AERB & PCPNDT), Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India Payal Agrawal, Resident Radiology, Jaslok Hospital and Research Center, Mumbai, India Pooja Punjani Vyas, Consultant in Ultrasonology, Jaslok Hospital and Research Center, Mumbai, India Poonam Narang, Director & Professor, G.B. Pant Hospital, New Delhi, India Priscilla Joshi, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India Radhika Batra, Associate Professor, Department of Radiodiagnosis, Maulana Azad Medical College, New Delhi, India Ramesh Chander, Professor and Head, Department of Radiodiagnosis, Punjab Institute of Medical Sciences, Jalandhar, India Rashmi Badhe, Senior Consultant Radiologist, Global Hospitals, Mumbai, India Ravi Mohanka, Chief Liver Transplant Surgeon, Global Hospitals, Mumbai, India Ritu K. Kashikar, Senior Consultant Radiologist, Jaslok Hopsital and Research center, Mumbai, India Rory L. Cochran, Massachusetts General Hospital, Department of Radiology, Harvard Medical School, Boston, USA

S. Murthy Chennapragada, Sydney Children’s Hospitals Network, The Children’s Hospital at Westmead, Westmead, Australia Samarjit Ghuman, Senior Consultant, Department of CT & MRI, Sir Ganga Ram Hospital, New Delhi, India Sanjeeva Kalva, Professor of Radiology, Massachusetts General Hospital, Harvard Medical School, USA Sapna Singh, Maulana Azad Medical College, New Delhi, India Satya Jha, Senior Resident, Department of Diagnostic & Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, India Seema Sud, Senior Consultant, Department of CT & MRI, Sir Ganga Ram Hospital, New Delhi, India Shaleen Rana, Consultant Radiologist (Diagnostic and Interventional Radiology), Paras Hospital, Panchkula, India Shreya Shukla, Senior Resident, Jaslok Hospital and Research Center, Mumbai, India Srikanth Moorthy, Head and Professor at the Department of Radiology, Amrita Institute, Kochi, India Subramaniyan Ramanathan, Weill Cornell Medicine-New York (Qatar campus), Consultant Clinical imaging, Al Wakra Hospital, Hamad Medical Corporation, Qatar Swapnil Sheth, Consultant, Department Radiology, Sir Ganga Ram Hospital, New Delhi, India T.B.S. Buxi, Director, Department of CT & MRI, Sir Ganga Ram Hospital, New Delhi, India Tahiya Salem Alyafei, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar Vandana Jahanvi, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India

Vijay Kumar K.R., Head of Department & Professor of Radiodiagnosis, Banglore Medical College and Research Institute, Banglore, India Vineetha Raghu, Department of Radiology, Columbia Asia Referral Hospital, Yeshwanthpur, India Vivek Shetty, Consultant Surgeon, Department of Surgical Gastroenterology, Jaslok Hospital and Research Center, Mumbai, India Section 10: Urinary Tract Disease Aakanksha Agarwal, Clinical Fellow, University of British Columbia, Vancouver, Canada Abhinav Ranwaka, Medcare Institute of Diagnostics, Mumbai, India Abhishek Mahajan, Consultant Radiologist, Department of Imaging, The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK Aditi Chaitanya Gujarathi-Saraf, Associate Consultant, Radiology, Deenanath Mangeshkar Hospital and Research Center, Pune, India Ajay Prashanth Dsouza, Al Jalila Children Specialty Hospital, Dubai, United Arab Emirates Akshay Kumar Saxena, Department of Radiodiagnosis, PGIMER, Chandigarh, India Amandeep Arora, Assistant Professor, Uro-oncology, Tata Memorial Centre, Mumbai, India Amit Kumar Kamble, Government Medical College, Chandrapur, India Amitha Vikrama, HOD Radiology and Intervention, Apollo Hospitals, Bangalore, India Amol Vishwanathrao Khandale, Manipal Hospital, Bangalore, India Anand Mukund Rahalkar, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India

Aniruddha Joshi, Consultant Radiologist, Deenanath Mangeshkar Hospital and Research Center, Pune, India Ankur Gupta, Mahajan Imaging, Sports Imaging Centre, Safdarjung Hospital, New Delhi, India Anmol Bhatia, Associate Professor, Department of Radiodiagnosis, PGIMER, Chandigarh, India Anu Bhandari, Professor, SMS Medical College, Jaipur, India Aparna Katdare, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Arya Mehta, Senior Clinical Fellow, Northampton General Hospital, UK Balasubramanyam Shankar, Manipal Hospital, Bangalore, India Bhalchandra Kashyapi, Urologic Cancer Surgeon, Deenanath Mangeshkar Hospital and Research Center, Pune, India Bhavana Girishekar, Manipal Hospital, Bangalore, India Bhavdeep Rabadiya, Infocus Diagnostics, Ahmedabad, India C. Obul Amani, Manipal Hospital, Bangalore, India Chandan J. Das, Additional Professor of Radiology, All India Institute of Medical Sciences, New Delhi, India Chellapilla Manimala Rupa, Manipal Hospital, Bangalore, India Deekshitha Devadas, Manipal Hospital, Bangalore, India Deepak Chandra Reddy, Military Hospital, Jammu, India Devasenathipathy Kandasamy, Professor, Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India

Dhananjay Bokare, Consultant Urologist, American Institute of Oncology, Nangia Speciality Hospital, Nagpur, India Dhanesh Kamerkar, Ruby Hall Clinic, Pune, India Dipak Patel, Infocus Diagnostics, Ahmedabad, India Divya Sankar, Radiologist, Manipal Hospital, Bangalore, India Drushi Patel, Consultant Radiologist, Gujarat Imaging Centre, Samved Hospital, Ahmedabad, India E. Sibi, Classified Specialist, Military Hospital, Hyderabad, India Gagan Prakash, Professor, Uro-oncology, Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Ganesh Bakshi, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Geetika Khanna, Associate Division Director Pediatric Radiology, Acting Professor of Radiology and Pediatrics, Emory University School of Medicine, Atlanta, Georgia Giriraj Singh, Command Hospital, Western Command Chandimandir Registered Hospital, Panchkula, India Govind B. Chavhan Staff Pediatric Radiologist, The Hospital for Sick Children; Professor, Medical Imaging, University of Toronto, Canada Gurdarshdeep Singh Madan, Department of Radiodiagnosis, Military Hospital, Chennai, India Jagneet Singh, Mahajan Imaging, New Delhi, India Jaitheerth Karthyarath, Manipal Hospital, Bangalore, India John D’Souza, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India

Jyotindu Debnath, Professor & HOD, Department of Radiodiagnosis, Army Hospital (Research), New Delhi, India Kavya S. Kaushik, Manipal Hospital, Bangalore, India Krishnendhu M.S., Manipal Hospital, Bangalore, India Kunal Gala, Fellowship in Interventional Radiology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India L Praveen Kumar, Urologist, Command Hospital Lucknow, India M.D. Rahalkar, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India M.H. Thakur, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Mangal Mahajan, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India MC Uthappa, Director Interventional Radiology, Gleneagles Global Hospital, Bengaluru, India Mridula Muthe, Assistant Professor, LTMMC & LTMGH, Mumbai, India Mrinal Matish, Manipal Hospital, Bangalore, India Mulla Muniza Murtuza, Manipal Hospital, Bangalore, India Nagesh Seth, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India Namita Singh, Consultant Radiologist, Telerad Solutions, New Delhi, India Naren Hemachandran, Fellow of Gastrointestinal Radiology & Intervention, Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India

Nilay Nimbalkar Director, Precision Scan and Research Centre; Consultant Radiologist, Seven Star Hospital, Nagpur, India Nilesh P. Sable, Professor and Radiologist ‘F’, Officer in charge, Conventional Radiology and Regulatory Norms (AERB & PCPNDT), Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India Nupur Bit, Consultant Vascular Surgeon, Ruby Hall Clinic, Pune, India Onkar B. Auti, Consultant Radiologist and Cardiac Imaging Specialist, Ruby Hall Clinic, Pune, India Palak Bhavesh Popat, Associate Professor and Consultant, Officer in Charge, Breast Imaging and Interventions, Department of Radiology, Tata Memorial Hospital, Mumbai, India Pooja G. Patil, Manipal Hospital, Bangalore, India Poonam Parameshwar Hegde, Manipal Hospital, Bangalore, India Pramesh Reddy, Manipal Hospital, Bangalore, India Prashant Dev, Consultant Radiologist, Ruby Hall Clinic, Pune, India Preeti Bhasin, Manipal Hospital, Bangalore, India Preeti Mundhada, Manipal Hospital, Bangalore, India Priscilla Joshi, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India Priyanka Kalidindi, Manipal Hospital, Bangalore, India Punya Jaydev, Radiologist, Manipal Hospital, Bangalore, India Rahul Suhas Whatkar, Ruby Hall Clinic, Pune, India Raju Augustine George, Professor & HOD, Department of Radiodiagnosis, Command Hospital (Air Force), Bengaluru, India

Rohan S. Valsangkar, Consultant Urologist, Deenanath Mangeshkar Hospital and Research Center, Pune, India Rohit Aggarwal, Professor Radiology, Armed Forces Medical College Pune & Command Hospital, Pune, India Roma Rai, Assistant Professor, INHS Patanjali, Karwar, India Rupa Ananthasivan, Manipal Hospital, Bangalore, India Rushabh Shah, Infocus Diagnostics, Ahmedabad, India S. Babu Peter, Professor, Department of Radiology, Madras Medical College, Chennai, India Sahana J., Manipal Hospital, Bangalore, India Samruddhi Sonawane, Ruby Hall Clinic, Pune, India Sanjay Mehta, Infocus Diagnostics, Ahmedabad, India Sannidhi K.S., Manipal Hospital, Bangalore, India Savinay Kapur, Mahajan Imaging, Sports Imaging Centre, Safdarjung Hospital, New Delhi, India Shivani Mahajan, Shree Krishna Hospital, Karamsad, India Sudarshan Rawat, Manipal Hospital, Bangalore, India Sunil Jhakhar, Associate Professor, SMS Medical College, Jaipur, India Suyash Kulkarni, Fellowship in Interventional Radiology, Professor, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Tanvi Vaidya, Consultant Radiologist, Ruby Hall Clinic, Pune, India Uday Patil, Manipal Hospital, Bangalore, India Ujjwal Nigam, Manipal Hospital, Bangalore, India Ullas V Acharya, Manipal Hospital, Bangalore, India Urvashi Jain, Manipal Hospital, Bangalore, India

Vandana Jahanvi, Professor, Department of Radiodiagnosis, Bharati Vidyapeeth DTU Medical College, Pune, India Vasantha Kumar Venugopal, Mahajan Imaging, Defence Colony, New Delhi, India Vikas Batra, Mahajan Imaging, Sports Imaging Centre, Safdarjung Hospital, New Delhi, India Vikash Jain, Consultant Interventional Radiologist, Wockhardt Hospital, Rajkot, India Vinay V. Belaval, Belcity Scan and Diagnostic Center, Belgavi, India Vishal Shah, Infocus Diagnostics, Ahmedabad, India Yusuf Masood, Manipal Hospital, Bangalore, India Section 11: Reproductive System Abhilash Kumar, Senior Resident I, Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India Ajay Kumar Singh, Senior Resident III, Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India Ajaykumar C. Morani, The University of Texas MD Anderson Cancer Center, Houston, Texas Akash Kumar B.Y., Consultant Radiologist, Sp Multispeciality Hospital Pvt Ltd, Trivandrum, India Amit Joshi, Professor, Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India Amithavikrama, Head of Department, Radiology and Intervention, Apollo Hospitals, Bangalore, India Anidudha Kulkarni, Professor of Radiology, Ashwini Medical college, Solapur, India Ankita Dhawan, Consultant Radiologist, Zydus Hospital, Ahmedabad, India Anupama Chandrasekharan, Professor, Department of Radiology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India

Aparna Katdare, Assistant Professor, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Athul D., Consultant Radiologist, Mar Baselios Medical Mission Hospital, Cochin, India Balaji Iyemperumal, Associate Professor, Thanjavur Medical College, Thanjavur, India Bhawna, Professor of Radiodiagnosis, Sri Ramachandra Institute of Higher Education & Research, Porur, Chennai, India Bobji Kettay, Consultant Radiologist, Sunway Athena Diagnostics, Chennai, India Dayala Sundaram, Consultant Radiologist, Anderson Diagnostics, Chennai, India Devasenathipathy Kandasamy, Professor, Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India Disha Lokhandwala, Chief Resident, Department of Radiology, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Fouzal, Assistant Professor, Department of Radiology, Tirunelveli Medical College, Tirunelveli, India Ganesh Bakshi, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India Ganesh Rajagopal, Senior Consultant Radiologist, Meenakshi Mission Hospital, Madurai, India Govind B. Chavhan Staff Pediatric Radiologist, The Hospital for Sick Children; Professor, Medical Imaging, University of Toronto, Canada Hanna Dalla Pria, The University of Texas MD Anderson Cancer Center, Houston, Texas Jaishree Rajakumar, Consultant Radiologist, Al Hilal Hospital, Kingdom of Bahrain

Jansi Vinod, Consultant Radiologist, Naruvi Hospital, Vellore, India Jay Mehta, Consultant Pathologist, Centre for Oncopathology (supported by Tata Trusts), Mumbai, India John De. Lindsay, Consultanat Radiologist, Metro Scans, Trivandrum, India K. Geetha, Associate Professor, Department of Radiology, Government Kilpauk Medical College, Kilpauk, Chennai, India Kingston Vijay, Consultant Radiologist, Nellai Scans and Diagnostic Centre, Tirunelveli, India Kumarsampath, Radiologist, Dr Kamakshi Memorial Hospital, Chennai, India M. Alamelu, Assistant Professor, Department of Radiology, Government Medical College, Pudukkottai, India M.H. Thakur, Professor, Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India Mayur Virarkar, The University of Texas MD Anderson Cancer Center, Houston, Texas Mohammed M. Saleh, The University of Texas MD Anderson Cancer Center, Houston, Texas Mohideen Ashraf A., Assistant Professor, Department of Radiology, BIR Madras Medical College, Chennai, India N. Sundari, Professor of Radiology, Madurai Medical college, Madurai, India Natasha Gupta, Consultant Radiology, UCMS & GTB Hospital and Chacha Nehru Bal Chikitsalaya Pediatric Superspecialty Hospital, New Delhi, India Neelam Jain, Consultant Radiologist, Discovery Diagnostics and Jain Ultrasound Centre, Jamshedpur, India

Nilesh P. Sable, Professor and Radiologist ‘F’, Officer in charge, Conventional Radiology and Regulatory Norms (AERB & PCPNDT), Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India P. Reginald Wesley, Consultant Radiologist, VJ Hospital, Tirunelveli, India P.K. Srivastava Ex Professor Radiodiagnosis, King George’s Medical University, Lucknow; Director – Yashdeep Ultrasound Centres Lucknow; Chairman – Ultrasound Education and Research Foundation, Lucknow, India Palak Bhavesh Popat, Associate Professor and Consultant, Officer in charge, Breast Imaging and Interventions, Department of Radiology, Tata Memorial Hospital, Mumbai, India Porkodi Dharmalingam, Radiologist, Kilpauk Medical College, Chennai, India Priya Bhosale, The University of Texas MD Anderson Cancer Center, Houston, Texas Pushpinder Khera, HOD, Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, India Rajani Gorantla, Associate Professor & Consultant Radiologist, NRI Academy of Medical Sciences, Chinakakani, India Ravichandran, Professor of Radiology, Madurai Medical College, Madurai, India Rijo Mathew Choorakuttil Chairman & Chief Radiologist, Insta Specialty Hospitals, Kochi, Kerala; Amma Centre for Diagnosis & Preventive Medicine, Kochi, India Rupa Renganathan, Lead Consultant – Breast and Women’s Imaging, Kovai Medical Center and Hospital,

Coimbatore, India Saloni Dagar, Department of Radiology, University College of Medical Sciences, Guru Teg Bahadur Hospital, New Delhi, India Saranya, Assistant Profesor, Department of Radiology, Government Kilpauk Medical College, Kilpauk, Chennai, India Shalini Warman, Specialist, Department of Obstetrics and Gynecology, Tata Main Hospital, Jamshedpur, India Siddhi Chawla, Department of Radiology, University College of Medical Sciences, Guru Teg Bahadur Hospital, New Delhi, India Sripriya Thiruvengadathan, Consultant, Sri Scans, Chennai, India Subhash Taylor, Consultant Radiologist, Subash Ultrasound Imaging Centre, Bhilwara, India Subhashree C, Professor and HOD, Department of Radiology, Government Medical College & ESI Hospital, Coimbatore, India Suchana Kushvaha, Senior Consultant, Daffodils (A unit of Artemis Hospitals), Gurugram, India Sudha Karnan, Radiologist, Anderson Diagnostics, Chennai, India Suhasini Balasubramaniam, Professor, Government Medical College, Omandurar Govt Estate, Chennai, India Sumathy, Professor, Madurai Medical College, Madurai, India Sumeena, Assistant Professor, Department of Radiology, Government Kilpauk Medical College, Kilpauk, Chennai, India Suriyaprakash Nagarajan, Assistant Professor, Department of Radiodiagnosis, Government Medical College Hospital, Tiruppur, India Suyash Kulkarni, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India

Ujjwal Bhure, Fellowship in PET/CT (Switzerland), Additional Director, Department of Nuclear Medicine and PET/CT, Sir H N Reliance Foundation Hospital and Research Center, Mumbai, India Usha Nandhini Ganeshan, Assistant Professor, Department of Radiology, Government Kilpauk Medical College, Kilpauk, Chennai, India V. Sivakumar, Consultant, Scans World, Chennai, India Vasumathy, Consultant Radiologist, Anderson diagnostics, Chennai, India Venkatraman Indiran, Professor, Sree Balaji Medical college & Hospital, Bharath Institute of Higher Education and Research, Chennai, India Vidya, Consultant Radiologist, Anderson Diagnostics, Chennai, India Vivek Kashyap Founder Director, Imaging Masterclasses; Chairman and Consultant in Reproductive Ultrasound, Dr. Kashyap’s Diagnostics, New Delhi, India Yash Sharma, Department of Radiology, University College of Medical Sciences, Guru Teg Bahadur Hospital, New Delhi, India Yashodhara Pradeep, Professor & HOD, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India Yuva Bala Kumaran, Associate Professor and Consultant Fetal Rradiologist, Department of Radiology, Melmaruvathur Adhiparasakthi Institute of Medical Sciences And Research (MAPIMS), Kanchipuram, India

List of Illustrations Fig. 7.1.1.1 Positioning for supine (anteroposterior) radiograph of the abdomen. Fig. 7.1.1.2 Positioning for prone (posteroanterior) radiograph of the abdomen. Fig. 7.1.1.3 Positioning for erect (anteroposterior) projection. Fig. 7.1.1.4 Positioning for left lateral decubitus (anteroposterior) projection. Fig. 7.1.1.5 Positioning for dorsal decubitus radiograph (right lateral view). Fig. 7.1.1.6 Positioning for left lateral abdominal radiograph. Fig. 7.1.1.7 The four abdominal quadrants. Fig. 7.1.1.8 Abdominal regions. Fig. 7.1.1.9 (A) Normal appearance of jejunum in left lumbar region with numerous closely spaced valvulae conniventes (arrow). (B) Comparatively fewer valvulae conniventes in ileal loops in right iliac region (block arrow). Gastric shadow (G) is also seen in left hypochondriac region. Fig. 7.1.1.10 Normal large bowel shows fecal shadows mixed with gas shadows, as seen in ascending colon (arrow). Fig. 7.1.1.11 Normal organs shadows seen on an abdominal radiograph – Liver (L), Kidneys (K), Spleen (S), Urinary bladder (U), Psoas muscles (P). Properitoneal fat stripe (F) is seen as a lucent line along bilateral flanks.

Fig. 7.1.1.12 Soft tissue density mass (arrowhead) seen in left hypochondrium, epigastric region extending to right hypochondrium with inferior displacement of transverse colon. This is due to overdistended stomach and partial gastric outlet obstruction. Fig. 7.1.1.13 Dilated small bowel loops (arrows) as seen on supine radiograph in distal obstruction. Valvulae conniventes (block arrow) help in identifying these loops as small bowel. Fig. 7.1.1.14 Multiple dilated bowel loops (arrows) in central part of abdomen with air fluid levels (arrowheads) due to distal small bowel obstruction. Note paucity of gas in colon with absent rectal gas. Fig. 7.1.1.15 Dilated proximal jejunal loops with rows of gas trapped between valvulae conniventes distally – string-of-pearls appearance (arrow). Fig. 7.1.1.16 Supine abdominal radiograph with dilated small bowel loops (block arrow). Pneumobilia is seen (arrow) consistent with gall stone ileus. Fig. 7.1.1.17 Inverted U appearance of sigmoid volvulus. The central opacity is formed by sigmoid mesocolon (arrow), flanked by dilated ahaustral loops of sigmoid colon (asterisk). Note the left bottom to right upward direction with liver overlap sign. Proximal large bowel loops are also dilated (arrowhead). Fig. 7.1.1.18 Dilated large bowel loop extending from right iliac to left hypochondriac quadrant, with an embryo like appearance (asterisk). Dilated small bowel loops (arrows) are seen with collapsed large bowel loops. Fig. 7.1.1.19 Soft tissue mass in distal transverse colon with crescent sign (arrows). Fig. 7.1.1.20 (A) Appendicolith (arrow) seen in right iliac region with prominent small bowel loops. (B) Blurring of properitoneal fat line (block arrow), minimal scoliosis with leftward convexity (arrowhead). Fig. 7.1.1.21 Supine radiograph with gross dilatation of large bowel loops, predominantly transverse colon (arrow) with loss of haustrations – toxic megacolon.

Fig. 7.1.1.22 Thickened large bowel haustra giving a thumbprint appearance (arrowheads) in transverse colon. This is seen in ischaemic bowel. Fig. 7.1.1.23 Gas shadows in right scrotal region (arrows) appearing like bowel loops – right inguinal hernia. Fig. 7.1.1.24 (A) Erect abdominal radiograph with free air under both domes of diaphragm (arrowheads) consistent with pneumoperitoneum. Few small bowel air fluid levels are seen in left lumbar region (block arrow). Note blurring of properitoneal fat line (arrow). (B) Erect chest posteroanterior radiograph demonstrating even a small amount of free air under the diaphragm (arrow). (C) Left lateral decubitus radiograph in another patient which demonstrates a small amount of free air (arrow) adjacent to right hepatic margin. (D) Air outlining the inner and outer aspect of bowel wall (arrows), known as Rigler’s sign. Fig. 7.1.1.25 (A) Hepatic edge sign air outlining the inferior hepatic edge (arrowhead) on a supine radiograph. Also see the lucency overlying the liver (asterisk) and pneumatosis intestinalis seen as gas lucencies along bowel wall (arrows). (B) Air in peritoneal cavity enhances visualization of the urachus (arrows) in hypogastric region. (C) Air foci are seen along large and small bowel wall (arrows) in right lumbar region and right iliac region, due to bowel ischaemia. Dilated small bowel loops with air fluid levels are seen in left half of the abdomen (arrowheads). Fig. 7.1.1.26 (A) Linear gas shadows (arrows) in right hypochondriac region, predominantly centrally located suggesting pneumobilia. (B) A pediatric radiograph with branching air shadows (arrowheads) in right hypochondriac region, reaching up to the periphery of liver suggestive of pneumoporta. Fig. 7.1.1.27 Air foci along the outline of right kidney (arrows) and right ureter (arrowhead), characteristic of emphysematous pyelonephritis.

Fig. 7.1.1.28 Chunky calcifications across the midline along T12–L2 levels, outlining the pancreatic parenchyma as seen in calcific pancreatitis. Fig. 7.1.1.29 (A) Gall stone (asterisk) appearing as a lamellated calcific density in right hypochondriac region, along inferior margin of liver (block arrows). It is differentiated from irregular right lower pole calyceal calculus (arrowhead) in figure (B) based on location and shape. See also right ureteric calculi overlapping L4 transverse process (arrow). Fig. 7.1.1.30 Faint calcific foci (arrows) forming a globular soft tissue density structure in lower abdomen, right paramedian region – calcified aortic aneurysm. Fig. 7.1.1.31 Multiple tooth-like calcific densities (arrows) in pelvis with adjacent fatty lucency (asterisk), characteristic of an ovarian dermoid. Fig. 7.1.1.32 Mottled densities (asterisk) in right upper and lower quadrants, with medial deviation of right sided DJ stent, raising possibility of a retroperitoneal abscess causing mass effect. Fig. 7.1.1.33 (A) Mottled, bubbly lucencies with air fluid levels (arrowheads) in right subdiaphragmatic region. (B) Tubular lucency with intermittent linear opacities (arrows) representing haustrations. This helps differentiate Chilaiditi syndrome from subdiaphragmatic abscess in A. Fig. 7.1.1.34 Enlarged liver shadow with lower margin of right lobe reaching iliac region. This could be due to diffuse hepatomegaly. Fig. 7.1.1.35 Bullet seen in right iliac region superimposed over right sacroiliac joint. Fig. 7.1.1.36 Incidental detection of dagger sign (arrow), bamboo spine appearance due to syndesmophytes (block arrow) with bilateral sacroiliac joint ankylosis (arrowheads), classical of ankylosing spondylitis. Fig. 7.1.1.37 Linear fibrotic changes (arrow) in left lower zone of lung, with lucency (arrowheads) below it

mimicking pneumoperitoneum. Fig. 7.1.1.38 Radiography is commonly done to check for appropriate positioning of DJ stents (arrow). Fig. 7.1.1.39 Patient with ileal perforation with air under the diaphragm (asterisk). Linear gas shadows (arrows) are seen overlapping left half of abdomen – subcutaneous abdominal wall emphysema. Fig. 7.1.2.1 (A) Normal pharynx AP radiograph. (B) Normal pharynx Lateral radiograph. (C) Lateral radiograph of pharynx. (D) Aspiration of barium. Note the barium outlining the trachea. (E) AP radiograph showing pharynx. Note the epiglottis seen as a crescentic filling defect and flow defect normally seen due to thyroid cartilage. (F) Lateral radiograph showing pharynx. (G) AP mucosal relief radiograph of pharynx. (H) Lateral mucosal relief radiograph of pharynx. Fig. 7.1.2.2 (A) AP radiograph Full column of thoracic oesophagus. (B) lateral radiograph of Full column of thoracic oesophagus. (C) Mucosal relief radiograph of thoracic oesophagus. Fig. 7.1.2.3 (A) AP full column radiograph of gastroesophageal junction. (B) AP mucosal relief radiograph of gastroesophageal junction. Fig. 7.1.2.4 Lateral view Full column oesophagogram of distal oesophagus and GE junction. Fig. 7.1.2.5 Pharyngeal ears. Fig. 7.1.2.6 Parts of oesophagus on oesophagogram: (A) supra aortic, (B) aortic, (C) interaortico bronchial, (D) retrobronchial, (E) retrocardiac, (F) epiphrenic. Fig. 7.1.2.7 Lateral cervical phase showing posterior impression of cricopharyngeus. Fig. 7.1.2.8 One single contrast LPO projection of proximal thoracic oesophagus showing pseudodiverticular appearance of inter aortic bronchial segment. Fig. 7.1.2.9 (A) Longitudinal folds of oesophagus. (B) Transverse folds.

Fig. 7.1.2.10 Cardiac rosette. Fig. 7.1.2.11 AP view(A) and Lateral view(B) of Oesophagogram shows the Z line. Fig. 7.1.2.12 (A) Intramural oesophageal mass (Leiomyoma). (B) Extrinsic impression over the retrocardiac segment along the left lateral wall due to enlarged left atrium. Note the estimated centre of extrinsic impression is extraluminal. Fig. 7.1.2.13 (A) PA chest radiograph in achalasia cardia showing air-fluid level and dilated oesophagus. (B) Achalasia cardia showing bird beak configuration. (C) Achalasia cardia with tertiary contractions. Note smooth high-grade narrowing. (D) Achalasia cardia with epiphrenic diverticulum. Fig. 7.1.2.14 (A) AP radiograph showing Cricopharyngeal achalasia. Note the radiolucent band at pharyngo oesophageal junction with proximal dilatation. (B) Lateral radiograph in the same patient shows prominence of the unrelaxed cricopharyngeus muscle posteriorly. Fig. 7.1.2.15 (A) Corkscrew oesophagus appearance in DES. (B) Lateral radiograph in the same patient with typical rosary bead appearance of DES. Fig. 7.1.2.16 (A) Oesophagogram in scleroderma patient. Note the dilated a peristaltic thoracic oesophagus. (B) Patulous GE junction in scleroderma. (C) Radiograph of hand in the same patient. Note the acro-osteolysis. (D) Frontal X-ray chest in the same patient showing reticular pattern consistent with ILD. Fig. 7.1.2.17 (A) Candida esophagitis with multiple plaque like lesions. Plaques have discrete borders and longitudinal orientation. (B) Candida esophagitis with a shaggy oesophagus. (C) Chronic mucocutaneous candidiasis with oesophageal stricture formation. Fig. 7.1.2.18 Herpes esophagitis. Note discrete superficial ulcers in retrobronchial and retrocardiac segments.

Fig. 7.1.2.19 (A) CMV esophagitis. Note multiple discrete superficial ulceration, mucosal nodularity and shallow ulceration. (B) CMV esophagitis. Fig. 7.1.2.20 (A) Tuberculous esophagitis. Note the sinus tract extending into mediastinum and the left hilar lymph node. (B) Tuberculous esophagitis. Note the sinus tract. Fig. 7.1.2.21 (A) Reflux esophagitis with hiatal hernia. (B) RT induced reflux esophagitis. Fig. 7.1.2.22 (A) Acute caustic esophagitis. Note oesophageal intramural pseudodiverticulosis. (B) Caustic esophagitis with involvement of upper oesophagus and pharynx. (C) Corrosive oesophageal stricture with asymmetric scarring causing irregular oesophageal contour. (D) Corrosive oesophageal stricture. Note long segment smooth stricture. (E) Case of corrosive esophagitis with involvement of stomach and gastric outlet obstruction. Fig. 7.1.2.23 (A) Oesophageal leiomyoma. (B) Oesophageal leiomyoma. Fig. 7.1.2.24 Oesophageal polyp seen as filling defect. Fig. 7.1.2.25 Oesophageal polyp giving etched in white appearance. Fig. 7.1.2.26 (A) Infiltrative oesophageal carcinoma. Note the irregular luminal narrowing, well-defined proximal and distal margins. (B) Infiltrative oesophageal carcinoma. Fig. 7.1.2.27 (A) Polypoidal oesophageal carcinoma. (B) Polypoidal oesophageal carcinoma. Fig. 7.1.2.28 (A) Ulceroproliferative oesophageal carcinoma. Note the oesophageal communication with the left main bronchus. (B) Ulcerative oesophageal carcinoma. Note the irregular longitudinal ulcer within the oesophageal mass. Fig. 7.1.2.29 Varicoid form of oesophageal carcinoma. Fig. 7.1.2.30 Tracheobronchial Fistula in a case of carcinoma oesophagus.

Fig. 7.1.2.31 Carcinoma oesophagus with tracheobronchial fistula. Fig. 7.1.2.32 Metastatic oesophageal carcinoma. Note the lytic lesion in C6 cervical vertebral body. Fig. 7.1.2.33 (A–D) Leiomyosarcoma in oesophagus. Note large, lobulated submucosal mass with breech in the anterior wall. Fig. 7.1.2.34 (A) AP radiograph of Epiphrenic diverticulum. (B) Lateral radiograph of Epiphrenic diverticulum. (C) Pulsion diverticula. Fig. 7.1.2.35 (A and B) AP and lateral radiographs in Killian Jamieson diverticulum. Fig. 7.1.2.36 (A and B) AP and lateral radiograph of Lateral pharyngeal diverticulum. Fig. 7.1.2.37 Schatzki ring. Fig. 7.1.2.38 Sliding hiatus hernia. Fig. 7.1.2.39 Paraoesophageal hiatus hernia. Fig. 7.1.2.40 (A and B) AP and lateral radiograph showing Type III hiatus hernia. Fig. 7.1.2.41 Smooth extrinsic impression on the anterior wall of retrocardiac segment of oesophagus due to enlarged left atrium. Fig. 7.1.2.42 Extrinsic impression over the retrocardiac segment due to tortuous aorta. Fig. 7.1.2.43 Extrinsic impression on posterior wall of oesophagus due to osteophytes and discs. Fig. 7.1.2.44 Beak like posterior impression of ARSA. Fig. 7.1.2.45 (A) AP radiograph showing Oesophageal and laryngeal web. Note the jet phenomenon. (B) Lateral radiograph showing oesophageal web. (C) AP radiograph in the same patient as in part (B). Fig. 7.1.2.46 Aspiration of barium. Fig. 7.1.2.1.47 (A) Spot image of Upper GI barium series showing cardiac rosette. (B) Supine RPO spot radiograph of Upper GI barium series showing cardiac

rosette and DC of fundus. (C) Upper GI barium spot image showing parts of stomach. (D) Spot radiograph of the duodenal bulb and C loop. Fig. 7.1.2.1.48 (A) Erect AP radiograph showing cascade stomach. (B) Erect lateral radiograph showing cascade stomach with cup and spill appearance. Fig. 7.1.2.1.49 (A) Pertinent radiological anatomy of D cap. (B) Spot film showing DC of D cap, D2 and D3. (C) Spot film showing C loops of duodenum. Fig. 7.1.2.1.50 (A) Spot radiograph showing Duodenum Inversum. (B) Spot radiograph showing Duodenum inversum with duodenitis (thick and irregular mucosal folds). Fig. 7.1.2.1.51 (A) Spot supine radiograph showing a dependent ulcer along the lesser curvature. (B) Spot radiograph showing Ulcer along the lesser curvature. Note the thickening of the gastric rugae in gastritis. (C) Spot radiograph showing a dependent ulcer along lesser curvature in the posterior wall. Note: Folds radiating to the edge of the ulcer crater. (D) Thickened gastric rugae in a case of gastritis. Fig. 7.1.2.1.52 (A) Spot radiograph of duodenum showing bulbar ulcer with radiating folds converging to the edge of ulcer. (B) Spot radiograph of duodenum showing bulbar ulcer. Fig. 7.1.2.1.53 (A) Spot radiograph showing post bulbar duodenal narrowing. (B) Spot radiograph DC showing post bulbar duodenal narrowing. (C) Gastric Outlet Obstruction in a case of chronic duodenal ulcer. Fig. 7.1.2.1.54 Spot film of duodenum showing trifoliate duodenum in a case of chronic duodenal ulcer. Fig. 7.1.2.1.55 (A) Gastritis. Polyps in non dependent wall with etched in white appearance. (B) Polyp on the dependant wall seen as a filling defect in the barium pool. Note other polyps seen in profile view in the fundus. Fig. 7.1.2.1.56 Gastric GIST. (A) Distortion of the fundus and proximal body of stomach due to GIST. (B)

Axial CT with oral contrast image showing a large lobulated GIST arising from fundus of the stomach. (C) Coronal CT image showing the Gastric GIST in the same patient. Fig. 7.1.2.1.57 (A) Polypoidal gastric Carcinoma. (B) Polypoidal gastric Carcinoma. (C) Carcinoma stomach with duodenal metastasis. (D) Tea pot deformity of the stomach due to gastric carcinoma. Fig. 7.1.2.1.58 Diffuse infiltrative (Scirrhous) Carcinoma of the stomach. Note the markedly narrowed gastric lumen in body and antrum with loss of distensibility. Fig. 7.1.2.1.59 Gastric Lymphoma. (A) Lymphomatous infiltration of the gastric wall. (B) Thickened irregular folds involving the body and fundus. Fig. 7.1.2.1.60 Gastric diverticulum. Fig. 7.1.2.1.61 (A) Duodenal diverticulae. (B) Duodenal diverticula with diverticulitis. Note the irregular shape. (C) Duodenal Pseudodiverticulum. Fig. 7.1.2.1.62 Organoaxial gastric volvulus. Fig. 7.1.2.1.63 Trichobezoar. (A) Abnormal radiopacity in the gastric lumen. (B) Axial CT image showing trichobezoar within the stomach. Fig. 7.1.2.1.64 Tuberculous Duodenal stricture with duodenal diverticulum (D2). Fig. 7.1.2.1.65 Gastric varices. Fig. 7.1.2.2.66 (A) Fifteen minutes supine radiograph. Note the normal feathery appearance of jejunum. (B) 30 minutes prone radiograph. Note the featureless appearance of ileum. (C) 1 hour radiograph. (D) 2 hours radiograph. (E) 3 hours radiograph. (F) 4 hours radiograph. (G) 5 hours radiograph. (H) Spot radiograph of IC junction. (I) Spot radiograph showing IC junction post air insufflation. Fig. 7.1.2.2.67 Peroral Pneumocolon.

Fig. 7.1.2.2.68 (A–C) Multiple jejunal polyps in a case of Peutz-Jeghers syndrome. Fig. 7.1.2.2.69 (A) Duodenal and jejunal diverticulae. (B) Jejunal diverticulosis. Fig. 7.1.2.2.70 Lymphoid hyperplasia. Fig. 7.1.2.2.71 (A) Multiple ileal strictures with SAIO. (B) Terminal ileal stricture. Fig. 7.1.2.2.72 Jejunojejunal Intussusception. Fig. 7.1.2.2.73 Postoperative adhesions. Fig. 7.1.2.2.74 (A) Sclerosing encapsulating peritonitis in a case of Koch’s. (B) Cocoon abdomen in a case of Peritoneal Koch’s. Fig. 7.1.2.2.75 (A) IC Koch’s with involvement of Ascending colon. Note the narrowed lumen of caecum and ascending colon. (B) Axial section of CT showing thickening of terminal ileum and caecum in the same patient. (C) IC Koch’s. Note the wide gaping of the ileocaecal valve and obliteration of caecal lumen. (D) IC Koch’s. Note the gooseneck deformity of the IC junction. There is no retention of the contrast in the caecum and ulcerations in terminal ileum. (E) Sterlin sign. Note lack of barium retention in the inflamed segments of the terminal ileum, caecum, ascending colon with mild dilatation of the ileal loops. Fig. 7.1.2.2.76 (A) Long segment terminal ileal stricture giving string sign in Crohn’s disease. (B) Crohn’s disease. Note multiple strictures and Pseudosacculations in ileum. (C) Crohn’s disease with ileocolic fistula. (D) Jejunocolic fistula. Fig. 7.1.2.2.77 (A) Nonrotation of gut. Note small bowel loops in the right side of abdomen in a 15 minutes film. (B) Nonrotation of gut. Note small bowel loops in the right side of abdomen and large bowel on the left in a 30 minutes film. Duodenojejunal junction is on the right side. Fig. 7.1.2.2.78 Malrotation with midgut volvulus.

Fig. 7.1.2.2.79 Midgut volvulus with cork screw appearance. Fig. 7.1.2.2.80 Internal hernia. Fig. 7.1.2.2.81 Ascaris Lumbricoides seen as a serpiginous filling defect in jejunum. Fig. 7.1.2.3.82 Nasojejunal feeding catheter. Fig. 7.1.2.3.83 Manoeuvre for enteroclysis tube placement. (A) If the tube repeatedly goes to the left and gets held up against the greater curvature, torque the guidewire to direct the tip away from the greater curvature. (B) If the tube cannot be easily advanced into the antrum, use the double-back manoeuvre. (C) While advancing the tube through the duodenal sweep, the guidewire should be withdrawn to the apex of the duodenal bulb before each advancement. (D) The optimal location of the tip of the tube is in the proximal jejunum. Fig. 7.1.2.3.84 (A and B) Spot compression film of barium filling the jejunal loops. Normal calibre and mucosal fold pattern is seen. Fig. 7.1.2.3.85 Frontal spot image from a normal enteroclysis. The thin regularly spaced radiolucent lines oriented perpendicular to longitudinal axis of bowel represent small bowel mucosal folds. Normal thickness measures 1–2 mm. Fig. 7.1.2.3.86 Overhead supine film taken at the end of study. The proximal jejunum has emptied (star), rest of jejunum and ileum are well distended. Caecum and ascending colon (block arrows) are also opacified. Fig. 7.1.2.3.87 Jejunal dilatation with normal folds (arrows) is seen in a patient with intestinal obstruction. Fig. 7.1.2.3.88 Small bowel study of a patient with SLE who presented with acute abdominal pain. Jejunal folds are thickened due to ischemia and haemorrhage in the bowel wall. In one loop, the uniformly thickened folds simulate a stack of coins (star). Large amount of oedema and hemorrhage produces thumbprinting (arrows).

Fig. 7.1.2.3.89 This patient developed acute abdominal pain few days after undergoing CABG. Small bowel study shows regular thickening of jejunal folds (star) and scalloping (arrows) due to bowel wall oedema and haemorrhage caused by mesenteric ischemia. Fig. 7.1.2.3.90 Regular thickening of jejunal folds (arrows) is seen in this patient with malabsorption. Intestinal lymphangiectasia was diagnosed on intestinal biopsy. Fig. 7.1.2.3.91 Irregular thickened mucosal folds (arrows) seen in jejunal loop due to Giardiasis. Luminal narrowing is due of spasm. Fig. 7.1.2.3.92 Narrowing of the terminal ileum is seen along with nodular thickening of the base of caecum, a common finding in ileocaecal tuberculosis. Fig. 7.1.2.3.93 TB stricture. (A) High grade focal stricture in the proximal ileum (arrows) causing dilatation of the proximal loop. (B) A segmental stricture (star) of the jejunum in a different patient. Fig. 7.1.2.3.94 Spot compression views of enteroclysis reveal a subtle stricture (arrow) in the jejunum. The proximal bowel is not dilated. Fig. 7.1.2.3.95 Mucosal fold thickening (star), ulceration and luminal narrowing due to spasm (arrows) is seen affecting multiple segments of the ileum with intervening normal bowel. Presence of skip lesions is characteristic of Crohn’s disease. Fig. 7.1.2.3.96 Radiographic appearances of small bowel tumours. Fig. 7.1.2.3.97 Jejunal leiomyoma. Compression spot film of enteroclysis (A) reveals a pedunculated polyp (long arrow) in the jejunum. In the oblique view (B), the peduncle is obscured. The surface of the polyp is slightly lobulated (small arrows). At surgery, a pedunculated leiomyoma was found. Fig. 7.1.2.3.98 Three smooth round filling defects (arrows) are seen in the small bowel representing multiple polyps.

Fig. 7.1.2.3.99 Enteroclysis study reveals two polyps (star) in the small bowel. Both show lobulated margins (arrows). Fig. 7.1.2.3.100 Large filling defect (star) in proximal ileum filling most of the lumen. Margins are irregular (arrow). The polyp turned out to be a metastasis from previously operated renal cell carcinoma. Fig. 7.1.2.3.101 Worm. Smooth tubular filling defect (arrow) represents a worm in the jejunum. Fig. 7.1.2.3.102 Roundworm. Tubular filling defect (small arrows) in the jejunum has a thin radiopaque line in the centre (long arrow). This represents barium ingested by the worm. This appearance is characteristic of ascaris. Fig. 7.1.2.3.103 Adhesion. Compression spot film of enteroclysis reveals a linear crossing defect (arrows) in a pelvic small bowel loop and dilated bowel proximal to it (star). At surgery a crossing adhesion was found. Fig. 7.1.2.3.104 Jejunal diverticulosis. Small outpouchings from the jejunum are seen at multiple levels representing jejunal diverticulosis. Fig. 7.1.2.4.105 Spot radiographs of normal barium enema. (A) AP Spot radiograph of rectum. (B) Lateral Spot radiograph of rectum. (C) Spot radiograph of sigmoid colon enema. (D) Spot radiograph of descending colon. (E) Spot radiograph of splenic flexure. (F) Spot radiograph of transverse colon. (G) Spot radiograph of hepatic flexure. (H) Spot radiograph of ascending colon. (I) IC junction. (J) Supine radiograph. (K) Prone radiograph. (L) Right lateral decubitus. (M) Left lateral decubitus. Fig. 7.1.2.4.106 Conical caecum: a normal anatomical variant. Fig. 7.1.2.4.107 Barium enema showing multiple enlarged lymphoid follicles. Fig. 7.1.2.4.108 (A) Illustration showing the sphincters of the colon, starting from the cecum: (a) Sphincter of Varolio (improperly called ileocecal valve); (b) sphincter

of Busi; (c) sphincter of Hirsch; (d) sphincter of CannonBoehm; (e) sphincter of Payr-Strauss; (f) sphincter of Balli; (g) sphincter of Moutier; (h) sphincter of Rossi. (B) Barium enema showing sphincter of Hirsch. (C) Barium enema showing sphincter of Cannon-Boehm. Fig. 7.1.2.4.109 Barium enema showing polyps as filling defects in the descending colon and etched in white appearance in the transverse colon. Fig. 7.1.2.4.110 (A) Single Contrast Barium enema showing polyp as a filling defect in descending colon. (B) Double-contrast Barium enema showing polyp as a ring shadow in descending colon. (C) Axial CECT abdomen in the same patient reveals the lesion to be lipoma. Fig. 7.1.2.4.111 Barium enema showing multiple diverticula arising from sigmoid colon. Note the bowler’s hat sign with dome pointing away from the lumen. Fig. 7.1.2.4.112 Double-contrast Barium enema showing Annular growth in descending colon. Fig. 7.1.2.4.113 Single contrast Barium enema showing polypoidal growth in the sigmoid colon. Fig. 7.1.2.4.114 Double-contrast Barium enema showing multiple sigmoid diverticula, incidentally noted annular growth in rectum. Fig. 7.1.2.4.115 (A and B) AP and lateral radiographs of Single contrast Barium enema showing diverticular disease with colovesical (sigmoid) fistula. (C) Lateral radiograph of Barium enema showing diverticular disease in sigmoid colon with air in the vaginal canal and colovaginal fistula. Note the coils anterior to L5–S1 intervertebral disc space secondary to uterine artery embolization in view of uncontrolled per vaginal bleeding. Fig. 7.1.2.4.116 (A) Barium enema showing beaded appearance of appendix in chronic appendicitis. (B) Smooth extrinsic impression at the base of caecum in case of appendicitis. Fig. 7.1.2.4.117 (A) Double-contrast barium enema showing granular mucosal pattern with loss of

haustrations in descending colon in early Ulcerative Colitis. (B) lateral radiograph of Double-contrast barium enema showing granular mucosal pattern in rectum and rectosigmoid junction in early Ulcerative Colitis. Fig. 7.1.2.4.118 Right decubitus radiograph of Barium enema showing pseudopolyposis in Ulcerative Colitis. Fig. 7.1.2.4.119 Barium enema in ulcerative colitis showing backwash ileitis. Fig. 7.1.2.4.120 Lateral radiograph of barium enema in ulcerative colitis showing widening of the presacral space with a blind ending sinus tract showing contrast leak. Fig. 7.1.2.4.121 Double-contrast barium enema in Crohn’s disease showing aphthoid ulceration in descending colon with classic bull’s eye appearance. Fig. 7.1.2.4.122 Barium enema showing cobblestone mucosa of the transverse and descending colon in Crohn’s disease. Fig. 7.1.2.4.123 (A) Spot film of a barium enema showing contracted caecum, stricture of IC junction and terminal ileum in a case of Koch’s. Incidentally noted situs inversus. (B) Axial CECT abdomen showing thickening of the IC junction and terminal ileum in the same patient. Fig. 7.1.2.4.124 (A and B) AP and lateral radiographs of barium enema in short segment Hirschsprung disease showing transition zone in sigmoid and descending colon junction. Fig. 7.1.2.4.125 Barium enema in a case of Total colonic aganglionosis. Fig. 7.1.2.4.126 (A and B) AP and lateral radiographs of Barium enema showing ultrashort type of Hirschsprung disease. Fig. 7.1.2.4.127 Single contrast Barium enema showing extrinsic mass effect and spiculation in sigmoid colon owing to poor wall distension in a case of endometriosis. Fig. 7.1.2.4.128 Barium enema showing irregular stricture of the rectosigmoid and sigmoid colon in a

k/c/o endometrial carcinoma who received radiotherapy. Fig. 7.1.2.4.129 Barium enema showing colocolic intussusception. Fig. 7.1.2.5.130 Goodsall’s rule. Fig. 7.1.2.5.131 Various types of fistulae by Park’s classification. Fig. 7.1.2.5.132 (A) Fistula in ano. (B) Fistula in ano. (C) Lateral radiograph of Fistula in ano in the same patient as in part (B). Fig. 7.1.2.5.133 (A) A small bowel series showing duodenocutaneous fistula. (B) Fistulogram in the same patient as in part (A). Fig. 7.1.2.5.134 (A) Ileocutaneous fistula seen on Distal cologram. (B) Lateral radiograph of the same patient as seen in part (A). Fig. 7.1.2.5.135 (A–C) Postoperative Ileocutaneous Fistula. The patient was a case of Ulcerative colitis who underwent total proctocolectomy with ileoanal anastomosis. (D) NCCT abdomen in the same patient shows ileocutaneous fistula. Fig. 7.1.2.5.136 Percutaneous fistula. Fig. 7.1.2.5.137 (A and B) AP and lateral radiograph of a fistulogram in Postoperative pericardiocutaneous fistula. Note the serpiginous tract coursing towards the cardiac shadow. (C) Reconstructed CT image of the same patient showing the pericardiocutaneous fistula. Fig. 7.1.2.5.138 (A and B) Fistulogram in Postoperative patient showing enterocutaneous fistula communicating with left lower lobe bronchus. Fig. 7.1.2.6.139 Normal female reproductive anatomy. Fig. 7.1.2.6.140 Parts of normal fallopian tube. Fig. 7.1.2.6.141 Schematic diagram of uterine development. Fig. 7.1.2.6.142 HSG tray.

Fig. 7.1.2.6.143 (A) plain radiograph. (B) Early filling phase. (C) Radiograph to demonstrate fallopian tube. (D) Radiograph to demonstrate free spill. Fig. 7.1.2.6.144 Normal HSG. Fig. 7.1.2.6.145 HSG showing bilateral cornual spasm. Fig. 7.1.2.6.146 HSG showing Prominent cervical glands. Of incidental note is bicornuate uterus. Fig. 7.1.2.6.147 (A) HSG showing Arcuate uterus. (B) HSG showing Arcuate uterus with right hydrosalpinx and loculated spill. (C) MRI image showing arcuate contour. (D) 3D USG image showing arcuate contour. Fig. 7.1.2.6.148 (A) Retroverted uterus. (B) HSG showing uterine deviation to the left secondary to right ovarian haemorrhagic cyst. Fig. 7.1.2.6.149 HSG showing Intravasation of contrast. Fig. 7.1.2.6.150 HSG showing air bubbles as a filling defect within the uterine cavity. Fig. 7.1.2.6.151 Plain radiograph showing bulky uterus in a case of adenomyosis. HSG of the same patient shown in Fig. 7.1.2.6.159. Fig. 7.1.2.6.152 HSG showing fimbrial block. Fig. 7.1.2.6.153 HSG showing bilateral hydrosalpinx with peritubal adhesions. Fig. 7.1.2.6.154 HSG showing bilateral hydrosalpinx. Round lucencies are seen in the endometrial cavity secondary to loculated fluid in a known case of Koch’s. Fig. 7.1.2.6.155 HSG showing Salphingitis isthmica nodosa, left tube shows hydrosalpinx, the endometrial cavity is ‘T’ shaped in a case of genital Koch’s. Fig. 7.1.2.6.156 (A) HSG showing Filling defect in the endometrial cavity due to submucosal uterine fibroid. (B) HSG showing intramural fundal fibroid with degeneration and communication with the uterine cavity. (C) Sagittal MRI image of the same patient pelvis

showing degenerating fundal fibroid having communication with the uterine cavity. Fig. 7.1.2.6.157 HSG showing polyp in the endometrial cavity. Fig. 7.1.2.6.158 (A) HSG showing multiple irregular filling defects within the uterine cavity in a case of uterine synechiae. (B) Asherman syndrome with intravasation of contrast. Fig. 7.1.2.6.159 HSG showing diffuse adenomyosis. Thin arrow points towards the outline of urinary bladder whereas thick arrow points towards the outline of the bulky uterus. Fig. 7.1.2.6.160 European Society of Human Reproduction and Embryology (ESHRE) Classification of female genital tract anomalies of uterus. Fig. 7.1.2.6.161 (A) HSG showing unicornuate uterus. (B) MRI image showing unicornuate uterus. (C) 3D USG image showing unicornuate uterus. Fig. 7.1.2.6.162 (A) HSG showing uterus didelphys. (B) MRI image showing uterus didelphys with two separate cervices. (C) 3D USG image showing uterus didelphys. Fig. 7.1.2.6.163 (A) HSG showing bicornuate uterus. (B) MRI image showing bicornuate uterus. (C) 3D USG image showing bicornuate uterus. Fig. 7.1.2.6.164 (A) HSG showing septate uterus. (B) MRI image showing septate uterus. (C) MRI image showing subseptate uterus. (D) 3D USG image showing septate uterus. Fig. 7.1.2.6.165 HSG showing retroverted uterus with hydrosalpinx of both tubes giving tobacco pouch appearance. Fig. 7.1.2.6.166 HSG showing retroverted uterus with fixed fallopian tubes and loculated spill due to pelvic adhesions. Fig. 7.1.2.6.167 HSG showing utero vesical fistulous tract in a case of Youssef syndrome.

Fig. 7.1.3.1 Transducers used for abdominal ultrasound. Fig. 7.1.3.2 Liver developing as a bud from the foregut (duodenum) and invading the septum transversum. Fig. 7.1.3.3 A: High-resolution ultrasound image showing multiple small focal lesions in liver. B: Image depicting liver elastography in a normal patient. Fig. 7.1.3.4 A and B: Normal smooth homogenous texture of liver with echotexture slightly higher than the right kidney. Fig. 7.1.3.5 A: On transverse section, the caudate lobe is seen as a small projection from right lobe, bounded posteriorly by IVC and anteriorly by LV. Note: The intense echoes produced by fibrotic LV. B: Longitudinal section in midsagittal plane showing the caudate lobe, with its anterior and posterior boundaries. Note: The AP length of caudate lobe is normally less than half the AP length of left lobe. LV, ligamentum venosum; IVC, inferior vena cava. Fig. 7.1.3.6 Subcostal oblique view showing the plane passing from IVC to gall bladder occupied by middle hepatic vein (MHV) diving the liver into right and left lobe. Fig. 7.1.3.7 Line diagram of right lobe seen from medial aspect. RHV, right hepatic vein. Fig. 7.1.3.8 Line diagram of right lobe seen from medial aspect along with Cauinaud’s segments. RHV, right hepatic vein; PV, portal vein. Fig. 7.1.3.9 Line diagram of left lobe seen from front, showing MHV (middle hepatic vein) forming its medial margin and left intersegmental fissure formed by LHV (left hepatic vein), LPV (ascending branch of left portal vein) and LT (ligamentum teres) dividing it into medial and lateral segments. Fig. 7.1.3.10 Line diagram of left lobe seen from front showing the imaginary transverse plane passing through portal pedicles dividing the medial and lateral segments into cranial and caudal segments.

Fig. 7.1.3.11 Development of Falciform ligament. Fig. 7.1.3.12 Line diagram showing relative position of portal vein (PV), bile duct (BD) and hepatic artery (HA) at the porta. Fig. 7.1.3.13 Transverse section at porta showing the division of main portal vein into right and left portal vein (RPV and LPV). Note: The position of bile duct (BD) and hepatic artery (HA) – anterolateral and anteromedial, respectively. Fig. 7.1.3.14 Doppler image: Transverse section at porta showing anterolateral position of common bile duct (CBD) and anterolateral position of hepatic artery (HA) with respect to main portal vein (MPV). Fig. 7.1.3.15 Oblique section of right lobe showing anterior and posterior branches of right portal vein. These branches are intrasegmental and supply the anterior and posterior segments of right lobe. Fig. 7.1.3.16 The left portal vein and its branches to various segments of left lobe produce a ‘H’ shaped or ‘jumping stud’ like appearance. Fig. 7.1.3.17 A: Colour Doppler image in longitudinal section at the level of porta with portal vein cut lengthways. The hepatic artery (HA) is seen anteromedial to the portal vein. B: Colour Doppler image in longitudinal section at porta with slight medial tilt reveals the length of hepatic artery (HA). C: Slightly further lateral longitudinal section at porta showing the characteristic position of hepatic artery (HA) in between the bile duct (BD) and main portal vein (MPV). Fig. 7.1.3.18 Subcostal oblique view showing the three hepatic veins joining the IVC. Generally, the right hepatic vein (RHV) opens separately into the IVC whereas the left and middle hepatic veins form a short common trunk together before draining into IVC. Fig. 7.1.3.19 Colour Doppler image: Right hepatic vein – coronal section of right lobe. This section taken through lower intercostal spaces is the best way to demonstrate the right hepatic vein.

Fig. 7.1.3.20 Colour Doppler image: Left hepatic vein – longitudinal section of left lobe in sagittal plane. Left hepatic vein lies in the midsagittal plane. Fig. 7.1.3.21 Middle hepatic vein – longitudinal section of right lobe in sagittal plane. The middle hepatic vein lies approximately in the midclavicular line as demonstrated by this section. Fig. 7.1.3.22 Measurements of liver in midsagittal section (A) and in midclavicular line (B). Fig. 7.1.3.23 Diagram representing embryology of gall bladder and biliary tract. Fig. 7.1.3.24 (A) Right subcostal approach showing gall bladder in the liver hilum. (B) Intercostal approach showing gall bladder posterior to the liver parenchyma. (C) Ultrasound image showing transverse view of gall bladder. (D) Transverse view of the body of the gall bladder. Fig. 7.1.3.25 Ultrasound image showing air-filled duodenum can mimic a gall bladder with calculus. Fig. 7.1.3.26 Ultrasound image showing parts of gall bladder: Fundus, body and neck. Fig. 7.1.3.27 Ultrasound image of gall bladder wall showing (A) three layers and (B) wall thickness. Fig. 7.1.3.28 Scanning technique for gall bladder in (A) supine, (B) right anterior oblique and (C) left lateral decubitus positions. Fig. 7.1.3.29 Ultrasound image of gall bladder showing ‘rolling stone’ sign. Fig. 7.1.3.30 Ultrasound image of cystic duct with valves of Heister (red arrows). Fig. 7.1.3.31 Line diagram representing biliary system. Fig. 7.1.3.32 Ultrasound image showing the right and left hepatic ducts and the common hepatic duct. Fig. 7.1.3.33 A: Ultrasound image depicting a ‘Mickey mouse’ sign. L, liver; GB, gall bladder. Hepatic artery (white arrow), portal vein (green arrow), bile duct (red

arrow). B: Common bile duct seen anterior to portal vein (showing flow) in Colour Doppler mode. C: Ultrasound image showing pancreatic portion of common bile duct and the main pancreatic duct. Fig. 7.1.3.34 Ultrasound image showing diameter of common bile duct measured from inside wall to inside wall. Fig. 7.1.3.35 Ultrasound image showing gall bladder in (A) partially distended and (B) collapsed states. Fig. 7.1.3.36 Ultrasound image showing gall bladder in (A) septum and (B) fold. Fig. 7.1.3.37 Ultrasound image showing ‘Wall Echo Shadow’. Fig. 7.1.3.38 Line diagram representing biliary system variants. Fig. 7.1.3.39 Development of pancreas. At 4 weeks dorsal (D, blue) and ventral (orange) pancreatic buds are seen on either side of junction of primitive foregut and midgut. Ventral bud also gives origin to gall bladder (GB), bile duct and liver (L). Fig. 7.1.3.40 Dorsal component of main pancreatic duct and accessory duct of Santorini arises from dorsal anlage and ventral component of main duct, duct of Wirsung arises from ventral anlage which fuses with dorsal duct to form main pancreatic duct. Fig. 7.1.3.41 Transverse image of pancreas (red arrow) showing its ventral and dorsal landmarks. Ventral to pancreas is stomach (white arrow) and dorsal to it is aorta (yellow arrow). Note: Stomach is filled with fluid making visualization of pancreas satisfactory. Fig. 7.1.3.42 Image shows different manoeuvres that are used for adequate visualization of pancreas. A: Transverse image of pancreas with compression over the abdomen results in displacement of the air in the stomach, hence better visualization of pancreas. B: Transverse image of pancreas acquired after asking patient to hold his breath. In inspiration liver acts as window for visualization. C: Patient is asked to blow his

belly and image of pancreas is acquired. D: Imaging of pancreas with fluid-filled stomach. Fig. 7.1.3.43 Transverse ultrasound image showing landmarks for identification of pancreatic head. V – superior mesenteric vein and A – superior mesenteric artery medially, IVC – inferior vena cava dorsally and GDA – gastroduodenal artery anterolaterally. Fig. 7.1.3.44 A: Transverse ultrasound image showing uncinate process (UP) of pancreas which is posteromedial to the superior mesenteric artery (A) and superior mesenteric vein (V). B: Transverse ultrasound image showing gastrocolic trunk (GCT) as a ventral landmark for uncinate process which enters the superior mesenteric vein (V) on right side anterior to pancreatic head. Note: The normal posteromedial relation of uncinate process with superior mesenteric artery (A) and superior mesenteric vein (V). Fig. 7.1.3.45 Transverse ultrasound image showing ventrolateral pancreatic head where gastroduodenal artery (yellow arrow) is a landmark which courses between duodenum (white arrow) and ventrolateral portion of head of pancreas. Fig. 7.1.3.46 Transverse ultrasound image showing portion of the pancreatic head (yellow arrow) adjacent to second part of duodenum (white arrow). Red arrow is gastroduodenal artery and bold red arrow is CBD (common bile duct). Fig. 7.1.3.47 A: Transverse ultrasound scan done at the level of splenic vein and superior mesenteric artery confluence showing pancreatic body. L – liver and ST – stomach anterior to it. Yellow arrow is pointing towards pancreatic neck which is the portion anterior to superior mesenteric artery and postsplenic confluence. B: Transverse ultrasound image is obtained by angulating the probe towards the left side for evaluation of entire pancreatic body (white arrow). Fig. 7.1.3.48 A: For pancreatic tail evaluation, patient is made right anterior oblique and tail of pancreas (yellow arrow) is seen through splenic hilum (bold white arrow)

anterior to the left kidney (white arrow). B: Longitudinal coronal scan through the spleen (S) and left kidney (LK) shows tail of pancreas (P) white arrow near splenic hilum. Splenic vein (SV) is a vascular landmark for identifying hilum and pancreatic tail. Fig. 7.1.3.49 A: Transverse ultrasound image of pancreas. Image of young patient showing echotexture of pancreas (yellow arrow) same as that of liver (white arrow). B: Image of 40-year-old female showing increased echotexture of pancreas as compared to liver. Fig. 7.1.3.50 Transverse ultrasound image showing pancreatic measurement. Fig. 7.1.3.51 Transverse ultrasound image of pancreas showing main pancreatic duct (white arrow). Fig. 7.1.3.52 Transverse ultrasound image of pancreas showing focal anterior bulge (white arrow) mimicking mass. Note: Echotexture of bulge and rest of the pancreas is same. Fig. 7.1.3.53 Schematic diagram showing peripancreatic structures. Fig. 7.1.3.54 Embryologic development of the spleen. Axial drawings of the upper abdomen. (A) Embryo 4–5 weeks: The mesentery anterior to the stomach is the ventral mesentery which is divided into two portions by the liver into the falciform ligament anteriorly and the gastrohepatic ligament or lesser omentum posteriorly. Posterior to the stomach is the dorsal mesentery, which contains the developing spleen. The dorsal mesentery is divided into two portions by the spleen: The splenogastric ligament anteriorly and the splenorenal ligament posteriorly. (B) Embryo 8 weeks: The stomach rotates counterclockwise, displacing the liver to the right and the spleen to the left. The portion of the dorsal mesentery containing the pancreas, splenic vessels and spleen begins to fuse to the anterior retroperitoneal surface, giving rise to the splenogastric ligament and the ‘bare area’ of the spleen. (C) Newborn: Fusion of the dorsal mesentery is now complete. The pancreas is now completely retroperitoneal, and a portion of the spleen

has fused with the retroperitoneum. Note: L, liver; Fl, Falciform ligament; Sp, spleen; St, stomach; P, pancreas; RK, right kidney; LK, left kidney; Du, duodenum; Ao, aorta; LO, lesser omentum; DM, dorsal mesentery. Fig. 7.1.3.55 Scanning technique and representative ultrasound image for scanning the spleen in supine and right lateral oblique positions to visualize the spleen in coronal plane (A), oblique plane (B) and transverse plane (C), respectively. Fig. 7.1.3.56 Longitudinal scan showing maximum craniocaudal (CC) length along with splenic hilum (H) showing both the poles. Yellow arrow: superomedial pole; blue arrow: inferolateral pole. Fig. 7.1.3.57 A: Ultrasound image showing splenic hilum – splenic artery (thin arrow) and splenic vein (broad arrow). B: Colour Doppler image showing splenic hilum – splenic artery (red) and splenic vein (blue). Fig. 7.1.3.58 Oblique scan showing spleen, left kidney (broad arrows) and diaphragm (thin arrows). Fig. 7.1.3.59 A: The image shows the method for measuring length, width and depth in centimetres on longitudinal and transverse plane. B: It shows the representative ultrasound image for measuring length, width and depth in centimetres on longitudinal and transverse plane. Fig. 7.1.3.60 Ultrasound image showing the splenunculi (yellow arrows). Fig. 7.1.3.61 A: The primary intestinal loop before rotation. B and C: There is herniation outside the abdominal cavity followed by 90 degrees anticlockwise rotation. They return to the abdomen by 10 weeks of gestation. D and E: Cecum returns last and along with transverse colon rotates by another 180 degree in anticlockwise direction around the superior mesenteric artery to achieve final position. Fig. 7.1.3.62 Oesophago-gastric junction in long section (arrow). The abdominal oesophagus and the oesophago-

gastric junction show the typical appearance of the bowel. Fig. 7.1.3.63 A: High-frequency image of pyloric antrum in a child with open and close position. B: Image shows collapsed pylorus in transverse section. It is seen posterior to the left liver lobe and anterior to the pancreatic body. C: Gastric cavity seen after filling with plain water. Fig. 7.1.3.64 A: Transverse ultrasound image showing portion second part of duodenum (white arrow) adjacent to the pancreatic head (yellow arrow). Red arrow is gastroduodenal artery and bold red arrow is CBD (common bile duct). B: Air (white arrow) in the first part of the duodenum anterior and superior to head of the pancreas and medial to the gall bladder. C: Gas in duodenum (white arrow) can mimic as gall bladder calculus. Change in patient position, giving few cups of water can held in differentiation. Fig. 7.1.3.65 Ultrasound image showing small bowel loops with and without compression. Fig. 7.1.3.66 A: Ultrasound image with high-frequency transducer showing jejunal folds. They are better evaluated in the presence of fluid in the lumen. B: Folds in collapse state. C: Ilial loops showing a smaller number of mucosal folds. Fig. 7.1.3.67 The ileocecal junction and cecum (star) in transverse ultrasound image. Terminal ileum is seen with collapsed lumen. Cecum shows air (arrow) in lumen. Fig. 7.1.3.68 A: Region posterior to cecum is not visualized due to gas. B: The retrocecal region is well visualized in left oblique position to move gas in cecum away from scanning field. Appendix (arrow) can traced by following the psoas muscle inferiorly. Fig. 7.1.3.69 A: Rectum in transverse and longitudinal plane showing air. B: Ultrasound image in long section shows colon as gas containing tubular organ.

Fig. 7.1.3.70 A: Perineal ultrasound female showing bladder with Foley’s bulb, vagina (yellow arrow), anal canal (white arrows) and rectum (air) (red arrows). B: In male showing prostate (star), anal canal and rectum (air). Fig. 7.1.3.71 High-resolution ultrasound showing five layers of stomach wall. Fig. 7.1.3.72 A: High-resolution ultrasound showing fluid-filled normal caliber bowel loop. B: Image showing dilated pylorus. Fig. 7.1.3.73 A: High-resolution ultrasound showing normal omentum (star) better visualized in presence of free fluid. –B: Thickened omentum with Colour Doppler. Fig. 7.1.3.74 A: High-resolution ultrasound showing normal mesentery showing echogenic fat. B: Mesenteric vessel surrounded by multiple enlarged mesenteric nodes. Colour Doppler shows hilar vessel in the node. Fig. 7.1.3.75 Right kidney (RK) visualized with anterior approach and liver (L) as acoustic window. Fig. 7.1.3.76 Left kidney (LK) visualized with posterior oblique approach with spleen (S) as acoustic window. Fig. 7.1.3.77 In the transverse scan, the right kidney appears as an incomplete ring, open medially at the renal hilum. Fig. 7.1.3.78 Graded compression technique showing the dilated distal ureter (U) as it crosses over the external iliac vessels. A – external iliac artery; V – external iliac vein. Fig. 7.1.3.79 Ureteral ostia (arrows) are visualized as small symmetrical raised areas on both sides of trigone on transverse scan. Fig. 7.1.3.80 The normal ureteric jet best seen on Colour Doppler evaluation. Fig. 7.1.3.81 Normal transverse and sagittal view of moderately filled bladder.

Fig. 7.1.3.82 Schematic representation of normal kidney and ultrasound image with measurement of cortical thickness (green double-headed arrow) and parenchymal thickness (blue double-headed arrow). Fig. 7.1.3.83 Infant kidneys showing echogenic cortex, prominent pyramid and less-echogenic renal sinus (and distended pelvicalyceal system). Fig. 7.1.3.84 The difference in the measurement of pole to pole length of right kidney due to oblique plane. Fig. 7.1.3.85 Foetal lobulations (arrows) seen in adult kidney. Fig. 7.1.3.86 Dromedary hump (white arrow) of left kidney. Fig. 7.1.3.87 Junctional cortical defect (arrow) seen in left kidney. Fig. 7.1.3.88 Hypertrophied column of Bertin (arrows) seen as smooth indentation over the renal sinus. Fig. 7.1.3.89 Malrotated kidney with hilum facing anteriorly. Fig. 7.1.3.90 Linear hyperechoic focus noted in cortex due to tiny vascular calcification. Fig. 7.1.3.91 Ultrasound image showing twinkling artifact from the calculus and the representative spectral Doppler evaluation. Fig. 7.1.3.92 Ultrasound image showing extrarenal pelvis. Fig. 7.1.3.93 Ultrasound image showing the parallel hyperechoic bands of the ligaments that stabilizes the urinary bladder at the superior aspect in the partially full bladder. Fig. 7.1.3.94 Development of prostate – showing mesodermal and endodermal derivatives of prostate. Fig. 7.1.3.95 Zonal anatomy of prostate. (A) Axial (B) Longitudinal section. Note: AFS, anterior fibromuscular stroma; TZ, transition zone; CZ, central zone; ED,

ejaculatory duct; U, urethra; SV, seminal vesicle; NVB, neurovascular bundle. Fig. 7.1.3.96 Position of transducer for: (A) Suprapubic axial view. (B) Longitudinal view. Fig. 7.1.3.97 Suprapubic axial view showing bilateral seminal vesicle (white arrows). Fig. 7.1.3.98 Suprapubic axial view showing base (single white arrow) and apex (multiple white arrows) of prostate. Fig. 7.1.3.99 Suprapubic axial view showing internal urethral sphincter which mimics the appearance of a transurethral resection defect. Fig. 7.1.3.100 Suprapubic longitudinal view showing right (A) and left (B) seminal vesicles (white arrow). Fig. 7.1.3.101 Suprapubic approach showing Foley’s bulb and catheter within bladder and prostatic urethra. Fig. 7.1.3.102 (A,B) Trans abdominal views of prostate gland (arrow). Fig. 7.1.3.103 TRUS axial view showing. (A) Bladder, prostate and rectum. (B) Apex of prostate (white arrow). (C) Blurred posterolateral margins showing entering of neurovascular bundle (small white arrows). (D) Urethra (thin white arrows) and peripheral zone (thick white arrows). (E) Base of prostate (small white arrows). (F) Vas deferens (thick white arrow) and seminal vesicle (thin white arrow). (G) Ejaculatory duct (thick arrow) and internal urethral sphincter (thin arrows). (H) Ejaculatory duct (thin arrow) and peripheral zone (thick arrow). Fig. 7.1.3.104 TRUS longitudinal view showing seminal vesicle of left (A) (white arrow) and right (B) (white arrows). (C) Peripheral zone (thick arrow) and seminal vesicle (thin arrow). Fig. 7.1.3.105 Colour Doppler USG image of prostate showing symmetrical flow in gland. Fig. 7.1.3.106 USG image showing measurement of prostate volume in suprapubic approach. (A) Suprapubic

axial view. (B) Longitudinal view. Fig. 7.1.3.107 Transperineal (A) coronal view of prostate showing base (thick white arrow) and apex of prostate (thin white arrow). (B) Longitudinal view of prostate where P, prostate; B, bladder; R, rectum; U, urethra. Fig. 7.1.3.108 Prostate elastography evaluating strain ratio. Fig. 7.1.3.109 Embryological origin of female reproductive system. Blue indicates origin from paramesonephric ducts, pink – mesonephric duct, yellow – urogenital sinus. Fig. 7.1.3.110 Coronal and sagittal transabdominal ultrasound images of the female pelvis showing U, uterus; B, urinary bladder; C, cervix; RO, right ovary; LO, left ovary; white line depicting the anteroposterior, transverse and sagittal dimensions of the uterus. Fig. 7.1.3.111 Sagittal and coronal transvaginal ultrasound images of the female pelvis showing U, uterus; C, cervix; LO, left ovary. Fig. 7.1.3.112 Magnified sagittal transabdominal ultrasound image of a normal uterus in a healthy 4-dayold girl. In the neonatal life stage, the normal cervix (thin line) is much wider than the uterine body (solid line). The cervical lips are denoted by A (anterior) and P (posterior). The corpus ©: cervix ratio is 1:2. Fig. 7.1.3.113 Longitudinal transabdominal ultrasound image obtained in a 3-year-old girl. Showing a tubular and wider uterine body than the cervix (six-point star). The endometrium (down white arrow) is visible faintly and will become more prominent after puberty. Urinary bladder (B). Fig. 7.1.3.114 Longitudinal transabdominal ultrasound image of a 25-year-old girl in ovulatory phase showing anteverted and anteflexed uterus. Down white arrow represents the uterus to cervical angle (flexion), up white arrow represents the cervix to vagina angle (version).

Fig. 7.1.3.115 Normal uterus in retroflexion in a 28year-old woman. Midsagittal transabdominal ultrasound image shows the uterus in the secretory phase. The angle of uterus to cervix has increased due to the backward rotation of the uterus in terms of cervix suggesting retroflexion (white arrow). Fig. 7.1.3.116 Normal uterus in retroversion in a 35year-old woman. Midsagittal transabdominal ultrasound image shows the uterus in the late proliferative phase. The angle of cervix to vagina (straight line) is more indicating the backward rotation of cervix (arrow) in terms of vagina suggesting retroversion. Fig. 7.1.3.117 Normal postpartum uterus in a 24-yearold woman. Midsagittal section in transabdominal ultrasound taken 4 days postpartum in normal vaginal delivery shows echogenic material within the endometrium (solid white arrow). The myometrium (five-point star) shows heterogenous echotexture. Fig. 7.1.3.118 Arcuate artery calcification in a 65-yearold postmenopausal female. Sagittal endovaginal ultrasound shows arcuate artery calcifications (open white arrows). The endometrium (ET) measures 3 mm consistent with postmenopausal status. V, adjacent arcuate veins. Fig. 7.1.3.119 Endometrial fluid in a menstruating female. Longitudinal endovaginal ultrasound image shows small amount of endometrial fluid (solid white arrow). An endometrial thickness is obtained after adding anterior (A) layer and posterior (P) layer thickness separately. Fig. 7.1.3.120 Normal premenopausal endometrium. Sagittal ultrasound image of the uterus obtained during the proliferative phase of the menstrual cycle demonstrates the endometrium with hypoechoic subendometrial myometrium (subendometrial halo) (upward white arrow). Fig. 7.1.3.121 Midsagittal transabdominal ultrasound image obtained near midcycle shows a normal striated pattern. At midcycle, endometrial thickness includes the

echogenic outer layer (open white arrow) and hypoechoic inner layer. The thin central hyperechoic line represents the interface between the anterior and posterior endometrial aspects. Four-point star – myometrium. Fig. 7.1.3.122 Midsagittal transvaginal ultrasound image shows the similar trilaminar (white arrow) appearance of the endometrium. Fig. 7.1.3.123 Sagittal transvaginal ultrasound image obtained in a different woman in the secretory phase of the menstrual cycle shows homogeneously echogenic endometrium (five-point star). Fig. 7.1.3.124 A transverse transvaginal ultrasound image demonstrates echogenic endometrium with subendometrial halo (five-point star) consistent with the secretory phase. Fig. 7.1.3.125 Longitudinal transabdominal ultrasound image of a 35-year-old woman in proliferative phase showing left ovary in pouch of Douglas (long arrow). A developing follicle (short arrow) is also visualized in the image, in consistent with the proliferative phase. Fig. 7.1.3.126 Sagittal transvaginal ultrasound image obtained in a 36-year-old woman in the proliferative phase of the menstrual cycle shows multiple developing follicles in the left ovary (arrow). Fig. 7.1.3.127 Transabdominal ultrasound image of small amount of fluid in cul-de-sac (solid white arrow) suggestive of rupture of follicle. The endometrium (fivepoint star) appears thick in consistent with the postovulatory state. Fig. 7.1.3.128 Transverse transabdominal ultrasound image shows a normal dominant follicle (five-point star) in a 23-year-old woman consistent with the preovulatory phase. Fig. 7.1.3.129 Ultrasound image showing small amount of free fluid in pelvis. Fig. 7.1.3.130 A: Image showing normal liver surface. B: Showing hyperechoic air with comet tail artefact between abdominal wall and liver.

Fig. 7.1.3.131 Preaortic lymph nodes. Fig. 7.1.3.132 Transverse ultrasound image showing right adrenal gland (white arrow) which is superior to the right kidney (yellow arrow) and posteroinferior to the right lobe of the liver (black arrow). Fig. 7.1.3.133 Transverse ultrasound image showing left adrenal gland (white arrow) between upper pole of left kidney (green arrow) and spleen (blue arrow). Fig. 7.1.3.134 Ultrasound showing normal newborn right adrenal gland (white arrow). The gland is larger and hypoechoic than adult adrenal glands. Fig. 7.1.3.135 Transverse ultrasound image showing inferior vena cava (hepatic portion near the diaphragmatic hiatus) showing site of diameter measurement. Fig. 7.1.3.136 Longitudinal ultrasound image of aorta showing normal wall. Fig. 7.1.3.137 Ultrasound image showing pneumothorax (A) seashore sign (B) barcode sign. Fig. 7.1.4.1 Anatomical diagram of the abdominal aorta showing the coeliac trunk with branch arteries, paired renal arteries, superior and inferior mesenteric arteries. Fig. 7.1.4.2 Normal and commonest branching anatomy of coeliac trunk into the common hepatic artery left gastric artery and splenic artery. Fig. 7.1.4.3 Common variations of coeliac axis branching patterns. CA, coeliac axis; CHA, common hepatic artery; LGA, left gastric artery. Fig. 7.1.4.4 Anatomical relationship of collateral pathways of the mesenteric vasculature. Fig. 7.1.4.5 Anatomic relationship of the main renal arteries and renal veins with aorta, IVC and either kidneys. Fig. 7.1.4.6 Anatomic depiction of renal artery branching pattern.

Fig. 7.1.4.7 A: Longitudinal colour and spectral Doppler image of the proximal and midsegment of normal abdominal aorta shows biphasic flow pattern, antegrade systolic flow and antegrade diastolic flow. B: Longitudinal colour and spectral Doppler image of the infrarenal aorta showing triphasic flow waveform due to high-resistive blood flow antegrade systolic flow with diastolic reversal and low-velocity antegrade flow. Fig. 7.1.4.8 A: Transverse colour image shows ‘T shaped ‘or ‘sea gull’ sign of coeliac trunk bifurcating into the common hepatic artery and splenic artery. B: Transverse section of coeliac artery with spectral Doppler tracing showing typical forward flow in systole and diastole with low-resistance flow pattern. Fig. 7.1.4.9 Transverse section of common hepatic artery branching from the coeliac trunk with spectral Doppler tracing demonstrating typical forward flow in systole and diastole with low-resistance flow pattern. Fig. 7.1.4.10 Transverse section with spectral Doppler of splenic artery showing typical low-resistance flow pattern with forward systolic and diastolic flow. Fig. 7.1.4.11 Sagittal section colour image demonstrating course of origin of superior mesenteric artery from the aorta. Fig. 7.1.4.12 Transverse section grey scale image demonstrating relationship of superior mesenteric artery (*) with superior mesenteric vein (V), splenic vein (SV), inferior vena cava (IVC), left renal vein (LRV) and aorta (Ao). Fig. 7.1.4.13 A: Sagittal colour and spectral Doppler image at origin of normal superior mesenteric artery in fasting state demonstrates high-resistance waveform forward systolic flow and low diastolic flow and high R.I. value. B: Sagittal colour and spectral Doppler image of superior mesenteric artery in post prandial state demonstrates typical increased systolic velocity and diastolic flow and relatively low R.I. value. Fig. 7.1.4.14 A: Transverse oblique colour image demonstrates origin of the inferior mesenteric artery

from the left anterior part of aorta and relatively straight course of inferior mesenteric artery. B: Longitudinal colour and spectral Doppler image at origin of the inferior mesenteric artery shows a prediastolic notch with a forward diastolic flow. Fig. 7.1.4.15 Anatomic diagram shows relationship of renal artery and renal vein. Fig. 7.1.4.16 A: Grey scale and power Doppler transverse ultrasound image demonstrating entire course of right renal artery from origin at aorta till the right renal hilum when patient is scanned in left decubitus position. B: Transverse power Doppler image of course of entire right renal artery till the hilum and segmental branches. Fig. 7.1.4.17 A: Longitudinal section at origin of the right main renal artery. Spectral Doppler tracing of the main renal artery showing classical low-resistance flow pattern with presystolic notch, sharp systolic peak with continuous forward diastolic flow. B: Longitudinal colour and spectral Doppler image at hilum of right main renal artery showing classical low-resistance flow pattern with a broader peak and a high continuous forward diastolic flow. C: Longitudinal section of renal segmental artery with spectral Doppler of the midsegmental artery shows normal acceleration index, that is systolic slope measured from start of the slope to the top of the first peak. Fig. 7.1.4.18 Anatomical relationship of IVC with portal vein tributaries, mesenteric veins and aorta. Fig. 7.1.4.19 A: Transverse abdominal colour image of IVC (blue) and its relation to aorta (red). B: Longitudinal colour image of course of IVC. Fig. 7.1.4.20 Transverse colour Doppler and spectral tracing demonstrating the typical triphasic flow pattern of IVC with respiratory variation. Fig. 7.1.4.21 A: The typical tracing of IVC or hepatic vein flow which shows three waves S, v and D below the baseline and a wave above the baseline. B: Colour

Doppler spectral pattern of the middle hepatic vein demonstrating the triphasic wave form. Fig. 7.1.4.22 A: Longitudinal split screen grey scale and colour Doppler image demonstrating portal vein at porta. B: Transverse colour Doppler and spectral tracing demonstrating the typical flow of portal vein with respiratory variation. Fig. 7.1.4.23 A,B: Transverse grey scale and colour Doppler image demonstrating the anatomic relationship and course of portal and splenic vein confluence posterior to the body of pancreas anteriorly and superior mesenteric artery and IVC posteriorly. Fig. 7.1.4.24 Transverse colour Doppler and spectral tracing demonstrating the monophasic flow of splenic vein with respiratory variation. Fig. 7.1.4.25 A: Transverse section power Doppler image demonstrating the course of right renal vein from renal hilum to confluence with IVC. B: The transverse colour Doppler spectral tracing obtained from the renal vein shows continuous waveform with respiratory variation. Also noted is transmitted arterial waveform. Fig. 7.1.5.1 Anatomy of abdominal aorta. Fig. 7.1.5.2 Sonography of abdominal aorta. Fig. 7.1.5.3 (A) (left) Probe positioning for longitudinal imaging of upper abdominal aorta. (B) (right top) Greyscale longitudinal image of upper abdominal aorta and (C) (right bottom) colour Doppler longitudinal image of upper abdominal aorta. Fig. 7.1.5.4 (A) (left) Probe positioning for transverse image of upper abdominal aorta. (B) (right) Transverse Doppler image of upper abdominal aorta at coeliac trunk – sea gull appearance. Fig. 7.1.5.5 (A) (left) Probe position for coronal plane of aortic bifurcation. (B) (right) Greyscale image of aortic bifurcation and common iliac arteries. Fig. 7.1.5.6 (A) (left) Monophonic Doppler waveform with a diastolic component in suprarenal abdominal

aorta. (B) (right) Triphasic Doppler waveform in infrarenal aorta. Fig. 7.1.5.7 Shows triphasic Doppler waveform in common iliac artery. Fig. 7.1.5.8 Longitudinal greyscale and colour Doppler images of suprarenal aorta show wall thickening and dilatation in aortoarteritis with colour aliasing in dilated segment and occlusion of SMA. Fig. 7.1.5.9 (A) (left) Greyscale transverse and (B) (right) longitudinal images shows heterogeneous wall thickening with calcific plaques and ectasia of abdominal aorta suggesting atherosclerosis. Fig. 7.1.5.10 (A) (left) Longitudinal colour Doppler image shows total occlusion of aortic bifurcation extending to the common iliac arteries. (B) (right) Spectral Doppler shows tardus-parvus waveform distal to occlusion in Leriche’s syndrome. Fig. 7.1.5.11 (A) (left) Transverse greyscale and (B) (right) colour Doppler images of aortic aneurysm with eccentric thrombus. Fig. 7.1.5.12 (A) (left) and (B) (right) Transverse and longitudinal greyscale images of abdominal aortic aneurysm with dissection flap. Fig. 7.1.5.13 (A) (left) Longitudinal greyscale image of acute aortic dissection with intimal flap. (B) (right) Longitudinal colour Doppler image of acute aortic dissection shows variable colour filling in true and false lumen. Fig. 7.1.5.14 (A) (left) Greyscale transverse and (B) (right) colour Doppler longitudinal images of aortic aneurysm with stent. (C) Longitudinal colour Doppler image of common iliac arteries with stent. Fig. 7.1.5.15 Embryology of IVC. Fig. 7.1.5.16 (A) (left) Transverse probe position for IVC. (B) (right top) Transverse greyscale and (C) (right bottom) transverse colour Doppler images of IVC.

Fig. 7.1.5.17 Doppler waveform pattern of IVC which reflects right atrial contractions. Fig. 7.1.5.18 (A) (left) Greyscale longitudinal image shows liver parenchymal changes, ascites and narrowing of IVC in Budd–Chiari syndrome. (B) (right) Colour Doppler transverse image shows absent Doppler flow in narrowed IVC. Fig. 7.1.5.19 (A) (left) shows colour Doppler longitudinal image of intrahepatic IVC stenosis. (B) (right) shows spectral Doppler image of intrahepatic IVC stenosis. Fig. 7.1.5.20 (A) (left) Longitudinal greyscale and (B) (right) transverse Doppler images show intraluminal hyper echoic contents and absent colour filling suggesting thrombosis of infra hepatic IVC. Fig. 7.1.5.21 (A) (left) Transverse and longitudinal greyscale images. (B) (right) Colour Doppler images showing IVC infiltration by renal neoplasm. Fig. 7.1.6.1 (A) Atheromatous aorta with (B) plaque at the origin of the SMA. Fig. 7.1.6.2 (A and B) Fifty-year-old female showing upper abdominal aortic thrombus. (C and D) CT pictures showing aortic thrombus. Fig. 7.1.6.3 (A) Upper mid abdominal aortic dissection with true and false lumen. (B) Note flow in the true lumen seen anteriorly (arrow). Fig. 7.1.6.4 (A) Patient with acute abdominal pain and urgent ultrasound study shows thrombosed proximal SMA. (B) Distal SMA shows tardus parvus flow (arrow) suggestive of significant proximal stenosis. Fig. 7.1.6.5 (A) Thrombosed portal vein with prominent hepatic artery near it. (B) Thrombosed superior mesenteric vein (SMV) with no flow on Colour Doppler. (C) Greyscale image of thickened bowel wall with mesenteric oedema. Fig. 7.1.6.6 (A) Severe CA stenosis at origin (showing high-velocity flow PSV = 320 cm/s) and (B) tardus

parvus flow in hepatic artery. Fig. 7.1.6.7 (A) SMA shows slightly high velocity of 288 cm/s, with colour alising (arrow). (B) PSV is >275 cm/s suggests significant stenosis. Fig. 7.1.6.8 IMA shows tight stenosis at origin as suggested by high PSV of 288 cm/sec. Fig. 7.1.6.9 In a patient with thrombosed SMA, the IMA is hypertrophic (arrow). Fig. 7.1.6.10 (A) Ultrasound shows an aneurysm arising from the celiac artery (CA) (arrow) with small dissection. (B) Colour Doppler with dissection, false lumen (arrow) and aneurysm. (C) True lumen is narrowed (arrow) and (D) some flow in false lumen is noticed (arrow). (E and F) CT angiography showing CA aneurysm (arrows). (G and H) CA aneurysm was treated with coil embolization with complete obliteration of its lumen. Coils seen in lumen (arrow). (I) On colour flow evaluation, no flow is seen in successfully coiled CA aneurysm (arrow). Fig. 7.1.6.11 (A) Incidentally detected aneurysm of the gastroduodenal artery (arrow) with slightly calcific walls and (B) yin and yang flow seen within the aneurysm sac. Fig. 7.1.6.12 (A) Young female with diffusely narrowed aorta with irregular thickened walls and (B) colour flow study shows aliasing, with high-velocity turbulent flow (these findings are consistent with Aorto arteritis or Takayasu arteritis. Fig. 7.1.6.13 (A) Upward bent celiac artery (CA) (may be seen in some normal individuals). (B) PSV in inspiration is 181 cm/s. (C) Significant increased PSV in expiration (355 cm/s) (D) and sitting posture PSV is normal (119 cm/s). These findings are suggestive of MALS. Fig. 7.1.6.14 (A and B) Movement of celiac artery (CA) during inspiration and expiration in relation to aortic axis is calculated, and if more than 50 degrees, it is significant for diagnosis of median arcuate ligament syndrome (MALS). It is called deflection angle. In this

patient, it is obviously more than 50 degrees (A) in deep inspiration and (B) in maximum expiration. Fig. 7.1.6.15 (A) SMA in proximal segment approx. 2.5 cm from origin shows severe stenosis with aliasing arrow and high velocity flow up to 320 cm/s. (B) Spectral waveform is not continuous as patient was tachypneic. (C) Prestenting selective SMA angiogram showing significant stenotic lesion of the SMA, (D) stent is deployed across the stenosis (courtesy Dr Tarun Gandhi). (E) Stent is seen on greyscale image with little extension in aorta. (F) Flow across the stent is well seen. (G) Poststenting spectral Doppler shows high velocity (305 cm/s) in-stent flow which can be sometime higher than threshold velocity of 275 cm/s for SMA. These baseline velocities are useful for follow up in assessing in-stent restenosis. (H and I) Post-SMA stenting fourth day, bowel ultrasound reveals reperfusion seen in bowel walls on power Doppler micro-flow imaging. Fig. 7.1.7.1.1 Axial (A) and coronal (B) transcutaneous perianal sonographic images of the anal canal showing the anal canal (AC), internal sphincter (IS) and the External sphincter (ES). Fig. 7.1.7.1.2 T2W axial (A) and coronal (B) images showing internal (1) and external (2) sphincters, ischioanal and ischiorectal fossae (3), and levator ani (4). Fig. 7.1.7.1.3 Parks classification. A = intersphincteric, B = transsphincteric, C = suprasphincteric, D = extrasphincteric. The external sphincter is the keystone of the Parks classification. Fig. 7.1.7.1.4 A and B: Transperianal sonography coronal images showing hypoechoic intersphinteric fistulous tract (marked by red arrows). Increased vascularity is noted on CFI (figure B). Fig. 7.1.7.1.5 Intersphincteric fistula – park’s classification. Grade II St. James University Hospital MR Imaging Classification. (A and B), Transperianal sonography coronal and sagittal images showing hypoechoic intersphincteric fistula (red arrow) with extrasphincteric abscess (blue arrow). On colour flow

imaging peripheral vascularity is noted. (C and D), MRI T2W FS axial and coronal image showing hyperintense extrasphincteric abscess (blue arrow). Fig. 7.1.7.1.6 Transperineal Ultrasound images, Coronal images (A, B) demonstrating thick walled hypoechoic transphincteric tract with echogenic air foci in its lumen (red arrows). Transperineal ultrasound image in sagittal plane (C) demonstrating transsphincteric fistula (white arrows) with corresponding MRI image (D) in axial plane. Fig. 7.1.7.1.7 Transphincteric fistula – park’s classification. Grade IV St. James University Hospital MR Imaging Classification. (A and B), Transperianal sonography coronal images showing primary fistulous tract (red arrow). Hyperechoic air foci are seen in its lumen. Small intersphincteric abscess is seen indenting external sphincter (blue arrow). Multiple air foci are seen in it. (C and D), MRI T2W FS and T1W post contrast axial images showing small hyperintense intersphincteric abscess (blue arrow). Flowchart 1 Summary of procedure for Barium Upper GI seroes. Flowchart 2 Pathophysiology of genital TB. Fig. 7.2.1.1 Illustrated diagram showing division of liver into 8 segments. Fig. 7.2.1.2 Segments of liver. (A) Axial section of upper abdomen at the level of lung bases. (B) Axial section at the level of confluence of hepatic veins into IVC (*roman numbers denote superior segments of liver as divided by hepatic veins). (C) Axial section at the level of left portal vein (LPV). (D) Axial section at the level of right portal vein (RPV). (E) Axial section at the level of portosplenic confluence showing inferior hepatic segments. Fig. 7.2.1.3 (A) Axial section showing parts of stomach. (B) Axial section showing parts of stomach. Fig. 7.2.1.4 (A) Axial section at the level of kidneys and pancreas. (B) Axial section at the level of kidneys and pancreas (further lower section).

Fig. 7.2.1.5 Axial section at the level of uncinate process of pancreas. Fig. 7.2.1.6 (A) Intrahepatic ductal anatomy in a patient with dilated right and left hepatic duct. (B) Further lower section showing confluence of right and left hepatic duct. (C) Further lower section showing common bile duct (CBD) and main pancreatic duct (MPD). Fig. 7.2.1.7 Muscles of abdominal wall. Fig. 7.2.1.8 Axial section at the level of renal veins. Fig. 7.2.1.9 Serial axial sections showing parts of colon: (A) At the level of hepatic flexure and splenic flexure, (B) At the level of transverse colon, and (C) At the level of ileo cecal junction. Fig. 7.2.1.10 Axial section of pelvis below the level of aortic bifurcation showing bowel loops, vessels and muscles of abdominal wall. Fig. 7.2.1.11 Axial section of pelvis below the bifurcation of common iliac artery. Fig. 7.2.1.12 Lower axial section of pelvis showing division of common iliac arteries. Fig. 7.2.1.13 Axial section of female pelvis at the level of mid sacrum. Fig. 7.2.1.14 (A) Axial sections of the male pelvis at the level of anorectum. (B) Axial sections of the male pelvis at the level of anal canal (further lower). Fig. 7.2.1.15 (A) Axial section of pelvis at the level of lower sacrum. (B) Axial section of pelvis at the level of lowermost sacrum and hip joint. (C) Axial section of pelvis at the level of coccyx. (D) Axial section of pelvis at the level of pubic symphysis and ischium. (E) Axial section of pelvis at the level of inferior pubic ramus. Fig. 7.2.1.16 (A) Axial sections of abdomen showing anatomy of major arteries. (B) Axial sections of abdomen showing anatomy of major arteries. (C) Mid sagittal section of abdomen (MIP) showing origin of celiac artery and superior mesenteric artery.

Fig. 7.2.1.17 (A) Coronal section of abdomen (MIP) showing branches of celiac axis origin of superior mesenteric artery. (B) Magnified coronal section of abdomen (MIP) showing branches of celiac axis and first branch of superior mesenteric artery. (C) Magnified coronal section of abdomen (MIP) showing origin, course and termination of gastroduodenal artery. Fig. 7.2.1.18 Coronal section of abdomen (MIP) showing branches of superior mesenteric artery. Fig. 7.2.1.19 Coronal section of abdomen (MIP) showing renal arteries arising from aorta and course of splenic artery along the pancreas splenic artery. Fig. 7.2.1.20 VRT image of inferior mesenteric artery. Fig. 7.2.1.21 (A) Coronal section of course of abdominal aorta and its bifurcation. (B) VRT image of abdominal aorta and its branches. Fig. 7.2.1.22 (A) CT sections showing various peritoneal reflections and spaces: parts of lesser omentum – hepatoduodenal and gastroduodenal ligaments. (B–G) CT sections showing various peritoneal reflections and spaces. (H) Fluid collection of lesser sac. Fig. 7.2.1.23 (A) Illustrated cross-section anatomy of the retroperitoneum. (B) CT sections showing parts of retro peritoneum. Fig. 7.2.2.1 Diagram of anterior surface of the liver depicting hepatic ligaments. Fig. 7.2.2.2 Couinaud’s functional segmental anatomy. RHV, Right hepatic vein; MHV, middle hepatic vein; LHV, left hepatic vein; RPV, right portal vein; LPV, left portal vein; GB, gallbladder. Fig. 7.2.2.3 Image shows sectional anatomy of liver on CT. Fig. 7.2.2.4 Normal anatomy of gallbladder and biliary tree. Fig. 7.2.2.5 Normal Gallbladder: (A) Distended (fasting), (B) Contracted (postprandial).

Fig. 7.2.2.6 USG image showing pancreatic head (H), Body (B) and Tail (T) and its relation with Portal Vein (PV) and Superior mesenteric vein (SMA). Fig. 7.2.2.7 Axial contrast enhanced CT image shows long axis of the pancreas seen with the tail (T) extending from the hilum toward the midline of the body (B). The body continues as the neck (N) anterior to the portal vein (PV). Fig. 7.2.2.8 Coronal MDCT angiography reveals parenchymal feeding vessels in the region of the pancreatic head. The superior mesenteric artery (SMA) and splenic artery are visualized. Fig. 7.2.2.9 Coronal MDCT image showing SMA arising from aorta posterior to neck of pancreas and runs inferiorly, anterior to uncinate process along with SMV. Fig. 7.2.2.10 Normal spleen on US. (A) Coronal and (B) axial views of the left upper quadrant show a normal spleen. The black line represents the splenic width, the white line in (A) represents the splenic length and the white line in (B) indicates the splenic depth. Fig. 7.2.2.11 Normal enhancement pattern of the spleen on CT. Axial CT images (A) before and (B) after intravenous administration of iodinated contrast material show heterogeneous enhancement of the splenic parenchyma during the arterial phase. Fig. 7.2.2.12 Ultrasound image showing normal liver size in AP dimension at mid clavicular line. Fig. 7.2.2.13 Ultrasound image showing normal middle hepatic vein. Fig. 7.2.2.14 Ultrasound image showing normal portal vein calibre at porta hepatis. Fig. 7.2.2.15 Ultrasound image showing normal common bile duct calibre at porta hepatis. Fig. 7.2.2.16 Coronal and axial sections of abdomen showing normal liver dimensions. Fig. 7.2.2.17 Ultrasound image showing normal pancreatic sizes at head, body and tail regions.

Fig. 7.2.2.18 Axial section of abdomen showing normal pancreas dimensions in the region of head, body and tail. Fig. 7.2.2.19 Ultrasound image showing normal spleen size. Fig. 7.2.2.20 Coronal section of abdomen showing normal length of spleen. Fig. 7.2.2.1.1 Michels’ classification of Hepatic artery variants. Fig. 7.2.2.1.2 Anatomical variants of portal vein. Fig. 7.2.2.1.3 Phrygian cap. Transverse MDCT shows a phrygian cap (arrow). Fig. 7.2.2.1.4 (A) Drawings show the normal anatomy, (B) trifurcation, (C) a short right hepatic duct, (D) continuation of the right posterior hepatic duct into the common hepatic duct, (E) drainage of the right posterior hepatic duct into the left hepatic duct, and (F) drainage of the right anterior hepatic duct into the left hepatic duct. Fig. 7.2.2.1.5 (A) Ventral pancreatic bud (VP) arises from hepatic diverticulum, and dorsal pancreatic bud (DP) arises from dorsal mesogastrium. (B-D) During 7th gestational week, expansion of duodenum causes ventral pancreatic bud to rotate and pass behind duodenum from right to left and fuse with dorsal pancreatic bud. Ventral bud forms posterior head and uncinate process, whereas dorsal bud forms anterior head, body, and tail. Finally, ventral and dorsal pancreatic ducts fuse, and pancreas predominantly is drained through ventral duct, which joins common bile duct at level of major papilla and dorsal duct drains at level of minor papilla. Fig. 7.3.1 Divisions of the oesophagus. Fig. 7.3.2 Oesophageal rings. Fig. 7.3.3 Measuring diameter of the oesophagus on axial CT image. Fig. 7.3.4 Upper oesophageal sphincter on barium swallow.

Fig. 7.3.5 Lower oesophageal sphincter on barium swallow. Fig. 7.3.6 Hiatus hernia. Fig. 7.3.7 Lateral chest radiograph showing tracheaoesophageal stripe. Fig. 7.3.8 Post gastric banding surgery – complication (slippage of the band). Phi angle is obtuse indicating slippage of the band. Anterior and posterior rings are not superimposed. Fig. 7.3.9 Hypertrophic pyloric stenosis – figure showing how to measure the thickness of the gastric pylorus on ultrasound. Fig. 7.3.10 Comparison of retrogastric space with vertebral body on Barium study. Fig. 7.3.11 Axis of rotation of organoaxial volvulus. Fig. 7.3.12 Axis of rotation of mesentroaxial volvulus. Fig. 7.3.13 Landmarks and measurements in defecography. Fig. 7.4.1.1 Midline epigastric scan showing symmetrically thickened hypoechoic muscle of the pylorus with central echogenic mucosa. Fig. 7.4.2.1 Barium swallow in a 50-year-old male with history of progressive dysphagia of one-year duration. Fig. 7.4.3.1 Barium swallow of the patient. Radiological technique: Barium swallow (barium oesophagography). Fig. 7.4.4.1 Barium swallow of the patient. Fig 7.4.5.1 Barium study of the patient. Fig 7.4.5.2 CECT of the patient. Fig 7.4.5.3 CECT of the patient. Fig. 7.4.6.1 CECT showing a mass in the head of pancreas. Fig. 7.4.7.1 Doppler sampling from SMA origin. Fig. 7.4.8.1 USG of abdomen showing the intraperitoneal multilocular cystic lesions.

Fig. 7.4.9.1 CECT of abdomen showing an enhancing lesion with spiculated margins in the region of mesentery. Fig. 7.4.11.1 Coronal contrast-enhanced CT images of a 50-year-old male patient. Fig. 7.4.11.2 Axial contrast-enhanced CT images of a 50-year-old male patient. Fig. 7.4.13.1 Fig. 7.4.14.1 NECT and multiphase CECT. Fig. 7.4.15.1 Contrast-enhanced CT shows lesion in the liver. Fig. 7.4.16.1 Contrast-enhanced MRI shows isodense lesion. Fig. 7.4.17.1 CT Technique: Contrast-enhanced multidetector CT scan. Fig. 7.4.18.1 Contrast-enhanced MRI shows large multiloculated cystic mass lesion. Fig. 7.4.18.2 Mucinous cystadenoma: Macrocystic lesion in the tail of the pancreas. Figure 7.4.19.1 (A and B) Diffusely thickened omentum with heterogeneous enhancement and loculated ascites in axial and coronal sections. Fig. 7.5.1.1 (A) AP radiograph of hip with B/L femur shows generalized increase in bone density with loss of medullary space (red arrow). (B) AP radiograph of B/L femur shows cortico-medullary appreciation with cortical thinning; fracture of the proximal right femur is also seen. (C) Lateral radiograph of DL Spine showing characteristic bone within bone appearance. (D) AP radiograph of hand shows characteristic bone within bone appearance. Fig. 7.5.1.2 AP radiograph of both hands in a patient with Pyknodysostosis showing generalized increase in bone density with acroosteolysis of terminal phalanges (yellow arrows).

Fig. 7.5.1.3 (A) Lateral radiograph skull of a patient with Pyknodysostosis showing obtuse mandibular angle (red arrow) and widely open cranial sutures. (B) Lateral radiograph skull of a patient with Osteopetrosis for comparison revealing normal suture lines and mandibular angle. Note the increased density of skull on both the radiographs. Fig. 7.5.1.4 AP radiograph of both hands shows Sclerosing wavy new bone formation in the left hand along one side of the bone. Fig. 7.5.1.5 AP radiograph of wrist showing juxtaarticular uniform-sized epiphyseal sclerotic foci. Fig. 7.5.1.6 (A and B) Osteogenesis imperfecta. Fig. 7.5.1.7 (A and B) AP radiograph of extremities in a patient with OGI type 3 show cystic changes involving the metaphyseal ends with significant metaphyseal widening and sparing of the diaphysis; also pathological fractures of the long bones without callus formation are seen. Fig. 7.5.1.8 (A) Lateral radiograph of spine shows anteroinferior beaking of vertebral body In Hurler’s syndrome. (B) AP radiograph of hand showing short and wide metacarpals In Hurler’s syndrome. (C) AP radiograph of shoulder shows characteristic varus deformity In Hurler’s syndrome. Fig. 7.5.1.9 (A) Lateral spine radiograph of a patient with Morquio’s syndrome showing classical anterior central beaking of the vertebral body. (B) AP radiograph of both hands showing proximal pointed metacarpals in Morquio’s syndrome. Fig. 7.5.1.10 (A) Lateral radiograph of DL spine in Achondroplasia shows bullet nose vertebra with exaggerated lumbar lordosis (red arrow) and protuberant abdomen; however, the trunk height is normal. (B) Lateral skull radiograph in Achondroplasia shows disproportionately large head with frontal bossing and narrow foramen magnum. (C) AP radiograph of hip in Achondroplasia shows characteristic champagne glass

pelvis with flattened acetabular roof and small sciatic notch. Fig. 7.5.1.11 Lateral spine radiograph of a patient with Spondyloepiphyseal dysplasia (SED) showing classical heaped-up vertebra with reduced disc space. Fig. 7.5.1.12 (A) Frontal radiograph of chest and upper extremity. (B) Frontal radiograph of the lower extremity showing Epiphyseal stippling (blue arrow) with metaphyseal flaring of the long bones and vertebral stippling, note the rhizomelic shortening of the proximal bones – humerus and femur. Fig. 7.5.1.13 Frontal radiograph of knee joint showing metaphyseal fraying, splaying and cupping. Fig. 7.5.1.14 Frontal radiograph of both knees in scurvy showing Wimberger ring sign in epiphysis of tibia and Pelkin spur. Fig. 7.5.1.15 (A) AP babygram of Achondroplasia. (B) Lateral babygram of achondroplasia. Fig. 7.5.1.16 AP babygram of an abortus with thanatophoric dysplasia. Fig. 7.5.1.17 Babygram (AP view) showing umbilical catheters and endotracheal tube (hollow arrow). Umbilical artery catheter (solid arrow) and Umbilical vein catheter (arrowhead) are abnormally high in position. Fig. 7.5.1.18 Babygram of diaphyseal aclasis. Fig. 7.5.1.19 (A) Patient position in an invertogram. (B) Invertogram in a patient with low ARM. Fig. 7.5.1.20 Schematic diagram depicting various lines and types of ARM (PCL, pubococcygeal line; I line, ischial line; P, pubis; I, ischium; S, sacrum). Fig. 7.5.1.21 Important landmarks in an invertogram. 1, inferior margin of spine; 2, pubis bone; 3, lower margin of ischium. Fig. 7.5.1.22 (A) Invertogram in high ARM shows gas in the urinary bladder suggestive of rectovesical fistula. (B)

Prone cross-table lateral view in a patient with high ARM shows anterior beaking of the distal-most rectal gas (arrow) with rectovesical fistula. (Urinary bladder gas marked as asterisk.) Fig. 7.5.1.23 (A) Patient position for prone cross-table lateral view. (B) Prone cross-table lateral view in a patient with high ARM. Fig. 7.5.2.1 Right anterior oblique view depicting the normal oesophagus (white arrows) clear off the spine. Fig. 7.5.2.2 Single contrast examination of the upper GI tract with water-soluble contrast in AP and lateral projections showing the normal impressions of the aortic arch (black line) and left atrium (white line) over the oesophagus in lateral view. Fig. 7.5.2.3 Single contrast examination of the upper GI tract depicting the oesophagus (white arrows), gastrooesophageal junction (black arrow) and stomach opacified with contrast in AP projection. The normal impression of the aortic arch is seen (star). Fig. 7.5.2.4 Upper GI series depicting the normal oesophagus, gastro-oesophageal junction and stomach. Fig. 7.5.2.5 AP view of an upper GI series showing the normal anatomy and parts of the duodenum (First part – red arrow, second part-yellow arrow, third part – blue arrow, fourth part – green arrow) of the duodenum. The third part of the duodenum crosses the spine and the duodenojejunal junction is located the left of the spine (orange circle). The normal GE junction is also seen in this projection (black arrowhead). Fig. 7.5.2.6 The lateral view of an upper GI series in an 8-year-old shows the normal appearance of the stomach and duodenum. The duodenum and duodenum bulb are posteriorly directed and located posteriorly. The duodenojuejunal junction may be located at the level of the duodenal bulb apex or slightly inferiorly. Fig. 7.5.2.7 Upper GI series, AP view of an infant with gastro-oesophageal reflux. There is reflux of contrast into the oesophagus. However, the duodenum (white arrows)

is well demonstrated in this study. The duodenojejunal junction (black arrow) is normally located to the left of the spine and behind the stomach. Fig. 7.5.2.8 Oblique view depicting pooling of barium in the fundus of the stomach. Also, the entire C loop of the duodenum (black arrows) is demonstrated. Fig. 7.5.2.9 Paediatric upper GI series technique. Step 1: Right side down laterally for lateral oesophagus. Step 2: Right side down laterally for gastric outlet and second part of duodenum which is seen through the gas-filled fundus of stomach. Step 3: Turn the baby supine for antrum of stomach and second part of duodenum. Step 4: Turn baby left side down so that barium fills the fundus and third part of duodenum. Step 5: Turn the baby supine straight to visualize the fundus and third and fourth parts of duodenum. Also, the duodenojejunal flexure should be seen through the gas-filled antrum. After the position of the duodenojejunal flexure is determined, additional views may be obtained as required. Fig. 7.5.2.10 Upper GI series in an infant depicting reflux of contrast up to the upper oesophagus in a case of gastro-oesophageal reflux disease. Fig. 7.5.2.11 Upper GI series of an infant presenting with projectile bilious vomiting shows the stomach to be grossly distended with contrast and a linear ‘string’ of contrast (white arrows) in the pylorus. Hypertrophic pyloric stenosis was confirmed intraoperatively. Fig. 7.5.2.12 A barium meal follow-through examination in a child with malrotation shows the duodenojejunal junction to the right of the midline (black arrow). The third part of the duodenum does not cross the midline. The jejunal loops are located in the right upper quadrant of the abdomen (white arrows). Fig. 7.5.2.13 Barium meal follow-through examination showing the classical corkscrew appearance of the duodenum in a case of malrotation with midgut volvulus. Fig. 7.5.2.14 A normal single contrast enema examination in a paediatric patient showing the rectum

(black arrows), sigmoid colon (white arrows), descending colon (black arrow heads), transverse colon (white arrow heads) and ascending colon (double black arrows). Fig. 7.5.2.15 AP and lateral projections of a normal contrast enema with water-soluble contrast in a 15-dayold infant. The lateral projection depicts the normal anatomy of the rectum (single black arrows). Fig. 7.5.2.16 Contrast enema in a child with Hirschsprung’s disease showing an abrupt change in calibre of colon (white arrow marks ‘transition zone’). Black double-headed arrow shows the smaller calibre of the aganglionic segment. White double-headed arrow shows the larger calibre innervated segment. Fig. 7.5.2.17 Contrast enema in another child showing long segment dilatation of the sigmoid colon and descending colon in Hirschsprung’s disease. Fig. 7.5.2.18 Contrast enema in a patient showing small calibre of the descending colon up to the splenic flexure. Lateral film of contrast enema showing the small calibre of the colon in another premature infant with small left colon syndrome. Fig. 7.5.2.19 Water-soluble contrast enema showing microcolon (white arrows) with dilated bowel loops suggestive of distal bowel obstruction. Fig. 7.5.2.20 Contrast enema in a newborn showing small calibre of the colon with rounded filling defects (black arrows) due to meconium pellets, giving the soap bubble appearance in meconium ileus. Fig. 7.5.3.1 Plain X-ray abdomen: NEC. Abdominal radiograph of a 7-day-old 25 week preterm with NEC, shows linear (arrows) and bubbly (open arrow) lucencies indicating intramural air. Fig. 7.5.3.2 Plain X-ray abdomen: pneumoperitoneum. Supine X-ray abdomen of a 1-year old boy with acute abdominal pain and distention shows increased transradiancy of the entire abdomen due to pneumoperitoneum. Triangles of lucency in between

bowel loops (arrows) also represents free intraperitoneal air. Fig. 7.5.3.3 Plain X-ray abdomen: small bowel obstruction. Supine X-ray abdomen of a 6-year-old boy with vomiting and abdominal distension shows multiple dilated small bowel loops with a collapsed colon. Fig. 7.5.3.4 Plain X-ray abdomen: bladder calculus. Xray abdomen of a 5-year-old boy with dysuria and lower abdominal pain shows a large rounded radio-opaque calculus (arrow) in the pelvis. The bladder calculus has a typical laminated appearance. Fig. 7.5.3.5 Plain X-ray abdomen: abdominal mass. Xray abdomen of a 10-year-old boy with abdominal pain for 2 months shows a heterogeneous lesion in the left side of abdomen containing a cluster of teeth-like calcifications (arrows) suggestive of a retroperitoneal teratoma. Fig. 7.5.3.6 Plain X-ray abdomen: Wolman’s disease. Xray abdomen of a 4-month-old infant with diarrhoea and failure to thrive shows diffuse punctate calcifications throughout both adrenals (arrows) which appear enlarged, but retain their normal shape. Fig. 7.5.3.7 Distal loopogram: anorectal malformation – preoperative imaging. Image from distal loopogram in a male patient demonstrates a fistulous connection (arrow) between the rectal pouch and the posterior urethra. Fig. 7.5.3.8 Barium follow-through study. Frontal image from barium follow-through series shows an abnormally positioned duodenojejunal junction (arrow). Jejunal loops are seen on the right side of the abdomen. Fig. 7.5.3.9 Acute appendicitis on ultrasound. (A) High frequency ultrasound image of the RIF shows a dilated blind ending tubular structure that measured 12 mm in width (marked between calipers). (B) Ultrasound image from another patient shows a dilated appendix (white arrow). Within the lumen, an appendicolith (open yellow arrow) with posterior acoustic shadowing is seen.

Fig. 7.5.3.10 Ultrasound: intussusception. Transverse ultrasound image of the right mid abdomen shows the ‘target sign’ of intussusception. This ‘target’ consists of two layers: a central echogenic intussusceptum (I) and outer hypoechoic intussuscipiens (arrows). Fig. 7.5.3.11 CT: pancreatic injury. Axial postcontrast CT abdomen of a 12-year-old boy with blunt trauma abdomen shows a pancreatic transection (long arrow) involving the proximal body of pancreas with peripancreatic fluid (short arrows). Fig. 7.5.3.12 CT KUB: ureteric calculus. CT KUB of a 16-year-old boy with left loin pain in whom ultrasound demonstrated dilatation of the collecting system. Coronal CT image shows an obstructing mid ureteric calculus on the left (arrow) with hydroureteronephrosis. Fig. 7.5.3.13 CT: renal injury. Postcontrast excretory phase CT abdomen of a 10-year-old girl who had sustained blunt trauma. Axial image at the level of the renal hila shows active extravasation of contrast (arrow) from the right renal pelvis due to PUJ injury. Right perinephric fluid is also seen. Fig. 7.5.3.14 MRE: active Crohn’s disease. (A) Coronal T2 HASTE demonstrates mural thickening and oedema (white arrowheads) involving the terminal ileum and multiple reactive lymph nodes within the mesentery (black arrowheads). (B) Axial T2 HASTE – corresponding section of the terminal ileum demonstrates areas of ulceration (arrowhead) in addition to the mural thickening and oedema. (C) Axial DWI B800 demonstrates mural high signal within the terminal ileum (arrowheads) consistent with active inflammation. Fig. 7.5.3.15 MRU: duplex kidney. 3D maximum intensity projection generated from precontrast T2weighted sequence shows a left duplex kidney. There is marked dilatation of the collecting system of the upper moiety (open arrow). Inferior to this, the nondilated pelvicalyceal system of the lower moiety (long arrow) is seen. The upper moiety ureter is dilated and tortuous with ectopic insertion (short arrow).

Fig. 7.5.3.16 MRCP. Normal MRCP image shows the intrahepatic and extrahepatic biliary tree, gallbladder and pancreatic duct. Fig. 7.5.3.17 Oncology imaging. (A and B) A 3-year-old girl with nonspecific abdominal pain. Coronal and axial T2W images show a large heterogeneous mass (arrows) in the left upper quadrant. This was an extra-adrenal neuroblastoma. Flowchart 1 Classification of skeletal dysplasias. Flowchart 2 The working approach to skeletal dysplasias. OGI, osteogenesis imperfecta; MPS, mucopolysaccharidoses. SEDC & SEDT, spondyloepiphyseal dysplasia congenita & tarda; SEMD, spondylo-epimetaphyseal dysplasia. E, epiphysis; M, metaphysis. *Though Morquio’s is osteopenic dysplasia it is included here because it has central beaking which is more characteristic. Fig. 7.6.1 Schematic diagram of normal development of rectum and anal canal. A: Early embryonic life (4 weeks); cloaca is formed and it communicates the allantois and hindgut. At the caudal end of it lies the cloacal membrane. Urorectal septum (URS) develops as a mesodermal ingrowth and grows caudally in to the cloaca (blue arrow). Simultaneously the embryo also undergoes inward folding and the cloacal membrane approaches the URS (red arrow). B: About 6/7 weeks, the URS and cloacal membrane meet each other and divide the cloaca in two halves: anterior urogenital sinus (UGS) and posterior rectum (R). Fig. 7.6.2 Classification of ARM on invertography. High type (A), intermediate (B) and low type (C). Fig. 7.6.3 Diagrammatic representation of fallacies of PC line. A: Normal PC line has to be drawn from the tip of coccyx (C) and midpoint of pubic bone (P). If the coccyx is not ossified, the line can be wrongly drawn from CX to PX, thus making the classification inaccurate. B: Using M line (drawn through the junction of upper two-thirds and lower one-third of ischium) as a landmark makes this classification more accurate.

Fig. 7.6.4 Pitfalls of using PC line as a reference for measurement. In a neonate with unossified coccyx, drawing PC line is not accurate. Hence, M line (red line) can be drawn at the junction of upper two-thirds and lower one-third of ischium (marked in yellow dotted line). The example was that of a high ARM. Fig. 7.6.5 Prone cross-table lateral view of a high ARM (PC line marked in red, lower margin of rectal pouch marked in yellow). Fig. 7.6.6 Appearances of normal pelvic floor muscles on MRI. Axial sections (A–C) and coronal (D) showing puborectalis (arrows in A and B). EAS (dotted arrows in B and D), superficial transversus perinei muscle (block arrow in C). Levator hammock (block arrow in D). Fig. 7.6.7 High ARM. Plain radiographs AP (A) and lateral (B) views show gas in the urinary bladder (asterisk), thereby suggesting a presence of fistula. Note the absence of rectal gas posterior to urinary bladder and dilated colonic loop (arrow in A). Fig. 7.6.8 High ARM. Anorectal agenesis without fistula. Distal cologram (A) shows a blind-ending rectal pouch without any fistula. MCU (B) also fails to demonstrate any fistula. Diagrammatic representation of the same (C). Fig. 7.6.9 High ARM in a male child. Rectoprostatic urethral fistula. Fistula is shown with an arrow. Note the posterior angulation (dotted arrow) at posterior urethra suggesting the site of fistulous communication. Fig. 7.6.10 H or N type fistula in a male child. MCU (A) shows the fistulous tract (dotted arrow) opening in the perineum. Note the abnormal morphology of the distal urethra (arrow). Diagrammatic representation (B). Fig. 7.6.11 High ARM in a male child. Rectovesical fistula. Fistula is shown with an arrow (R: rectum, UB: urinary bladder). Fig. 7.6.12 High ARM in a male child. Rectal atresia. The short atretic segment (arrow in A) is demonstrated by performing contrast study simultaneously from below

and through colostomy. Diagrammatic representation (B). Fig. 7.6.13 Schematic diagram of two types of rectobulbar urethral fistula. It can either be short and end proximally into the bulb (solid lines), or long and thin to enter the ventral surface of bulbar urethra (dotted line). Fig. 7.6.14 Intermediate type ARM in male. Rectobulbar urethral fistula. Passage of the catheter in distal cologram through the fistula into the urethra (A). Subsequent withdrawal of catheter and distal cologram (B) demonstrated the short fistula (arrow) in proximal bulbar urethra. Fig. 7.6.15 Schematic diagram of low type ARM (anocutaneous fistula). Fig. 7.6.16 Low type ARM in male. Anocutaneous fistula. Invertogram (flipped for the sake of similarity in comparison) (A) shows the distal bowel gas (marked yellow) lying below the I line (blue line). PC line is marked in red. Distal cologram (B) shows the fistula (arrow). Fig. 7.6.17 Rectovaginal fistula demonstrated on vaginogram. Difference in ‘high’ and ‘low’ rectovaginal fistulae lies in the level of blind bowel pouch and not on the site of entry of fistula into the vagina (R: rectum; V: vagina; BL, bladder; UT: uterus). Fig. 7.6.18 Schematic diagram of cloaca with long common canal (A) and short common canal (B) (CC: common canal). Fig. 7.6.19 Contrast study through the common canal shows opacification of urinary bladder (UB), vagina (V) with a cervical impression (arrow) and rectum (R). Fig. 7.6.20 Hydrometrocolpos in an infant with cloacal malformation. Plain radiograph (A) reveals large soft tissue opacity (asterisk) causing upward displacement of bowel loops. Contrast study through the common canal (B and C) shows opacification of the distended vagina and uterus (B).

Fig. 7.6.21 Rectovestibular fistula – demonstrated on retrograde contrast injection – note the long, narrow fistulous track (arrow). Schematic diagram of the same (B). Fig. 7.6.22 Schematic diagram of anovestibular fistula. Fig. 7.6.23 Pouch colon. Plain radiograph reveals massive focal dilatation of a localized segment of large bowel (arrow in A). Barium enema reveals gross dilation of the rectum and sigmoid (B). Fig. 7.6.24 Associated anomalies in ARM. Partial sacral agenesis (arrow in A) and vesico-ureteric reflux (B). Fig. 7.6.25 Currarino’s triad. Anterior sacral meningocele presenting as a presacral mass in a patient of operated low ARM. AP radiograph (A) showed a defect in midline sacrum (arrow). T2W sagittal MRI images (B and C) show a hyperintense cystic lesion (Cy), having a beak-like communication with the CSF space (arrow). Fig. 7.6.26 Imaging in postoperative incontinence. T2W axial MR image reveals an eccentrically located neorectum (arrow) within the sphincter and fat interposition (dotted arrow). Fig. 7.7.1 Enteric duplication cyst: Ultrasound image showing a unilocular anechoic, cyst in the mesentery with an echogenic inner lining and a hypoechoic outer layer the – ‘double layer’ sign. Fig. 7.7.2 (A and B) Duplication cyst: Ultrasound (A) and colour Doppler (B) images in a 9-year-old boy presenting with abdominal pain and tenderness. A cystic structure with thick walls showing all five layers of the gut is seen in the subhepatic region. Another cystic structure is seen adjacent to the aforementioned lesion with relatively thick walls but lack of wall layers (arrows). Some internal debris is noted in both the cysts. Vascularity within the wall is increased on colour Doppler and the surrounding fat is hyperechoic (B) – two complicated duplication cysts were confirmed at surgery.

Fig. 7.7.3 Enteric duplication cyst with fluid level: Ultrasound image showing a cystic lesion with the double layer sign. An intralesional fluid level is noted within due to haemorrhage. Also, note the change in shape of the cyst in (B) due to peristalsis. Fig. 7.7.4 Atypical complicated duplication cyst: Axial CECT abdomen of a 10-year-old child shows a unilocular cystic lesion with slightly thick enhancing walls and marked heterogeneity in the surrounding mesenteric fat suggesting inflammatory changes. The lesion does not appear to have any connexion with the adjacent gut. An infected duplication cyst was found at surgery. Fig. 7.7.5 Hypertrophic pyloric stenosis: Longitudinal scan obtained in the right subcostal region reveals a markedly thickened and elongated pylorus resembling the uterine cervix-pseudocervix appearance. Fig. 7.7.6 Hypertrophic pyloric stenosis: Longitudinal scan reveals a markedly thickened and elongated pylorus (callipers). Note the fluid-filled antrum proximally into which the redundant mucosa is seen to bulge-the mucosal nipple sign (curved arrow). Fig. 7.7.7 Peutz-Jeghers syndrome: MR enterography demonstrates multiple variable sized polyps in the small intestine in a child with peri-oral pigmentation. Note the presence of jejuno-jejunal intussusception due to a polyp acting as the lead point. Fig. 7.7.8 (A–E) Hemangioma colon: Axial T2 HASTE (A), T2 TRUFI (B), T1 FS (C) and post contrast T1 FS (D) MR images of a 14-year-old male presenting with rectal bleeding show a small T2 hyperintense lesion along the anterior wall with avid post contrast enhancement which was persistent (arrow). Colonoscopy image (E) shows submucosal soft tissue lesion in the hepatic flexure of colon with congested overlying mucosa. Fig. 7.7.9 (A–D) Lymphoma ileum: Longitudinal and transverse ultrasound images through the right flank in a 4-year-old boy reveal marked circumferential hypoechoic wall thickening producing a mass with a typical target

appearance on the transverse image (A) and a pseudokidney appearance on longitudinal section (B). Fig. 7.7.10 Lymphoma ileocaecal region: Barium meal follow through examination showing a long featureless segment of bowel with loss of mucosal folds, luminal dilatation, no luminal compromise or proximal obstruction (arrows) consistent with small bowel lymphoma. Fig. 7.7.11 (A-C) Lymphoma ileum: Axial, coronal and sagittal contrast enhanced CT images of the same child as Fig. 7.7.9 show marked hypodense wall thickening of the distal ileum with minimal enhancement. Note mild dilatation of the bowel lumen. The perilesional fat planes are well preserved and there is no proximal dilatation of the bowel. Findings typical for a small bowel lymphoma. DLBCL was found at biopsy. Fig. 7.7.12 Barium upper GI examination shows a central barium filled crater surrounded by a smooth wall thickening producing a typical bull’s eye appearance in an 18-year-old male with gastric lymphoma. Fig. 7.7.13 (A–C) Gastric GIST: Axial coronal and sagittal CECT images in a 14-year-old girl with history of haematemesis reveal a predominantly exophytic lesion showing heterogeneous enhancement). There is an area of ulceration that communicates with the gastric lumen visualized as a small irregular area of oral contrast extension into the mass. Fig. 7.7.14 Carcinoma colon: Double contrast barium enema shows a short segment narrowing with mucosal irregularity, overhanging proximal and distal margins producing a typical apple core lesion suggestive of carcinoma ascending colon. Fig. 7.7.15 (A and B) Carcinoma rectum: Axial CECT images reveal marked hypodense thickening of the rectum with specks of intratumoural calcification. There is loss of fat planes with the uterus anteriorly and infiltration of the mesorectal fascia. Note the presence of calcified lymphadenopathy along the right iliac vessels along with ascites – Mucinous adenocarcinoma rectum.

Fig. 7.7.16 Ileo caecal tuberculosis: Axial and coronal CECT images reveal homogeneously enhancing moderate wall thickening involving the terminal ileum and caecum which also appears pulled up. Small nodes are seen adjacent to the thickened ileocaecal region. Fig. 7.7.17 (A and B) Acute appendicitis: Highresolution ultrasound images of the right iliac fossa reveal an inflamed appendix seen as a tubular noncompressible structure (A) with a target appearance on transverse section (B) measuring 9 mm. There is increased echogenicity of the surrounding fat due to periappendiceal inflammation. Fig. 7.7.18 (A and B) Appendicular abscess in a patient with previously diagnosed acute appendicitis: Axial CECT image (A) reveals a poorly marginated collection in the right iliac fossa with a hypodense centre, mild peripheral enhancement and few air loculi within the lesion. It is closely abutting the right iliopsoas muscle. On the oblique coronal reconstruction (B), the collection is seen to extend up to the base of the caecum; however, no appendicolith or appendicular remnant is visualized. Fig. 7.7.19 Gastric bezoar: Barium upper GI examination reveals a mottled filling defect taking the shape of the stomach, which is distended. The mucosal outline of the stomach appears smooth – findings consistent with gastric bezoar. Fig. 7.7.20 Gastric bezoar: Coronal multiplanar reformatted CECT image with oral and intravenous contrast in a 16-year-old girl shows a large, heterogeneous predominantly low attenuation mottled mass which fills the gastric lumen. Oral contrast is seen to outline the lesion which is completely separated from the gastric wall – suggestive of gastric bezoar. Fig. 7.7.21 (A and B) Intussusception: ultrasound images of a 9-month-old girl through the right upper quadrant. Transverse image (A) shows the classic target appearance with central hyperechoic core due to the mesenteric fat and the outer hypoechoic rim representing the intussusceptum. On longitudinal section (B) with colour Doppler a pseudokidney

appearance can be seen with presence of some mesenteric vessels within the mesenteric fat well seen on colour Doppler. Fig. 7.7.22 (A and B) Ileocolic intussusception – transverse ultrasound image in the right subhepatic region (A) in a 1-year-old child with a palpable lump and acute abdominal pain reveals a classic crescent in target appearance. The outer hypoechoic rim represents oedematous colonic wall whereas eccentric hyperechoic crescent inside represents the mesenteric fat. The invaginating bowel loop which is slightly hypoechoic (arrow) is seen anteriorly. Colour Doppler image of the same (B) reveals good vascularity within the intussusception. Fig. 7.7.23 Transverse ultrasound image of an ileocolic intussusception showing the technique for measurement of inner fat core (red line) to outer wall thickness (yellow line) ratio. demonstrating and index of more than 1 or the fat, core diameter is greater than the outer wall thickness. Fig. 7.7.24 longitudinal oblique image through an intussusception reveals fluid between the intussusceptum and intussusceptions (FL) representing trapped peritoneal fluid. This suggests reduced chances of successful reduction by enema. Fig. 7.7.25 (A and B) Ileo-ileal intussusception in a 12year-old boy Axial CECT images reveal a target appearance of intussusception in transverse section, and an in oblong sausage shaped lesion as it is cut in long axis (B). The caecum is visualized separately in the right iliac fossa (arrow in A). The presence of intraluminal mesenteric fat and enhancing vessels is characteristic (arrows in B.) The bowel wall shows good enhancement and there is no stranding or free fluid. Proximal bowel loops appear to be dilated suggesting some obstruction. A small polyp was found at surgery as the lead point with no bowel wall necrosis. Fig. 7.8.1 Classification scheme for oesophageal atresia and tracheoesophageal fistula. A: Isolated oesophageal atresia, B: oesophageal atresia with proximal fistula, C:

oesophageal atresia with distal fistula, D: oesophageal atresia with proximal and distal fistula, E: H-type fistula with no atresia. Fig. 7.8.2 Oesophageal atresia. Radiograph shows a gasless abdomen and a coiled NG tube in a dilated proximal oesophageal pouch (arrows). This appearance is seen in Types A and B. Fig. 7.8.3 Oesophageal atresia with distal fistula. Coiled NG tube is seen in the proximal pouch (arrows). Air is seen in the stomach and small bowel loops indicating the presence of a distal fistula. This appearance is seen in Types C and D. Fig. 7.8.4 Oesophageal atresia and TEF with pyloric atresia. Coiled NG tube is seen in the proximal pouch (arrow) with gas in the stomach indicating a distal fistula. The stomach bubble is distended with absent gas distally. This is diagnostic of pyloric atresia. In the chest, right upper lobe changes are seen due aspiration pneumonitis. Fig. 7.8.5 Anastomotic leak post-TEF repair. Contrast study shows an anastomotic leak into the extrapleural space. Right pneumothorax is noted. Fig. 7.8.6 Anastomotic stricture post-TEF repair. Barium swallow shows concentric narrowing at the anastomotic site (arrows). Fig. 7.8.7 String sign. Barium upper GI study shows the typical appearance of the pyloric canal in HPS. The antropyloric canal is narrowed producing the string sign (long arrows) and there is eccentric lesser curve indentation by the hypertrophied muscle (short arrow). Fig. 7.8.8 Hypertrophic pyloric stenosis: ultrasound features. A: Longitudinal section shows an elongated pyloric canal (arrows) measuring 24 mm in length with thickened muscle. The central mucosa is echogenic. B: The pyloric muscle (between calipers) is thickened and measured 4 mm. C: In transverse section, the thickened muscle is seen as an echo poor rim (arrows). D: The redundant pyloric mucosa (arrows) projects into the

distended fluid-filled gastric lumen producing the ‘nipple sign’. Fig. 7.8.9 Pyloric atresia: various types. I. Complete atresia with no connection. II. Atresia with fibrous connection. III. Membranous atresia. S-stomach, Dduodenum. Fig. 7.8.10 Pyloric atresia. Supine radiograph shows marked distension of the stomach with absence of gas in the small bowel (‘single bubble’ appearance). Fig. 7.8.11 Pyloric membrane with hole. The stomach (S) is distended and filled with air; there is decreased gas in the small bowel loops (arrows). Fig. 7.8.12 Duodenal atresia. Radiograph of a 9-hour old neonate with bilious vomiting shows a ‘double bubble’ representing the dilated stomach (S) and the dilated duodenum (D) with no gas in the rest of the intestinal tract. Fig. 7.8.13 Duodenal stenosis. A: Upper GI contrast study in a neonate with bilious vomiting shows a dilated stomach and proximal duodenum with distal passage of contrast through a small opening. B: Ultrasound image of this baby shows a dilated D1 and narrowing at D2 level (arrow). S – stomach. Fig. 7.8.14 Duodenal diaphragm. Upper GI contrast study shows dilatation of the stomach and proximal duodenum. A duodenal diaphragm was found at surgery. Fig. 7.8.15 Annular pancreas. Upper GI contrast study in a 2-week-old neonate with bilious vomiting shows a dilated stomach and proximal duodenum with reflux of contrast into the biliary tree (arrow). Findings denote obstruction beyond ampulla of Vater. At surgery, annular pancreas along with duodenal web was found. Fig. 7.8.16 Annular pancreas: ultrasound. Axial image at level of head of pancreas shows circumferential pancreatic tissue (arrows) around the duodenum (d). p – pancreas. Fig. 7.8.17 Preduodenal portal vein. Ultrasound image illustrates the course of portal vein (arrows) anterior to

the head of pancreas (panc) and second part of duodenum (*). This neonate also had annular pancreas with duodenal stenosis. st – stomach, du – first part of duodenum, sv – splenic vein, smv – superior mesenteric vein. Fig. 7.8.18 Illustration showing normal intestinal rotation. A: Normal midgut rotation. B: Normal rotation of the caecum with its final place in the right lower quadrant. The DJ flexure is fixed in the left upper quadrant with a long intervening mesentery. Fig. 7.8.19 Illustration of Ladd bands. Two instances in the spectrum of malrotation are shown with Ladd bands extending from the caecum to the right upper quadrant crossing over and obstructing the duodenum. Fig. 7.8.20 SMA–SMV orientation on ultrasound. A: Transverse Doppler image shows normal anatomic relationship of the mesenteric vessels, with SMV (v) to the right of the SMA (a). B: Doppler image in a 12-dayold neonate with bilious vomiting shows reversal in position of the mesenteric vessels, with the SMV (arrow) to the left of the SMA (a). Fig. 7.8.21 Normal duodenum and rotation on ultrasound. Transverse ultrasound shows the fluid- and gas-filled third part of duodenum (short arrows) in normal retroperitoneal location crossing between the aorta (A) and IVC (I) posteriorly and the SMA (a) and SMV (v) anteriorly. Fig. 7.8.22 ‘Whirlpool sign’ of midgut volvulus. A: Transverse ultrasound image of a 6-day-old neonate with bilious vomiting shows duodenal dilatation with D3 deviated medially (arrow) as it enters into the midgut volvulus. B: Grayscale image shows the twisting of SMV and mesentery around the SMA which is in the centre of the volvulus (arrows). C: Doppler image shows the twisting of the superior mesenteric vein (arrows) around the centrally located superior mesenteric artery (A), which lacks flow. Fig. 7.8.23 Malrotation with midgut volvulus. Upper GI contrast study shows an abnormally positioned DJ

flexure and a twisted configuration of the proximal jejunum (‘corkscrew appearance’). Fig. 7.8.24 Midgut volvulus. Image from upper GI contrast series in a 5-day-old neonate with bilious vomiting shows a distended D2 (short arrow), with D3 showing a typical tapered narrowing resembling a beak (long arrow). There is no contrast in distal loops. This appearance is seen in volvulus with complete duodenal obstruction. Fig. 7.8.25 Classification of small bowel atresia. Type 1 – membranous atresia. Type 2 – atresia with intervening fibrous band. Type 3a – there is discontinuity of the bowel (no fibrous connecting band) with adjacent mesenteric defect. Type 3b – ‘Apple peel’ or ‘Christmas tree’ atresia. Long segment of atresia with a large mesenteric defect. Type 4 – multiple atresias. Fig. 7.8.26 Jejunal atresia. Radiograph shows dilated proximal loops with absent gas distally. Though the dilatation is marked, it involves only a few loops. Fig. 7.8.27 lleal atresia. Supine view shows numerous dilated bowel loops with no gas in the rectum indicating a distal bowel obstruction. Fig. 7.8.28 Paralytic ileus. A: Supine radiograph shows generalized gaseous dilatation of the entire gut; bowel loops look disorganized as is typically seen in paralytic ileus. B: Prone cross-table view of the same neonate shows gas in the rectum (arrow) thus ruling out a mechanical obstruction. C: Prone cross-table view in another neonate with abdominal distension and dilated bowel loops shows absence of gas in the rectum (*) indicating a mechanical obstruction. Fig. 7.8.29 Microcolon. Contrast enema demonstrates a small calibre colon consistent with a microcolon. Fig 7.8.30 Meconium ileus. Supine radiograph shows numerous distended bowel loops and no gas in the rectum consistent with a low GI obstruction. The loops in the right lower quadrant contain bubbly material (arrows), which represents air mixed with meconium.

Fig. 7.8.31 Meconium ileus: contrast enema. There is a microcolon with multiple nodular filling defects in the terminal ileum representing meconium pellets (arrows). Fig. 7.8.32 Complicated meconium ileus: meconium peritonitis. Radiograph of a newborn shows irregular calcification (arrow) in the lower abdomen indicating an in utero perforation. Fig. 7.8.33 Meconium pseudocyst. Radiograph of a newborn with bilious vomiting shows a mass with rim calcification (arrows) in the mid abdomen representing a meconium pseudocyst. Dilated bowel loops are seen suggestive of secondary obstruction. Fig. 7.8.34 Hypothyroidism. A: X-ray knees in a term neonate with hypothyroidism shows small distal femoral epiphyses (arrows). The proximal tibial epiphyses have not appeared. B: Normal neonate shows presence of distal femoral and proximal tibial epiphyses appropriate for age. Fig. 7.8.35 Short segment Hirschsprung disease. Lateral image of contrast enema shows transition zone in the rectosigmoid. The rectum is of small calibre and the sigmoid is dilated. Fig. 7.8.36 Long segment Hirschsprung disease. A transition zone is seen at proximal descending colon (arrow) distal to the splenic flexure with dilated upstream colon. Fig. 7.8.37 Hirschsprung disease: saw-tooth appearance. Long segment Hirschsprung disease with transition zone at splenic flexure. A saw-tooth/serrated appearance is seen in the descending colon (arrows) due to uncoordinated contractions in the aganglionic segment. Fig. 7.8.38 Meconium plug syndrome. Contrast enema demonstrates filling defects (arrows) within the colon which appears to be of normal calibre. Dilated gas-filled small bowel loops are seen. The degree of small bowel dilatation is less than that seen in ileal atresia or meconium ileus.

Fig. 7.8.39 Colonic atresia. A: Supine view from contrast enema study shows a microcolon ending abruptly. Proximal to this numerous dilated gas bowel loops are seen with bubbly meconium on the right side of abdomen. B: Lateral view demonstrates the blind-ending distal colon turned on itself to adopt a hook-like configuration. Fig. 7.8.40 Duplication cyst: barium series. Image from barium upper GI series shows a mass of soft tissue density (arrow) exerting mass effect (*) over the antropylorus and the proximal duodenum. On ultrasound examination, a duodenal duplication cyst was seen. Fig. 7.8.41 Duplication cyst: ultrasound features. Transverse ultrasound image shows a cystic lesion (dc) adjacent to the stomach (s) and closely related to the second part of duodenum (D2). The cyst shows the typical ‘double-wall’ sign with an inner echogenic mucosal layer and outer hypoechoic muscular layer. At surgery duodenal duplication cyst was found. Fig. 7.8.42 Oesophageal duplication cyst: CT. Postcontrast axial CT image at the level of the thoracic inlet shows a well-defined homogeneous low attenuation lesion (*) that displaces the oesophagus (short arrow) to the right and compresses it. The trachea (long arrow) is displaced anteriorly with narrowing of its lumen. Fig. 7.8.43 Necrotizing enterocolitis: pneumatosis intestinalis. A: Supine radiograph shows multiple distended bowel loops with cystic lucencies in the bowel wall. Bowel wall thickening is also seen in the right side of abdomen. B: Supine radiograph shows multiple dilated bowel loops with widespread linear and curvilinear lucencies in the bowel wall consistent with diffuse pneumatosis. Fig. 7.8.44 Necrotizing enterocolitis: portal venous gas. Supine radiograph shows portal venous gas as branching lucencies (black arrows) overlying the liver shadow. Radiograph also shows multiple dilated bowel loops with mottled lucencies representing intramural air (white arrows).

Fig. 7.8.45 Necrotizing enterocolitis: pneumoperitoneum. A: Supine radiograph shows increased transradiancy of the entire abdomen indicating a large pneumoperitoneum. B: Supine cross-table lateral view shows a large amount of free intraperitoneal air beneath the anterior abdominal wall. Fig. 7.8.46 NEC: ultrasound technique. The figure demonstrates the four-quadrant technique. Scan begins in the right lower quadrant and ends in the left lower quadrant moving in a clockwise direction. Fig. 7.8.47 NEC: ultrasound of bowel wall. Highfrequency ultrasound image in two different neonates with NEC demonstrating bowel wall abnormalities. A: The loops show wall thickening with increased mural echogenicity (arrows). B: A thinned loop (wall thickness measures 50% fibrosis (hypointense signals, dashed white arrow) with visible residual tumour (intermediate signal intensity, dashed yellow arrow), indicating moderate response (TRG 3). Corresponding DWI (E) and ADC (F) images show some areas of diffusion restriction (yellow arrows). Fig 8.5.38 Postneoadjuvant therapy slight response: TRG 4, in a 65-year-old-male. (A) Baseline axial T2weighted MR image shows intermediate signal intensity mass involving lower rectum (white arrow). Corresponding DWI (B) and ADC (C) images show marked diffusion restriction (white arrows). (D) Axial T2-weighted MR image after completion of neoadjuvant therapy shows little areas of fibrosis (hypointense signals, dashed white arrow) with majority residual tumour (intermediate signal intensity, dashed yellow arrow), indicating slight response (TRG 4). Corresponding DWI (E) and ADC (F) images show significant areas of diffusion restriction (yellow arrows). Fig 8.5.39 Four patterns were identified. Each pattern further divided into DWI (–) and DWI (+). Pattern A – Small tumour. After CRT, completely normal rectal wall and no high signal on DWI (A–) or a residual tumour (A+). Pattern B – Circular tumour. After CRT, spiculated and ill-defined fibrosis without high signal on DWI (B–) or with few foci of hyperintense signal within the fibrosis on DWI (B+). Pattern C – Semicircular tumour. After CRT, focal fibrotic wall thickening without high signal on DWI (C–) or with a focal hyperintensity at the inner margin of the fibrosis (C+). Pattern D – Polypoid tumour. After CRT, fibrosis at the stalk of the

polyp, either without high signal on DWI (D–) or with a focal high signal at the site of the fibrosis (D+). Fig 8.5.40 Rectal neuroendocrine tumour. Axial 68Ga DOTA TOC PET-CT showing rectal mass (arrow), mesorectal node (arrowhead) and multiple liver metastases (star) showing increased uptake in a patient of neuroendocrine tumour. Fig 8.5.41 Rectal melanoma with liver metastasis in a 69-year-old male. T1 (A) and T2-weighted (B) axial MR image of rectum showing rectal mass with hypointense and mildly hyperintense signals in T1, intermediate signals in T2-weighted image. Axial T1 (C) and T2weighted (D) MR image showing hepatic nodule with marked hyperintense signals in T1 and mixed signals in T2-weighted image. Fig 8.5.42 Gastrointestinal Stromal Tumour (GIST). Axial T2-weighted (A) and fat saturated post contrast T1weighted (B) images showing a large rectal mass (asterisk) with heterogeneous signals, necrosis, extramural extension. Histopathological examination showed features compatible with GIST. Fig 8.5.43 Rectal amoebiasis with liver abscess in a 58year-old man. (A) Axial T2-weighted MR image shows rectal wall thickening, hyperintense signals in submucosa, with maintained wall structure (white arrow) – oedematous change. (B) Axial DWI and (C) ADC images at the same level show no diffusion restriction (white arrows). (D) Sagittal T2-weighted MR image shows similar oedematous wall thickening at midrectum (white arrows) and surrounding mesorectal fat stranding. (E) Coronal T2-weighted MR image shows well marginated cystic lesions in liver (white arrowheads). (F) Corresponding coronal postcontrast fat saturated T1-weighted image shows thin rim enhancement (black arrowhead) and surrounding oedematous rim (yellow arrowhead) of the lesions – indicating liver abscesses. Fig 8.5.44 Parks classification of Perianal fistulas. Fig 8.5.45 St. James Classification of Perianal fistulas.

Fig 8.5.46 Perianal fistula in a 60-year-old man. (A) Coronal STIR MR image shows hyperintense linear tract (white arrow) communicating anal canal (A) to perianal skin through right ischioanal space. Cutaneous opening is marked with yellow arrow. (B) and (C) axial T2weighted MR images show the anal opening at 6–7 o’clock position (dashed white arrow in B) and the tract in right ischioanal space (dashed yellow arrow in C). Fig 8.5.47 Diagnostic algorithm for SCC Anal canal. Fig 8.5.48 Anal squamous cell cancer. T2-weighted sagittal (A) and axial (B) MR image in a 53-year-old female shows intermediate signal intensity mass (asterisk) involving the lower rectum up to anal verge. Histopathology showed moderately differentiated anal squamous cell cancer. Fig 8.5.49 Treatment algorithm of anal canal cancer and anal margin cancer. Fig 8.5.50 Anal squamous cell carcinoma posttherapy response. (A) Baseline axial T2-weighted MR image shows intermediate signal intensity mass involving anterolateral wall of anal canal with extension to sphincter complex (white arrow). Corresponding DWI (B) and ADC (C) images show marked diffusion restriction (white arrows). (D) Axial T2-weighted MR image after completion of chemoradiation therapy shows hypointense signals in the area of previous cancer, indicating response and fibrosis (yellow arrow). Corresponding DWI (E) and ADC (F) images show small focus of diffusion restriction (yellow arrows). Fig. 8.6.1 Different stages of embryonic development of the peritoneal cavity. Fig. 8.6.2 Peritoneal carcinomatosis from ovarian carcinoma. Ultrasound showing ovarian mass (A), ascites (B), omental deposit (arrow) (C) and hepatic surface deposit (star) (D). Fig. 8.6.3 MRI in peritoneal disease. Axial T2 (A), DWI (B) and postcontrast T1W images (C) showing superiority of DWI images in detection of subtle peritoneal disease (arrow).

Fig. 8.6.4 PET/CT in peritoneal disease. Multiple metabolically active peritoneal deposits (arrow) are better appreciated on fusion PET/CT images than standard CT images alone. Fig. 8.6.5 (A) Axial CT showing nonvisualization of peritoneal layers in normal individuals. (B) Axial and sagittal (C) CT in patient with tuberculosis showing thick enhancing parietal (arrow) and visceral (dotted arrow) layers of peritoneum. Fig. 8.6.6 Transverse mesocolon (marked as dotted line) in axial (A), sagittal (B) CT in normal subject, in patient with ascites (C). Fig. 8.6.7 Lesser omentum components. (A) Axial and coronal (B) CT showing gastrohepatic ligament (straight arrow), (C) axial and coronal (D) CT showing hepatoduodenal ligament (dotted arrow). Fig. 8.6.8 (A) Coronal and sagittal (B) CT showing gastrocolic ligament (line arrow) and greater omentum (dotted arrow), (C) axial and coronal (D) CT showing CT showing falciform ligament (elbow arrow). Fig. 8.6.9 Gastrosplenic ligament axial (arrow) (A) and coronal (B) CT, splenorenal ligament (dotted arrow) axial (C) and coronal (D) CT, mesentery root (line) coronal (E) and axial (F), sigmoid mesocolon (dotted line) axial (G) and sagittal (H) CT. Fig. 8.6.10 Depiction of the peritoneal cavity and subperitoneal space. Fig. 8.6.11 Peritoneal cavity subdivisions into the supramesocolic and inframesocolic compartment by transverse mesocolon. Fig. 8.6.12 Supramesocolic compartment. Axial and coronal CT images (A to H) showing falciform ligament (dotted arrow) dividing it into right supramesocolic (1) and left supramesocolic (2) compartments which are further subdivided into right subphrenic (3), left subphrenic (4), left perihepatic (5), anterior subhepatic (6) and posterior hepatic (Morrison’s pouch) spaces (7).

Fig. 8.6.13 Axial CT showing recesses of lesser sac including superior (A), inferior (B) and splenic recess (C) as well as foramen of Winslow. Fig. 8.6.14 Inframesocolic compartment. Coronal and axial CT images (A to C) showing mesentery (dotted arrow) dividing it into right inframesocolic (1) and left inframesocolic (2) compartments in addition to right paracolic gutter (3) and left paracolic gutter (4). Left paracolic gutter is separated form left supramesocolic space (5) by phrenicocolic ligament (arrow). Fig. 8.6.15 Pelvic peritoneal spaces in sagittal section in male and female. Fig. 8.6.16 Pelvic compartment. Axial CT image in male (A), sagittal CT images of pelvis in male (B) and female (C) showing median umbilical ligament (arrow), medial umbilical ligaments (dotted arrow) and lateral umbilical ligament (line). 1. Supravesicular space, 2. Medial inguinal fossae, 3. Lateral inguinal fossae, 4. Rectovesicular space, 5. Pararectal space. 6. Vesicouterine space, 7. Rectouterine space. Fig. 8.6.17 Duodenal recesses. Fig. 8.6.18 Caecal recesses. Fig. 8.6.19 Intraperitoneal seeding. (A and B) Under the influence of gravity the fluid in the inframesocolic compartment (1) first fills the pelvic recesses viz: rectovesical/rectouterine (2) and right/left paravesical spaces (3). The fluid then ascends into the paracolic gutters (4). The flow in the left paracolic gutter is slow because of the presence of sigmoid colon and the phrenic–colic ligament (dotted arrow) prevents the ascent of fluid into the left subphrenic space. Most flow is channelled from the right parabolic gutter into the right subhepatic (5), right subphrenic (6) and right subsplenic (7) spaces. Direct extension of fluid from right subphrenic space into left subphrenic space is prevented by the falciform ligament (dotted arrow). Fig. 8.6.20 Transdiaphragmatic extension of the recurrent liposarcoma. Axial (A) and coronal (B) CT

images showing spread of abdominal lesion into lower chest through the left diaphragm (arrow). Fig. 8.6.21 Difference in disease spread based on location of primary disease. Lesion along antimesenteric wall spreading to peritoneal cavity (transperitoneal spread) while lesion along mesenteric wall spreading along mesentery (subperitoneal spread). Fig. 8.6.22 Pneumoperitoneum. (A) Chest radiograph showing free air under right dome of diaphragm (arrow). (B) Abdominal radiograph showing free air as football sign (line) and (C) lateral shoot through radiograph showing free air between abdominal wall and bowel loops (dotted arrow). Fig. 8.6.23 Pneumoperitoneum. (A) Ultrasound showing free air along the perihepatic space showing reverberation artefact (arrow). Corresponding axial CT images in soft tissue window (B) and lung window (C) showing free air (dotted arrow). Fig. 8.6.24 Pneumoperitoneum from gastric ulcer. Axial (A, B) and coronal (C, D) CT images showing free air (arrow) epicentred in the perigastric region involving the gastrohepatic, gastropancreatic and gastrocolic ligaments. Fig. 8.6.25 Ascites. (A) Exudative ascites with (B) gall bladder oedema. Transudative ascites showing (C) fine echoes, (D) fluid–fluid level, (E) thick echoes and (F) multiple thick septa. Fig. 8.6.26 Hemoperitoneum due to ruptured ectopic pregnancy. Ultrasound of abdomen and pelvis showing ascites in Morrison’s pouch (A), ascites with echoes in right paracolic gutter (B), pelvic hematoma (arrow), (C) and ectopic gestational sac (star), (D) separate from ovary. Fig. 8.6.27 Hemoperitoneum. (A) Ultrasound showing posttraumatic splenic contusion with intraparenchymal hematoma (arrow) associated with hemoperitoneum (dotted arrow). Corresponding axial CT images in arterial (B), portal venous (C) and delayed phase

showing nonenhancing intraparenchymal hematoma (arrow) associated with hemoperitoneum (dotted arrow). Fig. 8.6.28 Hemoperitoneum. Axial CT images showing hemoperitoneum as fluid–fluid levels (arrow) in upper abdomen (A) and pelvis (B). CT angiography (C) shows gastroduodenal artery aneurysm (dotted arrow) with surrounding clot. Volume-rendered CT images (D) showing the aneurysm (dotted arrow). Fig. 8.6.29 Left paraduodenal hernia. Axial CT images (A), (B) and (C) showing entrapped jejunal loops within a sac (arrow) in the left anterior pararenal space. The inferior mesenteric vein (dotted arrow) is seen along the anteromedial border of the hernia sac. Fig. 8.6.30 Internal hernia (Petersen hernia) following laparoscopic gastric bypass surgery. Axial CT images (A), (B) and (C) showing internal hernia posterior to gastrojejunostomy with swirling of mesenteric vessels (arrow), mesenteric oedema (dotted arrow) and hypoenhancing bowel loops (line) indicative of ischaemia. Fig. 8.6.31 Biliary peritonitis in postcholecystectomy patient. (A) Axial and coronal (B) T2W images showing mild ascites and (C) MRCP images showing site of biliary leak (arrow) as streak like hyperintensity. Fig. 8.6.32 Encapsulating peritonitis/peritoneal sclerosis. Axial (A) and coronal (B) CT images showing conglomeration of bowel loops in left half of abdomen with surrounding thick peritoneal membrane (arrow) simulating a ‘cocoon’. Fig. 8.6.33 Peritoneal thickening. Case 1: Axial CT image (A) showing localized peritoneal thickening (dotted arrow) due to ileal perforation (star). Case 2: Axial CT images (B) showing diffuse peritoneal thickening (arrow) due to tubercular peritonitis. Fig. 8.6.34 •Case 2: (E) Necrotic mediastinal adenopathy (F) splenic hilar adenopathy (→). (G) Necrotic inframesocolic omental nodule (←). (H) Ascites

along with thickening, nodularity and enhancement of inframesocolic omentum (➢). Fig. 8.6.35 Pseudomyxoma peritonei. Axial CT (A to D) and coronal CT images (E) showing extensive hypoattenuating deposits in the supramesocolic and inframesocolic compartments. Fig. 8.6.36 Primary serous carcinoma of peritoneum. Axial CT images (A), (B) and (C) showing diffuse peritoneal–subperitoneal disease. Normal appearances of both the ovaries. Fig. 8.6.37 Peritoneal mesothelioma (wet type). Axial CT images (A to F) showing ascites, peritoneal thickening (arrow) and omental deposits (dotted arrow). Fig. 8.6.38 Peritoneal lymphomatosis. Axial CT images (A to F) showing ascites, peritoneal-subperitoneal deposits (arrow), mesenteric deposits (dotted arrow) and retroperitoneal lymphadenopathy (line). Fig. 8.6.39 Diseases involving the mesentery in ten different patients. (A) peritoneal carcinomatosis, (B) pseudomyxoma peritonei, (C) lymphomatosis, (D) tuberculosis, (E) mesothelioma, (F) hematoma, (G) mistiness due to portal hypertension, (H) inflammation due to pancreatitis, (I) mesenteric panniculitis, (J) inflammation due to bowel perforation. Fig. 8.6.40 Pathologies involving the omentum in eight different patients: (A) Omental oedema in portal hypertension, (B) omental cake in tuberculosis, (C) omental cake in peritoneal carcinomatosis, (D) omental cake in peritoneal lymphomatosis, (E) postoperative omental contusion, (F) omental hematoma, (G) omental collection in bowel perforation, (H) detached epiploic appendage. Fig. 8.6.41 Omental pathologies. Case 1: Left iliac fossa pain. (A) Ultrasonography, (B) axial CT, (C) coronal CT showing epiploic appendagitis adjoining the descending colon. Case 2: Right lumbar pain. (D) Ultrasonography, (E) axial CT, (F) sagittal CT showing omental infarction adjoining the ascending colon.

Fig. 8.6.42 Peritoneal carcinomatosis in the operated case of moderately differentiated carcinoma of lower lip (extraabdominal primary) with ipsilateral nodal metastasis. Axial CT (A) and (B) showing diffuse peritoneal and subperitoneal disease after 11 months off neck surgery. (C) CT-guided biopsy of omentum. PET images (D) and (E) showing disseminated peritoneal – subperitoneal process, and extensive skeletal deposits. Fig. 8.6.43 Cytoreductive surgery: (A) Cholecystectomy, (B) splenectomy, (C) lesser omentectomy, (D) greater omentectomy, (E) hysterectomy with bilateral oophorectomy and pelvic lymph node dissection, (F) midline abdominal incision, (G) subdiaphragmatic peritonectomy, (H) pelvic peritonectomy, (I) right hemicolectomy, (J) liver nonanatomic resection. Fig. 8.6.44 CT coronal image showing abdominal segmentation for calculation of peritoneal carcinomatosis index (PCI). Fig. 8.6.45 Surgically important sites of peritoneal metastasis. I(a,b): Mucinous cystadenocarcinoma of ovary. Hypoattenuating deposits in porta hepatis chinking the main portal vein (→). II(a,b): Mucinous adenocarcinoma. Heterogeneously enhancing lesion with hypoenhancing core noted posterior and to the left of SMA (mesenteric root) with periodontal fat stranding (⇠). III(a,b): Peritoneal carcinomatosis with pseudomyxoma peritonei. Nodular and plaque-like low attenuating deposits along the costal and diaphragmatic pleural reflections (➢). IV: Peritoneal mesothelioma. IV(a): Sheet enhancing subperitoneal deposits coating the serosal surfaces of pelvic ileal and sigmoid bowel loops resulting in localized aggregation and cocooning of these loops (yellow arrow). IV(b,c): Confluent serial deposits along the serosal surface of splenic flexure of colon(❋). Fig. 8.6.46 CT images showing laparoscopically blind spots (which can be missed in absence of imaging) include pleural deposits (A), hepatic parenchymal

deposits (B), splenic parenchymal deposits (C) and bowel intraluminal deposits (D) all marked with arrows. Fig. 8.6.47 Complications of cytoreductive surgery in four different patients: Sagittal (A) and (B) CT showing enterocutaneous fistula, sagittal (C) and axial (D) CT showing pelvic hematoma, axial (E) and coronal (F) CT showing bowel perforation, axial (G) and coronal (H) CT showing paralytic ileus. Fig. 8.6.48 Examples of recurrence after cytoreductive surgery: (A) and (B) Recurrent peritoneal-based nodules along the left paracolic gutter following a left hemicolectomy for a colonic adenocarcinoma, (C) baseline and follow-up, (D) showing pleural recurrence in case of pseudomyxoma peritonei, (E) baseline and follow-up, (F) showing lung nodule in colonic carcinoma. Fig. 8.6.49 Examples of recurrence after cytoreductive surgery: (A) scar site recurrence in treated case of ovarian carcinoma. (B) and (C) recurrent disease (low attenuation deposit) coating the serosal surface of the terminal ileum and ascending colon, (D) and (E) recurrent disease (low attenuation deposit) along the right combined interfacial reflection coats the right ureter resulting in hydroureteronephrosis. Fig. 8.6.50 Peritoneal biopsy. Ultrasound-guided omental thickening biopsy (A). CT-guided biopsy of peritoneal thickening (B), mesenteric lesion (C) and omental thickening (D). Flowchart 8.6.1 Development of peritoneal ligaments. Flowchart 8.6.2 Compartments of the peritoneal cavity. Flowchart 8.6.3 Division of pelvic peritoneal cavity. Flowchart 8.6.4 SAAG based evaluation of ascitic fluid. Flowchart 8.6.5 Differentiation of peritoneal thickening based on the type of enhancement (Ref. 58). Flowchart 8.6.6 Imaging of assessment of indeterminate findings on index postoperative scan.

Fig. 9.1.1 Simulated AP radiograph (Scanogram) showing a rounded calcification (black arrow) suggestive of rim calcification in a hydatid cyst. Fig. 9.1.2 AP radiograph of abdomen shows multiple faceted radiopaque calculi with internal lucency (arrows) in right hypochondrium suggesting gallbladder calculi. Fig. 9.1.3 AP radiograph showing gas around and within the walls of the gallbladder (black arrows) suggestive of emphysematous cholecystitis. Fig. 9.1.4 AP radiograph of abdomen shows branching lucency in right hypochondrium overlying the liver shadow suggesting pneumobilia (Black arrows). Fig. 9.1.5 AP radiograph of abdomen shows multiple calcific densities in the pancreatic bed in case of chronic pancreatitis (Black arrows). Fig. 9.1.6 (A) Right subcostal view showing gallbladder. (B) Short axis view for examining gallbladder wall (GB). Fig. 9.1.7 Oblique subcostal view for imaging the Portal vein and CBD which are seen in the region of the hepatoduodenal ligament. The CBD (between callipers) is anterior to the portal vein (PV). The gallbladder (GB) is seen further anteriorly. Fig. 9.1.8 Line diagram of liver showing Couinauds hepatic segmental anatomy. Fig. 9.1.9 Curvilinear transducer. Fig. 9.1.10 High-frequency linear array transducer. Fig. 9.1.11 (A) Line diagram showing transducer position in transverse subcostal view. (B) Corresponding greyscale image of liver showing right and left lobes. Fig. 9.1.12 (A) Line diagram showing transducer position mid transverse view. (B) Corresponding greyscale image showing segments of right and left lobes along with right and left portal veins. Fig. 9.1.13 (A) Line diagram showing transducer position in transverse view. (B) Corresponding greyscale image showing hepatic veins and IVC. The three

anechoic linear structures (RHV, Right Hepatic veins; MHV, Middle hepatic vein; LHV, Left hepatic vein; IVC, inferior vena cava) are seen converging superiorly towards IVC. Fig. 9.1.14 (A) Line diagram showing transducer position in right parasagittal view. (B) Corresponding greyscale image showing right lobe of liver and kidney. Fig. 9.1.15 (A) Line diagram showing transducer position in right midclavicular view. (B) Corresponding greyscale image showing the diaphragm superiorly and segments of the right lobe of liver. Fig. 9.1.16 (A) Line diagram showing transducer position in left parasagittal view. (B) Corresponding greyscale image showing segments of left lobe of liver. Fig. 9.1.17 (A) Line diagram showing transducer position in oblique view on right side. (B) Corresponding greyscale image showing portal vein and right lobe of liver. Fig. 9.1.18 Time-intensity curve of lesion and normal liver parenchymal in contrast-enhanced ultrasound. Sharp upstroke followed by gradual washout. Fig. 9.1.19 CEUS of hepatic hemangioma. (A) Greyscale ultrasound showing hyperechoic SOL in the liver. (B) CEUS in arterial phase showing peripheral nodular enhancement. (C) Portal phase showing continuous filling of lesion. (D) delayed phase showing complete filling of the lesion. Fig. 9.1.20 Liver Elastography – (A,B,C) Showing serial measurements taken and (D) showing average measurement generated. Fig. 9.1.21 (A) Line diagram showing transducer position in oblique view on right side. (B) corresponding colour flow image showing portal vein flow in red and right lobe of liver. Fig. 9.1.22 Showing doppler ultrasound of portal veinPortal venous waveform is monophasic with an undulating pattern with increased flow on inspiration.

The sample volume should be placed in the centre of the portal vein. Fig. 9.1.23 Hockey stick transducer for intraoperative ultrasound. Fig. 9.1.24 Bolus Triggering Technique – The X-axis represents time and the y axis the HU value within the ROI placed either at the level of diaphragm or coeliac axis. The scan is triggered at the present time after the HU value crosses over the threshold density (150 HU in this Case). Fig. 9.1.25 Early arterial phase images (A) and late arterial phase images (B) in a patient with cirrhosis and multifocal HCC. Note the greater conspicuity of lesions (arrows) on the later arterial phase as compared to the early arterial phase, highlighting importance of late arterial imaging in detection of HCC. Fig. 9.1.26 Dual Energy CT images with an iodine only image (A) and Virtual non contrast images (B). The technique obviates need for obtaining plain scan. It helps in characterising these two small lesions as totally non enhancing, because the iodine images shows no iodine within the lesion. These lesions may have been difficult to qualify on standard CECT due to small size. Fig. 9.1.27 Early Arterial (A), Pancreatic (B), and Portovenous (C) phase images in a patient with a small hypodense lesion in pancreatic head (arrowheads). The tumour to normal pancreas conspicuity is maximum in the pancreatic phase (B) as shown above, illustrating the importance of correct phase in imaging of pancreatic adenocarcinoma. Fig. 9.1.28 Early arterial (A) and portovenous (B) images in reveal intensely enhancing lesion (arrow) of the pancreatic neck on early arterial images. The lesion appears almost isodense on the portovenous images highlighting importance of Early arterial phase imaging for pancreatic neuroendocrine tumour. Fig. 9.1.29 Line Diagram Showing Coronal (A) and Sagittal (B) anatomy of the biliary tree. The left sided radicles are relatively anteriorly placed thus air tends to

collect in them on the supine images. Also note the anterior curve of the CBD as it descends inferiorly (RASD, Right anterior sectoral Duct; RPSD, Right posterior sectoral Duct; CBD, Common Bile Duct; RHD, Right Hepatic Duct; LHD, Left hepatic Duct; CHD, Common Hepatic Duct). Fig. 9.1.30 Normal anatomy of the pancreatic duct. The main duct drains, along with the common bile duct into the ampulla of Vater. It continues superiorly through the head and then turns at the ‘shoulder’ (black arrow) in the region of the neck to continue into the body and tail. The accessory pancreatic duct drains at the minor papilla proximal to the Ampulla. Fig. 9.1.31 CT ‘cholangiography’ using minimum intensity projection showing anatomy of low attenuation dilated intrahepatic biliary radicles on a background of enhanced liver with block in the region of the confluence (arrow) secondary to a cholangiocarcinoma. Note good visualisation of the anatomy of the intrahepatic ductal system. Fig. 9.1.32 Showing a normal T Tube Cholangiogram. Cystic Duct Stump (small black arrow) CBD with T tube in situ (large black arrow) Intrahepatic Biliary radicles are normally opacified with contrast noted passing into the duodenum (curved arrow). Fig. 9.1.33 T-Tube cholangiogram showing opacification of distal CBD with a filling defect suggestive of Calculus in the lower end (arrows). Fig. 9.1.34 Tube cholangiogram showing filling defects in CBD (arrow) and left hepatic duct (arrowhead), which shows relatively poor filling due to anterior position. These filling defects disappear on change of position suggesting air bubbles with better opacification of left hepatic duct seen on left oblique position. Fig. 9.1.35 Percutaneous biliary puncture using a fine needle (arrow) to opacify the biliary tree prior to percutaneous biliary drainage. Diagnostic percutaneous cholangiography is obsolete in the present imaging scenario.

Fig. 9.1.36 CT angiography (early arterial phase) images, providing exquisite details of the arterial tree in a liver donor. Note origin of the segment 4 artery (arrow) from the anterior division the right hepatic artery, which is a surgically important variation during right hepatectomy. Fig. 9.1.37 CT angiography (early arterial phase) images in a patient with hepatic trauma showing well-defined arterial focus of enhancement (A). Coronal reformats reveal pseudo aneurysm arising from anterior division of right hepatic artery (B). This is confirmed on the Volume rendered images (C). Fig. 9.1.38 Single step technique for drainage of abscess/collection – The trocar with the catheter is inserted into the lesion under guidance, followed by removal of the trocar. Fig. 9.1.39 Percutaneous transhepatic biliary drainagepuncture (A) under guidance to opacify the system. A catheter and wire system is inserted (B) and the stricture is negotiated, (C) thereafter internalization of stent is done. (D) In this case stent is narrowed post deployment (E) and balloon dilatation was subsequently required. Fig. 9.1.40 Percutaneous cholecystostomy. 10F dilator over a wire placed in gallbladder after transhepatic needle puncture. (A) Followed by a 10F interlocking loop catheter placed in gallbladder (B). Fig. 9.1.41 TACE – Enhancing lesion on background of cirrhosis seen in seg VI of liver suggestive of HCC. (A) Angiogram at the level of hepatic artery proper revealing a tumour blush. (B) This is followed by super selective canulation of the Posterior division of Right hepatic artery (C) and embolization. Check angiogram reveals occlusion of vessel with no blush on post TACE images (D). Fig. 9.1.42 Axial T1 image (A) shows motion artefacts. Axial HASTE image (B) shows dielectric artefacts with dark shading in centre of the image in a patient with ascites and abdominal wall oedema.

Fig. 9.1.43 Axial HASTE (A) and axial T2W fat saturated images of liver. Fig. 9.1.44 Axial T1W image shows a hyperintense nodular lesion (arrow) in liver in in-phase (A) with loss of signals in opposed-phase (B) suggesting a lipomatous nodule in background of cirrhotic liver. Fig. 9.1.45 Axial precontrast (A) and dynamic postcontrast spoiled GRE T1W FS (VIBE) axial images Precontrast (A) late arterial phase (B), portovenous/venous phase (C) and late venous/interstitial phase (D) in a patient with background of cirrhosis and ablated lesion in left lobe. Fig. 9.1.46 Diffusion weighted images (DWI) without gradient b = 0 (A), low (b = 50) b value (B), high (b = 800) b value (C) and ADC map (D). Fig. 9.1.47 Axial postcontrast VIBE using Gd-BOPTA in hepatobiliary phase show enhancement of liver parenchyma, no contrast in vascular system (PV, IVC, aorta), and excreted contrast in dilated biliary tree. Fig. 9.1.48 Haste single shot thick slab sequence showing the biliary tree. Fig. 9.1.49 MIP (A) and single shot HASTE (B) images showing a choledochal cyst, showing better spatial resolution on MIP images. Fig. 9.1.50 (A and B) Post IV, 1 hour delayed GdEOBDPTA T1W images in the axial (A) and coronal (B) plane showing contrast in the intra and extrahepatic biliary system (arrows) and in the gallbladder (short arrow). Fig. 9.1.51 (A and B) The MIP images do not show the intrahepatic calculi in the left main hepatic duct due to volume averaging, which are; however, well depicted on the 1 mm thin acquisition (arrows). Fig. 9.1.52 Prominent sphincter of Oddi showing a meniscus sign (arrow). Fig. 9.1.53 (A and B) A vessel coursing over a duct mimicking a stricture/stone (arrow) on the MRCP

images. T2W coronal images showing a vessel coursing over the common duct (curved arrow). Fig. 9.1.54 T2W axial image showing pneumonia (arrow) which is seen in the nondependent part of the duct. Fig. 9.1.55 (A and B) Flow related artefact can be seen in the CBD specially in a dilated system at the site of drainage of the cystic duct, seen as a hypointensity on the T2W axial images (arrow in A) as against a calculus (arrow in B) which is faceted or seen in the dependent part of CBD. Fig. 9.1.56 ERCP image in a postcholecystectomy patient showing faceted CBD calculi (white arrows). Note the change in orientation of MPD from Vertical in the region of the head to relatively horizontal position in the body and tail (curved arrow). Fig. 9.1.57 MRS of the liver showing a methylene peak of fat (CH2) (A) at a frequency of 1.3 ppm and water (H2O) (B) at a frequency of 4.7 ppm. Fig. 9.1.58 In and opposed phase images of the liver showing a normal nonfatty liver with no drop in signal on the opposed phase images (A) and a fatty liver showing drop in signal on the opposed phase images (B). Fig. 9.1.59 Complex chemical shift based water separation, wherein in (A) and opposed phased images (B) and water (C) and fat only (D) images are obtained at the same time. Fig. 9.1.60 Proton density fat fraction (PDFF) image. Fig. 9.1.61 R2/R2* is measured by taking a mid-section of the liver and drawing an ROI following the liver boundaries to generate a R2/R2* values. The hilar vessels are excluded in the ROI. Fig. 9.1.62 Postprocessing algorithms for calculating the R2/R2*values. Fig. 9.1.63 (A) Active acoustic driver that is placed outside the MRI room. (B) Passive acoustic driver that is placed on the patient’s abdomen.

Fig. 9.1.64 The passive driver is placed on the abdomen at the intersection of lines, the horizontal line at the inferior margin of the xiphisternum and vertical line in the mid clavicular line. Fig. 9.1.65 Four sets of images are acquired from the widest part of the liver, avoiding the diaphragm and the most inferior part of the liver. Fig. 9.1.66 ROI to generate 95% confidence map should not include the margin of the liver, the porta hepatis, gallbladder and the larger vessels. Fig. 9.1.67 (A) Grade 1–2 fibrosis depicted in yellow. (B) Grade 4 fibrosis depicted in red. Fig. 9.1.68 Poor wave propagation in iron overload (A) as compared to good wave propagation (B). Fig. 9.2.1 Pictorial representation of gross anatomy of liver. Diagram showing the hepatic lobes, porta hepatis and the bare area of the liver. Fig. 9.2.2 Hepatic fissures. Pictorial representation of the hepatic fissures and ligaments. Fig. 9.2.3 Microscopic anatomy of the liver. Histopathology image and pictorial representation of the hepatic lobule showing arrangement of bile duct, PV and artery. Fig. 9.2.4 Pictorial representation of division of liver into right and left lobes. Fig. 9.2.5 Segmental anatomy of liver based on vascular anatomy. Fig. 9.2.6 Pictorial and contrast-enhanced CT showing caudate lobe. Fig. 9.2.7 Pictorial and contrast-enhanced CT showing segment 2 or superior segment of left lateral segment. Fig. 9.2.8 Pictorial and contrast-enhanced CT showing segment 3 or inferior segment of left lateral segment. Fig. 9.2.9 Pictorial and contrast-enhanced CT showing segment 4a and 4b representing the left medial segments.

Fig. 9.2.10 Pictorial and contrast-enhanced CT showing segment 5 or inferior segment of right anterior section. Fig. 9.2.11 Pictorial and contrast-enhanced CT showing segment 6 or inferior segment of right posterior section. Fig. 9.2.12 Pictorial and contrast-enhanced CT showing segment 7 or superior segment of right posterior section. Fig. 9.2.13 Pictorial and contrast-enhanced CT showing segment 8 or superior segment of right anterior section. Fig. 9.2.14 Borderline hepatomegaly. Longitudinal scan in mid hepatic line showing liver span measuring 14.5 cm s/o borderline hepatomegaly. Fig. 9.2.15 Normal USG liver. Grey scale USG showing normal echogenicity of the liver interpreted by the veins (arrows). Fig. 9.2.16 Normal CT liver. Unenhanced (A) and contrast-enhanced CT (B–D) showing normal density with maximum enhancement in portal venous phase (C). Fig. 9.2.17 Ligamentum teres. Plain CT showing fissure for ligamentum teres (arrows) between medial and lateral segments of left lobe. Fig. 9.2.18 Fissure for ligamentum venosum. Plain CT showing fissure for ligamentum venosum between the caudate and left lobe. Fig. 9.2.19 Horizontal fissure. CT showing the horizontal fissure formed by invagination of hepatic pedicle. Fig. 9.2.20 Gallbladder fissure. Plain CT showing gallbladder fissure containing the gallbladder. Fig. 9.2.21 Normal hepatic signal on T1WI and T2W1 images. T1W1 (A and B) and T2W1 (C andD) images showing normal signal of the liver. The liver appears isointense to muscles and hyperintense to spleen on T1W1 images. On T2W1 images the liver is slightly hyperintense to paraspinal muscles, isointense to pancreas and hypointense to spleen.

Fig. 9.2.22 Delayed normal enhancement of liver. Contrast-enhanced MRI in late arterial, portal venous, venous and delayed hepatocyte phase showing normal enhancement of the liver with biliary excretion on hepatocyte phase (arrows). Fig. 9.2.23 Diaphragmatic slips. Contrast-enhanced CT (A–C) showing diaphragmatic slips causing indentation over hepatic surface. The apparent scalloping of underlying liver margins should not be misconstrued as cirrhosis. Fig. 9.2.24 Sliver of liver. Contrast-enhanced CT showing leftward extension of the lateral segment of the left hepatic lobe wrapping around spleen (arrows). Fig. 9.2.25 Papillary process of caudate lobe. Unenhanced CT (A and B) showing medial projection from caudate lobe of liver called the medial papillary process (arrows). This is a normal variant and should not be misinterpreted as a mass. Fig. 9.2.26 Reidel’s lobe. Contrast-enhanced CT in a young female showing inferior extension of the right lobe of liver. Fig. 9.2.27 Accessory lobe. Contrast-enhanced CT in venous phase showing accessory lobe (arrow). Note the branch of PV coursing through the liver tissue (arrows in D). Fig. 9.2.28 Hepatic artery Doppler. Hepatic artery Doppler showing normal waveform with normal RI (0.61) (arrows). Fig. 9.2.29 CT angiography of hepatic artery. Contrastenhanced CT angiography showing standard hepatic arterial anatomy. The CHA bifurcates hepatic artery proper and gastroduodenal artery. The HAP further divides into right and left arteries. Fig. 9.2.30 Michel’s classification of hepatic arterial variants. Pictorial representation of Michel’s classification of arterial anatomy. Fig. 9.2.31 Replaced RHA arising from SMA. CT angiogram showing replaced RHA taking origin from

superior mesenteric artery. Fig. 9.2.32 Replaced LHA from LGA. Ct angiogram showing replaced LHA taking origin form left gastric artery (arrows). Fig. 9.2.33 Accessory RHA with replaced LHA. CT angiogram showing accessory right arising from SMA (blue arrow) with replaced LHA (red arrow) arising from Left gastric artery. Fig. 9.2.34 Accessory right and left arteries. CT angiogram showing accessory RHA from SMA and accessory left arising from LGA. Fig. 9.2.35 Middle hepatic artery (segment 4 artery). CT angiogram showing origin of segment 4 artery from LHA. Fig. 9.2.36 Middle hepatic artery (segment 4 artery). CT angiogram reconstructed images showing replaced LHA with segment 4 artery arising from RHA. Fig. 9.2.37 Replaced RHA encased by head mass. CT angiogram images showing mass arising from pancreatic body with posterior infiltration into the retroperitoneum (arrows in A and B). The mass is encasing the superior mesenteric artery (arrows in B). The RHA is replaced and takes origin from SMA and is involved by the mass with narrowing and irregularity (arrows in C). Fig. 9.2.38 Normal portal venous Doppler. Doppler image showing hepatofugal flow in the PV with waveform showing respiratory phasicity. Fig. 9.2.39 Standard portal venous anatomy. Contrastenhanced CT showing standard portal venous anatomy. The MPV divides into right and left branches. The right PV further bifurcates into anterior and posterior segmental branches. The left PV divides into branches supplying segment 2, 3 and 4. Fig. 9.2.40 Noncontrast-enhanced MRI showing portal venous system. 3-D steady state free precession scan showing normal portal and hepatic veins (arrows).

Fig. 9.2.41 Type 2 portal venous anatomy. Contrastenhanced CT showing type 2 trifurcation pattern. The MPV (red arrow) trifurcates into right anterior, right posterior and left portal veins (blue arrows). No trunk of right portal vein is seen. Fig. 9.2.42 Type 2 portal venous anatomy. Contrastenhanced CT MIP (A) and volume-rendered images (B and C) showing trifurcation pattern. Fig. 9.2.43 Type 3 portal venous anatomy. Contrastenhanced CT and volume-rendered images showing type 3 variant anatomy. The right posterior division (red arrows) is the first branch of the PV. Fig. 9.2.44 Variant portal venous anatomy. Contrastenhanced CT MIP and VRT images showing bifurcation of main portal vein in right posterior division and left portal vein (red arrow). The right anterior portal vein (blue arrows) takes origin from left portal vein. Fig. 9.2.45 Nakamura’s type D and Cheng’s type 4. Contrast-enhanced CT showing origin of right anterior portal vein from left portal vein (arrows). Fig. 9.2.46 Portal vein embolization. Unenhanced (A), contrast-enhanced (B) and volumetric images (C, D) showing linear hyperdense material in branches of right portal vein (arrows). This represents lipiodol. Note the hypertrophy of the left lobe secondary to embolized right vein. Fig. 9.2.47 Doppler in hepatic vein. Colour Doppler with waveform showing normal hepatic vein with triphasic pattern of flow. Fig. 9.2.48 Superficial vein draining in LHV. Contrastenhanced CT in venous phase, MIP images showing left superficial vein, coursing beneath the diaphragmatic surface of segment 2 draining (arrows) into LHV. Fig. 9.2.49 Umbilical fissure vein. Contrast-enhanced CT in venous phase, MIP image showing fissural vein draining segment 4 and 3 joining the LHV. Fig. 9.2.50 Superior vein of segment 4. Contrastenhanced CT in venous phase, MIP image showing

superior vein of segment 4 draining into MHV (red arrows). Fig. 9.2.51 Inferior vein of segment 4. Contrastenhanced CT in venous phase, MIP image showing inferior vein of segment 4 draining the lower half of the segment (arrows). Fig. 9.2.52 Ventral vein for segment 8. Contrastenhanced CT in venous phase, MIP image showing ventral vein of segment 8 (arrows) draining into MHV near confluence. Fig. 9.2.53 Ventral and intermediate vein of segment 8. Contrast-enhanced CT in venous phase, MIP images showing ventral and intermediate veins of segment 8 (red arrows) draining into MHV. Fig. 9.2.54 Segment 5 vein uniting with segment 4b to form the MHV. Contrast-enhanced CT in venous phase, MIP images showing segment 5 veins (arrows) uniting with segment 4b branches to form the MHV. Fig. 9.2.55 Right superficial veins draining into RHV. Contrast-enhanced CT in venous phase, MIP images showing right superficial vein (arrows) draining cranial portion of segment 7. Fig. 9.2.56 Dorsal vein of segment 8 draining in RHV and ventral vein draining in MHV. Contrast-enhanced CT in venous phase, MIP images showing dorsal vein of segment 8 vein draining into MHV. Fig. 9.2.57 Right inferior accessory vein draining into IVC. Contrast-enhanced CT in venous phase, MIP images showing small right inferior accessory vein draining into IVC. Fig. 9.2.58 Large Right inferior accessory veins draining into IVC. Contrast-enhanced CT in venous phase, MIP images showing two large inferior accessory veins draining into IVC. Fig. 9.2.59 Type 1 Nakamura’s classification. Contrastenhanced CT in venous phase, MIP images showing large right hepatic vein draining segments 6, 7 and dorsal and lateral part of segment 8.

Fig. 9.2.60 Nakamura’s Type 2 anatomy. Contrastenhanced CT in venous phase, MIP images showing medium-sized right hepatic vein with small inferior accessory veins. Fig. 9.2.61 Type 1 Marcos’s classification. Contrastenhanced CT in venous phase, MIP images showing equal size segments 5 and 4b with equal drainage areas. Fig. 9.2.62 Marcos’s type 2. Contrast-enhanced CT in venous phase, MIP images showing multiple segment 4 veins with short segment 5 veins. Drainage of segment 4 veins is larger than 5. Fig. 9.2.63 Marcos’s type 3 hepatic venous anatomy. Contrast-enhanced CT in venous phase, MIP images showing early proximal branching with medium-sized segments 4 and 5 branches. Fig. 9.2.64 Kawasaki type 1 classification. Contrastenhanced CT in venous phase, MIP images showing segment 4 b draining into MHV. Fig. 9.2.65 Normal USG gallbladder. Grey scale USG showing normal gallbladder with anechoic contents and thin echogenic wall. Fig. 9.2.66 Normal CT of gallbladder. Contrastenhanced CT A and B showing normal gallbladder appearing as a hypodense cystic structure with homogenous contents and thin wall. Fig. 9.2.67 Normal gallbladder on MRI. T2W1 images showing normal gallbladder appearing as hyperintense cystic structure with thin smooth hypointense wall. Fig. 9.2.68 Normal anatomy of intrahepatic duct. MRCP images showing normal anatomy of the intrahepatic radicals. The right anterior and posterior sectoral ducts join to form the RHD. The segment 2/3 ducts and segment 4 ducts unite to form the LHD. Fig. 9.2.69 Variants in right ductal anatomy. Table and diagrammatic representation of right ductal anatomy. Fig. 9.2.70 Type 1 right duct anatomy. MRCP images showing standard anatomy of the right hepatic duct. The

anterior and posterior sectoral ducts (arrows) are uniting to form the RHD. Fig. 9.2.71 Type 3 anatomy of the RHD. MRCP images showing right posterior duct (arrows) draining into LHD. Fig. 9.2.72 Type 2 anatomy of the RHD. MRCP images showing the trifurcation pattern. Fig. 9.2.73 Anomalous right posterior draining into CHD. MRCP images showing anomalous aberrant right posterior sectoral duct draining into CHD (arrows). Fig. 9.2.74 Accessory right posterior sectoral duct draining into CHD close to cystic insertion. MRCP images showing accessory right posterior sectoral duct (red arrow) draining into CHD posterior to the gallbladder. This anomaly should be recognized and reported on MRCP. Inadvertent injury to the duct may occur during gallbladder surgeries. Note the patient has a right posterior sectoral duct (blue arrow) uniting with anterior duct to form the RHD. Fig. 9.2.75 Variations in left ductal system. Table and diagrammatic representation of variant anatomy of left ductal system. Fig. 9.2.76 Normal anatomy of left ductal system. MRCP images showing normal anatomy of the LHD, the segment 4 and 2/3 ducts unite to form the LHD. Fig. 9.2.77 Accessory right posterior duct. MRCP image showing accessory right posterior duct draining into CHD (red arrows). Another smaller right posterior duct (blue arrows)is seen draining into CHD near the confluence. Fig. 9.2.78 MRCP showing cystic duct. Normal insertion of cystic duct (arrows) in CHD. The corrugated appearance is normal. Fig. 9.2.79 Variant anatomy of cystic duct. Pictorial representation of variants in cystic duct anatomy. Fig. 9.2.80 Parallel course of cystic duct. MRCP images in a postcholecystectomy patient showing cystic duct coursing parallel to the CHD for a length of 2 cm.

Fig. 9.2.81 Low insertion of cystic duct. MRCP image in a patient with choledocholithiasis showing insertion of cystic duct into the distal extrahepatic duct (arrows). Fig. 9.2.82 –Short cystic duct. MRCP image showing a short cystic duct with length of 4 mm (arrows). Fig. 9.2.83 Segments of the CBD. MRCP image showing the supraduodenal, retroduodenal, intrapancreatic and intraduodenal segments of the CBD. Fig. 9.2.84 Normal CBD in CT. Contrast-enhanced CT in venous phase showing normal CBD appearing as a thin-walled hypodense linear structure (arrows). Fig. 9.2.85 Normal CBD on MRCP. MRCP image showing normal CBD appearing as bright fluid intensity linear structure (red arrows). The cystic duct (blue arrows) is seen inserting into CHD (yellow arrows). Fig. 9.2.86 Normal common channel. MRCP image showing normal common channel between the CBD and pancreatic duct (arrows) measuring 6.6 mm. Fig. 9.2.87 Relations of pancreas. Diagrammatic representation of important relations of pancreas. Fig. 9.2.88 Arterial and venous supply of pancreas. Illustration showing arterial and venous supply of the pancreas. Fig. 9.2.89 Lymphatic drainage of pancreas. Diagrammatic representation of nodal drainage of the pancreas. Fig. 9.2.90 Normal Pancreas on USG. Grey scale USG showing normal pancreatic head and body (arrows). Fig. 9.2.91 Normal CT appearance of pancreas. Unenhanced and contrast-enhanced CT showing normal pancreas. the pancreas reveals maximum enhancement in pancreatic parenchymal phase (C). It is in this phase the lesion pancreas contrast is maximum. Fig. 9.2.92 Normal pancreas on MRI. T1W1 images showing normal pancreas appearing hyperintense to liver. the pancreas is the brightest organ in abdomen on T1W1 images (arrows). T2W1 images showing the

normal pancreas appearing slightly hyperintense to paraspinal muscles. Fig. 9.2.93 Case of cystic fibrosis showing complete fatty replacement. Contrast-enhanced CT in a patient with cystic fibrosis showing diffuse fatty replacement of pancreas (arrows). Fig. 9.2.94 MRI in a patient with cystic fibrosis showing fatty replacement. T1W1 (a), T2W1 (b) image showing no identifiable pancreatic parenchyma with fat replacing the gland, confirmed on T2W1 FS images (arrows in C). A dilated pancreatic duct is seen on MRCP images (arrows in D) differentiating the condition from pancreatic agenesis. Fig. 9.2.95 Fatty replacement of pancreas. T2W1 (A and B) and TIW1 (C and D) images showing fatty replacement of entire pancreas (arrows). Note peribiliary sparing (yellow arrows). Fig. 9.2.96 Normal pancreatic duct. MRCP image showing normal pancreatic duct. Fig. 9.2.97 MRCP showing normal pancreatic ductal anatomy. Normal pancreatic duct seen as tubular fluid filled structure. The diameter of the duct may vary and is usually maximum in head (arrows). Fig. 9.2.98 Variant anatomy of pancreatic course. Top row showing diagrammatic representation of four variations in pancreatic course descending, vertical, sigmoid and loop configuration. Bottom row showing variant anatomy on MRCP images. The descending course is the commonest. Fig. 9.2.99 Variants in pancreatic ductal configuration. Diagrammatic representation showing variants in pancreatic ductal configuration. Fig. 9.2.100 Bifid ductal configuration with persistent duct of Santorini. MRCP image showing Bifid configuration of duct (red arrows) with dominant duct of Santorini. Fig. 9.2.101 Pancreatic divisum. MRCP (A) and T2W1 coronal images (B) showing complete pancreatic

divisum. The duct draining the entire gland (red arrow) is seen crossing the CBD (yellow arrow) and draining into minor papilla. Fig. 9.2.102 Splenic ligaments. Diagrammatic representation of the splenic ligaments. The gastrosplenic and splenorenal ligaments are demarcated with arrows. Fig. 9.2.103 Normal USG spleen. Grey scale USG normal appearance of spleen. Fig. 9.2.104 Normal CT of spleen. Contrast-enhanced CT in the arterial phase showing marked heterogeneous enhancement of the spleen (arrows in A) appearing homogenous on subsequent phases. Fig. 9.2.105 Normal spleen on MRI. T2W1 image (A) showing normal splee appearing slightly hyperintese to liver. The spleen appears hypointese to liver on T1W1 images (B). Fig. 9.2.106 Normal MRI spleen. Contrast-enhanced MRI showing heterogenous enhancement of the spleen in the arterial phase (arrows in A). Subsequent phases show more homogenous enhancement (similar to CT). Fig. 9.2.107 Splenic lobulations. Unenhanced and contrast-enhanced CT showing gentle lobulations along medial surface of spleen (arrows). Fig. 9.2.108 Splenunculus. Unenhanced (A–B) and contrast-enhanced CT (C–D) showing a small splenunclus anterior to the spleen appearing a rounded structure showing enhancement similar to spleen in all phases (arrows). Fig. 9.2.109 Splenenculus mimicking NET. Unenhanced and contrast-enhanced CT showing a welldefined hypodense lesion embedded in the pancreatic tail (arrows) showing heterogeneous enhancement (arrows in C and D). Enhancement is similar to that of spleen in all phases, however, location in the tail raises suspicion on NET. T2W1 (D) and T1W1 (E) shows similar to spleen confirming diagnosis of splenenculus.

Fig. 9.3.1 Longitudinal measurement showing a span of 14.5 cm. Fig. 9.3.2 Longitudinal measurement of liver showing span of 16.5 cm suggestive of hepatomegaly. Fig. 9.3.3 Non-enhanced CT showing borderline hepatomegaly with size measuring 15 cm in midclavicular line. Fig. 9.3.4 Measurement of caudate lobe. Contrastenhanced CT (A) and diagrammatic representation showing method to calculate caudate lobe size. Fig. 9.3.5 Caudate lobe hypertrophy in cirrhosis. Unenhanced and enhanced CT showing enlarged caudate lobe with CL/RL ratio of >0.73. Fig. 9.3.6 Normal liver volume. CT volumetry of an average adult male showing normal volumes of liver, right and left lobes. Fig. 9.3.7 Normal CT angiogram. CT angiogram showing normal length and width of common hepatic artery. Fig. 9.3.8 Normal CT angiogram. CT angiogram showing normal diameter of the left hepatic and middle hepatic artery. Fig. 9.3.9 Normal CT angiogram. CT angiogram showing long normal calibre replaced right hepatic artery. Fig. 9.3.10 Normal portal vein on USG. USG and colour Doppler showing normal portal vein measuring 11 mm in diameter with hepatopetal flow on Doppler. Fig. 9.3.11 Normal measurements of portal vein on CT. Contrast-enhanced coronal reconstructed images showing normal dimensions of main and right portal vein. Fig. 9.3.12 Normal measurements of portal vein on CT. Contrast-enhanced CT portal venous phase, reconstructed images showing normal main, right and left portal veins.

Fig. 9.3.13 Normal ultrasound appearance of gallbladder. Grey scale USG showing normally distended gallbladder with wall thickness of 2 mm. Fig. 9.3.14 Normal gallbladder on CT. Contrastenhanced CT showing normal distension of gallbladder with normal wall thickness. Fig. 9.3.15 Normal cystic duct on MRCP. Thick slab images showing normal diameter of cystic duct. Length of the duct maybe variable. The corrugated appearance is normal. Fig. 9.3.16 Normal calibre biliary radicals. MRCP images showing normal calibre intrahepatic biliary radicals. Fig. 9.3.17 Dilated intrahepatic biliary radicals. MRCP images in a patient with distal common bile duct (CBD) cholangiocarcinoma showing dilated intrahepatic biliary radicals and extrahepatic biliary tree. Fig. 9.3.18 Normal USG measurement of the CBD section to measure the calibre of the extrahepatic tree anterior to the portal vein. This is actually a measure of the CHD. Fig. 9.3.19 CBD on MRCP. MRCP images showing normal calibre CBD. Fig. 9.3.20 Postcholecystectomy prominence of CBD. MRCP images in a healthy asymptomatic patient showing dilated extrahepatic tree (arrows). Fig. 9.3.21 Normal USG pancreas. Normal pancreatic head and body on grey scale USG. Fig. 9.3.22 Normal measurement of pancreas on CT. Contrast-enhanced CT showing normal AP measurements of pancreatic head, body and tail. Fig. 9.3.23 Normal pancreatic duct on MRCP. MRCP images showing normal calibre pancreatic duct in different patients. Note the normal variations in calibre in head, body and tail. Fig. 9.3.24 Normal splenic size on USG. USG showing normal spleen, measuring 7.7 cm in length.

Fig. 9.3.25 CT showing normal splenic size. Contrastenhanced CT showing normal splenic size. The maximum anteroposterior dimension is measured in axial plane. Fig. 9.6.1 Sequence of the formation of the liver and the bile ducts. (A) Formation of the hepatic bud from the ventral aspect of the terminal part of foregut. (B) Division of the hepatic bud into two. (C) Extension and migration of the liver toward the septum transversum. (D) The enlargement and division of the liver. Fig. 9.6.2 Intrahepatic biliary radicle. Fig. 9.6.3 Sagittal section of the illustrated embryo depicting the relationship of liver with the adjacent peritoneal structures. Fig. 9.6.4 (A) The vitelline veins lie on the left and right of the duodenum. (B) Figure of eight formation by the transverse anastomosis between the vitelline veins, ventral anastomosis superiorly and inferiorly and dorsal anastomosis in between. (C) Splenic vein and SMV join the left vitelline vein at the level of the dorsal anastomosis. Formation of the final portal vein: (1) Part of left vitelline vein, (2) dorsal anastomosis, (3) part of right vitelline vein, (4) the cranial ventral anastomosis becomes the left branch of the portal vein and (5) right vitelline cranial to cranial ventral anastomosis forms right branch. Fig. 9.6.5 (A) The umbilical veins (UVs) and vitelline veins (VVs) passing through the septum transversum to reach the sinus venosus. (B) Growth of liver cells within the septum transversum breaks up part of the UV and VV into capillaries. Blood reaching the liver through the UV and VV now goes to the heart through the right and left hepatocardiac channels. (C) Left hepatocardiac channel disappears. (D) Right hepatocardiac channel (which later forms part of the IVC) now drains the liver. Right umbilical veins disappear. All the blood from the placenta now reaches the liver through the left umbilical vein. Formation of ductus venosus short-circuits the blood to the right hepatocardiac channel.

Fig. 9.6.6 Ductus venosus: Classical triphasic waveform where the flow should be in the forward direction, directed to the heart. Fig. 9.6.7 Riedel’s lobe of the liver. Fig. 9.6.8 Sliver of the liver. Fig. 9.6.9 Papillary process of the caudate lobe as indicated by the white arrow. Fig. 9.6.10 Accessory hepatic lobe as indicated by the white arrow. Fig. 9.6.11 Diaphragmatic slips. Fig. 9.6.12 (A and B) USD findings of triangular cord sign. (C) Gallbladder ghost triad. Fig. 9.6.13 Colour Doppler of hepatic arterial flow extending to the hepatic surface – subcapsular telangiectasia. Fig. 9.6.14 Hepatobiliary iminodiacetic acid (HIDA) scan. Fig. 9.6.15 Ductal plate malformation. Fig. 9.6.16 MRI of the liver demonstrates multiple tiny T2 hyperintense cystic lesions consistent with biliary hamartoma. Fig. 9.6.17 Pathologically proven case of congenital hepatic fibrosis with presence of Caroli’s disease. Fig. 9.6.18 Multiple cysts of varying sizes and shapes in both lobes of the liver. Fig. 9.6.19 ‘Central dot’ sign: Enhancing dots within the dilated intrahepatic bile ducts, representing portal radicles on CT. US: Dilated IHBR with intraductal bridging that appears as echogenic septa traversing the dilated bile duct lumen. Fig. 9.6.20 Extrahepatic Duct System of Biliary Apparatus. Fig. 9.6.21 Phrygian cap. Fig. 9.6.22 Hartmann’s pouch.

Fig. 9.6.23 Multiseptated gallbladder. Fig. 9.6.24 Bilobed gallbladder. Fig. 9.6.25 Intrahepatic gallbladder. Fig. 9.6.26 Duplication of gallbladder. Fig. 9.6.27 (A to F) Septated gallbladder; duplication of the fundus; duplication of the body with single cystic duct; duplication of the entire gallbladder with two cystic ducts that unite into a single CBD giving a ‘Y shape’; complete/ductular duplication – the two cystic ducts enter separately into the biliary tree, giving an ‘H shape’; bilateral gallbladder. Fig. 9.6.28 (A) Normal. (B) Right and left hepatic ducts join within liver parenchyma. (C) Long hepatic ducts. (D) Extra-long cystic duct. Fig. 9.6.29 (E) Normal. (F and G) Joins left side of CHD, passing either in front of it or behind it. (H) Ends in the right hepatic duct. Fig. 9.6.30 (A) Complete agenesis. (B) Gallbladder and cystic duct absent. (C) Cystic duct absent. (D) Hepatic duct absent. (E) Bile duct absent. (F) Terminal part of bile duct is absent. Fig. 9.6.31 Choledochal cysts. Fig. 9.6.32 Conventional cholangiography images demonstrating the types as depicted above. Fig. 9.6.33 (A) Smaller caudally located ventral bud seen arising in close relationship with the hepatic bud. (B) Rotation of duodenal loop to the right, the ventral pancreatic bud along with primitive bile duct comes to the right, and the dorsal bud to the left of the duodenum. (C) Ventral pancreatic bud along with primitive bile duct shifts to the left, closer to the dorsal pancreatic bud. (D) Fusion of the ducts. (E) Fusion of the pancreatic parenchyma. Fig. 9.6.34 (A) Duct of the ventral pancreatic bud along with primitive bile duct have a common opening into the duodenum and lie caudal to the duct of the dorsal pancreatic bud. (B) Anastomosis of the dorsal and

ventral pancreatic ducts forming an S-shaped main pancreatic duct. (C) Narrowing of the proximal part of the dorsal pancreatic duct, forming the accessory pancreatic duct (duct of Santorini). Fig. 9.6.35 Annular pancreas. Fig. 9.6.36 Encerclage of the pancreatic tissue around the second part of duodenum (D) as indicated by the asterisk, indicative of complete annular pancreas. Note made of the CBD (C) as it enters the second part of the duodenum. Fig. 9.6.37 Crocodile jaw appearance. Fig. 9.6.38 Visualization of the head and uncinate process with thinning of body and absence of tail of pancreas. Fig. 9.6.39 Smooth filling defect in gastric antrum. Central umbilication is present within lesion – suggestive of ectopic pancreas. Fig. 9.6.XVII No evidence of communication between the two ducts. Minor papilla drains the body and tail of the pancreas and minor papilla drains the bile duct, head and uncinate process of the pancreas. Fig. 9.6.40 Single mass of spleen. Fig. 9.6.41 Splenic mass projects in the left layer of the dorsal mesogastrium. Fig. 9.6.42 Posterior abdominal wall extends between the spleen and the left kidney forming the lienorenal ligament. Fig. 9.6.43 Spleen comes to lie on the left side and takes part in forming left boundary of the lesser sac of peritoneum. Fig. 9.6.44 Accessory spleen as indicated by the white arrow; and as located at the hila. Fig. 9.6.45 (A) Splenic lobulations. (B) Splenic clefts. Fig. 9.6.46 Polysplenia. Fig. 9.6.47 Situs inversus.

Fig. 9.6.48 Enlarged spleen noted in the pelvis as indicated by the asterisk. Absence of spleen in the left hypochondrium as indicated on the coronal and sagittal images. Fig. 9.7.1 Biliary atresia in a 45-day-old male. A. Ultrasound shows positive triangular cord sign measuring 6 mm (arrow). B. Ultrasound shows small gallbladder, 1.6 cm in length with irregular lumen (arrow). C. Ultrasound shows enlarged hepatic artery measuring 2.4 mm (arrow). D. HIDA scan shows no bowel excretion on 24-hours delayed film. Fig. 9.7.2 Type I choledochal cysts. A. Axial T2weighted MRI shows focal cystic dilatation of proximal CBD (asterisk) suggesting type IA choledochal cyst. B. Coronal MRCP shows focal saccular dilatation along lateral aspect of CBD (asterisk) compressing the gallbladder (arrow) representing type IB choledochal cyst. C. Coronal MRCP shows fusiform saccular dilatation of CBD (long arrow) with no intrahepatic dilatation (short arrow) and distended gallbladder (asterisk) representing type IC choledochal cyst. Fig. 9.7.3 Type III choledochal cyst. Focal cystic dilatation of the intramural segment of common bile duct into duodenal lumen (long arrow) representing choledochocele. Normal main pancreatic duct (short arrow). Fig. 9.7.4 Type IVA choledochal cyst. A. Ultrasound shows cystic dilatations of intrahepatic (arrow) and extrahepatic (asterisk) biliary ducts. B. Axial T2 fat sat image shows diffuse cystic dilatation of intrahepatic ducts (arrows). C. Coronal MRCP shows diffuse cystic dilatation of CBD (asterisk) with cystic dilatation of intrahepatic ducts (arrow). Fig. 9.7.5 Type IVB choledochal cyst. Coronal MRCP shows cystic dilatation of extrahepatic right and left ducts and proximal CBD (long arrow) with normal intrahepatic ducts (short arrow). GB – gallbladder. Fig. 9.7.6 Caroli’s disease. A. Axial T2-weighted MRI shows multiple cystic dilatation of intrahepatic biliary

ducts with central dot sign (short arrow). B. Axial T2weighted MRI shows multiple cystic dilatation of intrahepatic biliary ducts with some of them showing intraductal calculi (long arrow). Fig. 9.7.7 Polycystic liver disease. A. Coronal T2weighted MRI shows multiple small simple hepatic cysts (arrow) with associated bilateral autosomal dominant polycystic kidney disease (asterisks). B. Axial T2weighted MRI of upper part of liver shows multiple simple hepatic cysts (arrow). Fig. 9.7.8 5-year-old male presented with portal hypertension and diagnosed as congenital hepatic fibrosis. A. Axial trufi MRI of liver shows right lobe atrophy (R) with hypertrophy of medial (M) and lateral (L) segments of left lobe. B. Axial T2-weighted MRI of liver shows atrophic right lobe (R) and hypertrophic medial segment of left lobe (M) with nodular surface in keeping with cirrhosis. C. Axial post contrast MRI of liver shows atrophic right lobe (R) and hypertrophic medial segment of left lobe (M) with nodular surface (arrows) in keeping with cirrhosis. Fig. 9.7.9 Biliary hamartoma. A. Axial T2-weighted MRI shows numerous tiny T2 hyperintense foci in both lobes of liver with no definite biliary communication (arrow). B. Coronal reformatted MIP images show numerous tiny T2 hyperintense foci in both lobes of liver with no definite biliary communication. C. Coronal post contrast MRI shows no enhancement of cystic lesions (arrow). Fig. 9.8.1.1 Fatty liver. Axial CECT image of a 14-yearold child showing significantly reduced attenuation of liver parenchyma compared to splenic parenchyma, indicative of hepatic steatosis. Fig. 9.8.1.2 Fatty liver. Axial MR in-phase (A, B) of two patients showing similar parenchymal signal intensity. Out-of-phase (C) image of first patient (normal liver) showing no reduction in signal whereas patient with fatty liver (D) shows reduction in signal intensity.

Fig. 9.8.1.3 US features of liver cirrhosis. (A) US image of a cirrhotic liver showing irregular surface and mild adjacent perihepatic ascites (white arrow). (B) Coarsened hepatic echotexture (*) noted in cirrhotic liver. (C) Portal vein showing hepatopetal colour Doppler flow suggestive of absence of portal hypertension. (D) Doppler showing hepatofugal flow in a patient with portal hypertension. Fig. 9.8.1.4 Caroli’s disease. (A) Axial CT images showing multiple cysts in segment VI of liver (white arrow) with few showing accompanying portal radical (black arrow). (B) Axial T2-weighted and (C) coronal HASTE MRCP images showing multiple cysts showing communication with biliary tree (white arrows). Fig. 9.8.1.5 Congenital hepatic fibrosis. (A) Axial CT images showing heterogeneously enhancing hepatic parenchyma with hypodense periportal cuffing (black arrow). (B) Coronal image of the same patient shows autosomal recessive polycystic kidneys (ARPKD) (*). Fig. 9.8.1.6 Iron deposition in liver. (A) Axial T2weighted MR image in a patient of beta thalassemia with multiple transfusions showing hypointense liver parenchyma. (B) Quantitative iron estimation using liver: muscle signal intensity ratio method. Three ROIs are drawn in liver parenchyma and one on each paraspinal muscles and the obtained values are entered in free online calculator provided by the University of Renne which calculates liver iron concentration. Fig. 9.8.1.7 Gaucher disease. (A) US image showing echogenic homogeneous lesion (arrows). (B) CECT axial image showing hypodense lesions (arrows) in right lobe of liver along with hepatomegaly. These lesions represent ‘Gaucheroma’. Fig. 9.8.1.8 Congestive hepatopathy. CECT image of a patient with congestive heart failure showing heterogeneous and reticular enhancement of liver parenchyma (black arrows) and hepatomegaly. Note is made of bilateral pleural effusion (PE). Fig. 9.8.1.9 Langerhans cell histiocytosis. (A) Axial CECT image in a patient of Langerhans cell histiocytosis

showing bilobar dilated and intrahepatic biliary radicals showing thickened walls (black arrows). (B) CT of thorax of same patient showing cystic lesions in bilateral lungs (white arrows). Fig. 9.8.2.1 Axial CECT arterial phase image (A) showing a lesion with intense enhancement along the periphery with centripetal fill-in and enhancement of the entire lesion on delayed phase image (B) suggestive of hemangioma. Fig. 9.8.2.2 Congenital hemangioma in a 7-day-old baby. The lesion is hyperintense on T2WI (A). Dynamic imaging shows avid arterial peripheral enhancement (B) with gradual centripetal filling on portal venous (C), delayed (D) and five minutes scan (E) images. Fig. 9.8.2.3 Gray scale ultrasound image in an 8-yearold boy showing a heterogenous lesion in the liver, which on colour Doppler showing central as well as peripheral areas of vascularity. This was subsequently characterized as FNH on MRI (Fig. 9.8.2.4). Fig. 9.8.2.4 MRI images showing a lesion in the left lobe of liver, which is isointense on T2WI (A) and T1WI (B) with a central T2 hyperintense (arrow in A) and T1 hypointense (arrow in B) scar. Dynamic images (C and D) showing homogenously enhancing lesion with nonenhancing scar in arterial phase (arrow in C) which is enhancing on delayed phase (D). Diffusion restriction is seen in the lesion on DWI (E) and ADC (F) images. Fig. 9.8.2.5 Ultrasound image in a 1-year-old boy showing a multiseptated lesion which was seen arising from the liver with internal echoes suggestive of mesenchymal hamartoma. Fig. 9.8.2.6 Axial (A) and coronal (B) CECT images in a 1-year-old boy showing a large multiseptated cystic lesion in the right lobe of liver suggestive of mesenchymal hamartoma. Fig. 9.8.2.7 MR images of liver in a 2-year-old boy with mesenchymal hamartoma. T2WI (A) and T1WI (B) images are showing a multiseptated cystic lesion in right lobe of liver with T1 hyperintense signal in one of the

cysts suggestive of proteinaceous contents. Postcontrast T1WI (C) image is showing enhancement of the septae. Fig. 9.8.2.8 Ultrasound image of liver in a 2-year-old boy with glycogen storage disorder showing a welldefined hypoechoic lesion suggestive of adenoma. Fig. 9.8.2.9 Axial CECT images in an adolescent girl with glycogen storage disorder. Arterial phase image (A) showing multiple enhancing lesions in the background of fatty liver in both lobes of liver, which are isodense to the liver on portal venous phase image (B). Fig. 9.8.2.10 Adenoma in a 17-year-old girl with glycogen storage disorder. The lesion is hyperintense on T2WI (arrow in A). It shows fat on in-phase (arrow in B) and out-phase (arrow in C) images. Dynamic imaging shows avid arterial enhancement (arrow in D) with isointensity in portal venous (arrow in E) and equilibrium (arrow in F) phases. Fig. 9.8.2.11 Axial CECT images (A and B) in a child with inflammatory pseudotumour showing an ill-defined heterogenous lesion in the left lobe of liver. Minimal periphepatic fluid and pericardial effusion is seen. The lesion was biopsied and reported as inflammatory pseudotumour. Fig. 9.8.2.12 MRI images showing regenerative nodules in a child in the background of chronic liver disease. Axial T2W (A) and T1W (B) images showing multiple T2 hypointense and T1 hyperintense lesions in both lobes of liver which are predominantly hypointense to the surrounding liver on postcontrast image (C). No evidence of diffusion restriction seen on DWI (D) and ADC (E) images. Fig. 9.8.2.13 Ultrasound image of liver in child with pyogenic abscess showing an ill-defined hypoechoic to hyperechoic lesion. Fig. 9.8.2.14 Axial CECT images of liver in a child with pyogenic abscesses showing two well-defined hypodense lesions with irregular shaggy walls and surrounding edema.

Fig. 9.8.2.15 Axial CECT image of liver in a child with ALL showing two well-defined hypodense lesions in right lobe of liver with subtle peripheral enhancement. FNA was done which showed mucormycosis. Fig. 9.8.2.16 Ultrasound image of liver (A) in a child showing a well-defined anechoic cystic lesion in the liver suggestive of type I hydatid cyst. Ultrasound image of liver (B) in another child showing hydatid cysts in different stages: anechoic cyst, cyst with internal debris and cyst with peripheral calcification. Fig. 9.8.2.17 Coronal CECT image (A) in a child showing hydatid cysts with internal membranes and daughter cysts. Axial T2WI image (B) in another child showing a well-defined hydatid cyst in the left lobe of liver with a small daughter cyst along the periphery (arrow). Fig. 9.8.2.18 Ultrasound image of liver in a child with amoebic liver abscess showing a well-defined rounded lesion with shaggy walls and diffuse internal echoes. Fig. 9.8.3.1 Axial (A) and coronal (B) CECT abdomen images in a 3-year-old child reveal a large, heterogeneously enhancing mass with necrotic areas within the right hepatic lobe suggestive of hepatoblastoma. Axial CECT chest image (C) shows multiple variable-sized nodules in both lungs suggestive of metastases. Axial (D) and coronal (E) CECT abdomen images of the same child show increase in the size of the lesion with progression of pulmonary metastatic disease as seen on axial CECT chest images (F and G), after three cycles of chemotherapy. Fig. 9.8.3.2 Abdominal radiograph in a 6-year-old male child with pain abdomen reveals hepatomegaly with amorphous foci of calcification in the right hypochondrium. Fig. 9.8.3.3 USG images (A and B) reveal a heterogeneously hyperechoic mass lesion involving both lobes of liver showing internal vascularity within. Fig. 9.8.3.4 USG images (A and B) reveal a heterogeneously hyperechoic mass involving right lobe of

liver with areas of internal vascularity within, hypoechoic fibrous septae are seen. Fig. 9.8.3.5 Axial NCCT (A), axial (B) and coronal (C) CECT abdomen images reveal a large, heterogeneously enhancing mass lesion with a large exophytic component and intralesional calcification involving the right lobe of liver in a 2-year-old child suggestive of hepatoblastoma. Mild ascites is seen. Fig. 9.8.3.6 Axial (A) and coronal (B) sections of CECT abdomen reveal a large, predominantly exophytic, heterogeneously enhancing mass lesion showing chunky calcification arising from segments V and VI of right lobe of liver suggestive of hepatoblastoma. Fig. 9.8.3.7 NCCT (A) and CECT (B–D) images through the abdomen show large, heterogeneously enhancing mass lesions with areas of necrosis within involving both lobes of liver. The largest lesion shows chunky calcification. Mild ascites is present. Findings suggestive of multifocal hepatoblastoma. Fig. 9.8.3.8 In a known case of hepatoblastoma, MRI abdomen images of patient show a large heterogeneous mass predominantly in left lobe of liver appearing hyperintense on T2W images (A and B) and isointense to hypointense on T1W image (C), showing a large necrotic component. Heterogeneous postcontrast enhancement is seen (D). Fig. 9.8.3.9 Axial CECT abdomen images (A and B) show a large, mixed solid and cystic tumour in the right and left lobes of liver with some calcific foci within in a known case of mesenchymal hamartoma which is a differential for hepatoblastoma, especially if solid areas are present within the mesenchymal hamartoma. Fig. 9.8.3.10 Axial (A) and coronal (B) CECT images of the abdomen in a 15-months-old male child with abdominal distention and AFP levels of 1,21,000 show hepatomegaly with a large heterogeneously enhancing mass lesion involving both lobes of liver suggestive of hepatoblastoma (scan done in December 2017). Axial (C) and coronal (D) CECT images of the abdomen in the

same child after four cycles of chemotherapy show decrease in the size of the lesion (Scan done in February 2018). After one more cycle of chemotherapy and left portal vein ligation, note is made of increase in the volume of the residual right lobe as seen on these axial CECT images (E and F). Fig. 9.8.3.11 USG images of a 7-year-old boy reveal a heterogeneous focal lesion of mixed echogenicity in left lobe of liver (A) showing areas of internal vascularity on Doppler imaging (B). The well-defined hyperechoic area within the lesion is suggestive of fat component within (arrow in A). Multiphasic CECT of the abdomen of the same child shows a hypodense lesion with areas of fat and calcification within the left lobe of liver as seen on NCCT (arrow in C) showing enhancement in the arterial phase (D) with washout in the portal venous phase (E and F) in a case of hepatocellular carcinoma. Fig. 9.8.3.12 Axial (A) and coronal (B) CECT images of the abdomen reveal presence of a large, lobulated mass lesion in right lobe of liver showing peripheral enhancement with central hypodense scar suggestive of fibrolamellar carcinoma which was subsequently proven on histopathology. Fig. 9.8.3.13 Axial NCCT and CECT images of the abdomen in a 7-year-old child show presence of an isodense mass lesion in the right lobe of liver on NCCT (A) which shows intense enhancement on postcontrast scan (B) with a hypodense central scar as evident on delayed scan (arrow in C) suggestive of focal nodular hyperplasia. Fig. 9.8.3.14 In a known case of Caroli disease, USG image (A) reveals noncommunicating cystic areas in the liver parenchyma with one of them showing presence of nondependent echogenic soft tissue along its walls. Axial CECT abdomen image (B) reveals presence of enhancing soft tissue along the walls of one of the cystic lesions in segment IV of left lobe of liver (arrow in B) suggestive of development of cholangiocarcinoma, which was proven on histopathology. Note is made of hyperdense sludge

and calculi within the dilated cystic areas, central dot sign is also seen within some of the cysts. Fig. 9.8.3.15 USG images (A–C) in a 3-year-old child reveals a markedly dilated common bile duct showing presence of a heterogeneously hypoechoic lesion within suggestive of embryonal rhabdomyosarcoma; bilobar intrahepatic biliary radical dilatation is seen. Fig. 9.8.3.16 Axial (A) and coronal (B) CECT abdomen images show few hypodense focal lesions in the liver suggestive of metastases from a large neuroblastoma seen in left side of abdomen. Fig. 9.8.3.17 Axial CECT image of the abdomen reveals multiple hypodense lesions scattered in both lobes of liver and in the spleen along with retroperitoneal lymphadenopathy suggestive of secondary lymphoma. Fig. 9.8.3.18 Axial CECT image of the abdomen reveals an enlarged liver with diffusely heterogeneous attenuation of the liver parenchyma indicating infiltrative pattern of lymphoma, note made of hypodense lesions in spleen and retroperitoneal lymphadenopathy. Fig. 9.8.4.1 Hepatic artery pseudoaneurysm (PA) secondary to blunt trauma abdomen. A. Axial enhanced CT image shows a collection in the segment V/VIII of the liver, with a focal contrast-filled outpouching along its medial aspect (arrow). B. Coronal reformat depicts the collection along with irregular linear lacerations along its periphery and the PA. C. There is breach of liver capsule and extension of hematoma into the perihepatic space (arrow). Fig. 9.8.4.2 Incidentally detected preduodenal portal vein (PV) in a patient with hyperbilirubinemia. A. Axial CT image shows the anomalous course of the PV (arrow), which is seen coursing anterior to the duodenum and the gallbladder. The gallbladder shows mural thickening (solid arrow). B. Coronal MIP image depicts the course of PV anterior to the second part of duodenum. C. The patient also had associated anomalies in the form of polysplenia (white arrow). Intrahepatic biliary radical

dilatation (black arrow) and hepatic subcapsular collection (*) were noted. Fig. 9.8.4.3 Portal vein thrombosis in a 3-year male child. A. US through the superior segments of the right lobe shows multiple hypoechoic liver abscesses in segment VII (arrow). B. There is echogenic intraluminal content in the main portal vein (arrow). C. Axial enhanced CT shows the clustered liver abscess in segment VII (arrow). D. There is thrombosis of the main portal vein as well as its branches (black arrow). Associated chest wall abscess is also seen (solid arrow). Fig. 9.8.4.4 Fifteen-year female with extrahepatic portal venous obstruction (EHPVO). A. Axial enhanced CT image shows absent min portal vein (MPV) and multiple collaterals. Few of these are portoportal in pericholecystic location (white arrow), while the majority are portosystemic (gray arrow). B. Coronal reformatted image better depicts the multiple tortuous collateral replacing portal vein (arrow). Massive splenomegaly is seen. C. Maximum intensity projection (MIP) shows the portosystemic collaterals, from the intact splenic vein (arrow) and the left gastric vein. Fig. 9.8.4.5 EHPVO in a 12-year male child. A. Axial CT image reveals a single large collateral seen at the hepatic hilum (arrow). Few smaller collaterals are seen adjacent to it. B. In a cranial section, multiple azygous collaterals are also seen (arrow). C. Coronal MIP image shows the Normal intrahepatic portal vein (arrow), the collaterals at porta, as well as left gastric collaterals draining into systemic circulation (solid arrow). Fig. 9.8.4.6 Budd–Chiari syndrome in a 4-year-old male child. A. Axial fat-saturated T2 image shows loss of the IVC flow void. There is peripheral T2 hyperintensity in the liver parenchyma. Caudate hypertrophy is also noted. B. Coronal TRUFISP image shows only the right hepatic vein is patent (black arrow). There is a venovenous collateral (white arrow). C. The comma-shaped veno-venous collateral (arrow) is better seen in axial TRUFISP image. D. Post-gadolinium (venous phase) scan shows the caudate lobe hyperenhancement, as well

as the peripheral heterogeneous enhancement, suggesting subacute disease. Fig. 9.8.4.7 Congenital arterioportal shunt (APS) in a 7year-old male child. A. Transverse section through the superior segments of the right hepatic lobe shows a large anechoic structure in segment VIII, which is in continuity with the portal venous branch (arrow). B. On colour Doppler, turbulent bidirectional flow is seen in the portal vein as well as the lesion, confirming its vascular nature. C. There is pulsatile, bidirectional flow on spectral doppler suggesting an APS. Fig. 9.8.4.8 Hepatic arteriovenous malformation. A. On digital subtraction angiography (DSA), a nidus of dysplastic vessels is seen in the right hypochondrium (arrow). This was previously drawing feeders from the left gastric artery, which was embolized. Coil mass seen in situ (solid arrow). B. The nidus is now seen drawing feeders from the common hepatic artery (arrow). Early draining veins are also seen (solid arrow). C. The nidus was embolized using liquid embolic agent, N-butyl cyanoacrylate (NBCA). D. Complete embolization was achieved in this setting. Fig. 9.8.4.9 Congenital porto-systemic shunt (CPS) in a 19-day-old male child. A. Longitudinal section through the right lobe shows a tubular anechoic structure. B. On transverse scan, the structure is seen draining into the intrahepatic inferior vena cava C. Superiorly, it is seen to join the dilated portal vein. There is unidirectional flow into the IVC on Color doppler. D. Enhanced CT images show the dilated vascular channel connecting right PV and IVC (arrow). E. Coronal reformatted image better depicts the connecting channel. This is type I intrahepatic portosystemic shunt. Fig. 9.8.4.10 Abernethy malformation in a 5-year-old male. A. Axial TRUFISP sequence shows common trunk, that is the portal vein (arrow) at hepatic hilum draining into the IVC through a shunt vessel (solid arrow). B. On the axial HASTE sequence, flow voids are seen in the PV, IVC and the shunt vessel. C. Post-gadolinium sequence shows similar findings. No intrahepatic portal venous

radicles are seen. This is suggestive of an end-to-end shunt (Type Ib). Fig. 9.8.4.11 Abernethy malformation in an 11-year male child. A. The common trunk formed by union of splenic and superior mesenteric vein is seen, with distal varix (arrow). B. The side-to-side shunt between portal vein and IVC has been ligated (black arrow). Intrahepatic branches of the PV are seen (white arrow). C. Commashaped intrahepatic portosystemic collaterals are also seen (arrow). This was a type II malformation. Fig. 9.8.4.12 Hereditary hemorrhagic telangiectasia (HHT). A. Axial section of the thorax reveals a pulmonary nodule with an enlarged artery leading to it. B. A dilated draining vein is also seen, suggestive of pulmonary arteriovenous malformation. C. The segment II of liver shows ill-defined hypodensity (arrow) D. Similar lesion is also seen in segment III (arrow). These are transient attenuation defects. E. An enlarged hepatic artery is also seen, secondary to hyperdynamic circulation (arrow). Fig. 9.8.4.13 Proposed algorithm for diagnosis of hepatic vascular shunts. RI, resistive index; CT, computed tomography; MR, magnetic resonance; DSA, digital subtraction angiography. Fig. 9.8.4.14 Infantile hepatic hemangioma CT (MPCT) in a 7-month male child. A. Arterial phase image shows a hypodense lesion in segment VII with peripheral nodular arterial enhancement. B. There is progressive centripetal filling in the venous phase. C. There is near-complete filling seen in delayed phase with few nonenhancing areas. D. The volume-rendered image shows abrupt change in calibre of abdominal aorta below the origin of the celiac axis (white arrow). The celiac trunk and hepatic artery are hypertrophic (gray arrow). Fig. 9.8.5.1 Cholelithiasis: Ultrasound image of the gallbladder shows a small gallstone (black block arrow). Fig. 9.8.5.2 A. Choledocholithiasis: Ultrasound image shows dilated common bile duct (CBD) with sludge (black arrow) and a calculus (white arrow) in distal part

of CBD. Note, sludge (black block arrow) is also seen in gallbladder lumen. B. Choledocholithiasis: Ultrasound image shows a calculus (white arrow) in distal part of CBD in head region of pancreas. Fig. 9.8.5.3 Pseudolithiasis: Ultrasound images show hyperechogenic sludge (block white arrows) within the gallbladder lumen consistent with pseudolithiasis. Fig. 9.8.5.4 Axial abdominal ultrasound scan of the gallbladder shows an echogenic polypoid (white arrow) lesion arising from fundal wall of gallbladder. Fig. 9.8.5.5 Ultrasound image shows normal wall thickness of infundibulum (block black arrow); central portion with wall thickening and luminal narrowing (black arrow) along with mild concentric wall thickening of fundal region (white arrow) consistent with adenomyomatosis of the gallbladder. Fig. 9.8.6.1 (A) Schematic drawing demonstrates Couinaud’s segments of the liver and left lateral lobe segments used for split liver grafts. (B) Split liver transplantation: Schematic representation of the donor organ divided into a larger right lobe graft (usually used for the adult recipient) and the smaller left lobe graft (typically used for the paediatric recipient). Fig. 9.8.6.2 Split liver graft: vascular and biliary enteric anastomoses. IVC: inferior vena cava; LHV: Left hepatic vein; LPV: left portal vein; PV: main portal vein; HA: Hepatic artery. Fig. 9.8.6.3 APOLT: partial liver graft is implanted in a recipient alongside part of the native liver. (A) Schematic diagram showing the graft and native liver with anastomoses. (B) Intraoperative picture showing the graft and native liver in situ. (C and D) Axial and coronal CT images demonstrate the graft and native liver in situ with respective vascular anastomoses. Fig. 9.8.6.4 Posttransplantation DISIDA scan is helpful for assessment of uptake of the tracer activity in the graft (hepatic extraction), and the rate of excretion of tracer activity in the Roux loop and the small bowel at 1 hour (hepatic excretion)

Fig. 9.8.6.5 Normal Doppler patterns post-transplant: Hepatic artery interrogation shows low resistance waveforms with sharp systolic peak and diastolic forward flow. Normal resistive index (RI) ranges between 0.5 and 0.8; the systolic acceleration time (SAT) is 3 mm) in size in both lobes (arrows), with interspersed reticulation (yellow arrows). These nodules appear isointense to one another on delayed phase of dynamic study (arrows in D) and do not show arterial enhancement (not shown). Fig. 9.9.50 Siderotic nodules. (A and B) T1W1 in- and opposed-phase images showing multiple tiny hypointense nodules in both lobes (arrows). Fig. 9.9.51 DN in cirrhosis. (A and B) T2W1 images showing a well-defined hypointense nodules (2.2 cm) protruding from the surface of segment 5. Nodule appears hyperintense on T1W1 images (arrows in C). Fig. 9.9.52 Nodule in nodule appearance. (A) T2W1 images showing a 3 cm hypointense nodule in 4/5. The lesion appears hyperintense T1W1 images (arrows in B) with central hypointense area (red arrow). The small central nodule shows arterial enhancement with washout (arrows in C, E and F). This suggests DN with central focus of malignancy.

Fig. 9.9.53 HCC in cirrhotic liver. (A) T2W1 images showing a well-defined heterogeneously hyperintense lesion in segment 7. Lesion shows heterogeneous arterial enhancement (arrows in B) and another smaller nodule is seen adjacent to it (red arrows). Delayed phase images show washout (arrow in D). Fig. 9.9.54 Infiltrative HCC in cirrhosis. (A) T2W1 images showing an ill-defined infiltrative hyperintense lesion in right lobe of liver (arrow in A) showing diffusion restriction (arrow in B). Contrast-enhanced venous phase images show permeative nature of lesion composed of multiple tiny nodules with ill-defined margins (yellow arrow in C). A large tumour thrombus is seen in the right PV (red arrow in C). (D) Hepatocyte phase images show good tumour liver contrast. Fig. 9.9.55 MRE. Normal MRE in a healthy patient with mean stiffness index 2.5. Fig. 9.9.56 MRE in cirrhotic. MRE image in a patient with cirrhosis showing mean stiffness index 9–11 kPa. Fig. 9.9.57 LR-5. A 4.2 cm lesion in segment 7 showing arterial enhancement (arrow in A) with portal venous washout (arrow in B). Fig. 9.9.58 LR-5. A 1.2 cm nodule showing arterial enhancement (arrow in A) and portal venous washout and capsule appearance (arrow in B). Fig. 9.9.59 LR-4. Contrast-enhanced CT showing 18 mm arterial enhancing nodule in segment 4b (arrows) showing washout without capsule appearance. Fig. 9.9.60 LR-3. (A) T2W1 image showing a welldefined hypointense lesion measuring 1.8 cm in segment 7 (arrow). Lesion does not arterial enhancement (arrow in C) with washout appearance of delayed phase (arrow in D). Fig. 9.9.61 LR-2. T1W1 in- and opposed-phase images and (C) T2W1 images showing multiple tiny regenerating siderotic nodules in both lobes. Fig. 9.9.62 LR-1 perfusion defects. (A and B) Contrastenhanced MRI in late arterial phase showing multiple

patchy arterial enhancing foci in both lobes (arrows). These are isointense to background liver on venous phase images. Fig. 9.9.63 LR-1 confluent fibrosis. (A) T2W1 image and (B) contrast-enhanced venous phase showing an illdefined wedge-shaped hyperintense area in segment 7 showing delayed enhancement. Fig. 9.9.64 LR-5M. T2W1 and postcontrast images showing an ill-defined, nontargetoid mass in left lobe suggestive of infiltrative HCC. Fig. 9.9.65 (A) L1-RADS measurement of viable tumour posttreatment. (B) L1-RADS measurement of viable tumour posttreatment. Fig. 9.9.66 Residual viable tumour. (A and B) Late arterial phase of dynamic contrast-enhanced CT in a lesion treated with radiofrequency ablation (RFA) showing peripheral nodular enhancement (arrows) compatible with viable disease. Fig. 9.10.1 Ct protocol in diffuse liver disease. Unenhanced (A) and enhanced CT (A, B and C) with arterial, portal venous and venous phase should be obtained. Fig. 9.10.2 MR sequences in evaluating diffuse liver disease. T2W1 (A) provide information regarding altered signal. TIW1 in-opp phases (B and C) are used in diagnosing fatty liver. Calculation of hepatic fat fraction can be done with Dixon imaging (D). MR elastography (E) is used in evaluation of liver stiffness. Fig. 9.10.3 Spectrum of NAFLD. Fig. 9.10.4 Fatty liver. USG shows a diffuse increase in hepatic echogenicity with preserved visualization of periportal and diaphragmatic echogenicity suggesting mild fatty liver. Fig. 9.10.5 Fatty liver. USG shows a diffuse increase in hepatic echogenicity with obscuration of periportal echogenicity but preserved diaphragmatic visualization suggesting moderate changes.

Fig. 9.10.6 CT in fatty liver. Non enhanced CT showing mild decrease in normal liver attenuation (45–55 HU) suggesting mild fatty changes. Fig. 9.10.7 CT in fatty liver. Non enhanced CT showing severe decrease in normal liver attenuation (13–18 HU) suggesting severe fatty changes. Fig. 9.10.8 CT LAI. Nonenhanced CT images (A to C) showing ROI on each hepatic segment. At least 25 ROI s are drawn in liver. Similar size approximately 5 ROI are drawn in the spleen. The average attenuation is calculated for both and the difference is called the Liver attenuation index. Fig. 9.10.9 Chemical shift imaging. T2W1 images (A and B) showing hepatomegaly with increase in parenchymal signal. T1 W1 in and opp phase images (C and D) showing signal drop on opp phase imaging. Fig. 9.10.10 Calculation of hepatic fat fraction using MRI. TIWI in and opp phase images (A and B) showing mild signal drop on opp phase images. Fat fraction calculation using Dixon technology (C) shows 12% fat suggesting mild changes. Fig. 9.10.11 Calculation of hepatic fat fraction using MRI. TIWI in and opp phase images (A and B) showing significant signal drop on opp phase images. Fat fraction calculation using Dixon technology (C) shows 28% fat suggesting severe changes. Fig. 9.10.12 Magnetic resonance spectroscopy spectrum of hepatic fat. Water and fat peaks are displayed at different frequencies; water appears as a single peak at 4.7 ppm, whereas fat appears as four peaks, including the dominant methylene (CH2) peak at 1.3 ppm (3), a methyl (CH3) peat at 0.9 ppm (4), an α – olefinic and α – carboxyl peak at 2.1 ppm (2), and a diacyl peak at 2.75 ppm (1); the areas of these four fat peaks and the water peak can be measured by spectral tracing. PDFF can be calculated as (sum of fat peaks) ÷ (sum of fat peaks + water peak).

Fig. 9.10.13 Focal fat. Unenhanced CT (A) showing geographic hypodense area in the left lobe of liver. Contrast-enhanced CT in late arterial (B), portal venous (C) and venous phase (D) showing persistent hypodense without mass effect with normal vessels coursing through the affected region. Fig. 9.10.14 Multifocal fat deposition. Unenhanced CT images (A–C) showing patchy mass like hypodense areas in both lobes of liver (arrows). Enhanced CT in portal venous (D–F) and venous phase showing confluents relatively hypoenhancing areas with vessels coursing through them (arrows). Fig. 9.10.15 Perivascular fat. Contrast-enhanced CT (A) showing hypodense areas of fat deposition in the perivenular location (arrows). Findings are confirmed on T1W1 in and opposed phase images (B and C) which show signal drop on opp phase (arrows). Fig. 9.10.16 Lipid containing lesions. Unenhanced CT (A) showing large hypodense mass in right lobe with areas of macroscopic fat along its inferior aspect (arrows). Postcontrast arterial phase images (B) showing neovascularity (arrows). Postcontrast venous phase images (C) showing heterogenous enhancement of the mass with relatively nonenhacing fatty areas (arrows). Fig. 9.10.17 Perfusion abnormalities. Contrastenhanced late arterial phase images (A and B) showing wedge-shaped areas of hyperenhancement in the periphery of segment 8/4A (arrows). These areas are isodense to liver on venous phase (C) and were not seen on unenhanced scan (not shown). Fig. 9.10.18 Periportal oedema/cuffing. Contrastenhanced CT in a patient with acute viral hepatitis showing hepatomegaly with symmetric hypodensity in the periportal regions (arrows). Fig. 9.10.19 Cirrhosis inpatient with iron overload. Known case of thalassemia with repeated blood transfusions showing significant decrease in hepatic signal on T2W1 images (A) with changes of frank

cirrhosis with multiple siderotic nodules and portal hypertension with splenomegaly (arrows in B and C). Fig. 9.10.20 CT in iron overload. Nonenhanced CT images (A–C) showing diffuse increase in hepatic density (100–104 Hu). Fig. 9.10.21 MRI in haemochromatosis. T2W1 image (A–C) showing significant decrease in hepatic signal intensity relative to the paraspinal muscles. Fig. 9.10.22 Dual echo in haemochromatosis. Known case of secondary haemochromatosis showing marked signal drop on in-phase images (B) compared to opp phase (A). Fig. 9.10.23 Haemochromatosis with fatty changes. In this known case of haemochromatosis T1W1 opp phase images (C and D) show signal drop compared to in-phase due to concomitant presence of fat in liver. Fig. 9.10.24 Diagrammatic representation of signal intensity ratio method. Fig. 9.10.25 SIR method for estimation of liver iron. GRE images (only 2 shown) show significant decrease in hepatic signal intensity relative to the paraspinal muscles (ROI). Fig. 9.10.26 Calculation of T2* and R2*. Multi echo gradient imaging for calculation of liver iron in a normal volunteer. Fig. 9.10.27 Parenchymal deposition pattern. T2W1 images (A, B) showing low signal of liver and pancreas (arrow in B). Fig. 9.10.28 Hepatic adenomatosis in a patient with glycogen storage disease. Contrast-enhanced CT (A–D) showing multiple (>10) well defined arterial enhancing lesions diffusely distributed in both lobes consistent with adenomatosis. Fig. 9.10.29 Ct inpatient with Wilson’s disease. Unenhanced (A) and Contrast-enhanced (B and C). CT in a known case of Wilson’s disease showing features of frank cirrhosis with portal hypertension. T2W1 MRI

images in same patient showing symmetric T2 hyperintensities in basal ganglia and lateral thalami (arrows), a finding classic of Wilsons disease-related neurodegeneration. Fig. 9.10.30 Amiodarone toxicity. Nonenhanced CT in a patient with chronic amiodarone consumption shows hyperdense liver (HU 90). Lung window shows fibrosis (arrows). Fig. 9.10.31 MR in Acute hepatitis. T2W1 axial images (A) showing hepatomegaly with heterogeneous hyperintensity. Postcontrast arterial phase (B) showing heterogeneous enhancement. Fig. 9.10.32 MRI in acute hepatitis showing hepatomegaly with periportal cuffing (arrows in B). Gall bladder wall oedema is seen (arrows in C). Mild perihepatic fluid is seen (arrows in D). Note patient is a known case of pancreatitis with walled-off necrosis in body (blue arrow in B). Fig. 9.10.33 Gaucher’s cell infiltration. Contrastenhanced CT (arterial (A), portal venous (B) and venous phase C–E) in a 10-year male with known Gaucher’s disease showing ill-defined hypodense lesion in segment 6/7 of liver (blue arrow) representing infiltration with Gaucher’s cells. Vessels are seen coursing through the abnormality (orange arrow) with attenuation in calibre and resultant atrophy. Others similar non confluent patches are seen in left lobe (yellow arrows). Gross splenomegaly is seen. Fig. 9.10.34 CT in leukaemic infiltration. Unenhanced and contrast-enhanced CT shows hepatomegaly with coarse architecture secondary to infiltration. Associated marked splenomegaly is also seen. Fig. 9.10.35 Histiocytosis. Contrast-enhanced CT (A– D) in a 2-year-old boy showing gross hepatosplenomegaly with multiple tiny nodules diffusely distributed in liver (arrows). Lung window image (E) shows ground glass attenuation in right lower lobe. Bone window (F) shows lyticlesion in left iliac bone (arrow).

Fig. 9.10.36 Histiocytosis. Contrast-enhanced CT of the abdomen in a 10-year-old boy shows hepatomegaly with multiple hypodense nodules in both lobes. HRCT window shows multiple cysts (arrows). Lytic lesions are seen in skull bone, mandible and petrous bone (arrows). Fig. 9.11.1 Multiphase CT of liver showing plain, early arterial, late arterial, portal venous and hepatic venous phase. Note maximum enhancement of the liver parenchyma in the portal venous phase. Fig. 9.11.2 Precontrast and postcontrast MRI protocol. The precontrast protocol includes T2W1, T1 in- and opposed-phase, diffusion-weighted imaging (DWI), T2W1 fat suppressed (FS) and 3D T1 gradient-recalled echo (GRE) and 3D magnetic resonance cholangiopancreatography (MRCP), if needed. The postcontrast phase is parallel to that of CT. Note delayed phase showing excreted contrast in the biliary tree and gallbladder is obtained when using a hepatocyte-specific agent. Fig. 9.11.3 Grey scale USG showing hyperechoic haemangiomas in liver with posterior acoustic enhancement. Fig. 9.11.4 CT in haemangioma. Contrast-enhanced CT in arterial, portal venous and delayed phases showing two haemangiomas in the same patient in segments 6 and 3. Both show peripheral nodular discontinuous enhancement in arterial phase with density paralleling that of aorta (arrows in A and D). Gradual centripetal filling-in is seen subsequently (arrows in C, F and G). Note the larger haemangioma does not fill-in completely, a feature common in slightly larger haemangiomas. Fig. 9.11.5 (A) T2WI axial images showing a welldefined hyperintense (light bulb) lesion in segment 8 of the liver (arrow in A). The lesion retains signal on long echo images (arrow in B) suggestive of slow flow. (C and D) Postcontrast images showing peripheral nodular enhancement in arterial phase (arrow in C) and subsequent centripetal filling (arrow in D).

Fig. 9.11.6 Giant haemangiomas. (A to D) Postcontrast images showing well-defined lesion with peripheral nodular arterial enhancement and centripetal filling (arrow in A). There is, however, failure to completely fill-in with no enhancement of the central scar (arrow in C and D). This pattern is usually seen in giant haemangiomas. Fig. 9.11.7 Haemangioma with scar. (A to E) Precontrast MRI images showing a well-defined T2 hyperintense lesion with central necrosis in segment 6 (arrows in B and C). Note diffusion restriction in the lesion without ADC drop (arrows in D and E). (F to J) Postcontrast images showing centripetal enhancement pattern with filling of the lesion on delayed phase with the exception of the central scar (arrows). Fig. 9.11.8 Flash haemangioma. (A and B) Late arterial phase and (C and D) venous phase showing three welldefined flash enhancing lesions with surrounding halo in segments 7 and 8 (arrows). The lesions are isodense to the background liver in venous phase and are not identified as such. Fig. 9.11.9 (A to E) Contrast-enhanced multiphase CT images showing exophytic haemangioma arising from left lobe. (F to J) Scan done 8 years, hence shows decrease in size with lack of characteristic enhancement pattern suggestive of hyalinization (arrows). Fig. 9.11.10 Focal nodular hyperplasia. (A) CT abdomen obtained in arterial, (B) venous and (C) delayed images showing a well-defined lobulated arterial enhancing lesion in segment 8 of liver with central nonenhancing scar. Enhancement of the scar seen on delayed phase (arrow in C). Fig. 9.11.11 Focal nodular hyperplasia. (A to C) CT angiogram images obtained in arterial phase showing vascular malformation in the central scar of the FNH (arrow in A). There are, in addition, large feeding arteries in the lesion periphery and centre (arrow in B and C).

Fig. 9.11.12 MRI in FNH. (A) T2W1 images showing a well-defined mildly hyperintense lesion in segment 7/8 with central hyperintense scar (arrow). The lesion shows arterial enhancement (arrow in B) with progressive enhancement in venous phase with exception of the scar. (D) Delayed phase images show enhancement of central scar (arrow). Fig. 9.11.13 MRI in FNH. (A) T2W1 image shows a welldefined mildly hyperintense lesion in segment 4b with exophytic extension. Central dilated vascular channels are seen in arterial phase (arrow in B). (D) The lesion shows intense late arterial/portal venous enhancement with the exception of the central scar. Delayed phase shows scar enhancement (arrow in E). Fig. 9.11.14 Hepatic adenomatosis in a patient with GSD. (A to D) Arterial phase images of showing multiple (more than 10) enhancing lesions in both lobes of the liver (arrows). Fig. 9.11.15 Hepatic adenoma CT. (A) CT abdomen in plain, (B to D) arterial, venous and parenchymal phases showing well-defined arterial enhancing lesion in segments 2 and 3 (arrow in A) with delayed washout. Note: There is marked fatty infiltration of the background liver, hence the lesion appears hyperdense on plain and delayed phases. Fig. 9.11.16 Hepatic adenoma. (A) T2WI images showing large well-defined hyperintense lesion with central heterogeneity. (B) The lesion is mildly hyperintense on T1WI images. (C and D) In- and opposed-phase images revealed signal drop in opposedphase suggestive of intralesion fat (arrows). (E) The lesion reveals heterogeneous enhancement in arterial phase with peripheral subcapsular vessels (arrows). (G) On delayed phase, the lesion is hypo- to isointense to the background liver. No obvious pseudocapsule is seen. Fig. 9.11.17 Adenoma with atoll sign. T2WI axial image showing an inflammatory adenoma with atoll sign. Note: Isointensity of the centre of lesion on T2WI images (red arrow) with hyperintense signal band in the periphery resembling an atoll (blue arrow).

Fig. 9.11.18 HNF alpha-mutated adenoma. (A and B) T2W1 images showing an ill-defined mixed signal intensity lesion in segment 7 (arrows). (C and D) TIW1 in- and opposed-phase images showing signal drop in the lesion suggesting intralesional fat (arrows). The lesion shows mild diffuse enhancement with washout on delayed phase (arrows). Fig. 9.11.19 Angiomyolipoma of liver. Plain CT abdomen showing a large fat density lesion in right lobe with thin intralesional septae (arrows). Another small lesion is seen in segment 3 biopsy confirmed HAML. Fig. 9.11.20 Focal fatty infiltration. (A to C) CT abdomen obtained in plain, arterial and venous phases showing a hypodense area with geographic pattern involving left lobe of the liver (arrow in A). Note: The hepatic vasculature is seen coursing through this area without displacement (arrows in B and C). Fig. 9.11.21 Vascular dynamics in THAD. Fig. 9.11.22a Lobar THAD in a patient with left portal vein thrombosis. CT abdomen obtained in (A) arterial, (B) late arterial and (C and D) parenchymal phases showing a wedge-shaped arterial enhancing area involving the left lobe with normal vasculature coursing through it (arrows in A and B). This area then subsequently appears isodense to the background liver. Note: Thrombus in the left portal vein (arrow in D). Fig. 9.11.22b Polymorphous THAD in a patient with acute cholecystitis. (A and B) Patchy areas of hyperenhancement in segments 4b and 5 of the liver around the inflamed gallbladder in arterial phase becoming isodense to liver in venous phase. Fig. 9.11.23 Grey scale USG showing simple cyst in liver. Well-defined hypoechoic lesion with posterior acoustic enhancement. Fig. 9.11.24 Simple cyst. Unenhanced and enhanced CT images showing a well-defined hypodense cystic lesion with exophytic extension in segment 5 (arrows). Note the lesion has imperceptible walls with no enhancing septae.

Fig. 9.11.25 MRI showing simple cyst. (A and B) T2W1 and long echo T2W1 images showing well-defined hyperintense lesion in segment 2 (arrows), appearing hypointense on T1W1 images and showing thin peripheral wall enhancement (arrow in D). Fig. 9.11.26 Septated liver cyst. (A) CT abdomen arterial and (B and C) venous phases showing hypodense cystic lesion in segment 5 with thin internal septae without nodularity. Fig. 9.11.27 (A to E) Nonenhanced CT images in a patient with autosomal dominant kidney disease show innumerable hypodense cysts of varying sizes in both lobes of liver (arrows). Few of the cysts are seen coalescing in one another (yellow arrow). Patient also with multiple cysts in both kidneys (blue arrows). Fig. 9.11.28 MRI showing biliary hamartoma. Heavily T2WI images (arrows in A to C) showing multiple tiny T2 hyperintense lesions in both lobes of liver not communicating with the biliary tree. Fig. 9.11.29 MRI in Caroli’s disease. (A to E) T2W1 axial and coronal images in case of Caroli’s disease showing cystic dilatation of intrahepatic biliary radicals (red arrows). Note extensive hepatolithiasis (white arrows). This patient also had medullary sponge disease of the kidneys (blue arrow in E) showing ectatic tubules. Fig. 9.11.30 HCC on grey scale USG. Fig. 9.11.31 Colour Doppler USG showing neovascularity in HCC. Colour Doppler image showing linear neovascular channels in HCC (arrow in A). Note the basket pattern of vascularity around the lesion (arrow in B). Fig. 9.11.32 Contrast-enhanced USG in HCC. Contrastenhanced USG in HCC showing hyperenhancement of lesion (arrows). Fig. 9.11.33 CT abdominal showing a well-defined arterial enhancing lesion. Washout of contrast is seen in venous phase. (C) Delayed phase images showing a ‘capsule’ around the lesion (arrow).

Fig. 9.11.34 HCC in cirrhotic liver with peripheral corona enhancement. (A) T2W1 axial image showing mildly hyperintense lesion in segment 6. Lesion shows predominantly peripheral enhancement in arterial enhancement (arrow in B), which persists on subsequent phase. Peripheral arterial enhancement should not be misconstrued as capsule appearance. Fig. 9.11.35 Hypovascular HCC. T2W1 axial image shows a predominantly hypointense lesion, measuring 3.5 cm in segment 2 with exophytic extension (arrows). Lesion is slightly hyperintense to liver on T1W1 images (arrow in B). (C) No arterial enhancement is seen, which was confirmed on subtraction images. Delayed phase shows peripheral pseudocapsule (arrow in D). Retention of lipiodol following TACE in lesion confirms malignancy (arrow in E). Fig. 9.11.36 HCC with malignant portal vein thrombus. (A and B) T2WI coronal images showing a heterogeneously hyperintense mass in segment 7 (arrows). A hyperintense thrombus is visualized in the portal vein which is distended (blue arrows in A and B). Neovascularity of the thrombus seen in arterial phase (arrow in C) and there is restricted diffusion within the tumour and thrombus (arrows in E). Fig. 9.11.37 Malignant hepatic venous and IVC thrombus. (A to C) Venous phase CT images showing thrombus with neovascularity in the middle and left hepatic veins (arrows in C) with extension of the thrombus seen into the IVC and right atrium (arrows in A and B). Note: Ill-defined infiltrative tumour in the left lobe. Fig. 9.11.38 T2 hyperintensity in HCC. (A) T2WI images showing a well-defined minimally hyperintense lesion in segment 7 (arrow in A). The lesion reveals restricted diffusion (arrow in B). There is enhancement of the lesion in arterial phase with washout and capsule appearance on venous phase (arrows in C and D). Fig. 9.11.39 HCC – mosaic appearance. Arterial phase CT showing heterogeneous mosaic pattern of enhancement in large right lobar HCC with extensive

neovascularity. This pattern of enhancement is always suggestive of malignant neoplasm. Fig. 9.11.40 Detection of small HCC with hepatocytespecific agents. Contrast-enhanced MR using hepatocyte-specific agents showing small (1.2 cm) arterial enhancing nodule in segment 5 of liver appearing hypointense to background liver on hepatocyte phase with capsule appearance (arrow in B). Fig. 9.11.41 Diffuse infiltrative HCC. (A) T2WI axial images showing ill-defined minimally hyperintense lesion occupying almost the entire right lobe of the liver. The lesion shows markedly restricted diffusion (arrow in B). (C) Postcontrast arterial phase images revealed minimal enhancement. There is patchy enhancement in the portal venous phase with multiple tiny nodules interspersed within (arrow in B). (E) Delayed phase images reveal hypointensity within the area compared to the background liver. These findings suggestive an infiltrative pattern of HCC with permeative type of spread. Note: The hepatic veins are coursing through this region (arrow in D). Such features can be seen in this particular variant of HCC. Fig. 9.11.42 Fat containing HCC. (A and B) T1W1 inand opposed-phase images showing a well-defined fat containing nodule measuring 2.1 cm in segment 8. Note: (B) Signal suppression within the lesion on opposedphase images, confirming intralesional fat. Fig. 9.11.43 Ruptured HCC. A 45–year-old cirrhotic patient with acute pain and in shock. (A) Unenhanced CT showing large mixed density exophytic mass in right lobe with linear hypodense areas within the interstitium (arrows). Note: Mixed density subcapsular fluid around the lesion and the liver (blue arrow). (B) Arterial phase images show only mild enhancement. The linear areas of rupture are well appreciated on the portal venous and venous phase appearing as hypodensities within the exophytic component (arrows). Fig. 9.11.44 Multifocal HCC. (A and B) T2W1 showing innumerable discreet lesions in both lobes of liver in a patient with hepatitis C cirrhosis.

Fig. 9.11.45 Confluent hepatic fibrosis. Biopsy proven case of confluent hepatic fibrosis showing wedge-shaped T2 hyperintense lesion in segment 5 of liver (arrow in A and B). (C) Postcontrast venous phase images, showing enhancement (arrow), which persists in (D) delayed phase. Fig. 9.11.46 Mixed HCC–IHC. (A to C) T2W1 images showing an ill-defined hyperintense lesion in segments 8,7 and 4a of the liver with peripheral biliary dilatation (arrow in B). A hyperintense thrombus is seen in right portal vein (arrow in C). The mass and thrombus show enhancement on contrast study (arrows in D and E). Lesion shows both biliary dilatation and a tumour thrombus and hence has mixed features. Fig. 9.11.47 Mixed HCC – cholangiocarcinoma. (A and B) T2W1 images showing a large well-defined hyperintense lesion in left lobe and segment 8, causing bilobar biliary dilatation (red arrows in B). Tumour is seen invading the lumen of the right, left and main portal veins (blue arrows in B and D) with resultant tumour thrombus and is otherwise hypovascular. Fig. 9.11.48 Post-CT-guided RFA. (A) Preablation arterial phase images showing well-defined arterial enhancing nodule measuring approximately 3.5 cm in segment 8/4a. Postablation scan showing thin peripheral enhancement indicating postprocedural hyperaemia (arrows). Fig. 9.11.49 Post-RFA – ring-like enhancement. Fig. 9.11.50 Residual tumour post-RFA. (A and B) Contrast-enhanced arterial phase showing peripheral nodular arterial enhancement suggesting residual disease (arrows). Fig. 9.11.51 Post-TACE follow-up. (A) Unenhanced CT showing hyperdense areas of lipiodol deposition in segment 8 HCC (arrow). No arterial enhancement is seen within the lesion (arrow in B) suggesting nonviable tumour. Fig. 9.11.52 Postradioembolization. Postcontrast arterial phase images in a patient who underwent TARE

for segment 8 HCC with vascular thrombus shows illdefined hypoenhancing area suggesting nonviable tissue. Hyperintense areas along superior aspect of lesion haemorrhagic necrosis (arrows) and were seen on precontrast images as well. Fig. 9.11.53 Fat containing HCC. Noncontrast CT showing a well-defined hypodense lesion occupying the right lobe with eccentrically located area of fatty metamorphosis (blue arrow). Neovascularity identified within the lesion on arterial phase (arrow in B). (D) Delayed phase images show washout compared to background liver with pseudocapsule (arrow). Fig. 9.11.54 HCC in noncirrhotic patient. (B) Late arterial phase images showing a well-defined intensely enhancing mass in segments 4, 8 and 5 of the liver with central nonenhancing area (arrow). (E and F) Delayed phase images show washout of contrast from the lesion with a thick surrounding capsule (arrows). Note: Enhancement of the central scar-like area on the delayed phase (yellow arrow). This is an HCC in a noncirrhotic liver with scar-like tissue. Fig. 9.11.55 Fibrolamellar carcinoma. (A) Plain CT abdomen showing a lobulated hypodense lesion with calcification in segments 4b, 5 and 6 of the liver (arrow). (B) Arterial phase images showing heterogeneous mosaic pattern of enhancing with intense neovascularity. An eccentrically located scar is visualized within the lesion (arrows in D and E). (E) No enhancement of the scar is seen on the delayed phase. Fig. 9.11.56 Intrahepatic cholangiocarcinoma. (A) Arterial phase image showing a well-defined lobulated lesion in segments 6 and 7 of liver showing irregular continuous peripheral enhancement. Gradual centripetal filling of the lesion is seen on subsequent phases. Note: Involvement of right portal vein and its posterior division by the mass with atrophy of segments 6 and 7 (arrows in B and C). There is in addition, dilatation of biliary radicles with crowding in segment 7 (blue arrow in D). A small satellite nodule is also visualized suggestive of metastasis (yellow arrow in B and C). (D)

Delayed phase images showing contrast within the centre of the lesion with washout from the periphery representing the peripheral washout sign. Fig. 9.11.57 MRI in ICC. (A and B) T2W1 images showing a large well-defined hyperintense lesion in left lobe extending into segment 8. Note: Lesion is causing distal biliary dilatation in segment 2 (arrow in B). Late arterial phase shows peripheral and heterogeneous enhancement (arrows). Delayed phase shows peripheral washout sign with enhancement of central fibrotic component. Fig. 9.11.58 Periductal infiltrating C. Portal venous and parenchymal phases’ images showing an ill-defined hypodense minimally enhancing lesion along the biliary radicles in segment 8 of the liver. Involvement of anterior branch of right portal vein is seen. There is mild bilobar biliary dilatation (arrows in C). Small cholangitic abscesses are seen in right posterior segments (yellow arrows). Fig. 9.11.59 Intraductal cholangiocarcinoma. Venous phase images showing heterogeneously enhancing polypoidal lesion within biliary radicles in segments 8, 5 and their branches extending into the right hepatic duct (arrows in A and B). Resultant bilobar biliary dilatation is visualized. Fig. 9.11.60 CT in epithelioid haemangioendothelioma. (A to C) CT abdomen in the late arterial and (D and E) parenchymal phase showing multifocal well-defined hypodense lesions with peripheral enhancement (arrows in A and C) and gradual filling on parenchymal phase. This is a biopsy-proven case of multifocal epithelioid haemangioendothelioma. Fig. 9.11.61 Hepatic epithelioid haemangioendothelioma. T2W1 and postcontrast arterial, venous and delayed phases showing multiple coalescing T2 hyperintense lesions in entire left lobe and part of right lobe causing capsular retraction. Lesions cause peripheral enhancement on early phases and fill-in on delayed phase. Note the enhancing dot-like venous

radical terminating at the lesional periphery called the lollipop sign (arrows in D and E). Fig. 9.11.62 Primary hepatic lymphomas. (A and B) CT abdomen plain and (C) postcontrast images in a 40-yearold male with marked fatty infiltration of the liver showing multiple minimally enhancing lesions which are hyperattenuating to background liver on nonenhanced CT (arrows in A and B). This is a biopsy-proven case lymphomatous deposit in the liver. Fig. 9.11.63 Primary hepatic lymphoma. (A and B) T2WI axial images showing well-defined lobulated heterogeneous intensity lesions in segments 7, 8, 4 and 2 of the liver (arrows). The lesion shows central hyperintensity with thick nodular T2 isointense periphery. Restricted diffusion is visualized within the lesion periphery (arrow in C). (D) Arterial phase images reveal intense enhancement of the lesion periphery (arrow). On the delayed phase, there is filling-in of the centre of the lesion with contrast with washout from the periphery suggestive of peripheral washout sign (arrows in G and H). This is a biopsy-proven case of primary hepatic lymphoma. Fig. 9.11.64 Biliary cystadenoma. Contrast-enhanced CT showing a well-defined cystic lesion is segments 2 and 3 with enhancing internal septae (arrows in B and C). Note the attenuation of the left portal with involvement of segment 2/3 branch and left lobar atrophy (blue arrow in C). Crowding of biliary radicals is seen in left lobe (arrows in D). Fig. 9.11.65 Biliary cystadenoma. (A to D) Contrastenhanced CT images showing a well-defined cystic lesion with internal septa in segment 4. Associated mild biliary dilatation is seen (arrow in C). Previously done imaging diagnosed lesion as an abscess, hence lesion was pigtailed (arrow in D). MRI done 2 weeks later shows increase in size of lesion with progression of biliary dilatation (arrows in E). Patient was subsequently operated with final diagnosis of biliary cystadenoma. Fig. 9.11.66 Hepatic PEComa. (A) Nonenhanced scan showing a well-defined subcapsular lesion in segment 4

with intralesional fat (arrow). Intense enhancement is seen in arterial phase (arrow in B). Fig. 9.11.67 Hypervascular metastasis in HCC. K/c/o neuroendocrine tumour of uncinate process (arrow in F) shows multiple varying size heterogeneously hypervascular lesions in both lobes. Fig. 9.11.68 Peripheral washout sign in metastasis from rectal cancer. (A and B) T2W1 images show multiple well-defined hyperintense lesions in both lobes. The larger lesion in segments 8 and 7 shows peripheral enhancement in late arterial phase (arrows in C) with peripheral washout in delayed phase (arrow in F). Fig. 9.11.69 Peripheral washout sign in metastasis from neuroendocrine tumour. K/c/o neuroendocrine tumour showing a well-defined lobulated lesion in segments 8 and 4 showing peripheral arterial enhancement with central scar-like structure (arrow in B). Delayed phase shows peripheral washout (yellow arrow in C) with filling-in of the central scar-like structure (arrows). Fig. 9.11.70 Ring-like enhancing metastasis from colorectal cancer. Multiple ring-like enhancing lesions in both lobes of liver suggestive of metastasis. Fig. 9.11.71 Cystic metastasis in a patient with rectal cancer. K/c/o mucinous carcinoma of the rectum showing innumerable cystic peripheral ring-like enhancing lesions in both lobes. Fig. 9.11.72 Diffuse metastasis in case of breast carcinoma. K/c/o metastatic Ca breast with deranged LFTs. Contrast-enhanced MRI showing gross hepatomegaly with heterogeneous enhancement suggesting diffuse infiltrative metastasis. Fig. 9.11.73 Diffusion-weighted images in liver metastasis. (A) T2W1 and (B) DWI images of liver. More lesions are detected on diffusion-weighted images compared to T2 (arrows). Flowchart 9.11.1 Preneoplastic phase HCC. Flowchart 9.11.2 Neoplastic phase HCC.

Flowchart 9.11.3 Cellular changes. Flowchart 9.11.4 Vascular changes. Flowchart 9.11.5 Molecular changes. Flowchart 9.11.6 Fig. 9.12.1 Circulation in embryo. Fig. 9.12.2 Portal venous tributaries. Fig. 9.12.3 Schematic representation of different types of Abernethy’s syndrome. Fig. 9.12.4 Abernethy malformation with FNH. Case of extrahepatic portosystemic shunt (yellow arrow in F) with aneurysmal dilatation of the portal vein (yellow arrows in B). Associated large FNH is seen in the left lobe (blue arrows). Fig. 9.12.5 Congenital intrahepatic portal venous shunt with multiple large regenerating nodules and FNH. Fig. 9.12.6 Case of congenital intrahepatic portosystemic shunt. Contrast-enhanced CT in venous phase showing shunts between portal vein and hepatic veins (arrows). Fig. 9.12.7 USG in portal vein thrombus. Grey scale USG showing echogenic thrombus occluding the lumen of the main portal vein (arrows). Fig. 9.12.8 MRI showing malignant portal venous thrombus. T2W1 (A) showing hyperintense thrombus within the lumen of the right portal vein and its branches (arrows). Thrombus appears as filling defect on portal venous phase (arrows in B). T2 hyperintense portal thrombi are usually malignant, particularly in the setting of cirrhosis. Fig. 9.12.9 Diagram showing occlusion of the main portal vein with collaterals in the periportal and peribiliary regions with biliary dilatation. Fig. 9.12.10 Diagram showing occlusion of main portal vein with periportal, para and epicholedochal collaterals with biliary dilatation.

Fig. 9.12.11 USG showing EHPVO. Grey scale ultrasound image (A) showing multiple anechoic channels in periportal region (arrows). Colour Doppler images (B) showing collaterals (arrows). Fig. 9.12.12 Classic cavernoma formation in EHPVO. Contrast-enhanced portal venous phase images (A,B) shows occlusion of portal vein with cavernoma formation (arrows). Note that despite patient having longstanding portal occlusion, the liver is not cirrhotic. Fig. 9.12.13 C/o EHPVO with portal cavernoma formation. Contrast-enhanced CT in portal venous phase showing cavernoma with collaterals in periportal, pericholecystic and pericholedochal regions. Note the gross splenomegaly which is classically seen in patients with EHPVO. Fig. 9.12.14 EHPVO with predominantly left-sided collaterals. Portal venous phase images (A to C) in a patient with EHPVO showing large left-sided, peripancreatic collaterals. Note the paracholedochal collaterals around the CBD (arrows). Fig. 9.12.15 Portal biliopathy. k/c/o EHPVO showing multiple periportal collaterals with cavernoma formation (arrows from A–C). Note the extensive paracholedochal collaterals causing biliary dilatation (arrows in D–F). Fig. 9.12.16 Longstanding EHPVO with fibrotic cavernoma cholangiopathy. Contrast-enhanced CT in portal venous phase (A–D) showing plaque-like enhancing fibrosis around the bile ducts (arrows in A–C) T2WI images in axial and coronal plain (F–G) showing hypointense soft tissue around the bile ducts (arrows). Not the stenosis of the mid CBD secondary to fibrosis on MRCP images (H,I). Fig. 9.12.17 Longstanding EHPVO with portal biliopathy. T2W1 images (A, B) showing hypointense plaque-like fibrosis around the bile ducts (arrows). MRCP images (C,D) showing stricture in the CBD and right duct at confluence (arrows). Contrast-enhanced venous phase shows occluded portosplenic system with

collaterals postcontrast coronal images show plaque-like enhancement of the fibrotic cholangiopathy. Fig. 9.12.18 Shunt procedures in EHPVO. Fig. 9.12.19 Portal venous gas. Contrast-enhanced CT in portal venous phase showing gas in the portal vein (arrows). Fig. 9.12.20 Hepatic arterial thrombosis. Contrast enhanced CT showing occluded hepatic artery. The intrahepatic artery is seen reforming through collaterals. Fig. 9.12.21 Hepatic artery stenosis on Doppler. Contrast-enhanced CT in arterial phase in a patient who underwent liver transplant shows stenosis of hepatic artery (arrows in A) with elevated peak velocities. Dampening of intrahepatic waveform is seen (arrow in B). Fig. 9.12.22 Hepatic artery aneurysms in a patient with polyarteritis nodosa. Fig. 9.12.23 Hepatic artery pseudoaneurysm in a patient with blunt abdominal trauma. Contrastenhanced axial late arterial phase (A) and reformatted coronal images (B) show pseudoaneurysm of the hepatic artery (arrows). Note the large contusion/laceration in the liver with haematoma. Air foci are the result of surgical packing with gauze to achieve tamponade. Fig. 9.12.24 Thrombosed echogenic cord-like RHV. Grey scale ultrasound showing hypoechoic thrombosed cord-like right hepatic vein (arrows). Fig. 9.12.25 Turbulent flow in IVC. Grey scale (A) and Doppler images (B) showing stenosis of IVC (yellow arrows) with turbulent flow on Doppler. Fig. 9.12.26 Narrowing of IVC with turbulent flow. Grey scale USG images (A) showing IVC stenosis (yellow arrows). Turbulent flow is seen on Doppler (arrows) with high velocities and loss of phasicity. Fig. 9.12.27 Hepatic venous aneurysm in Budd–Chiari syndrome. Grey scale and colour doppler images show aneuysmal dilatation of right hepatic vein (arrows).

Fig. 9.12.28 Narrowing with ectasia Of the IVC. Case of Budd–Chairi syndrome showing areas of narrowing with ectasia in the hepatic veins. Fig. 9.12.29 Turbulent flow in hepatic veins. Case of Budd–Chiari syndrome showing turbulent flow in the left hepatic vein (arrows). Fig. 9.12.30 Dampened flow in hepatic veins. Dampening of flow in hepatic veins with loss of phasicity in Budd–Chiari syndrome. Fig. 9.12.31 Heterogeneous liver enhancement in acute BCS. Case of Budd–Chiari syndrome showing hepatomegaly with caudate hypertrophy (arrows in A). Note heterogeneous enhancement of the liver in the arterial phase with early hyperenhacement of the central portion (arrows in C). Washout of contrast is seen in venous phase (flip–flop pattern). The hepatic veins are not seen and multiple collaterals are identified (yellow arrow). Fig. 9.12.32 Acute Budd–Chiari with heterogeneous liver enhancement. Postcontrast MRI (A to C) showing morphological changes in the form of patchy decreased enhancement in the liver periphery (yellow arrow), while central portions and caudate lobe enhance normally (white arrows). Parenchymal phase images (D) show thrombus in hepatic veins (blue arrows). Note multiple intrahepatic collaterals in E (red arrows). Fig. 9.12.33 Case of chronic Budd–Chiari syndrome with cirrhosis. T21W1 (A and B) showing changes of cirrhosis of liver with gross splenomegaly. T1W1 images (C and D) showing multiple large hyperintense nodules in both lobes (arrows). Postcontrast T1W1 images in portal venous phase shows mild enhancement of these nodules (yellow arrows) (confirmed on subtraction images) with multiple other hypoenhancing nodules in both lobes (blue arrows). Venous phase images reveal abnormal configuration of the hepatic veins (arrows) with intrahepatic collaterals. Note stenosis of the IVC on coronal T1W1 images (arrows).

Fig. 9.12.34 A 32-year-old male with Budd–Chiari syndrome. T2W1 images (A and B) show hepatomegaly with changes of cirrhosis and gross ascites. Postcontrast T1W1 images (C and D) showing marbled pattern of enhancement (arrows). Postcontrast coronal T1W1 image showing stenosis of IVC (arrows) and axial images showing ostial stenosis of MHV and LHV (arrows). Fig. 9.12.35 Venous changes in Budd–Chiari syndrome. Axial images showing thrombosis of right hepatic vein (blue arrows). Multiple intrahepatic collaterals are seen with abnormal configuration (arrows in E). Stenosis of IVC is seen because of enlarged caudate lobe (arrows in F and G). Fig. 9.12.36 T2W1 (A) and postcontrast venogram images (B–D) showing nonvisualization of hepatic veins with multiple intrahepatic collaterals (arrows in B and C). Coronal image (D) showing mild compression over intrahepatic IVC (arrows). Fig. 9.12.37 Contrast-enhanced CT in Budd–Chiari syndrome. Contrast-enhanced CT showing multiple peripherally enhancing nodules in left lobe of liver (biopsy-proven regenerating nodules), heterogeneous enhancement of the liver is seen with stenosis at RHV insertion (arrows). Rest of the hepative veins are not seen. Fig. 9.12.38 Case of chronic Budd–Chiari syndrome with multiple HCC. Contrast-enhanced CT in arterial phase (A,B) showing cirrhotic liver with large neovascular lesions in left lobe and segment 7 (arrows). Venous phase images (C–G) shows nonvisualization of hepatic veins with stenosis of IVC (arrows in D,F,G). Note heterogeneous enhancement of the liver with marbled appearance the result of longstanding venous occlusion. Fig. 9.12.39 BCS secondary to HCC with tumour thrombus in IVC and hepatic veins. Contrast-enhanced CT in the late arterial phase shows ill-defined heterogeneous lesion in segment 4a and 8 (yellow arrows) invading into the lumen of the hepatic veins (blue arrows). Resultant enhancing thrombus is seen

extending up to the right atrium (blue arrows in C and D). The liver shows heterogeneous enhancement. Fig. 9.12.40 Passive hepatic congestion. Contrastenhanced CT in arterial phase (A,B) shows reflux of contrast from the right atrium into the IVC and hepatic veins (arrows). The liver is enlarged in size and shows mottled enhancement pattern called nutmeg liver (arrows). Associated cardiomegaly is seen (arrows in D). Fig. 9.12.41 Posttransplant IVC obstruction. Contrastenhanced CT in a patient with history of liver transplantation shows filling defect in hepatic vein (arrows). An air containing abscess is seen adjacent to the cut surface of liver (yellow arrow). Fig. 9.12.42 Olser–Weber–Rendu syndrome. K/c/o Osler–Weber–Rendu syndrome showing well-defined intensely enhancing lesion in segment 8, which likely represents nodular regenerative hyperplasia (arrows in A and B). Gross aneurysmal dilatation of the splenic vein is seen, the result of arteriovenous shunting (arrows in C and D). Note the dilated tortuous splenic artery (blue arrows in E). Flowchart 9.12.1 Portal vein atresia/stenosis. Flowchart 9.12.2 Congenital extrahepatic portosystemic shunt (Abernethy malformation). Flowchart 9.12.3 Liver lesions in Abernethy. Flowchart 9.12.4 Portal venous thrombosis leads to development of cavernoma. These extensive portoportal collaterals develop in an attempt to preserve hepatopetal flow. The collaterals are formed via the two wellformed venous plexi of the bile ducts: paracholedochal and epicholedochal plexi of Petren and Saint, respectively. These collaterals are however, insufficient to bypass the entire splenomesenteric inflow resulting in development of portal hypertension with formation of portosystemic shunts (primarily via the left gastric vein and the perisplenic veins) and splenic enlargement. Since portal hypertension occurs in the presence of a

functionally and morphologically normal liver it is termed noncirrhotic portal hypertension. Flowchart 9.12.5 Pathophysiology of BCS. Fig. 9.14.1 Types of portal vein thrombosis and their management for liver transplant. Fig. 9.14.2 Acute PV and SMV bland thrombus in a patient with chronic liver disease. Fig. 9.14.3 T2 hyperintense filling defect in the right portal vein causing its distension (arrowhead in A) and arterial hyperenhancement (arrow in B) consistent with a tumour thrombus. Fig. 9.14.4 Case of biliary atresia with severely attenuated entire extrahepatic PV (blue arrow head) and a good calibre SMV. The other two images are postLDLT for the same patient coronal and sagittal sections with left lobe transplant and a jump graft seen between the PV to the SMV (arrows). Fig. 9.14.5 (A and B) Mesocaval shunt in a liver transplant recipient. (C) The shunt seen on the DSA with catheter tip seen in the shunt. (D) Preoperative closure of the shunt using the coils. Fig. 9.14.6 Normal position of TIPS seen in (C). (A) Superior end of shunt at the level of diaphragm (arrow). (B) Measurement of PV length proximal to the TIPS. Fig. 9.14.7 Image of significant celiac stenosis (straight arrow) with and fishhook appearance and prominent diaphragmatic crus (curved arrow). Fig. 9.14.8 Splenic artery aneurysm (arrow) near the splenic hilum measuring 18 mm in diameter seen on pretransplant evaluation. Fig. 9.14.9 (A and B) Arterially enhancing 2 lesions (3.4 and 4.4 cm in size) in liver showing subsequent wash-out in the 5 minutes delayed scans (C and D) suggestive of HCC. Two lesions, combined size 500 cm/s) on spectral waveforms. Also note prestenotic dilatation of cephalic vein (star). Fig. 10.18.3.8 Case of patent arteriovenous fistula where outflow cephalic vein filled with isoechoic thrombus (arrow) causing total occlusion (A). Colour Doppler shows absent flow in cephalic vein (B). Fig. 10.18.3.9 Maximum intensity projection (A) and volume-rendering (B) reconstructions showing patent radio-cephalic arteriovenous fistula (arrow) and severe narrowing of cephalic vein (arrowhead) cranial to fistula. Fig. 10.18.3.10 MIP images demonstrating patent brachiocephalic fistula (arrows) and cephalic vein showing multiple fusiform aneurysmal dilatations (arrowheads). Fig. 10.18.3.11 Cases of central venous thrombosis (A and B) and central venous compression by mass lesion (C and D). Thrombosis is shown as hypodense filling defects in the right internal jugular vein and SVC (white

arrow). (C and D) SVC (black arrows) compression by enhancing mass lesion (star). Fig. 10.18.3.12 MIP images of CT angiography in first (A) and second (B) run showing brachio-cephalic fistula with large pseudoaneurysm (arrow) arising from brachial artery just proximal to fistula. Fig. 10.19.1 Ureterovesical reimplantation (anterolateral bladder wall) an in right iliac fossa extraperitonially by creating submucosal tunnel for ureter to create non refluxing anastomosis. Fig. 10.19.2 Nephrostogram showing leak urinoma. ( Fig. 10.19.3 VCUG showing low grade reflux in left iliac fossa transplant. Fig. 10.19.4 Lymphocele causing mild hydronephrosis by compression. Fig. 10.19.5 Transplant kidney hydronephrosis due to thickened bladder which turned out to be bladder malignancy causing ureteric block. Fig. 10.19.6 (A and B) worsening HNdue to ureteric stricture post transplant. ( Fig. 10.19.7 (A–D) In same case, nephrostogram showing ureteric stricture (arrow) with balloon dilatation and antegrde stenting. Fig. 10.20.1 A 35-year-old female patient with beaded right renal artery secondary to fibromyscular dysplasia. Fig. 10.20.2 A 70-year-old patient with refractory hypertension and worsening renal function. (A) Extensively calcified right renal artery stenosis. (B) Angioplasty done with 4 × 10 mm balloon. (C) Renal artery stenting done with 6 × 15 mm balloon expandable bare metal stent through radial approach. Fig. 10.20.3 No-touch technique: It prevents the guide catheter from scraping the aortic wall, thereby minimizing the risk of atheroembolization. (A) A 0.035inch J tip guide wire is positioned through the guide catheter distally during initial engagement. It prevents the guide catheter from scrapping aortic wall. (B) When

the renal artery is engaged, a 0.014-inch wire is inserted alongside the 0.035-inch J wire and advanced into the target vessel. (C) Once the 0.014-inch wire is placed across the target lesion, the 0.035-inch wire is removed and angioplasty is done as per conventional method. Fig. 10.20.4 A 60-year-old patient with flash pulmonary edema and refractory hypertension presents for renal angiogram and stenting; Catheter in catheter technique: (A) Angiogram demonstrates 90% left renal artery stenosis. (B) Lesion crossed with hydrophilic wire and diagnostic catheter placed across the stenosis. (C) Guide catheter dottered over diagnostic catheter. (D) 6 × 18 mm balloon expandable bare metal stent is positioned across the stenosis. Fig. 10.21.1.1 Real-time USG-guided renal biopsy. Arrows pointing to the needle targeting the lower pole cortex. Fig. 10.21.1.2 Illustration showing cortical nontangential and tangential biopsy. Fig. 10.21.1.3 (A) USG screening of a graft kidney before the biopsy. (B) USG-guided trucut biopsy with cortical tangential approach. Arrows pointing to the needle trajectory. (C) Track embolization of the needle track by using gelfoam. Arrow shows gel foam along the needle track within the cortex. Arrow head shows gelfoam just outside the capsule with reverberation artefacts. (D–F) Transjugular renal biopsy. (D) Multipurpose catheter (arrow) within the renal vein to get a renal venogram. Arrow head points to the renal vein. (E) 10F sheath and metallic cannula (arrow) with the biopsy needle within. (F) Plunging of the biopsy needle (arrow) into the renal parenchyma. Fig. 10.21.1.4 Illustration showing the steps of the PCN procedure. (A) Puncture of the lower calyx with a needle. (B) A guidewire passed through the needle into the pelvicalyceal system. (C) A pigtail catheter that has been passed over the guidewire, with the holes within the collecting system.

Fig. 10.21.1.5 (A and B) CECT images with bilateral hydronephrosis. (C) Fluoroscopic image with bilateral PCN drainage tubes within the dilated collecting system. Fig. 10.21.1.6 (A) The patient draped in prone position for PCN, USG probe in a sterile covering. (B) The materials required for the postoperative changes are noted in the anterior abdominal wall and in the sternum. (C) Local anaesthesia being injected. (D) USG-guided puncture of the renal collecting system. (E and F) Wire inserted through the needle into the collecting system. (G and H) Fasical dilators over the guidewire. (I and J) Drainage catheter with stay sutures. Fig. 10.21.1.7 (A) DJ stent insertion within the graft kidney in the right iliac fossa. Urterogram done through the PCN drain showing leakage in the mid ureter with contrast extravasation (arrowhead). (B) Arrow shows insertion of 8F malecots drain. Fig. 10.21.1.8 Radio frequency ablation of the right renal exophytic renal cell carcinoma. (A) Enhancing exophytic cortical tumour. (B) The RFA probe within the lesion. (C) Postablation CT with completely ablated nonenhancing lesion. Fig. 10.21.2.1 Table depicting various postrenal transplant complications. Fig. 10.21.2.2 A 54-year-old male underwent renal transplant. (A and B) Patient presented with deranged renal function and Doppler scan demonstrated spectral broadening and tardus-parvus waveform, conventional angiogram showed a renal artery stenosis. (B) Coronal multiplanar CT angiogram shows nonfilling of the hepatic artery suggestive of hepatic artery thrombosis. (C and D) A balloon angioplasty was performed across the stenosis with follow up angiography run demonstrating good flow with relief of stenosis. Fig. 10.21.2.3 A 48-year-old female underwent renal transplant presenting with poor Doppler flow across the renal graft, reassessment of the graft on table showed features of dissection. (A) Dissection was demonstrated in the graft kidney. (B) Repeat balloon plasty was

performed which initially showed improvement with recurrence of the dissection flap. (C and D) A stent was placed with good flow established in the renal artery of follow-up run. Fig. 10.21.2.4 A 52-year-old male underwent renal transplant presenting with dull abdominal pain and poor urine flow. (A) Postcontrast CT axial sections shows hydronephrosis in the transplant kidney. (B and C) Percutaneous nephrostomy was performed on the transplant kidney, which demonstrated a distal ureteric stenosis, which was negotiated with a wire. (D) A balloon plasty was performed across the ureteric stricture. (E) Post balloon plasty, a ureteric stent was placed and a good flow was noted across the stent. No covering nephrostomy was placed. Fig. 10.21.2.5 A 43-year-old female underwent renal transplant presenting with renal function at 6 months. (A) Ultrasound scan of the transplant kidney shows hydrouretronephrosis. (B and C) A nonfunctioning ureteric stent was noted, a percutaneous nephrostomy was performed to improvise outflow of urine in the obstructed system. Fig. 10.21.2.6 Various types of perinephric fluid collections, their imaging findings and the various interventions. Fig. 10.22.1.1 This depicts the standard renal transplant anastomosis. The donor artery is anastomosed end-to-side to the CIA and the donor vein is anastomosed end-to-side to the CIV. Fig. 10.22.1.2 Main and accessory renal artery anastomosis to right exteranal illiac artery. Fig. 10.22.1.3 Dual kidney transplant in right illiac fossa. Fig. 10.22.1.4 Main and accessory renal artery combined anastomosis to right exteranal illiac artery. Fig. 10.22.1.5 Standard incision in the right iliac fossa for a renal transplant.

Fig. 10.22.1.6 If there are 3 renal arteries, then this is considered. One renal artery to the anterior division of the IIA, second renal artery to the posterior division of the IIA and the third renal artery to the inferior epigastric artery. Fig. 10.22.1.7 (A) Intraoperative photograph showing the transplanted live donor kidney with renal artery anastomosed end-to-end to recipient IIA (internal iliac artery) and renal vein anastomosed end-to-side to recipient EIV. The ureter is yet to be anastomosed to the bladder. (B) This intraoperative photograph shows live donor kidney where the lower polar artery was missed on a preop conventional angiogram leading to a surprise after harvest. The main renal artery was anastomosed end-to-end to IIA (black arrow) and the smaller polar artery was anastomosed end-to-side to the EIA. The renal vein was anastomosed to the EIV (blue arrow). Fig. 10.22.1.8 This intraoperative photograph in a live donor kidney shows the urine pulsing out of the cut end of the donor ureter as soon as the anastomoses are completed and the clamps are released. Fig. 10.22.2.1 Hutch diverticulum. A cystogram demonstrates reflux into the left ureter and a diverticulum adjacent to the ureter. Fig. 10.22.2.2 Postlaparoscopy pneumoperitoneum. Fig. 10.22.2.3 MRI showing complex vesico-rectovaginal fistula due to advance cancer cervix. Fig. 10.22.2.4 Sagittal T2-weighted image of a track between the dome of the bladder and sigmoid colon. Fig. 10.23.1.1 (A) CEUS enhancement of normal kidney. Cortical phase with the unenhanced pyramids and medulla appearing hypoechoic. (B) CEUS enhancement of normal kidney. Parenchymal phase with the enhancement of both cortex and medulla. The pelvicalyceal system (arrow) appears hypoechoic as the UCAs are not excreted by the kidneys. Fig. 10.23.1.2 (A) Column of Bertini. Conventional US shows an isoechoic mass in the interpolar region (arrow).

(B) Column of Bertini. The mass demonstrates identical enhancement to the cortex in the cortical and parenchymal phase (arrow). Fig. 10.23.1.3 Enhancing septum. A cyst with enhancing septum (arrow) is seen in the kidney of a patient with autosomal dominant polycystic kidney disease. Fig. 10.23.1.4 Complex cystic mass. Conventional US (left) shows a large complex cystic mass with thick enhancing septations (arrow) seen on right. Fig. 10.23.1.5 Renal cell carcinoma. A large necrotic mass is seen with thick enhancing walls (arrow) and nodular components (arrowhead). Fig. 10.23.1.6 (A) Renal metastasis. Conventional US reveals a well-defined isoechoic mass at the lower pole (arrow). (B) Renal metastasis. The lesion appears hypoenhancing on the parenchymal phase (arrow). Fig. 10.23.2.1 Schematic diagram of three different dual-energy CT systems. (A) Dual-source CT. (B) Rapid peak kilovoltage (kVp) switching CT. (C) Multilayer-layer CT. Fig. 10.23.2.2 (A) Image obtained at 80 kVp. (B) Image obtained at 140 kVp. (C) DE ratio calculated to be 1.6 suggestive of calcium containing calculus. Fig. 10.23.3.1 Different phases of CT urography. (A) Unenhanced plain CT scan showing hypodense renal parenchyma. (B) Nephrographic phase depicting differentiation of cortex and medulla with homogeneous enhancement of renal parenchyma. (C) Excretory/Urographic phase showing excreted contrast in renal pelvis and ureters. Fig. 10.23.3.2 Delayed CT urography images showing contrast-filled bladder also called as CT cystography. Images show diffuse bladder wall thickening with multiple diverticula. Fig. 10.23.3.3 Reconstructed MIP (A) and VRT (B) of expiratory phase demonstrating right-sided double ureters.

Fig. 10.23.3.4 (A) Suspicious left upper uretriic calculus, which is very well confirmed on excretory urography phase with VRT (C) and MIP (D) reconstruction, showing partial obstruction. (B) shows nonobstructing lower polar right renal calculus. Fig. 10.23.3.5 (A) Axial image showing some small rounded calcific foci with surrounding soft tissue rim sign suggesting right distal ureteric calculus. (B) A calculus is demonstrated on coronal images in the right distal surface ureter. Fig. 10.23.3.6 (A and B) Enhancing intraluminal lobulated soft tissue lesion along lateral wall of bladder suggesting transitional cell carcinoma. (C) Resultant moderate dilatation of right-sided upper ureter and pelvicalyceal system with incidentally found right-sided double moiety. Fig. 10.23.3.7 (A and B) Large heterogeneously enhancing lesion is noted arising from anterior portion of interpolar region of right kidney suggesting neoplastic aetiology. Fig. 10.23.3.8 (A and B) Peripherally enhancing perinephric hypodense collection on left side suggestive of renal abscess. (C) Coronal MIP image shows multiple nonobstructing right lower pole calyceal calculi. Fig. 10.23.3.9 (A and B) Nonenhanced plain CT scan of renal fossa reveals multiple left renal calyceal calculi. Fig. 10.23.4.1 Coronal MIP reconstruction of excretory MRU showing normal appearances of kidneys, ureters and bladder. Fig. 10.23.4.2 (A) Static fluid MR urography in a patient with left vesicoureteric junction calculus and resultant hydronephrosis and hydroureter on left side. (B) Postprocessed image in the same patient after removing fluid in bowel, spinal canal and biliary tract. Fig. 10.23.4.3 Normal MR renogram. (A) T2W coronal image of the abdomen showing placement of ROIs around both kidneys. (B) Signal intensity versus time curves obtained for both kidneys.

Fig. 10.23.4.4 (A to D) MRI in a patient with bladder carcinoma (black arrow in A and B and white arrow in (C). (A) Precontrast and (B) postcontrast T1 SPGR axial images of the bladder showing mass lesion with extension beyond the vesical wall and with involvement of the right ureteric orifice. (A) DWI-b1000 image showing hyperintensity within the mass and the corresponding area in (D) ADC image is hypointense. Fig. 10.23.4.5 (A) Static fluid MRU with (B) MIP reconstruction showing pelviureteric junction obstruction (white arrow) on left side and extra renal pelvis on the right side. Fig. 10.23.4.6 (A) T2 coronal and (B) T2 axial images showing a mass (black arrow) in left renal collecting system in a 44-year-old male patient who presented with haematuria. DWI (C) and ADC (D) images of the lesion show restriction of diffusion. HPE proved the lesion to be a transitional cell carcinoma. Fig. 10.23.4.7 (A) Static fluid MRU with (B) MIP reconstruction showing significantly distended bladder with bilateral Grade V vesicoureteric reflux in a patient with neurogenic bladder. Fig. 10.23.4.8 Static fluid MRU in a pregnant patient showing calculus seen as a filling defect in the right renal pelvis (white arrow) and a partially duplicated collecting system in the left kidney. Flowchart 10.23.2.1 Characterisation of renal lesions in iodine density display. Fig. 11.1.1.1 (A) Normally distended urinary bladder and prostate. (B) Polypoidal multiple lesions arising from opposing walls of urinary bladder (kissing lesions) transitional cell carcinoma. Fig. 11.1.1.2 (A) Bladder wall thickening (diffuse). (B) Bladder diverticulum (white arrows). Fig. 11.1.2.1 Sonogram of testis appearing as ovoid structure with intermediate echogenicity. Fig. 11.1.2.2 Epididymal head close relation to superior pole of testis.

Fig. 11.1.2.3 Mediastinum testis appearing as an echogenic band along the posteromedial border of testicle. Fig. 11.1.2.4 Appendix of testis, small isoechoic ovalshaped structure seen between epididymal head and testis (arrow). Fig. 11.1.3.1 (A) Transrectal scan shows an enlarged prostate gland in both sagittal and transverse planes. (B) same patient with enlarged prostate with calcification seen on a transabdominal scan. (C) Normal zonal anatomy of prostate. Fig. 11.1.3.2 (A) Prostatic enlargement shows a welldefined hyperechogenic nodule with multiple small retention cysts. (B) 3D of the enlarged prostate shows a slit like narrowed urethra in the centre. Fig. 11.1.3.3 (A) In prostatitis, colour Doppler shows hypervascularity within the enlarged prostate (B) cyst within the prostate. Fig. 11.1.3.4 (A) Hypoechoic lesion in the complete peripheral zone. (B) Increased flow on colour Doppler. Fig. 11.1.3.5 Scattered calcifications within the prostate are largely a benign feature. Fig. 11.1.3.6 (A) Mesh-like cystic mass in the peripheral zone, unchanged largely since last 5 years. (B) Amorphous hyperechogenic lesion involving the transitional and peripheral zone casting acoustic shadows. These lesions should be biopsied, since there is a high chance of CA prostate. Fig. 11.1.3.7 (A) TRUS shows prostate with an illdefined hypoechogenicity in the peripheral zone (B). Power Doppler shows increased flow in the same lesion. Fig. 11.1.4.1 Longitudinal scanning method. Fig. 11.1.4.2 Transverse views. Fig. 11.1.4.3 Demonstrating scanning method. Fig. 11.1.4.4 Demonstrating various patient positions for visualization of ovaries.

Fig. 11.1.4.5 A and B show the measurement technique for uterus. Fig. 11.1.4.6 Demonstrating (A) anteversion– anteflexion; (B) anteversion–retroflexion; (C) retroversion–anteflexion; (D) retroversion–retroflexion. Fig. 11.1.4.7 (A–D) Various stages of endometrium. Fig. 11.1.4.8 (A,B) Endometrium and endomyometrial junction. Fig. 11.1.4.9 (A) Postacoustic enhancement. (B) Sidelobe artefact. (C) Posterior acoustic shadowing. Fig. 11.1.4.10 Systolic and diastolic component of a wave. Fig. 11.1.5.1 Transvaginal sonography (TVS) – endovaginal probe is inserted through the vagina. Fig. 11.1.5.2 Transvaginal probe. Fig. 11.1.5.3 TVS image of uterus. Fig. 11.1.6.1 (A) 3D USG of normal uterus. (B) 3D USG of septate uterus. (C) 3D USG of arcuate uterus. (D) 3D USG of unicornuate uterus. Fig. 11.1.6.2 3D USG multiplanar reconstruction of uterus. Fig. 11.1.6.3 3D USG image of volume contrast imaging (VCI). Fig. 11.1.6.4 3D USG image of junctional zone of uterus. Fig. 11.1.6.5 3D USG image of endometrial polyp (arrow). Fig. 11.1.6.6 3D USG image of saline infusion sonography (SIS). Fig. 11.1.6.7 3D USG image of saline infusion sonography (SIS) showing synechiae. Fig. 11.1.6.8 3D USG image of fibroid uterus showing vascularity. Fig. 11.1.6.9 3D USG image of perifollicular angiogenesis.

Fig. 11.1.6.10 3D USG image of calculation of endometrial volume. Fig. 11.1.6.11 3D USG image of calculation of ovarian volume. Fig. 11.1.6.12 (A) 3D USG image of calculation of endometrial flow. (B) 3D USG image ofcalculation of ovarian flow. Fig. 11.1.6.13 (A) 3D USG image of SonoAVC technique. (B) 3D USG image of SonoAVC report. Fig. 11.1.6.14 3D USG image of threshold volume. Fig. 11.1.6.15 (A) 3D USG image of TUI sagittal sections. (B) 3D USG image of TUI coronal sections. (C) 3D USG image TUI axial sections. Fig. 11.1.6.16 (A) 3D USG surface rendering image of pelvic floor. (B) 3D USG volume contrast imaging (VCI) of pelvic floor. Fig. 11.1.7.1 Hysterosalpingogram showing normal uterine cavity and bilateral fallopian tube with peritoneal spill on both sides. Fig. 11.1.7.2 Hysterosalpingogram showing leftward shift of uterus and stretched right tube due to a right broad ligament fibroid. Fig. 11.1.7.3 (A). Hysterosalpingogram showing abnormal-shaped uterus with partial visualization of fundus due to inadequate traction of cervix. (B). With traction the uterus looks normal. Fig. 11.1.7.4 Hysterosalpingogram showing narrow cervical canal. The cavity is small and the upper uterine segment is short giving ‘T’ configuration. Fig. 11.1.7.5 Hysterosalpingogram showing mild smooth indentation of fundal endometrial cavity. Fig. 11.1.7.6 Hysterosalpingogram showing complete septate uterus. Fig. 11.1.7.7 Hysterosalpingogram showing filling defect in right cornual region corresponds to endometrial polyp.

Fig. 11.1.7.8 Hysterosalpingogram showing filling defect in fundal region and along right lateral wall projecting into the cavity due to multifocal adenomyoma. Fig. 11.1.7.9 Hysterosalpingogram showing right tubal and cornual polyp causing tubal block. Fig. 11.1.7.10 Hysterosalpingogram showing filling defect in cervical canal due to linear cervical polyp. Fig. 11.1.7.11 Hysterosalpingogram showing filling defect in lower uterine cavity extending into the upper cervical canal due to fibroid polyp. Fig. 11.1.7.12 Hysterosalpingogram showing filling defect in the fundus and lower uterine cavity due to synechiae. Fig. 11.1.7.13 Hysterosalpingogram showing filling defects in right cornual region and endometrial irregularity. Focal multiple linear extravasation of dye into the adenomyosis glands in fundus due to diffuse uterine adenomyosis. Fig. 11.1.7.14 Hysterosalpingogram showing small cavity uterus with dilated blind ending right fallopian tube pooled with contrast and no peritoneal spill. The left tube shows beaded appearance with peritoneal spill. These features are suggestive of bilateral postinfective or inflammatory tubal pathology. Fig. 11.1.7.15 Hysterosalpingogram showing bilateral tubal occlusion at the level isthumus. Posttubal ligation status. Fig. 11.1.7.16 Hysterosalpingogram showing salpingitis isthmica nodosa of right tube which is narrowed and there is no peritoneal spill. Also noted is irregular endometrial surface and airpockets in fundus. Fig. 11.1.7.17 Hysterosalpingogram showing pooling of spilled contrast in left side due to peritubal adhesions. Fig. 11.1.7.18 Hysterosalpingogram showing venous intravasation of contrast in left side. Fig. 11.1.7.19 Hysterosalpingogram showing stretched left fallopian tube due to left ovarian cyst.

Fig. 11.1.7.20 Hysterosalpingogram showing extravasation of dye into previous caesarean scar. Fig. 11.1.8.1 Sonosalpingogram showing echogenic nodular polyp along the posterior wall. Fig. 11.1.8.2 Sonosalpingogram showing nodular polyps along the anterior and posterior wall. Fig. 11.1.9.1 MR HSG of 31 years nullipara with previous history of two spontaneous first trimester abortions showing bilateral tubal spill. (A) Coronal T1 CUBE phase 2 image showing contrast within uterine cavity and bilateral fallopian tubes. (B) Coronal T1 CUBE phase 3 image showing bilateral peritoneal spill. (C) Subtracted images reformatted showing contrast within endometrial cavity and bilateral peritoneal spill. (D) Conventional HSG showing uterine cavity, bilateral peritoneal spill. Fig. 11.1.9.2 30 years old, MRHSG done for posttubal reanastamosis status. (A) Coronal T2W image with balloon catheter placed in situ just beyond the level of internal os. (B) Coronal T1 CUBE phase 1 image prior to the instillation of 1:100 gadodiamide in saline. (C) Coronal T1CUBE phase 2 image showing contrast within the endometrial cavity, absence of peritoneal spill on both sides, reflux of contrast in the vagina. (D) Subtracted images reformatted showing contrast within endometrial cavity and absence of peritoneal spill, reflux of contrast in the vagina. (E) Conventional HSG showing uterine cavity and bilateral tubal block. Fig. 11.1.9.3 MR HSG of 35 years for secondary infertility with suspected hydrosalphinx showing the entire blocked bilateral fallopian tubes and confirms that is an ovarian cyst and not hydrosalphinx. (A) Axial and sagittal T2W images showing T2 hyperintense oblong cystic lesion in right adnexa with few internal septations mimicking right hydrosalphinx. (B) Coronal T1 CUBE images. Phase 2 showing left tube and Phase 3 showing right tube and absence of peritoneal spill. (C) Subtracted reformatted images showing bilateral tubes and distal block and no peritoneal spill, refluxed contrast in the

vagina. (D) Conventional HSG showing bilateral fimbrial block and no peritoneal spill. Fig. 11.1.9.4 25 years P2L1, posttubal reanastamosis status showing left tubal spill. (A) Subtracted reformatted image showing uterine cavity. (B and C) Subtracted reformatted image showing left tubal spill and corresponding conventional image showing left tubal spill. Fig. 11.1.10.1 CT image reproduces a cross section of the part of the body under study. Fig. 11.1.10.2 In multislice CT, several independent detectors arranged side by side. The required data are sampled from locations within the X-ray beam. Fig. 11.1.11.1 MRI axial view of the cervix. Fig. 11.1.11.2 MRI axial view of the uterus. Fig. 11.1.11.3 Sagittal of the uterus. Fig. 11.1.11.4 Coronal of the uterus. Fig. 11.1.11.5 Axial of the vagina. Fig. 11.1.12.1 Maximum intensity projection (MIP) image showing diffusely increased 18F-FDG uptake in colon in a patient on Tab. metformin. Fig. 11.1.12.2 Maximum intensity projection (MIP) images of 18F-FDG (A) and 68Ga PSMA PET (B) showing physiological uptake. Fig. 11.1.12.3 Tracer (68Ga PSMA) excreted in left ureter (arrow) mimicking as a lymph node in a case of cancer prostate. Fig. 11.1.12.4 Renal cell carcinoma of left kidney. Exophytic mass (asterisk) with heterogeneous enhancement in lower pole of the left kidney (A) showing mild FDG uptake. Fig. 11.2.1.1 Ultrasound image of normal testis with hyperechoic mediastinum testis (M). Fig. 11.2.1.2 (A and B) Ultrasound image of head (H), body (B) and tail (Ta) regions of epididymis.

Fig. 11.2.1.3 Ultrasound image of cord structures (C) at the level of inguinal canal. Fig. 11.2.1.4 (A) MR T2 and (B) T1 images of testis (T), showing the homogeneous hyperintense signals of testis in T2 and hypointense in T1-weighted sequences. Fig. 11.2.1.5 MR images of epididymis (E). (A) T1weighted image and (B) T2-weighted image. Fig. 11.2.1.6 Ultrasound prostate. (A) Transabdominal and (B) TRUS images. Fig. 11.2.1.7 T2-weighted MR image of prostate showing peripheral (P) and central (C) glands with hypointense capsule (Ca – arrow). Fig. 11.2.1.8 TRUS image showing bow tie appearance of seminal vesicle (SV). Fig. 11.2.1.9 MR images of SVs. (A) T1-weighted image and (B) T2-weighted image. Fig. 11.2.1.10 T2-weighted MR image of vas deferans (VD) and ampulla of vas (A). Fig. 11.2.1.11 US image of penis showing paired corpora cavernosa (Cc) and corpora spongiosum (Cs). Fig. 11.2.1.12 T2-weighted MR images of penis showing paired corpora cavernosa (Cc) and corpora spongiosum (Cs). Fig. 11.2.2.1 (A) Sagittal and (B) axial ultrasound images of female pelvis shows uterus and cervix with thick echogenic endometrium (arrow). Fig. 11.2.2.2 Normal uterus and ovaries. (A) Axial CT image showing normal uterus (white arrow) and bilateral ovaries (yellow arrows). (B) Sagittal CT image showing normal uterus (red arrow). (C) Coronal CT images showing normal uterus (red arrow) and bilateral ovaries (yellow arrows). Fig. 11.2.2.3 Normal uterus and ovaries. (A) Axial T2-weighted MR image showing normal uterus (red arrow) and bilateral ovaries (yellow arrows). (B)

Sagittal T2-weighted image showing normal uterus (yellow arrow) and ovary. Fig. 11.2.2.4 Ultrasound image showing normal ovary with anechoic follicles and echogenic stroma. Fig. 11.2.2.5 Sagittal T2-weighted MR image shows normal ovary with hyperintense follicles and hypointense capsule. Fig. 11.2.3.1 Diagrammatic representation of axial section through foetal abdomen. Parietal peritoneum is shown in blue, visceral peritoneum in green and body wall in brown. LIV: liver develops in ventral mesogastrium; S: spleen develops in dorsal mesogastrium; G: gut; RP: retroperitoneum. Fig. 11.2.3.2 Axial contrast-enhanced CT (CECT) abdomen in a woman with tuberculous peritonitis. Visceral peritoneum is shown in green and parietal peritoneum in blue colour. Greater omentum is outlined in yellow and shows nodular infiltration. Fig. 11.2.3.3 Longitudinal sonogram through liver in a patient with portal hypertension shows recanalized umbilical vein (UMBV.) running along the free edge of falciform ligament (FL). Fig. 11.2.3.4 Transverse section through upper abdomen in patient with ascites shows gastrohepatic ligament (GHL) outlines above and below by fluid in the greater and lesser sacs, respectively. Fig. 11.2.3.5 Transverse USG image through upper abdomen shows gastrohepatic ligament (GHL) extending from stomach (STO) to insert into fissure for ligamentum venosum (FLV). Fissure for ligamentum teres (FLT). Fig. 11.2.3.6 Axial section plain CT through the epigastrium shows inflamed pancreas within the anterior pararenal space (APS). Inflammation also is seen tracking into through transverse mesocolon (TMC) into transverse colon (TC). Fig. 11.2.3.7 Coronal MPR in a woman with ascites. Observe that the right perihepatic spaces (RPHS) are

continuous inferiorly with the right paracolic space (RPCS) and communicate with the pelvis. On the left side, the sigmoid mesocolon (SMC) separates the left paracolic space from the pelvis. Fig. 11.2.4.1 Agenesis of prostate. (A) Axial T2weighted MR image shows an empty prostate fossa. (B and C) Coronal and sagittal T2-weighted MR images show the absence of prostate around the prostatic urethral segment. Fig. 11.2.4.2 Prostatic utricle cyst. (A) Axial T2weighted MR image shows a hyperintense midline cyst in the prostate. (B) Sagittal T2-weighted MRI shows the cyst not extending above the base of prostate. Fig. 11.2.4.3 Müllerian duct cyst. (A) Axial STIR MR image shows a hyperintense midline cyst in the prostate. (B and C) Coronal and sagittal STIR MRI shows the cyst extending above the base of prostate. Fig. 11.2.4.4 Seminal vesicle cyst. (A to C) Axial, coronal and sagittal T2-weighted MR images show a hyperintense cyst in the left seminal vesicle. Fig. 11.2.4.5 Various Cysts in prostate and seminal vesicle. Fig. 11.2.6.1 Posterior urethral valve types. Fig. 11.2.6.2 Effman classification of urethral duplication. Fig. 11.2.6.3 Megalourethra types. Fig. 11.2.6.4 Hypospadias and epispadias. Fig. 11.3.1 First, the sagittal image of the uterus is taken. Length is measured from the outer margin of the fundus up to the external os of the cervix. Depth (anteroposterior diameter) is measured from the most anterior to the posterior margin of the uterine walls perpendicular to the length. The probe is then rotated 90 degrees to the sagittal plane. In transverse image, the maximum width of the uterus is measured. Fig. 11.3.2 Transvaginal ultrasound images showing the endometrium in various stages of menstrual cycle. (A)

Menstrual phase, (B) proliferative phase, (C) LH and ovulatory phase, (D) secretary phase and (E) postmenopausal endometrium. Fig. 11.3.3 Transvaginal ultrasound showing the technique of measuring the endometrium. Fig. 11.3.4 Ovarian volume measurement is performed using the simplified formula for a prolate ellipsoid: Ovarian volume = length × width × thickness × 0.5. Fig. 11.3.5 Ultrasound image showing the technique of measuring the (A) ovarian area and (B) stromal area. Fig. 11.3.6 Transabdominal ultrasound image showing enlarged multifollicular ovary with normal stroma. Fig. 11.3.7 Transabdominal ultrasound image showing dilated periuterine and paraovarian veins measuring 6 mm in maximum diameter. Fig. 11.3.8 Transabdominal ultrasound image showing the left fallopian tube. Fig. 11.3.9 Schematic representation showing distinction between septate and bicornutate uterus. The technique can be used in 3D ultrasound and MRI. Fig. 11.3.10 Schematic representation showing distinction between septate and bicornutate uterus based on intercornual angle. Fig. 11.3.11 Technique to measure the volume of the testis. Fig. 11.3.12 Longitudinal and transverse images of the testes showing atrophy. Fig. 11.3.13 B-mode scrotal ultrasound image of the testis in transverse and longitudinal sections showing few echogenic foci of 1–2 mm size without posterior acoustic shadowing suggestive of limited type of testicular microlithiasis. Fig. 11.3.14 The transverse diameter is measured in the axial plane and the anteroposterior and longitudinal diameters are measured in sagittal plane.

Fig. 11.3.15 Midsagittal image of the prostate showing the technique to measure the intravesical prostatic protrusion. Fig. 11.3.16 Grey scale ultrasound preinjection and postinjection images of corpora cavernosa showing dilation of the cavernosal artery following intracavernosal injection of papaverine. Fig. 11.3.17 (A) Penile Doppler ultrasound of the cavernosal artery shows normal PSV of 40 cm/s at 10 min postinjection indicating normal arterial flow. (B) Penile Doppler ultrasound of the cavernosal artery shows normal diastolic reversal at 15 min postinjection ruling out venous insufficiency. Fig. 11.3.18 Arterial dysfunction – Penile Doppler ultrasound image 15 min postinjection shows reduced PSV (20 cm/s) in the cavernosal artery. Fig. 11.3.19 Venous dysfunction – Penile Doppler ultrasound image 20 min postinjection shows elevated EDV (11 cm/s) in the cavernosal artery. Fig. 11.3.20 (A) TRUS transverse image at the level of the seminal vesicles shows bilateral normal size symmetric seminal vesicles with normal echotexture and wall thickness. (B) TRUS oblique image showing the distal aspect of right vas deferens with normal diameter and wall thickness. Fig. 11.3.21 TRUS parasagittal image showing dilatation of the right ejaculatory duct up to the verumontanum, which developed as a sequelae of seminal vesiculitis. Fig. 11.3.22 TRUS image at the level of seminal vesicles showing bilateral dilated seminal vesicles with wall thickening (⇐) and fluid of increased echogenicity (⇓) within the dilated seminal vesicles. Fig. 11.3.23 TRUS axial image at the level superior to the prostate showing absent left (⇐) and hypoplastic right seminal vesicle (⇓). Fig. 11.3.24 (A) Scrotal ultrasound B mode image showing dilated intrascrotal veins near the inferior pole

of the testis measuring 3 mm in diameter. (B) Scrotal ultrasound colour Doppler image with the patient performing valsalva manoeuvre showing reflux in the dilated intrascrotal veins. Fig. 11.3.25 Scrotal ultrasound colour Doppler image with the patient performing valsalva manoeuvre showing peak reflux velocity. Fig. 11.4.1.1 Plain radiograph showing soft tissue opacity in the midline of pelvis (marked in yellow colour) – distended bladder. Fig. 11.4.1.2 Ultrasonogram showing septations within the cyst (A), anechoic cyst without septation (B), septal vascularity (C) and soft tissue component with vascularity (D). Fig. 11.4.1.3 USG shows anenchoic fluid-filled structure in the midline of pelvis. Ureteric jet visualized in grey scale (arrow) and colour Doppler (arrowhead) imaging. Fig. 11.4.2.1 Imaging differential diagnosis of pelvic masses. Fig. 11.4.2.2 Stepwise imaging approach for diagnosis and characterization. Fig. 11.4.2.3 A 53-year-old female with large abdominopelvic mass lesion on USG. T2-weighted MRI images of pelvis. Figure B demonstrates Localization: Both the ovaries are seen separate from the mass (black arrows). Claw sign – the mass was seen attached to the left lateral wall of uterus with uterine parenchyma draping around its base (arrowheads). Bridging vessel sign – multiple vessels are seen as flow voids traversing from the uterine wall into the mass (white arrows). Characterization: The lesion is solid and has predominantly T2 hypointense signal with cystic degeneration. Probable diagnosis: Uterine fibroid with cystic degeneration. Final diagnosis: Uterine fibroid with cystic degeneration. Fig. 11.4.2.4 A 33-year-old female with indeterminate mass on USG. Localization: Both the uterus (star) and the right ovary (arrow) are seen separately from the

mass. Ovarian beak sign: There is splaying of the left ovarian parenchyma around the inferior surface of the mass (white arrows). Draining vessel sign: Left gonadal vein is seen draining the mass shown on sagittal post gadolinium image (arrowheads). Characterization: The lesion is solid and has predominantly T2 hypointense signal with heterogeneous enhancement on delayed images. Probable diagnosis: solid lesion left ovarian lesion with T2 hypointensity likely fibroma/thecoma. Final diagnosis: Benign sex cord stromal tumour – fibroma. Fig. 11.4.2.5 A 77-year-old postmenopausal female with indeterminate mass in pouch of Douglas on USG. Localization: There is a dumb-bell-shaped mass in the pouch of Douglas with unclear/lost interface with the posterior uterine wall (arrow) and intraluminal rectal component (star). DWI: The lesion is clearly seen to be separate from the uterus on DWI image. The lost fat plane on T2 image is due to oedema in the peritumoral fat. Characterization: The lesion is solid and has hyperintense signal on T2. Probable diagnosis: Rectal carcinoma. Final diagnosis: Rectal carcinoma. Fig. 11.4.2.6 A 25-year-old female with indeterminate right adnexal lesion on USG. Localization: Both the ovaries and the uterus (black star) are seen separate from the mass. The mass lies in presacral space displacing the rectum towards left and anteriorly (white star). Characterization: The lesion is cystic with nodular enhancement at the periphery (arrow). No fat/calcification was seen on CT (not shown here). No bony erosions/intra foraminal extension is noted. Probable diagnosis: Presacral cystic tumour likely schwannoma with cystic degeneration. Final diagnosis: Schwannoma. Fig. 11.4.3.1 Irregular hypoechoic lesion arising from the posterior wall. Separate fat plane seen between prostate and the mass (yellow arrow). Fig. 11.4.3.2 Large irregular isoechoic hanging bladder mass from right lateral wall of the urinary bladder.

Fig. 11.4.3.3 Enlarged prostate with intravesicle enlargement of median lobe. Fig. 11.4.4.1 A 42-year-old female with lower abdomen pain. Axial T2WI (A and B) shows hypointense mass in right adnexa (red arrow) with nonvisualization of right ovary – phantom sign. Normal (C) left ovary (yellow arrow) noted. Fig. 11.4.4.2 Axial CECT (A) shows a large abdominopelvic heterodense mass with heterogenous enhancement. Coronal (B) and sagittal (C) MIP image reveals asymmetric dilated ipsilateral right gonadal vein draining into IVC proximally and terminating in the mass distally – ovarian vascular pedicle sign. Fig. 11.4.5.1 Tubular folded ‘S’-shaped (A) and ‘C’shaped (B) hydrosalpinx with incomplete septae (white arrows) in two different patients with pelvic inflammatory disease. A short linear projection (curved arrow) is also seen (A). Fig. 11.4.5.2 ‘Waist sign’ (arrows) in hydrosalpinx in a 46-year-old lady, post hysterectomy (A) and in a 32year-old lady with endometriosis (B). Waist sign within a tubular cystic adnexal lesion is representative of hydrosalpinx. Fig. 11.4.5.3 (A) Hydrosalpinx in a 33-year-old lady with endometriosis shows a small eccentric echogenic focus protruding along the wall protruding into the lumen (white arrow) and internal echoes. (B) Spinal T2WI of the same patient shows septae (black arrows) Fig. 11.4.5.4 ‘S’-shaped and ‘C’-shaped configuration of hydrosalpinx in a 39-year-old lady. Axial T2WI (A) shows an ‘S’ shaped tubular folded left adnexal cystic lesion with the same lesion appearing ‘C’ shaped coronal (B) and sagittal (C) sections. Incomplete septae are present (arrows). (C) Ipsilateral ovary is seen separately in the sagittal plane (curved arrow in C). Fig. 11.4.5.5 Ovarian cyst mimicking hydrosalpinx – Axial (A), Coronal (B) and Sagittal (C) section in a 42year-old lady with abnormal uterine bleeding shows a mildly elongated cystic left adnexal lesion with an

incomplete septa (arrows). Final diagnosis following surgery and HPE – benign ovarian serous cystadenoma. Fig. 11.4.5.6 Complex ovarian cyst mimicking haematosalphinx – USG (A and B) and MRI (C–F) in a 37-year-old lady with complaints of pelvic pain and dyspareunia showed a complex cystic adnexal lesion with incomplete septae (arrows). Extensive internal echoes with an echogenic component (arrowhead) were seen on USG. The contents of the cyst were hyperintense on T2WI (C and D), T1WI (E) and FST1WI (F). No solid components identified. Imaging findings favoured haematosalpinx rather than mucinous or haemorrhagic complex ovarian cyst. Final diagnosis following surgery and HPE was benign mucinous cystadenofibroma of the left ovary. Incidentally on the follicles in the left ovary also appeared hyperintense on T2WI, T1WI and FST1WI (curved arrows). Fig. 11.4.7.1 Schematic diagram for differentiation of ovarian torsion and OHSS. Fig. 11.4.8.1 Young female patient with pelvic pain. MR images demonstrate a T2 STIR hyperintense cyst in the vagina, a classic location for a Gartner’s duct cyst. Fig. 11.4.8.2 A 25-year-old female who underwent LSCS 8 weeks back presented with complaints of pain at scar site. Diffusion restricting T1 hypointense/T2 hyperintense cystic lesion with fluid levels noted in upper vagina above the level of pubic symphysis – infected Gartner’s duct cyst. Fig. 11.4.8.3 Well-circumscribed oval-shaped anechoic cyst noted in lower vagina close to labia – Bartholin’s gland cyst. Fig. 11.4.8.4 A 33-year-old female with complaints of perineal pain and fever. Diffusion restricting T1 hypointense, T2 STIR hyperintense thick-walled collection with surrounding inflammatory changes noted in left posterolateral wall of lower vagina – Bartholin’s gland abscess. Fig. 11.6.1 Formation of the genital ridge. A. A 3-week embryo showing the primordial germ cells in the wall of

the yolk sac close to the allantois. B. Migrational path of the primordial germ cells along the wall of the hindgut and the dorsal mesentery into the genital ridge. Fig. 11.6.2 Transverse section through the lumbar region of a 6-week embryo showing the indifferent gonad with the primitive sex cords. Some of the primordial germ cells are surrounded by cells of the primitive sex cords. Fig. 11.6.3 A. Transverse section through the testis in the 8th week, showing the tunica albuginea, testis cords, rete testis and primordial germ cells. B. Testis and genital duct in the 4th month. The horseshoe-shaped testis cords are continuous with the rete testis cords. Note the ductuli efferentes (excretory mesonephric tubules), which enter the mesonephric duct. Fig. 11.6.4 Transverse section of the ovary at the 7th week. In the absence of SRY, the somatic support cells differentiate into follicle cells. These cells surround the oocytes to form primordial follicles, which tend to localize to the outer cortical region of the ovary. The excretory mesonephric tubules (efferent ductules) do not communicate with the rete. Fig. 11.6.5 Genital ducts in the 6th week in the male (A) and female (B). The mesonephric and paramesonephric ducts are present in both. Note the relation of excretory tubules of the mesonephros with the developing gonad in both sexes. Fig. 11.6.6 A. Genital ducts in the male in the 4th month. Cranial and caudal (paragenital tubule) segments of the mesonephric system regress. B. Genital ducts after descent of the testis. Note the horseshoe-shaped testis cords, rete testis and efferent ductules entering the ductus deferens. The paradidymis is formed by remnants of the paragenital mesonephric tubules. The paramesonephric duct has degenerated except for the appendix testis. The prostatic utricle is an outpocketing from the urethra. Fig. 11.6.7 Development of the seminal vesicles, prostate and bulbourethral glands. These glands are

induced by androgens between the 10th and 12th weeks. Fig. 11.6.8 A. Genital ducts in the female at the end of the second month. Note the paramesonephric (Müllerian) tubercle and formation of the uterine canal. B. Genital ducts after descent of the ovary. The only parts remaining from the mesonephric system are the epoophoron, paroophoron and Gartner’s cyst. Note the suspensory ligament of the ovary, ligament of the ovary proper and round ligament of the uterus. Fig. 11.6.9 Formation of the uterus and vagina. A. 9 weeks. Note the disappearance of the uterine septum. B. At the end of the 3rd month. Note the tissue of the sinovaginal bulbs. C. Newborn. The fornices and the upper portion of the vagina are formed by vacuolization of the paramesonephric tissue, and the lower portion of the vagina is formed by vacuolization of the sinovaginal bulbs. Fig. 11.6.10 Sagittal sections showing formation of the uterus and vagina at various stages of development. A. 9 weeks. B. End of 3rd month. C. Newborn. Fig. 11.6.11 The external genitalia form from a pair of labioscrotal folds, a pair of urogenital folds and an anterior genital tubercle. Male and female genitalia are morphologically indistinguishable at this stage. Fig. 11.6.12 In males, the urogenital folds fuse and the genital tubercle elongates to form the shaft and glans of the penis. Fusion of the urethral folds encloses the phallic portion of the urogenital sinus to form the penile urethra. The distal urethra is formed by canalization of a solid endodermal extension of the urethral plate into the glans. The labioscrotal folds fuse to form the scrotum. Fig. 11.6.13 In females, the genital tubercle bends inferiorly to form the clitoris, and the urogenital folds remain separated to form the labia minora. The labioscrotal folds form the labia majora. Fig. 11.6.14 At the indifferent gonad stage, two ligaments, a cranial suspensory ligament and the gubernaculum, anchor the mesonephric-gonadal complex. The cranial suspensory ligament runs from the

cranial portion of the mesonephric-gonadal complex to the diaphragm. The gubernaculum is attached to the caudal portion of the gonad and extends to the peritoneal floor, where it is attached to the fascia between the developing external and internal oblique abdominal muscles in the region of the labioscrotal swellings. Fig. 11.6.15 Descent of the testes. A–C. Between 7th week and birth, shortening of the gubernaculum testis causes the testes to descend from the tenth thoracic level into the scrotum. The testes pass through the inguinal canal in the anterior abdominal wall. D. Cross-section of the gubernaculum showing the layers of the tunica vaginalis and processus vaginalis at the level of the labioscrotal swelling. Fig. 11.6.16 A and B. In females, the gubernaculum does not swell or shorten. Nevertheless, the ovaries still descend to some extent during the 3rd month and are swept out into a peritoneal fold called the broad ligament of the uterus. This translocation occurs because the gubernaculum becomes attached to the developing Mullerian ducts. As the Mullerian ducts zip together from their caudal ends, they sweep out the broad ligaments and simultaneously pull the ovaries into these peritoneal folds. As a consequence, the remnant of the female gubernaculum connects the labia majora with the wall of the uterus and is then reflected laterally, attaching to the ovary. C. Completely formed broad ligament containing ovaries and ovarian round ligament. D. The round ligament of the uterus (remnant of the gubernaculum) exits the abdominal cavity via the deep and superficial inguinal rings and connects to the base of the labia majora. Fig. 11.6.17 Transverse sections through the urogenital ridge at progressively lower levels. A and B. The paramesonephric ducts approach each other in the midline and fuse. C. As a result of fusion, a transverse fold, the broad ligament of the uterus, forms in the pelvis. The gonads come to lie at the posterior aspect of the transverse fold.

Fig. 11.7.1 Embryology of sex differentiation. TDF = testis determining factor. Fig. 11.7.2 Male pseudohermaphroditism (46 XY DSD). Clinical Photograph of a child with ambiguous genitalia. The phallus is underdeveloped and testes are not found in the scrotal sacs. Fig. 11.7.3 Diagnostic algorithm chart. Fig. 11.7.4 Changing appearances of uterus during childhood on ultrasound images. (A) Uterus in a newborn is pear-shaped with cervix bulkier than the fundus. (B) Uterus in a 7-year-old child has a typical prepubertal appearance, it is small with length of 2.8 cm and thickness 1 month) chest with IV (oropharyngeal/retrosternal) contrast Fluoroscopic single contrast oesophagogram

May Be Appropriate Fluoroscopic modified barium swallow Fluoroscopic biphasic oesophagogram Oesophageal transit nuclear medicine scan

Not Appropriate CT neck and chest with or/and without IV contrast Fluoroscopy pharynx dynamic and static imaging

Imaging techniques Radiography – Radiographs are extremely valuable while evaluating foreign body ingestion, and a smooth foreign body may get lodge in four sites of normal physiological narrowing of oesophagus. Sharp foreign bodies may cause oesophageal perforations which may not be apparent initially but pneumomediastinum and complication may be seen subsequently. Large benign lesions, oesophageal duplication cysts and diverticulum can be identified as mass arising from the posterior mediastinum. Achalasia cardia (double cardiac contour/air fluid level), oesophageal perforation (pneumomediastinum/left sided pneumothorax) and gastric pull-up surgery may produce typical appearance on routine chest radiograph. Careful examination for contour and thickness of azygoesophageal recess, posterior tracheal stripe, posterior junctional line and presence of posterior tracheal indentation may be subtle signs of oesophageal disease which can be identified on careful evaluation. Contrast oesophagogram – The contrast oesophagogram has combined advantage of functional and structural evaluation. A comprehensive contrast oesophagogram consists of combination of fluoroscopic assessment and analysis of spot views. Barium is commonly utilized either as a 100% w/v paste (microbar paste 100 g/100 mL; Eskay Chemical, Mumbai), 200%w/v HD Granules (300 g is dissolved in 75 mL of water to produce 150 mL of 200% w/v suspension; microbar HD 100 g/100 mL; Eskay Chemical, Mumbai) or as 95% w/v suspension (microbar suspension; Eskay Chemical, Mumbai). Alternatively, a 13 mm barium pill (BAR-TEST, Glenwood, Inc., Tenafly, NJ) or food bolus coated with barium can be used to evaluate oesophageal strictures/webs. The correct preparation of the contrast media as per the guidelines illustrated by manufacturer to ensure optimal mucosal coating and avoiding artefacts. The routine barium study of oesophagus can be single contrast or double contrast. Double contrast is ensured by ingestion of effervescent agents (e.g. microbar Gas) which produce approximately 300–400 mL of carbon dioxide. Modified barium swallow is used for evaluating upper aerodigestive track and is covered along with barium examination of the pharynx. A potential limitation of HD barium is its low viscosity resulting in suboptimal lining and evaluation of finer folds. The oesophageal mucosa is featureless and normal oesophageal folds are longitudinal measure 1–3 mm in width. Presence of transverse folds also known as Feline oesophagus occurs due to contraction of muscularis mucosae muscle which is longitudinally oriented. The presence of transverse oesophageal folds on barium oesophagogram correlates strongly to gastro-oesophageal reflux disease. There are extrinsic impressions at level of aortic arch, left main bronchus and the left atrium. Additionally, cricopharyngeal bar and diaphragmatic hiatus may also be identified on oesophagogram. Vascular anatomical variants like aberrant right subclavian artery and aberrant left pulmonary artery may also cause an impression on oesophagus. The dysphagia caused by significant narrowing of the oesophagus by the aberrant vessel is called dysphagia lusoria. The principal indications and suggested approach are illustrated in Table 8.1.2.

It should be understood that the procedure needs to be modified to answer the clinical dilemma and provided relevant information from the test. The channel of communication between the patient, referring clinician and the radiologist is vital for optimal investigation. Certain modifications like straight leg raising, valsalva, coughing, inclining the fluoroscopy table head down or coughing may help in demonstrating gastro-oesophageal reflux disease (GERD). The fact that oesophagogram is neither specific nor sensitive for GERD must also be kept in mind. The presence of incomplete peristalsis is common in older individuals (presbyoesophagus). However, a small amount of proximal barium escape at level of aortic arch is a normal finding and it occurs at the junction of striated and smooth muscle of oesophagus. In motility disorders, the oesophagogram is complementary to manometry studies and provide additional information to assist the diagnosis. Isolated reports are there which show abnormality on oesophagogram in achalasia cardia in absence of manometric findings. Computed tomography (CT) and CT oesophagogram – The long tubular muscular oesophagus appears as a well-demarcated ovoid to circular structure on axial images. The lumen is collapsed. However, occasional intraluminal air pocket should not be considered abnormal. The normal wall-thickness of collapsed oesophagus is less than 3 mm. The normal transverse and anteroposterior diameter of oesophagus is 25 and 16 mm, respectively. CT evaluation of oesophagus can be a part of chest and mediastinal evaluation or can be tailored specifically for a suspected oesophageal pathology. Multidetector CT advancement has provided reconstruction in any plane in isotropic voxels.

TABLE 8.1.2 Fluoroscopic Oesophagogram ( Fig. 8.1.5) TYPES Single Contrast Indication

Introduction and history taking

Patient preparation

Procedure

• History symptoms of dysphagia, odynophagia, atypical chest pain • High-grade oesophageal obstruction • Oesophageal motility disorders • Hiatal hernia and GERD

Double Contrast • Mucosal abnormalities • Oesophageal narrowing or filling defect • Other indication of single contrast oesophagogram • No air contrast given if patient is debilitated/unable to tolerate effervescent agents/extremely nauseous/suspected to have high-grade contrast

Water-Soluble Contrast • In setting of suspected oesophageal perforation • Postoesophagectomy oesophagogram • If endoscopy is planned immediately after oesophagogram

• Introduce yourself • Explain the procedure and why it needs to be done, reassure and briefly enumerate risks of the surgery • Be professional and courteous • Elicit dysphagia history • Solid or liquid • Location of stuck bolus • Prior intervention/surgery and evaluate previous imaging study if any • Remember the sensation of perceived obstruction may not correlate with site of pathology at times • Discuss with the treating team for the questions need to be answered in postoesophagectomy oesophagogram • NPO for 2–4 hours prior to the exam • 13 mm Barium pill may be required if evaluating stricture/oesophageal web • You may arrange/ask for food bolus causing obstruction

• History of contrast allergy • Enteric tube need to be placed if patient is unable to take orally • Important to know about opening in the enteric tube – endon; side-on; or both

• Evaluation of pharynx, larynx and hypopharynx required if cervical dysphagia is suspected. Detail procedure with modified barium swallow is covered in relevant chapter.

• If contrast is administered through enteric tube (especially high cervical tube position), exercise caution to prevent aspiration.

TYPES Single Contrast • Patient is in a semirecumbent right anterior oblique position. • Patient is given a single swallow worth of thick barium paste or suspension and swallowing is observed under fluoroscopy – single swallow at a time. Fluoroscopy will start a second prior patient swallows at 2–3 fps. • Asking patient to open mouth after swallowing ensures subsequent swallowing. • Oesophageal clearing time >20 seconds is abnormal. • Repeat three or four such swallows. • Relevant static images are obtained. • Mucosal relief image of the oesophagus may be obtained after last swallow for thickened oesophageal folds or varices. Hiatal Hernia Modifications

• Patient in RAO – semirecumbent • Image GE junction • Large swallow of thin barium followed by Valsalva

Double Contrast • Patient upright in left posterior oblique to offset oesophagus from spine. • Patient is given effervescent agents to swallow followed by sip of water. Ask patient not to burp, to ensure maximum distension of esophagus • Structural evaluation – Ask patient to take multiple gulps of barium paste or suspension to distend the oesophagus. • Obtain image of the upper, mid and lower third (including gastrooesophageal junction) of the oesophagus.

Water-Soluble Contrast • Be mindful of presence and location of side-hole in enteric tube. • Patient is kept as upright as feasible. • Start procedure with water-soluble contrast. • If no perforation is detected with watersoluble contrast, procedure is repeated immediately with thin barium. • Take at least two views – AP and oblique. More including bilateral obliques if required.

GERD • Presence of sufficient thin barium in stomach • Patient in RAO – on flat table and asked to roll to LAO position from left • Image GE junction under fluoroscopy

FIG. 8.1.5 Normal anatomy. (A–M) Conventional fluoroscopic procedure depicting normal esophagogram. Source: (Image courtsey: Dr Padma Badhe, Seth GSMC and KEM Hospital, Mumbai). Mazzeo et al. and Carrascosa et al. have described technique of virtual oesophageal endoscopy with use of air insufflation via catheter inserted into the upper oesophagus and by use of effervescent agents like those used in fluoroscopic oesophagogram. However, despite these technological assessments, the sensitivity of CT scan in identifying T1 and T2 disease is limited. The CT scan is also limited in identifying normal-sized metastatic lymph node. The limitation can only be partially addressed by using morphological appearance like extracapsular spread and central necrosis. National Comprehensive Cancer Network (NCCN) guidelines for oesophageal and oesophagogastric Ca recommends CECT chest and abdomen with oral and IV contrast in staging assessment of cancers T3 and above. CT is indicated in assessment of early and delayed postoperative complications. Lantos et al. and Upponi et al. have demonstrated slightly better sensitivity of CT in detecting early postoperative complications. However, it is marred by poor specificity in the same period. In delayed postoperative dysphagia, use of CT oesophagogram has demonstrated increase in sensitivity in identifying recurrent disease, abnormality caused by surgical hardware/technique or a late onset seroma. CT oesophagogram (Table 8.1.3) can be

performed by preparing 3% iodinated contrast in water or thickening agent like Simply Thick to form a honey- or nectar-like consistency swallowed on the table with last gulp taken immediately prior to the acquisition. The images are reconstructed in curved multiplanar reformats in soft tissue window. TABLE 8.1.3 CECT Chest and CT Oesophagogram CT and CT Oesophagogram

CECT Chest Position Supine Respiration Breath hold (inspiration) FOV Patient thorax to include ribs and chest wall Effervescent Not required agents Oral Not required contrast IV Contrast

Required

CT Oesophagogram Supine Breath-hold preferable Same as CECT. However, narrow FOV could be done May be used prior to oral contrast 3% of water-soluble contrast in water or in flavoured food-thickening agent made to nectar/honey thick consistency Not required

MRI and MR oesophagogram – Quint et al. was the first, however, unsuccessful attempt evaluation of oesophagus on a 0.35T MRI, 35 years back. Since then, there has been substantial advancement in the MRI technology with evolution of quicker and dynamic sequences, and advancement of k space filling technology leads to further shortening of scan times. Yamada et al. used MRI in vitro staging of Ca oesophagus with 4.7 T MRI in 1997. Subsequently, high-field MRI up to 7T have been used in evaluation oesophageal specimen and advanced MRI imaging techniques like diffusion tensor MRI and tractography have been used. In spite of these advancement in evaluation of ex vivo specimen, the advancement and utilization of MRI for clinical purposes has been gradual and sparse. In 2005, Riddell et al. used surface coil MRI in staging of oesophageal

carcinoma. Sakurada et al. showed promising results in staging of T3 and T4 Ca oesophagus patients using T2WI and DWI. Over the recent years, the advancements in in vivo MRI of oesophageal Ca have been focused on identification of lymph nodal involvement (Alper et al.), staging postconcurrent radio-chemotherapy (Wang et al.), postoperative nodal recurrence (Shuto et al.) and gross tumour volume delineation (Hou et al.). Pavone et al. (1992) used Gadopentetate dimeglumine – barium paste in distending and opacifying and assessment of concentric/eccentric tumour growth in patients of Ca oesophagus and identifying a case of oesophageal leiomyoma in their study. In 1996, Ogawa et al. used ferric ammonium citrate-cellulose paste for oesophageal lumen opacification with excellent luminal opacification in 84% of the sagittal images and 79% of the axial images. Subsequently, Zhang et al. (2012) utilized high T2* signal of water to provide good contrast in MR oesophagogram. For easy intake of water, the head of patients was padded slightly high and water swallowing was done through a pipe/straw and patients were instructed to swallow the water continuously during the acquisition. Without respiratory triggering, sagittal and axial True fast imaging with steady state procession (True FISP) T2*weighted images were obtained. The diagnostic quality of water swallow was graded excellent in 97.7% of the sagittal images and in 81.8% of the axial images the cases. Even after the advances elucidated above, the present utility of MRI in diagnosis of oesophageal disease is more as an occasional adjunct for resolving specific clinical dilemmas rather than as a primary investigation. However, the future of the modality is bright and promising with continuous improvement in acquisition technology and the hardware. Role of endoscopic ultrasonography in oesophageal lesions (Fig. 8.1.6) EUS is a specialized endoscope with an ultrasonographic probe to evaluate hollow visceral organs. It is useful to visualize oesophagus and stomach lining. Adjacent organs can also be visualized like liver, pancreas, GB, para-aortic region and mediastinum.

FIG. 8.1.6 Diagnostic and therapeutic role of an endoscopic ultrasound. Source: (Image courtsey: Dr Sagar Dembla, Medical gastroenterologist and endosopist, Gandhidham, Gujarat). EUS is done under mild sedation. EUS is available in two types of probes, that is Linear and Radial Probe. Gastrointestinal tract is visible in a healthy patient as five layers. These are first layer – superficial mucosa, second – mucosal, third – submucosal, fourth – muscularis propria and fifth – oesophageal adventitia. EUS is helpful mainly in characterizing the lesion as benign or malignant. On a standard endoscopy study, these lesions are usually seen as a bulge within wall. EUS helps in determining the location of lesion, whether it is within wall or outside the wall. Also it helps in determining the extent of involvement of lesion and its relationship with surrounding structures. It also has a role in looking for secondary causes of motility disorder like achalasia. However, its diagnostic as well as therapeutic role in oesophageal cancer is noteworthy. EUS in oesophageal cancer Endoscopic ultrasound plays a vital role in local staging of oesophageal cancer. Staging of oesophageal cancer is essential to choose appropriate therapy. Surgery is the gold standard for staging of oesophageal cancer. Usually in clinical practice, most patients undergo preoperative therapy as chemoradiation which is followed by surgery. Thus, for pretreatment staging, EUS findings are complementary with radiological imaging like MRI, CT scan and PET scan. Standard protocol is to perform EUS in most cases of oesophageal cancer. EUS is useful in early stages of oesophageal cancer, that is T1a and T1b. It is helpful in evaluating lymph node enlargement. Whenever a patient is assessed for feasibility of early cancer for mucosal resection via endoscopic procedure, it is important to rule out deeper tissue invasion and lymph node metastasis. EUS also plays essential role in lymph node FNA and biopsy in doubtful lesions. Role of EUS in advanced oesophageal cancer is limited. Usually EUS cannot be used to differentiate between T3 and T4. Distant metastasis is usually well diagnosed on crosssectional imaging. EUS can only detect invasion into aorta as T4 which is better visualized in CT scan. EUS has limitations like it cannot look into metastases where CT scan and PET scan are useful. Role of EUS in postradiation or chemotherapy is under evaluation. EUS is technically difficult and has a significant learning curve.

8.1 .3

ALGORITHMIC APPROACH TO A PATIENT WITH OESOPHAGEAL DYSPHAGIA Gurdarshdeep Singh Madan, Ankita Dhawan Swallowing is essential not only for maintaining the nutrition for life but also a major determinant in one of the pleasures of life. The voluntary component of swallowing is the initial 10% and is initiated by collecting the food bolus onto the tongue and voluntarily propelling the bolus into the oropharynx. This initiates a wave of involuntary contraction and relaxation of pharyngeal muscles which pushes the food through cricopharynx into the oesophagus. Closure of glottis and cessation of respiration are reflex activities. Thereafter, the ‘peristaltic’ ring of oesophageal muscle contraction pushes the food towards the stomach at a rate of approximately 3.0–4.5 cm/s. The semisolid and liquid food falls by gravity, ahead of the peristaltic wave when the individual is upright. In cases where there is incomplete clearing of the oesophagus, secondary peristaltic waves are generated which are weaker than the primary peristaltic wave and aid in clearing the oesophagus. Unlike the rest of oesophagus, lower oesophageal sphincter (LES) is contracted at rest and relaxes on swallowing, which prevents reflux of gastric contents into the stomach while permitting the food bolus into the stomach (Fig. 8.1.7).

FIG. 8.1.7 Physiology of swallowing. Difficulty in swallowing is a common problem affecting approximately 3%–15% of general population. This prevalence increases in elderly population and in patients with other comorbidities. Understanding the symptomatology and pathophysiology of dysphagia is essential for the radiologist to plan the correct investigation and to remain clinically relevant in management of the patient. The symptoms of difficulty on swallowing has been further classified into various terminology, each highlighting a specific association and hence clinically leading to a smaller set of differential diagnosis (Table 8.1.4).

TABLE 8.1.4 Dysphagia can be Subclassified on the Basis of Location or Mechanism of Dysphagia Dysphagia

Symptom of difficulty on act of swallowing and is frequently associated with sensation of hold up of bolus of food. It may or may not be associated with pain. Odynophagia Painful swallowing. It is generally associated with dysphagia. However, the reverse is not always true. Aphagia Complete obstruction to the pharynx or oesophagus. Phagophobia Morbid fear of swallowing – may be psychogenic or secondary to anxiety about aspiration or food impaction in organic oropharyngeal/oesophageal abnormalities including neuromuscular/motility disorders. Globus It is a sensation of foreign body stuck in neck which at times is relieved pharyngeus temporarily by act of swallowing. It is commonly associated with pharyngeal abnormalities. Transfer It is a disorder pertaining to transfer of food bolus from dysphagia oral/oropharyngeal phase to oesophageal phase of swallowing. It may or may not result in nasal or tracheobronchial aspiration. Commonly associated with neuromuscular/motility disorders. Depending on location, dysphagia may be localized to oral, oro-pharyngeal or oesophageal regions. Dysphagia can also be subclassified as Structural dysphagia – caused by mismatch between the size of food bolus and the lumen of the aerodigestive track/oesophagus that is a large food bolus or the narrow lumen. It is classically described as difficulty in swallowing solid food. Motor dysphagia – it is caused by abnormalities of peristalsis/impaired upper oesophageal sphincter relaxation/closure and impaired lower oesophageal sphincter relaxation. It is difficulty in swallowing both solid and liquid foods. There are certain limitations to such generalization of symptoms. For example, Scleroderma, which is primarily an oesophageal motility disorder, presents initially with mild dysphagia on swallowing solid bolus. Also, in patients with oropharyngeal structural pathology, patient may be more symptomatic and concerned due to inability to handle fluids and causing aspiration. In other subset of patients, more than one mechanism may be responsible causing both improper propulsion of food and associated secondary luminal narrowing by stricture formation. Odynophagia generally arises due to passage of bolus along inflamed or ulcerated mucosa causing irritation, which may be due to foreign body ingestion, infective, chemical or inflammatory oesophagitis. Associated symptoms like cranial nerve abnormalities, hoarseness and other general and systemic symptoms and signs may point towards the location and cause of dysphagia. The patient may be able to localize the location of dysphagia. However, the sensation of dysphagia in oesophagus (especially in distal two-thirds) may be proximally referred in a third of the cases. Inability to produce sufficient saliva (Xerostomia) may also be perceived as dysphagia, especially common in elderly (see Fig. 8.1.8).

FIG. 8.1.8 Clinical approach to a patient of dysphagia. Oesophageal dysphagia Adult oesophagus measures approximately 17–26 cm in length and extend from cricopharynx to the lower oesophageal sphincter. Oesophagus can be anatomically divided into cervical oesophagus (cricopharynx to suprasternal notch) and thoracic oesophagus. The structural causes of the dysphagia manifest when the lumen of the oesophagus has been reduced to one-third (~13 mm in size). Dysphagia in a setting of Gastro-oesophageal Reflux Disease is very common and is multifactorial in pathophysiology – increased mucosal sensitivity, impaired distensibility and motor function, formation of strictures. Propulsive/motor disorders can be due to abnormality of peristalsis (both excessive and reduced) or relaxation of lower oesophageal sphincter (see Figs. 8.1.9–8.1.13).

FIG. 8.1.9 Oesophageal dysphagia in adults.

FIG. 8.1.10 Oesophageal Web. Source: (Image courtsey: Dr Padma Badhe, Seth GSMC and KEM Hospital, Mumbai).

FIG. 8.1.11 Oesophageal Diverticulum. Source: (Image courtsey: Dr Padma Badhe, Seth GSMC and KEM Hospital, Mumbai).

FIG. 8.1.12 Corrosive strictures. Source: (Image courtsey: Dr Padma Badhe, Seth GSMC and KEM Hospital, Mumbai).

FIG. 8.1.13 Carcinoma oesophagus. Source: (Image courtsey: Dr Padma Badhe, Seth GSMC and KEM Hospital, Mumbai). Few common causes of oesophageal dysphagia are enumerated below: Motor Dysphagia GERD with weak peristalsis Achalasia DES/Corkscrew oesophagus Connective tissue disorders

Structural Dysphagia Schatzki ring Peptic strictures Neoplasia Hiatal hernia

Odynophagia Infective oesophagitis Pill oesophagitis Caustic injury Inflammatory bowel disease

Special considerations Presentation and causes of dysphagia in neonates and infants tend to be different from adults. They may present as aspirations, incessant crying in addition to choking and inability to feed. In neonates, the causes may be neuromuscular or central in origin affecting swallowing or could be congenital in nature affecting oral or pharyngoesophageal phase of swallowing (Fig. 8.1.14).

FIG. 8.1.14 Dysphagia in neonates. In older children and toddlers, ingestion of foreign body is one of the most common cause of dysphagia/choking. In these cases endoscopy is therapeutic. Ingestion of caustic agents can cause severe caustic oesophagitis which can be potentially fatal. In children, high index of suspicion should be present and relevant history for ingestion of caustic agents should be elicited. Other causes of dysphagia (Fig. 8.1.15) in paediatric age group are covered in detail in relevant chapters.

FIG. 8.1.15 Dysphagia in children. Which investigation to choose: The armamentarium available for a clinician while evaluating dysphagia are mentioned below: Investigation to Evaluate Dysphagia Endoscopy +/− Biopsy Barium swallow (13 mm tablet/marshmallow/bread soaked in barium) with video fluoroscopy Oesophageal manometry (high resolution impedance manometry) High-frequency intraluminal endoscopic ultrasound (EUS) Routine chest radiograph PET CT CT scan with contrast Ambulatory reflux monitoring Bernstein testing (obsolete) Before the advent of flexible upper gastrointestinal endoscopic techniques, contrast (barium) upper gastrointestinal radiological studies especially barium swallow were the cornerstone in evaluating dysphagia. However, endoscopic examination of the oesophagus is presently the first line investigation of choice for oesophageal dysphagia. Endoscopy offers the advantage of mucosal assessment and characterization, ability to identify Barrett’s metaplasia and offer diagnostic and therapeutic interventions in a single sitting. Endoscopy is relatively deficient in diagnosing motility disorders and identifying benign conditions which cause dysphagia but do not cause mucosal abnormalities. Oesophageal Endoscopy Advantages Assessment of mucosal abnormalities Offer diagnostic (biopsy) and therapeutic interventions (endoscopic ablation/resection) Can be combined with endoscopic ultrasound

Disadvantages Cannot assess motility disorders Difficult to evaluate beyond stenotic segment Lesions with no mucosal abnormalities may be missed Poor patient comfort

Barium swallow should be done as a first line investigation of choice where dysmotility or oesophageal ring/webs/subtle strictures are suspected. A wellplanned barium study with barium-coated appropriate bolus such as bread/marshmallow/barium pill may demonstrate oesophageal ring causing hold up of contrast. Barium swallow is also the first line investigation of choice for Achalasia. It may also be used for characterization of hiatal hernia.

Barium Oesophagogram Advantages Inexpensive, easily available Can be tailored depending on patient presentation Video-fluoroscopy allows adequate/physiological assessment of oesophageal motility Barium is not absorbed and hence allergic reactions are rare

Disadvantages Appropriateness limited on use of spot images and by proficiency/experience of technician/doctor Negative barium study does not rule out need of endoscopy No cross-sectional information obtained Barium can elicit severe mediastinitis when used in oesophageal perforations

Oesophageal manometry/HRIM (high resolution impedance manometry) is specifically done in patients in whom endoscopy and barium studies are noncontributory. They show high pressure at upper and lower oesophageal sphincter with mid oesophagus showing waves of peristalsis. It is the gold standard to diagnose achalasia with certainty. It is also of immense value in diffuse oesophageal spasm and nutcracker oesophagus. Oesophageal Manometry Uses Done primarily in case of dysphagia after noncontributory endoscopy; in evaluation of GERD and noncardiac chest pain. Limitations May miss transient relaxations of LES in GERD; and transient contractions of oesophagus in nutcracker oesophagus/DES. Procedure may be uncomfortable for some patient. Endoscopic ultrasound combines the advantage of an endoscope with high-frequency ultrasound, providing improved spatial resolution, which is useful for staging of oesophageal carcinoma and allows taking directed biopsies for histopathology. It can also be used to assess Barrett’s metaplasia and evaluating other submucosal tumours/paraoesophageal lymph nodes. Endoscopic Ultrasound Advantages Good spatial resolution and identification of oesophageal wall layers and assess depth of invasion. Evaluation of loco-regional lymph nodes. Investigation of choice for follow up in postendoscopic ablation/resection patients. Limitations Operator dependent. Use of high-resolution probe limits evaluation of deeper structures. Distant lymph node metastasis needs to be evaluated separately. PET-CT scan is a preferred modality of oesophageal and oesophago-gastric junction Ca and includes PET CT from skull base to mid-thigh in absence of M1 disease. Early disease may not be detectable on PET-CT as depth of invasion cannot be accurately assessed. Assessment of locoregional lymph node is limited as uptake from oesophageal lesion cannot be differentiated from uptake from periesophageal lymph nodes due to limited spatial resolution of PET. Nonregional or distant lymph node involvement can be well identified and assist in accurately upstaging and planning treatment of Ca oesophagus.

PET-CT Advantages Provides metabolic imaging. Preferred investigation in patients of oesophageal Ca in absence of M1 disease. PET combined with CT scan provides good anatomic images for planning. High sensitivity in identifying distal solid organ/lymph node metastasis.

Disadvantages Assessment of local lymph nodes is limited by spatial resolution of the PET component. Availability and cost of PET-CT might be a limitation.

CT scan has limited value in identifying early oesophageal Ca and identifying nonregional lymph nodes. It can be used in assessing recurrence and to check for integrity postoesophagectomy. Computed Tomography Advantages Easy availability

Disadvantages Low sensitivity in picking up small metastatic lymph nodes Preferred investigation in posttreatment follow up No metabolic information of oesophageal Ca patients Used for assessment of immediate postop complications after oesophagectomy Ambulatory reflux monitoring is useful in diagnosing GERD without oesophagitis. Endoscopy is normal in these patients with hypersensitive oesophageal mucosa – causing pain. The electrode tip is placed in distal oesophagus and pH is measured over 24/48 hours. The outcome is expressed as percentage duration when the distal oesophageal pH was less than 4. This can be combined with impedance monitoring to increase sensitivity. They also serve as a guide to evaluate poor response to therapy for GERD. A reading of more than 6% is considered abnormal. Additional newer advances like use of Functional Lumen Imaging Probe (FLIP) has been evaluated to assess oesophagogastric junction distensibility and distension-mediated peristalsis in oesophageal motility disorders. The investigations are often guided by clinician’s preferences, availability of the investigation and likelihood of a probable diagnosis on history taking and clinical examination.

8.1 .4

OESOPHAGEAL MOTILITY DISORDERS

Ankita Dhawan

Introduction Oesophagus is around 25–40 cm muscular tube in posterior mediastinum. It comprises both striated and smooth muscles. It extends from the level of upper oesophageal sphincter (UES – at the level of cricopharyngeal muscle) and lower down till the level of lower oesophageal sphincter (LES – present at the junction of lower end of oesophagus and cardia of stomach).

Normal oesophageal physiology Resting phase Lumen UES and LES

– –

Collapsed Contracted

Normal function of oesophagus is to transport both solids and liquids to stomach, which is mainly attributed to oesophageal peristalsis and gravitational force. Therefore, radiographic evaluation of oesophageal peristalsis is done in recumbent position to remove the contribution from gravity. Types of oesophageal peristalsis Primary: Initiated by swallowing, which is composed of sequential wave of inhibition and contraction lasting for 6–8 seconds. Sequential relaxation of UES followed by LES is seen. Secondary: Initiated by local oesophageal stimulation or distension. Tertiary or nonperistaltic contractions: These are haphazard waves seen spontaneously or during swallowing. They do not have a particular characteristic formation. Oesophageal motility disorders have been clinically defined as symptoms such as dysphagia, chest pain or heart-burn which are attributed to neuromuscular dysfunction. Types of motility disorders include: 1. Primary 2. Secondary

Achalasia It is characterized by incomplete LES relaxation, increased LES tone and lack of peristalsis of the oesophagus. Types – primary and secondary based on aetiology. Primary achalasia is characterized by degeneration and loss of ganglion cells within myenteric plexuses which is located in oesophageal wall. Secondary achalasia (or pseudoachalasia) is related to extraoesophageal pathologies which include carcinoma at GE junction, metastatic disease, lymphoma, Chagas disease and postoperative states like – fundoplication and gastric banding. Investigations Endoscopy • First line of investigation for new onset dysphagia. • Diagnostic role to find structural abnormality including growth, ring or web. • Aids in taking biopsies even in normal appearing mucosa to rule out eosinophilic oesophagitis. • Therapeutic role – dilatation in webs or stricture and banding in varices. Chest x-ray • Useful in advanced stage. • Both AP AND LATERAL views are useful. Classical features seen: 1. Mediastinal widening; double contour of mediastinal border with outer border representing the dilated oesophagus. 2. Air fluid level in mediastinum with small or absent gastric bubble. 3. Anterior bowing of trachea. 4. Lower lobes may show decreased volume. Barium studies Primary Achalasia Markedly dilated oesophagus (>4 cm) Complete absence of peristalsis Distal segment of oesophagus including GE junction shows marked narrowing with narrow segment showing characteristic smooth and symmetric margins – forming the classical ‘bird beak appearance’) Studies show length of narrow segment 4 cm Air fluid level within the dilated portion Narrow segment present involving distal part of oesophagus Malignant Mild dilatation of oesophagus Nodular wall thickening involving the narrowed segment Involvement of perioesophageal tissues Enlarged necrotic mediastinal, perioesophageal or peri-gastric lymphadenopathy Nuclear studies

• Oesophageal transit scintigraphy is done. • Its role is limited. • Radio-isotope with a relatively short half-life is preferable for the study. • 9mTc-sulphur colloid with half-life of 6 hours is normally used. Its physical property to bind with cooked food and not being absorbed by gastrointestinal tract thus leading to lower radiation exposure are its favourable properties. • Study is conducted in both supine and erect positions. • Diagnostic criteria for achalasia includes marked delay in transit of bolus through the entire length of oesophagus with oesophageal transit time >30 seconds and >50% retention in 10-minute delay film which shows no significant change even in upright position. ACR appropriateness criteria for dysphagia Unexplained dysphagia Various above-mentioned investigations are graded depending on their relevance and importance. Grade I: Biphasic fluoroscopic evaluation of both pharynx and oesophagus. Both dynamic and static imaging of pharynx done. Both single- and double-contrast techniques, including full-column, mucosal relief with double-contrast view of the oesophagus to be included. Grade II: X-ray barium swallow modified. (This is a videofluoroscopic procedure in which study of the oral cavity, pharynx and cervical oesophagus is done for assessment of oral and pharyngeal swallowing phases abnormalities.) Single contrast barium swallow. Grade III: Technetium (Tc)-99m transit scintigraphy oesophagus. Differential diagnosis 1. Scleroderma 2. Oesophageal carcinoma 3. Gastric carcinoma 4. Oesophagitis with stricture 5. Neuromuscular disorders 6. Postsurgical/Postvagotomy KE Y PO INT S • Oesophageal carcinoma should always be kept in mind whenever case of achalasia comes. • Gold standard diagnostic test for achalasia is oesophageal manometry. • Bird beak appearance on barium studies is considered synonymous. Reporting template Chest X-ray PA and lateral views: There is a large abnormal, right-sided, vertically placed tubular radiolucency present in mediastinum, parallel to the trachea and extending from thoracic inlet till the level of hiatus. The lateral margin of radiolucency projects beyond lateral margin of the normally placed right and left paratracheal stripes. There is absence of gastric fundic air with raised left hemidiaphragm. Lateral chest radiograph shows that the radiolucency has caused anterior displacement of trachea. Barium studies Primary achalasia Single-contrast barium swallow shows markedly dilated and tortuous oesophagus with smooth tapered beak-like narrowing involving lower oesophagus with extension to involve GE junction. On fluoroscopy, primary peristalsis in oesophagus was absent. Secondary achalasia

Single-contrast barium studies show long segment stricture formation involving distal oesophagus with margins of oesophagus showing nodular irregularity and mass-like shouldering with proximally mildly dilated oesophagus. On fluoroscopy, peristalsis was present. CT scan Oesophagus in its almost entire length excluding the distal most part shows marked dilatation (>4 cm in horizontal dimension) with distal most part showing marked luminal narrowing. Smooth tapering is noted at the transitional zone. Proximal and mid part of thoracic oesophagus shows presence of food residue within.

Management Surgical candidate A. Heller’s myotomy: Laparoscopic approach in which incision is made in lower oesophageal muscles along with fundoplication. This is the gold standard treatment. B. POEM (per oral endoscopic myotomy): It is a newer endoscopic therapy which is minimally invasive and is becoming increasingly popular internationally as first line therapy for achalasia. Nonsurgical candidate A. Medical management: Includes drugs which decrease LES pressure – nitrates and CCB’s. B. Botulinum toxin injected in lower oesophagus is recommended in elderly people who cannot undergo surgery. C. Pneumatic dilatation: It is an endoscopic-guided balloon dilatation of lower oesophageal sphincter; however, is associated with small risk of perforation. Also, patient might require repetitive dilatations.

Some important causes of secondary achalasia 1. Scleroderma It is a multisystemic idiopathic connective tissue disorder which is characterized by various changes in microvasculature, immune system and connective tissue. Gastrointestinal scleroderma is a common manifestation. The immune complexes tend to cause progressive damage and collagen deposition and finally replacement of muscularis. These changes are most prominent in lower two-thirds of oesophagus. This is the reason for classical radiographic hose pipe-like appearance of lower oesophagus. The LES in case of scleroderma becomes patulous and therefore hiatus hernia and reflux oesophagitis can be concurrently present. Barium studies are important in diagnosing this condition. Marked dilatation of lower two-thirds of oesophagus Apparent shortening of oesophagus Absence of normal peristalsis in lower oesophagus Relative delayed emptying of administered oral contrast from distal oesophagus Stricture formation at distal most end of dilated segment Associated hiatus hernia and GERD can be documented Reporting template: Barium oesophagogram shows dilated mid and lower thoracic oesophagus with associated presence of hiatus hernia and reflux. Video fluoroscopy findings show absence of normal primary peristaltic contractions in distal oesophagus.

Key point: Dilated oesophagus is common in both achalasia as well as scleroderma. However, the status of LES is a differentiating feature for both. Therefore, associated finding of hiatus hernia with features suggestive of reflux are consistent with oesophageal scleroderma. 2. Oesophageal carcinoma: It will be dealt in separate chapter. 3. Gastric carcinoma: Gastric cardia malignancy with extension into distal oesophagus can mimic achalasia. Distal part of oesophagus can be dilated and show absence of primary peristalsis. In such cases, endoscopy and biopsy can help in coming to a conclusion. 4. Metastatic deposits: Metastatic deposits in case of prostatic carcinoma, lung carcinoma, pancreatic carcinoma, HCC as well as lymphoma can infiltrate oesophageal wall at the level of GE junction and cause resultant malignant obstruction and dilatation of proximal oesophagus, thus cause secondary achalasia. 5. Reflux oesophagitis with stricture: Peptic stricture with GERD can simulate achalasia. There can be associated presence of hiatus hernia. Endoscopic evaluation can aid in reaching to a diagnosis. 6. Postoperative: Achalasia can be seen in patients with postfundoplication and postvagotomy status.

Diffuse oesophageal spasm It is a common oesophageal motility disorder with patient mainly presenting with complains of dysphagia. There are different theories to explain the pathophysiology behind this disorder, but the most common accepted theory suggests that there are abnormal intermittently placed oesophageal peristaltic waves with variable functioning LES. Manometry findings Abnormal oesophageal peristaltic waves with few interspersed normal peristaltic waves. Impaired or completely absent LES relaxation. Barium studies The classical feature which represents DES shows the intermittently placed repetitive, lumen obliterating peristaltic and nonperistaltic waves, which produce different organized sections within the oesophagus and thus reflecting similar ‘cork screw’ or rosary bead/shish kebab appearance. However, recent studies show that these classical pattern might not be present with most patients showing absence of nonperistaltic and thus a classical ‘cork-screw’ appearance. Hence, results of both manometric study and barium studies should be considered to arrive at an appropriate diagnosis. Also, on video-fluoroscopy contrast can be seen moving in two opposite directions. Also, there can be associated diverticula or sacculation. Key point: DES is synonymous with ‘corkscrew appearance’. However, its absence on barium studies does not rule out presence of DES. Reporting Template: Barium oesophagogram shows presence of nonspecific peristaltic contractions producing a classical corkscrew appearance involving most of oesophagus. On fluoroscopy, tertiary pattern of peristaltic waves are present with contrast showing movement in opposite directions.

Nutcracker oesophagus It is also known as hypercontractile or jackhammer oesophagus. This is particularly present in elderly age group who show hypertensive peristaltic oesophagus. The patients normally complain of chest pain which could mimic acute coronary disorders. This disorder is diagnosed on oesophageal manometry which shows high amplitude contractions. Barium studies are usually normal. 8.1 .5

APPROACH TO INDIGESTION, NAUSEA, VOMITING AND GASTRO-OESOPHAGEAL REFLUX Gurdarshdeep Singh Madan

Introduction The upper gastrointestinal symptoms of indigestion, regurgitation, nausea and vomiting are one of the commonest ailments affecting the population today. With advent of the industrial age, change in dietary habits, increase use of beverages and prolonged life expectancy has contributed in the incidence. While in most instances, the symptoms are short lived and do not require any detailed investigation. Long-standing symptoms, simultaneous presence of warning signs or intolerance to the symptoms affecting quality of life necessitate detailed investigation.

Indigestion Indigestion means different to different people and what the patient means by indigestion is also codetermined by the cultural setting. It may mean dyspepsia, early satiety, gastrooesophageal reflux, burping, flatulence, abdominal pain or even halitosis (Table 8.1.5). Hence, detailed history, clarifications of symptoms (including asking leading questions) helps in better understanding of symptoms. TABLE 8.1.5 Consortium of Symptoms Under Patient Complain of Indigestion

Nausea and vomiting

Simply put, nausea is the feeling of the need to vomit. Vomiting is oral expulsion of the gastrointestinal contents caused by retrograde contraction of the gut and contraction of abdominal wall muscles. Vomiting is coordinated by the brainstem nuclei and significant contribution of autonomic nervous system. Tachycardia, excessive salivation, sweating, breath holding are autonomic symptoms which are seen closely with nausea and vomiting. Regurgitation and rumination Effortless passage of food contents from stomach to oesophagus or to the mouth is regurgitation. The regurgitated contents may pass spontaneously back into the stomach by gravity or oesophageal peristalsis. In certain cases, when the regurgitated food reaches the mouth, it is chewed and again swallowed. This is called rumination. Causes Nausea and Vomiting – Both central, vestibular and gastrointestinal causes result in symptomatology of nausea and vomiting. In addition, cardiovascular diseases, infections, pregnancy, psychiatric diseases also cause nausea and vomiting. The causes of vomiting in neonates may be completely different and can include causes like hypertrophic pyloric stenosis, duodenal/jejunal atresia. Inability to feed in patients of trachea-oesophageal atresia/fistula can be misconstrued as vomiting. In an older infant, the causes may include malrotation of gut, intussusception and gastro-oesophageal reflux. Congenital hypertrophic pyloric stenosis (CHPS) may be suspected in late neonatal period to early postneonatal period with classic findings of succussion splash with olive-sized mass in right upper abdomen. Presence of bilious vomiting is a red flag sign for a significant obstruction. Presence of meconium or colostrum in vomitus suggest distal small bowel obstruction. Other systemic causes of vomiting like infectious diseases, meningitis, inborn errors of metabolism (IEM), hormonal diseases (like Diabetic ketoacidosis (DKA) and congenital adrenal hyperplasia (CAH)/adrenal insufficiency) and neurological causes causing raised intracranial pressure are also important causing of vomiting in a young child. In an older child, along with infections, disease like oeosinophilic oesophagitis, gastro-oesophageal reflux need consideration. Accidental poisoning and foreign body ingestion are particularly important in toddlers. Table 8.1.6 enumerates causes of vomiting in paediatric age group. Like in children, the causes of vomiting in adults can be varied and determined by underlying pathological or pharmacological processes affecting vomiting pathway either centrally or peripherally. From central causes like raised intracranial pressure, involvement of chemoreceptor trigger zone (CTZ), stimulation of vestibular apparatus causing giddiness, vertigo and vomiting to gastrointestinal causes like bowel obstruction and pancreatitis. The causes of vomiting in adult age group are enumerated in Table 8.1.7. Most of the causes may be apparent during the course of detailed history and physical examination. For the remaining, the investigations may be required to first find the common causes and exclude the life-threatening ones. An approach to vomiting is suggested in Table 8.1.8. Neurological disease may present with neck rigidity, neurological deficit, altered sensorium with or without fever and raised ICT. They can be evaluated with imaging followed by CSF analysis where required. Bulging fontanelle in a calm child suggests presence of raised ICT in otherwise listless child. Presence of spasmodic colicky pain may be biliary/urinary or intestinal in origin. On the other hand, pain originating due to peritoneal irritation by inflamed appendix, Meckel’s diverticulum, perforated bowel. These may be assessed by radiography, sonography or CT scan of the abdomen. Literature also documents use of MRI in evaluation of acute abdomen especially appendicitis and diverticulitis. In patients who have no localizing feature but still have severe or warning symptoms like weight loss, haematemesis, bilious vomiting or abdominal tenderness should be evaluated further with endoscopy, metabolic workup and imaging studies of the abdomen like enterography or CECT abdomen. When this workup is also normal, patient may be evaluated for psychological ailments and gastric dysmotility like gastroparesis.

Regurgitation (GERD) with or without reflux oesophagitis – Presenting as heartburn- gastro-oesophageal reflux is one of the commoner gastrointestinal disease in the west affecting approximately one-fifth of the population. The incidence and prevalence have shown increase over the years due to increased life span, change in dietary habits, increase in consumption of caffeinated and alcoholic beverages. Gastro-oesophageal reflux is characterized by reflux of gastric contents into oesophagus and irritating the oesophageal lining. The definition was standardized in 2006 by Montreal consensus which now describes GERD as ‘a condition that develops when the reflux of stomach contents into the oesophagus causes troublesome symptoms and/or complications’. It includes patients both with and without reflux oesophagitis. On the contrary, reflux oesophagitis is an oesophageal mucosal injury secondary to retrograde reflux of gastric contents into the oesophagus. Long-term reflux oesophagitis can lead to lower oesophageal stricture. Barrett’s oesophagus also is considered as a sequelae of repeated reflux oesophagitis in which there is metaplastic replacement of normal squamous epithelium of lower oesophagus into columnar epithelium. Barrett’s oesophagus – intestinal metaplasia is considered a premalignant lesion for the development of oesophagogastric adenocarcinoma. The relationship of severity of symptoms with gastro-oesophageal reflux is nonlinear. They correlate not only with frequency of episodes of gastrooesophageal reflux but also with duration, intrinsic resistance of oesophageal mucosa and hypersensitivity of the oesophageal mucosa. The episodes occurring at night tend to cause relatively severe symptoms as compared to day episodes. This may be because of gravity-aided clearance during the day when the patient is upright and poor oesophageal clearance during sleep. Similarly, the patients with reduced oesophageal motility like scleroderma tend to have severe and more frequent reflux oesophagitis. Clinical features of gastro-oesophageal reflux include postprandial pain in retrosternal region commonly referred to as heart-burn. There may be occasional reflux of food into the stomach associated with brackish and sour taste in mouth. Aspirations, choking, pharyngitis, laryngitis and other associated lower respiratory infections are also seen in severe cases. As it has been mentioned earlier, the sensation of pain does not correlate well with oesophageal pH monitoring and may be secondary to oesophageal mucosal hypersensitivity and mediated by oesophageal neuronal dysfunctional. Pathophysiologically, the gastro-oesophageal reflux may be mediated either by transient relaxation of the lower oesophageal sphincter (LES), anatomical abnormalities like hiatus hernia (both sliding and rolling) or reduced tone in LES (LES hypotension). Even though, maximal damage to the oesophageal mucosa is contributed by acidic stomach contents. The acidity of the stomach contents, in absence of reflux, is not a significant contributing factor. It may also be pertinent to mention that along with acid, other gastric contents like pepsin, bile and pancreatic enzyme may also contribute in development of reflux oesophagitis. Reflux oesophagitis is also observed in half of the patients suffering with Zollinger–Ellison Syndrome. Diagnosis is generally made on endoscopy with biopsy. Peptic reflux oesophagitis shows distal ulceration in the mucosa and they are more common solitary rather than multiple. Los Angeles (LA) system has classified the appearance of reflux oesophagitis on endoscopy (Table 8.1.9). In addition, endoscopy can give information about ulceration and strictures. Barrett’s oesophagus appears as salmon pink in colour with matted appearance as compared to shiny bright pink appearance of normal oesophageal mucosa. However, the finding of Barrett’s oesophagus must be confirmed on histopathology. The microscopic changes on biopsy include relative papilla elongation, increase in thickness of basal layer of epithelium, dilatation of intercellular spaces and presence of intraepithelial neutrophils and eosinophils. Up to 50% of patients with GERD show abnormal oesophageal motility on manometric studies. The changes include oesophageal dysmotility and poor tone of the LES. However, the loss of tone in the LES may be transient and may not be assessed during manometric study.

Ambulatory reflux monitoring or pH monitoring can be done by placing the electrode tip in the distal oesophagus using endoscopy and the readings can be taken by telemetry. The electrode spontaneous detaches and is passed in faeces after 24 hours. A percentage duration of oesophageal pH less than 4 is calculated. A reading of more than 6% is considered abnormal. Presently, impedance measurement electrodes are also used along with pH monitoring which assess reflux of other substances than acid which contribute to reflux oesophagitis. Bernstein testing is a historical test to measure distal oesophageal mucosa sensitivity to acidic stimulus. 0.1 M hydrochloric acid is perfused alternatively with normal saline through nasoesophageal tube and replication of patient’s symptoms with hydrochloric acid and not with placebo (saline) is considered positive for gastro-oesophageal reflux. It is occasionally performed now to assess for oesophageal mucosa hypersensitivity. Contrast studies of oesophagus show observation of spontaneous reflux of barium from stomach to oesophagus after oesophageal clearing either in resting condition or by provocative manoeuvers like coughing, valsalva or leg raising. The upper extent of refluxed barium in the oesophagus has been correlated with severity. In addition, oesophageal aperistalsis may also be seen, which may be due to preexisting disease such as scleroderma or could be secondary to neuronal damage of the oesophageal autonomic nervous system (Auerbach’s plexus) by ongoing oesophagitis. In addition to this, presence of transverse oesophageal folds has been closely related with gastro-oesophageal reflux. Longitudinal oesophageal folds may also be thickened (>3 mm) when viewed in mucosal relief film. In early cases, the oesophageal mucosa may show fine nodular appearance on double-contrast spot film in distal third of oesophagus. Severe cases show oesophageal ulcerations seen in stellate, punctate or linear appearance. They are classically seen close to the gastrooesophageal junction and are solitary in early/mild cases. Long-standing patients may show stricture and oesophagogastric mucosal polyps seen as filling defects or abnormal folds lined with barium on double-contrast studies. In addition, the oesophagogram helps document hiatal hernia which may be contributing factor in the disease and is essential when planning surgical management such as fundoplication. As compared to this, Barrett’s oesophagus appears as mid oesophageal ulcer/stricture seen at the proximal elevated squamo-columnar junction. The ulcers can be seen en face or in profile. Reticular mucosal pattern has also been typically described in description of Barrett’s oesophagus. Water siphon test – Water siphon test may also be performed to increase the sensitivity and positive predictive value of the oesophagogram. It was initially described by De Carvalho in 1951 and a subsequent modification was described by Crummy about a decade and a half later. It is done with patient in supine RPO position and drinking water continuously with a straw. Reflux of barium completely filling the oesophageal lumen is considered positive for oesophageal reflux. It is considered more positive for gastro-oesophageal reflux rather than spontaneous reflux of barium into the oesophagus. The choice of modalities for the diagnosis of gastro-oesophageal reflux disease are determined by recommendation of various professional societies as well as experience of referring physician and proficiency of radiologist performing oesophagogram. Gastroenterology literature does not recommend the use of barium oesophagogram in diagnosis of GERD due to its poor sensitivity and specificity. Even the role of histopathology in diagnosing reflux oesophagitis and gastro-oesophageal reflux has been questioned in various gastroenterology literatures. On the other hand, Society of abdominal radiology recommends use of oesophagogram including water siphon test for the diagnosis. Water siphon manoeuver increases the sensitivity of oesophagogram but it still suffers with poor specificity. Needless to say, the diagnosis of gastro-oesophageal reflux still tends to be an enigma and holistic multidisciplinary diagnostic approach may be needed to cut this Gordian knot.

TABLE 8.1.6 Cause of Vomiting in Paediatric Age Group Vomiting in Child Red flag signs

Age

Bilious vomiting

Neck rigidity

Hypotension

Vomiting with meconium/colostrum Haematemesis

High fever

Abdominal distension/tenderness Rigidity/photophobia

Neonate

Common causes Common • Infant reflux • Neonatal sepsis • Necrotizing enterocolitis – especially in preterm • Intolerance to formula feed Other causes

Neurological symptoms Listless child Postneonatal period Common • Infant reflux • Gastroenteritis • Food allergy

Respiratory distress/choking Older child (>1 year) Common • Gastroenteritis • Pharyngitis • Foreign body • Accidental poisoning • Otitis media, vestibular neuronitis

Infectious Gastroenteritis, meningitis, pyelonephritis Neurological Hydrocephalus, intracranial neoplasm Metabolic

Miscellaneous Child abuse, accidental and nonaccidental poisoning, foreign body

DKA, IEM, CAH Gastrointestinal causes

• Oesophageal atresia with or without trachea-esophageal fistula • Malrotation of gut with or without volvulus • Pyloric atresia including CH PS • Atresia of small bowel, Hirschsprung disease • Meconium plug, Meconium ileus • Lacto-bezoar (uncommon)

• Pyloric stenosis • Intussusception • Malrotation with or without volvulus • Gastrooesophageal reflux

Other causes • Celiac disease • Gastritis • Cyclical vomiting syndrome • Gastroparesis • Neurological and metabolic diseases • Infantile Gastrooesophageal reflux disease • Intussusception • Eosinophilic oesophagitis • Appendicitis • Food allergy

TABLE 8.1.7 Causes of Vomiting in Adults

TABLE 8.1.8 Diagnostic Approach to Vomiting

TABLE 8.1.9 Los Angeles Classification of Reflux Oesophagitis on Endoscopy LA System Classification of Reflux Oesophagitis on Endoscopy Grade Findings Grade One (or more) mucosal break no longer than 5 mm that does not extend between A the tops of two mucosal folds Grade At least one mucosal break >5 mm but not continuous between the tops of two B mucosal folds Grade At least one mucosal break that is continuous between the tops of two mucosal C folds but which is not circumferential (180°) along the long or short axis, leading to variable degree of gastric obstruction, which can be of a closed-loop type resulting in strangulation. The exact incidence of gastric volvulus is unclear as patients with a chronic presentation may never be diagnosed.2 Approximately, 10%–20% cases of gastric volvulus occur in children less than 1 year, while the other 80% cases are detected in adults, of which 80%–90% are often encountered in the fifth decade of life.3 No significant predilection is seen with either sex or races. Gastric volvulus can be classified on the basis of aetiology, axis of rotation and duration of onset. While classification based on axis of rotation by Singleton is widely accepted and more relevant to the radiologist, classification based on duration of onset of symptoms is more relevant in clinical assessment. On the basis of axis of rotation (Fig. 8.2.15), gastric volvulus is divided into organoaxial volvulus, mesenteroaxial volvulus and the rarest combined/mixed type.

FIG. 8.2.15 Volvulus types schematic diagram. A. Rotation of the stomach along its long-axis results in Organo-axial volvulus, B. Rotation of the stomach along its short-axis results in Mesenteroaxial volvulus. Organo-axial volvulus, by far, the most common type of gastric volvulus, encountered often in the elderly, is characterized by rotation of the stomach along its long axis, that is, cardio-pyloric axis, and resulting in an ‘inverted stomach’ with a horizontal orientation, in the form of anterosuperior displacement of the antrum and posteroinferior rotation of the fundus, so that the greater curvature is displaced superiorly and lesser curvature caudally in the abdomen (Fig. 8.2.16). The site of obstruction in this type of volvulus is at the cardia or at pylorus. It has a higher predisposition towards strangulation and ischaemia. Organo-axial volvulus also shows association with the paraoesophageal hernia or diaphragmatic defects, which allows abnormal movement of the stomach along the long axis. If the degree of rotation is less than 180 degrees, the patient may have an incomplete or partial volvulus which is not completely obstructing and may be asymptomatic; it may be more appropriate to describe it as organo-axial position rather than volvulus.

FIG. 8.2.16 Organo-axial volvulus. Barium meal in an infant reveals flipping of the stomach along its long axis with the greater curvature positioned superiorly, antropylorus located superiorly to the right and the fundus located inferiorly with stretching of the GE junction (not visible on these images). Mesenteroaxial volvulus is less commonly encountered (30%) and accounts for about 29% of cases, is reported more often in young adults or children. It occurs when the stomach rotates around its short (transverse) axis, that is, line connecting the midpoint between the lesser curvature and the greater curvature of the stomach, leading to a vertically oriented stomach, with anterior rotation of the pylorus, antrum and resultant displacement of the antrum above the gastrooesophageal junction (Figs 8.2.17 and 8.2.18). The site of obstruction is usually at antropyloric region. It is usually not associated with a diaphragmatic defect and is often idiopathic.

FIG. 8.2.17 Mesentero-axial volvulus. The gastroesophageal junction (GEJ) and fundus are normally positioned with the body and antrum located superiorly and the gastroduodenal junction is at the same level as the GEJ. (Source: Courtesy of Dr Govind R Jankharia. Picture by Jankharia, Mumbai.)

FIG. 8.2.18 Mesenteroaxial volvulus. 70/F with anemia, suspected volvulus on upper GI scopy. A fluid filled dilated thoracic esophagus with normally positioned gastroesophageal junction (GEJ) and the pylorus and distal body of stomach along with omentum have herniated through the esophageal hiatus into the posterior mediastinum with the gastroduodenal junction (GDJ) above the GEJ, consistent with mesenteroaxial volvulus. The first segment of duodenum is stretched as a result. The gastric fundus (F) and proximal body (B) lie below the level of diaphragm and are filled with fluid. The third and rarest type of gastric volvulus is the combined type when the stomach shows both rotation along the short and long axes. Based on aetiology of rotation, gastric volvulus can be subdivided into either primary or secondary. Primary gastric volvulus representing 25%–30% of the cases, is more common in the adults. It occurs in the subdiaphragmatic location due to abnormality in the gastric fixation, exclusively because of disruption, laxity or absence of the gastric ligaments which anchor the stomach in place. These ligaments namely the gastrohepatic, gastrocolic, gastrophrenic, gastrosplenic and gastropancreatic ligaments, along with gastro-oesophageal junction and pylorus, provide anchorage and fix the stomach in place intra-abdominally, and prevent abnormal rotation of the mesentery. The primary gastric volvulus usually presents with the mesenteroaxial type of anatomical configuration.

Around 70% of patients present with secondary gastric volvulus occurring due to abnormal rotation around the lead point formed by associated disease. The most common association of gastric volvulus is seen with paraoesophageal hiatus hernia. Other causative factors of volvulus include congenital or traumatic diaphragmatic hernia, diaphragmatic paralysis, eventration, connective tissue disorders, previous surgery, adhesions, peptic ulcer, neoplasm, splenomegaly or absence of the spleen and colonic overdistension. On basis of clinical presentation and speed of onset, gastric volvulus can be acute, subacute or chronic. Acute gastric volvulus is a surgical emergency and usually presents with sudden onset epigastric pain, distension, non-bilious vomiting or severe retching, depending on the degree of obstruction. The Borchardt triad of acute volvulus comprises severe epigastric pain and distention, retching but inability to vomit, and difficulty or impossibility of passing a nasogastric tube and may be observed in 70% of cases. Other symptoms include hematemesis due to mucosal sloughing in stomach gangrene or mucosal tear due to retching, dysphagia and dyspnea. Even after prompt treatment, mortality of acute gastric volvulus can be up to 30%–50%, likely secondary to gastric ischaemia, perforation or necrosis resulting from severe gastric obstruction (closed-loop obstruction) causing vascular compromise, making it a life-threatening surgical emergency. Chronic gastric volvulus represents spectrum of diseases from long-standing partially obstructed volvulized stomach with incomplete gastric obstruction on the one side, and intermittent volvulus of stomach with recurrent episode of acute symptoms as the other presentation. Chronic gastric volvulus usually presents with intermittent complaints of vague epigastric pain, non-bilious vomiting, dysphagia or early satiety, dyspepsia and sometimes regurgitation. Due to nonspecific clinical symptoms, diagnosing gastric volvulus is very challenging on the first instance and requires a high clinical suspicion. Diagnostic imaging, along with clinical findings are usually required to achieve the correct diagnosis, and also plays major role in excluding the other common differential diagnosis, like pancreatitis, cholecystitis or pneumonitis etc. The diagnostic modalities useful in suspected cases of gastric volvulus are plain radiographs, upper gastrointestinal contrast (barium) studies, computed tomography and upper gastrointestinal endoscopy. Plain chest and abdominal radiographs may reveal a radiolucent hollow viscus, with or without an air-fluid level, in the chest (when associated with PEH) or upper abdomen. The presence of a nasogastric tube may assist in identifying a malpositioned stomach, and administration of contrast via the nasogastric tube may be confirmatory in this regard. Furthermore, chest radiographs may identify evidence of underlying anatomic abnormalities predisposing to gastric volvulus, including elevated hemidiaphragm due to phrenic nerve palsy or diaphragmatic eventration and rib fractures suggesting prior thoracoabdominal blunt trauma. The plain radiographs may show two air-fluid levels in the antrum and fundus, or a single air

bubble with no additional luminal gas in the supine position. A retrocardiac air-fluid level may be seen secondary to hernia and presence of intramural air (gastric emphysema) can be visualized as a radiolucent stripe in the gastric wall. At times a large hiatus hernia may be complicated by volvulus (Fig. 8.2.19).

FIG. 8.2.19 Hiatus Hernia with volvulus. A. A large air-fluid level is seen on the chest radiograph in the midline in retrocardiac and subdiaphragmatic location, B. Barium meal reveals herniation of the stomach into the mediastinum with GE junction located above the diaphragmatic hiatus (not visible on this image) and the greater gastric curvature flipped superiorly to the right, fundus inferiorly to the left and the duodenal C loop located to the left of the midline. This favours a hiatus hernia with associated volvulus. C. Post operative chest radiograph reveals resolution of findings with gastric air bubble seen in left subdiaphragmatic location. Passage of orally administered contrast like barium can demonstrate the anatomy and also assess the degree of obstruction. As mentioned above, the position of the gastric curvatures and the gastrooesophageal junction are useful in differentiating the anatomical subtype of volvulus. Computed tomography may be more feasible in an acute emergency setting in order to identify abnormal gastric position, axis and multiplanar reconstructions, especially in the coronal plane, can well elucidate the findings and an associated complication like ischaemia. CT has an overall 90% accuracy in the diagnosis with identification of gastro-oesophageal junction and pylorus lying in close proximity to each other and the transition point at the pylorus known to have 100% sensitivity and specificity. Abnormal antral folds may be

seen secondary to the twisting. Stenosis at the neck of the hernia is the CT finding with the second-highest sensitivity (77%–80%) and specificity (94%–97%). CT findings of oedematous or hypoenhancing gastric wall, pneumatosis, pleural effusion or pneumoperitoneum, as indicators of gastric ischaemia are not common but specific when identified. An upper gastrointestinal endoscopy confers both diagnostic and therapeutic benefit, although it may establish the diagnosis in only 28%–45% patients and also, the endoscopic procedure may reduce the volvulus missing the diagnosis by an unwary endoscopist. However, it still remains the best method to detect mucosal ischaemia. Flexible endoscopy also has the advantage of placing a nasogastric tube as it may not be possible with a blind technique at the bedside in the setting of organoaxial volvulus and an obstructed gastro-oesophageal junction. Nasogastric decompression forms the initial management of gastric volvulus with emergent laparotomy or laparoscopy to assess gastric viability, resect gangrenous portion if any and perform de-rotation and gastropexy (fixation of the stomach to the diaphragm and/or the anterior abdominal wall) with or without gastrostomy with repair of secondary factors like paraoesophageal hernia.

Gastric erosions Erosions are focal shallow areas of ulcerations confined to the epithelium or lamina propria without extending through the muscularis mucosae into the submucosa. NSAIDs are the most common cause of gastric erosions while other incriminated factors include Helicobacter pylori infection, alcohol, viral infections, Crohn’s disease, stress and iatrogenic trauma. Erosions may be visible on double-contrast barium examination obtained with good mucosal coating, as multiple tiny 1- to 2-mm collections of barium, often with a surrounding mound of oedema appearing as a filling defect in the barium pool (Fig. 8.2.20). They are usually located in the gastric antrum and tend to occur along thickened folds.

FIG. 8.2.20 Gastric erosions. Erosions are seen as small pits of barium surrounded by an edematous mucosa (seen as radiolucent halo).

Gastric ulcer A gastric ulcer is a focal area of mucosal disruption that penetrates through the submucosa and frequently the muscularis mucosae into the deeper layers of the gastric wall. Almost 95% of the gastric ulcers are benign, with majority caused by H. pylori infection. Other causes include NSAIDs abuse, alcohol, stress, burns, corticosteroids, coffee, smoking, gastric reflux of bile acids and hereditary factors. Patients usually complain of epigastric pain, retrosternal burning and/or discomfort. They may also experience nausea, bloating, belching and vomiting. Gastric ulcers typically present with symptoms immediately after a meal, vis-à-vis duodenal ulcers which present usually two hours after a meal. Some patients may present with ulcer complications like perforation, obstruction (due to fibrosis) or bleeding resulting in hematemesis or melena. Gastric adenocarcinoma is also a known secondary complication of chronic gastric ulceration. The biphasic double-contrast barium technique was used for radiologic diagnosis and characterization of gastric ulcers, although this has now been superseded by upper GI endoscopy establishing itself as the primary diagnostic investigation of choice. Yet, to be familiar with the radiographic appearances for the gastrointestinal radiologist, ulcers may be seen in profile or en face. Based on the radiological features, differentiation between benign or malignant

features can be done, and biopsy of those with malignant features is a must. A benign gastric ulcer is typically seen as a focal outpouching or ulcer crater with associated smooth, symmetric, thickened folds radiating to the edge of the crater (Fig. 8.2.21). Ulcer craters most often appear as round or ovoid collections of barium but may sometimes appear linear or flame-shaped. A thin radiolucent line of inflammation/oedema known as ‘Hampton’s line’ may be seen demarcating barium in the ulcer crater at its neck from the gastric lumen. With increasing oedema adjacent to the ulcer, a wide radiolucent band or ulcer collar may be seen. Occasionally, inflammatory swelling forming an ulcer mound surrounding the crater appears mass-like, seen in profile as smooth masses projecting into the lumen on both sides of the crater, the ulcer seen in the centre of the mound. In double-contrast barium, the ulcer crater may be empty and the peripheral outline of the crater may be seen as a rim.

FIG. 8.2.21 Benign gastric ulcer. A smoothly marginated ulcer crater opacified with barium with mucosal folds radiating till the ulcer crater, suggests a benign etiology like a peptic ulcer. Most benign gastric ulcers are located on the lesser curvature and adjacent posterior wall with 90% affecting the antrum or body. Less commonly, they are located along the greater curvature or anterior wall. Most benign gastric ulcers are less than 1 cm in diameter, are usually round or ovoid but may also have a serpentine, flame shape or rod-shaped morphology. Most often, they are solitary but can be multiple in 20% cases. Upright compression views are helpful for evaluating ulcers on the lesser curvature. Ulcers on the dependent

posterior wall or the greater curvature fill with barium in the supine or oblique position, revealing the characteristic ulcer crater. Anterior wall ulcers may appear as ring shadows with barium coating the rim of an unfilled crater, and prone compression views may demonstrate the ulcer filling with barium. Benign gastric ulcers usually respond well to medical treatment. With healing, the crater decreases in size and may change shape; the earliest radiographic sign of a healed ulcer is the presence of folds converging to the site of the ulcer crater. Healing ulcers can result in deformity and tapered luminal narrowing. Although malignant ulcers also occur commonly in the antrum, an ulcer in the proximal stomach unless proved otherwise, should be suspected for a malignancy. These ulcers typically protrude into the gastric lumen, show irregularly thick margins (Fig. 8.2.22), and are seen more eccentrically within an ulcer mound depending upon the tumour vascularity. Adjoining mucosal folds show irregular thickening and do not converge to the ulcer crater.

FIG. 8.2.22 Malignant gastric ulcer. A. Irregularly marginated ulcer crater opacified with barium (straight arrow) with a radiolucent halo due to heaped up thickened mucosa forming an irregular collar (dashed arrow). B. An irregularly marginated lobulated mural-based lesion along the greater curvature of the inferior gastric body bulging into the lumen (due to tumour induced desmoplasia). (Source: Courtesy of Dr Govind R Jankharia. Picture by Jankharia, Mumbai.) CT findings in patients with gastric ulcers are often nonspecific. It may show focal gastric wall thickening, and a focal outpouching containing oral contrast may sometimes be seen. CT is useful to assess for complications of gastric ulcers like perforation with pneumoperitoneum, peritonitis and extravasated positive oral contrast. Active haemorrhage with an ulcer may be demonstrated as extravasated intravenous contrast on a dynamic CT scan. CT may also show findings of gastric outlet obstruction related to antral narrowing. MRI sequences done to demonstrate peptic ulcer include T2weighted HASTE, gadolinium-enhanced standard and fat-suppressed SGE images. Enhancement of peptic ulcers appears slightly hyperintense relative to the gastric wall on the immediate

postgadolinium images and moderately hyperintense on the 2-minute post-gadolinium fat-suppressed SGE images. KE Y PO INT S • Gastric ulcers are less common than duodenal ulcers but are more likely to bleed. • Benign gastric ulcers usually appear as focal ulcer craters with associated smooth, symmetric, thickened folds radiating to the edge. • Benign ulcers are most often located on the lesser curvature or posterior wall of the antrum or body, but may occur in the distal greater curvature with NSAID use. • A small percentage of gastric ulcers are malignant. Ulcers on the high greater curvature should be considered malignant until proven otherwise.

Gastric Ulcer Age Sex Location

Benign

Adults of all ages Male = female Antrum, majority in lesser curvature Ulcer crater Central Ulcer shape Usually round Ulcer collar Uniform Mucosal fold Uniform shape Fold To edge of crater convergence Projection beyond gastric wall Carman Meniscus sign Multiplicity Associated duodenal ulcer Focal wall thickening Contrast enhancement on CT Perigastric abnormality

Yes

Malignant elderly More in males Antrum, body, but can occur elsewhere Eccentric, nodular Irregular Irregular Irregular and distorted Not reach ulcer margin, ‘moth-eaten’ folds near crater edge and or clubbed/fused folds No Large flat ulcer with heapedup edges

20%–25% patients Frequent

Convex inner margin to the lumen Uncommon Uncommon Usually >5 mm

Both ulcer base and surrounding ulcer wall show contrast enhancement –

Greater contrast enhancement but hypovascularity may be typically seen in signet cell cancers Adenopathy, liver metastases

Complications of peptic ulcer include perforation which could be free perforation or the contained type. Penetrating ulcers on the anterior wall of the stomach may perforate directly into the peritoneal cavity, whereas those on the posterior wall of the stomach or duodenum usually result in a walled-off or confined perforation. Free perforation can occur when ulcers along the anterior gastric wall directly communicate with the peritoneal cavity, with pneumoperitoneum being identified on a plain abdominal radiograph, however, the absence of pneumoperitoneum does not exclude the diagnosis. In acutely ill patients with suspected visceral perforation, if there is no pneumoperitoneum visualized on the radiograph, a CT scan may be performed following oral administration of water-soluble positive enteric contrast to demonstrate leak of fluid from the gastric lumen into the subhepatic space or freely into the peritoneal cavity.

The resultant secondary inflammatory changes at the site of perforation can also be visualized. Less frequently, ulcers on the posterior gastric wall can perforate into the lesser sac with concomitant peripancreatic inflammation. More often, ulcers at these locations tend to perforate but localized inflammation and fibrous adhesions ten to confine the leak. The ulcer can penetrate adjoining structures like the pancreas, transverse mesocolon, liver (resulting in a hepatic abscess) and less commonly the spleen or colon. Some penetrating ulcers may also fistulize into other hollow organs, like gastrocolic, gastroduodenal fistula or occasionally into the pericardial cavity. The double-channel pylorus is an acquired gastroduodenal fistula caused by a penetrating ulcer in the distal antrum usually along the lesser curvature, which directly erodes directly into the base of the duodenal bulb. The development of a double-channel can paradoxically cause symptomatic improvement due to better gastric emptying. Although the double-channel pylorus is difficult to visualize on endoscopy, it is readily detected on barium studies, typically manifested by two discrete tracks extending from the distal antrum into the base of the duodenal bulb. The track towards the greater curvature usually represents the true pyloric channel, whereas the track towards the lesser curvature side represents the acquired fistula; both barium-filled tracks may be separated by a thin radiolucent septum. Approach to gastric ulcer Aetiology: • H. pylori • NSAIDs, Aspirin • Systemic disease: Crohn’s, sarcoidosis, amyloidosis, esonophic gastroenteritis, vasculitis • Hyperacidity: Zollinger–Ellison syndrome • Other infections: CMV, HSV < TB, syphilis, fungal Risk Factors for Idiopathic Peptic Ulcer Disease • Demographics: white race, old age • Psychoactive substances: tobacco, alcohol • Genetic: mucin genes, HLA- DQA1 • Co-morbidities: Cirrhosis, end stage renal disease, DM, CVA, malignancy • Chronic mesenteric ischaemia • Psychological stress Diagnostic Work-Up: • To exclude H. pylori • History of ulcerogenic drugs

• Biopsy to exclude occult carcinoma, inflammatory bowel disease, vasculitis • To exclude ZES: • Fasting serum gastrin and chromogranin A • Basal and maximum gastric acid secretion • Secretin test • CT/MRI to rule out gastrinoma • Somatostatin receptor scintigraphy (investigation of choice if available), e.g. 68Ga-Dotatoc, 68Ga-Dotanoc, 68Ga-Dotatate) • Endoscopy: multiple peptic ulcers or ulcers distal to D1 in the presence of hypergastrinemia • To exclude other infections

Gastric wall thickening Gastric wall thickening may be focal or diffuse and a broad algorithmic approach to the finding is illustrated in Table 8.2.1. TABLE 8.2.1 Approach to Thickened Gastric Folds

Gastric Wall Thickening (Wall Thickness >7 mm With Adequate Luminal Distension) Localized Gastritis Lymphoid hyperplasia Infections – TB, viral, fungal or abscess Infiltrative – sarcoid, amyloid, eosinophilic

Diffuse Gastritis (most common cause) Infiltrative – sarcoid, amyloid, eosinophilic Zollinger–Ellison syndrome Acute pancreatitis

Crohn’s disease Zollinger–Ellison syndrome Varices Menetrier’s disease Ectopic pancreatic tissue Gastric lipoma, leiomyoma Carcinoma

Carcinoma

Lymphoma

Lymphoma

Metastasis

Metastasis

Gastritis Gastritis is characterized by inflammation of the stomach wall and can be broadly classified into acute and chronic types. Acute gastritis may be infective (aetiological agents including H. pylori, other bacteria, viruses or parasites) or noninfective (drugs like nonsteroidal antiinflammatory drugs, alcohol abuse, stress, uremia). Chronic gastritis may be immune or non-immune. Although barium examinations were initially the tool to identify gastritis induced thickening of folds, these are obsolete now for this indication. Ultrasonography can be used effectively to evaluate the stomach and duodenum and mucosal thickness more than 4 mm in the gastric antrum may suggest the presence of gastritis. Normally gut signature on ultrasonography is identified as a hyperechoic mucosal stripe with hypoechoic muscularis mucosa, hyperechoic submucosal layer, hypoechoic muscularis propria with an overlying hyperechoic serosa. Marked transmural gastric mural thickening (with typically increased thickness of the hypoechoic mucosal layer) is typical of gastritis, and would typically resolve following appropriate therapy. Loss of the normal multilaminar gut signature along the posterior gastric antrum is another useful sonographic characteristic of inflammation. CT scanning can also suggest the diagnosis when there is smooth rugal thickening, and the presence of mural stratification on a post contrast CT, in the absence of

a distorting mass or perigastric adenopathy, suggests gastritis. However, CT has a significant limitation as suboptimal luminal distension can mimic thickening of folds, hence optimal gastric distension is required before suggesting the diagnosis. 18-F FDG PETCT can also incidentally reveal a mildly increased FDG uptake in gastritis but is not specific for the diagnosis. The undisputed gold standard investigation of choice for gastritis is endoscopy as it is more sensitive and specific and also enables a biopsy for tissue diagnosis. H. pylori gastritis H. pylori has been implicated as a common cause of gastritis and peptic ulcer. It is a gram-negative bacillus which frequently colonizes the submucosal layer of the stomach and typically within the antrum. It is more common in the developing countries and amongst the lower socioeconomic strata in the developed countries. H. pylori has been recognized to cause acute and chronic gastritis, atrophic gastritis, gastric and duodenal ulcers, gastric carcinoma and gastric lymphoma. The H. pylori bacterium causes an increased production of ammonia, which is toxic to the gastric mucosa. As part of the host’s inflammatory response to the organism and ammonia production, excessive gastrin is produced which stimulates the gastric parietal cells to produce more hydrochloric acid, initiating a mucosal inflammatory response. The inflammatory mucosal degeneration is associated with compensatory regenerative proliferation of the mucosa. Secondary to chronic inflammation and hyperacidity, in addition to the mucosal layer which is affected, there is subsequent spread of inflammation to the muscularis mucosa which causes compensatory thickening of this layer. The gastric antrum is most commonly involved, but the proximal or entire stomach may be affected. On double-contrast barium examination, there may be thickened rugal folds with enlarged areae gastricae greater than 3 mm in diameter, more so in the gastric antrum and are of uniform size and shape. Careful inspection for possible gastric and/or duodenal ulcers should be made. Gastritis may not involve the stomach diffusely and only cause focal thickening, which can simulate a gastric neoplasm. Because the appearances of gastritis and tumours can overlap, endoscopy and a histopathologic analysis is often necessary for a definitive diagnosis. The gastric surface pattern should be carefully assessed - focal disruption of reticular pattern, loss of polygonal contour, and more round or ovoid nodularity of varying size and shape should raise the suspicion for MALT lymphoma. The CT findings of H. pylori gastritis though nonspecific, include gastric wall thickening which is most often circumferential and involving the gastric antrum. Diagnosis of H. pylori gastritis is made by endoscopic brushings or biopsy demonstrating histologic evidence of the organism, positive culture, or evidence of urease activity. Non-invasive tests for H. pylori —such as the urea breath test, serum pepsinogen test, including

pepsinogen I/II, pepsinogen II and immunoglobulin G antibody for H. pylori also have good sensitivity and specificity. H. pylori infection can be eradicated with combination treatment consisting of antimicrobial and antisecretory agents. Atrophic gastritis There are two types of atrophic gastritis, A and B. Type A is seen in elderly and is thought to have an autoimmune aetiology with preferential affection of the gastric fundus and body. Majority of patients with pernicious anaemia have this type and is most frequently seen in northern Europe and Scandinavia. Type B atrophic gastritis which is more common than type A, thought to be multifactorial and/or environmental in aetiology, is more prevalent in China and Japan and less often seen in western world. It typically affects the antrum with chronic H. pylori infection being the common aetiology. Other associated factors may include biliary reflux into the stomach or alcohol. The pathogenetic mechanism involves destruction of the gastric parietal cells, leading to hypochlorhydria and elevated gastrin levels. The parietal cell loss results in loss of protein intrinsic factor (IF) protein production, which is necessary for normal vitamin B12 absorption in the terminal ileum. Lack of IF results in vitamin B12 malabsorption presenting as megaloblastic-type of anaemia. The hypochlorhydria or achlorhydria from parietal cell destruction results in mucosal atrophy, gastritis, with absent or reduced gastric folds and almost complete loss of the gastric fundal mucosal pattern. It can also result in intestinal metaplasia which can be a precursor for gastric cancer. Atrophic gastritis in pernicious anaemia appears as a tubular, narrowed stomach with decreased or absent mucosal folds predominantly in the body and fundus, producing a ‘bald fundus’ appearance (Fig. 8.2.23) on single contrast barium examination. On double-contrast barium examination, patients with atrophic gastritis demonstrate a fundal diameter of less than or equal to 8 cm, absent mucosal folds in the gastric body or fundus, and small (1–2 mm) or absent areae gastricae.

FIG. 8.2.23 Atrophic gastritis. Upper GI endoscopy in a case of anemia revealed atrophic gastritis. Contrast enhanced CT scan images (A, B: Axial images and C, D: coronal reconstructions) show lack of gastric rugal folds (‘bald stomach’). When atrophic gastritis is suspected, an additional clinical evaluation should be undertaken to diagnose and treat pernicious anaemia before irreversible symptoms develop. Patients with pernicious anaemia and occult GI bleeding should undergo evaluation for a superimposed gastric carcinoma. D IFFE R E NT IAL D IAGNO SIS FO R GAST R IC LU MINAL NAR R O WING • Linitis Plastica (scirrhous carcinoma): Gastric luminal narrowing associated with decreased distensibility; but thickened, irregular folds; and distorted, nodular mucosa. Cf. in atrophic gastritis, the mucosa is smooth and featureless with decreased or absent folds. • Additional disorders causing luminal narrowing: scarring from peptic ulcer disease, caustic ingestion, granulomatous gastritis (Crohn’s, tuberculosis, sarcoid) and eosinophilic gastritis. Other associated findings will also be usually seen.

Hypertrophic gastritis Hypertrophic gastritis is characterized by inflammation of stomach resulting in thickened folds (>10 mm in width) predominantly in the fundus and body of the stomach (Fig. 8.2.24). The areae gastricae measuring about 4–5 mm in diameter has a polygonal shape and may be associated with gastric and duodenal ulcers. Underling H. pylori infection needs to be tested for.

FIG. 8.2.24 Hypertrophic gastritis. Oblique and lateral projections from a barium meal reveal markedly coarse (hypertrophied) gastric rugal folds consistent with gastritis. (Source: Courtesy of Dr Govind R Jankharia. Picture by Jankharia, Mumbai.) Menetrier’s disease Menetrier’s disease is a rare disease with a characteristic appearance. It usually occurs in males over age of 40. There is marked gastric fold thickening with gastric glandular hypertrophy, especially in the proximal stomach with reduced gastric acid production (achlorhydria) and a protein-losing enteropathy (hypoproteinaemia) due to increased mucus production which prevents adequate mucosal coating on

barium studies. CT shows markedly bizarre gastric fold thickening in proximal stomach and along the greater curvature but may also extend to the antrum in half of the patients, thus involving the entire stomach. This entity is considered to be a predisposition for gastric cancer. Preserved pliability of the folds of Menetrier’s disease differentiates the a peristaltic/rigid folds in malignancy. Eosinophilic gastritis Eosinophilic gastritis is an uncommon disease characterized by eosinophilic infiltration of gastric wall and can affect the oesophagus, small and large bowel as well. The patient may present with abdominal pain, diarrhoea, nausea or vomiting and weight loss. Half of the patients may have atopy or asthma. Peripheral eosinophilia may be seen in majority of the patients. Imaging studies like fluoroscopy or CT show non-specific wall thickening, especially involving the antrum and can also reveal focal erosions or ulceration (Fig. 8.2.25). There may be associated luminal narrowing and rigidity. Chronic disease resulting in fibrosis can cause significant constriction of the gastric antrum and body, making it difficult to differentiate from linitis plastica.

FIG. 8.2.25 Eosinophilic gastritis and enteritis resulting in small bowel obstruction. 40-year-old male with diffuse abdominal pain and nausea. CT reveals asymmetric irregular nodular annular thickening (A, B) with ulceration (dashed arrow, B) in the gastric antrum which shows reduced distensibility with proximal gastric dilatation. Small bowel obstruction is noted (C) with short segment mural stratification causing luminal narrowing at the zone of transition (D) and skip areas of short segment hyperenhancing mural thickening (D, E) are noted without ‘comb’ sign. No ascites or adenopathy. Endoscopic biopsy confirmed eosinophilic gastritis and enteritis. Eosinophilic gastroenteritis may be a predominantly mucosal, muscular, subserosal or pan mural bowel wall involvement. Eosinophilic ascites may be seen in patients with pan mural involvement. Amyloidosis It is characterized by extracellular deposition of amyloid, an insoluble, fibrillar protein, in the stomach. It involves the stomach as part of a systemic disorder, with isolated gastric deposition being rare. Amyloidosis could be primary (which more commonly affects the gastrointestinal tract) or secondary (manifest as chronic lung disease like rheumatoid arthritis, tuberculosis/bronchiectasis and myeloma). Focal deposition in the gastric wall may result in submucosal tumourlike masses and nodular wall thickening, while diffuse deposition may cause mucosal erosions and ulcerations. Diagnosis is confirmed by

tissue biopsy of an affected organ with Congo red stain which demonstrates green birefringence under polarized light. Pancreatitis Gastric mucosal and mural inflammation is often seen in patients of severe pancreatitis and can result in diffuse wall thickening. Peripancreatic acute fluid collections can cause mass effect on the stomach and cause symptoms of gastric outlet obstruction, and this can also persist in the presence of a large chronic pancreatic pseudocyst in the lesser sac. Crohn’s and other granulomatous disease Granulomatous gastritis can be caused by infectious disease like tuberculosis, sarcoidosis, Crohn’s disease, or maybe part of vasculitis syndrome. Crohn’s is an inflammatory bowel disease which predominantly affects the ileum. However, there may be gastroduodenal involvement in one-fifth of the patients, along with ileocolitis. Isolated stomach involvement is not common. Early disease shows aphthous ulcers, mucosal fold thickening and nodular mucosa with ‘cobble-stone’ appearance. Fibrosis and scarring in chronic disease lead to a normal-appearing gastric body and antrum along with pyloric narrowing showing a funnel or ‘ram’s-horn’ shape. Other infective causes include Candidiasis in the immunocompromised, although gastric acid usually neutralizes the fungus. Candidiasis can be seen as multiple plaque-like mucosal defects which can ulcerate and cause bleeding. Zollinger–ellison syndrome It is a condition in which gastrin-secreting tumour causes hyperstimulation of the parietal cells with overproduction of gastric acid, resulting in recurrent peptic ulcers which can be massive, particularly involving the gastric antrum and proximal small bowel. The hyperacidity in the small bowel also causes excessive small bowel hypersecretion, resulting in diarrhoea and malabsorption. Chronic ulceration can heal with fibrosis and consequently narrowed gastric antrum which may be profound enough to give linitis plastica appearance to the stomach. The aetiological neuroendocrine tumour is gastrinoma, a non-beta islet cell tumour which is mostly located in the pancreas, but may be found in the duodenal wall or maybe extraintestinal. It may be sporadic or multiple (typically as part of multiple endocrine neoplasia type I) and malignant, metastasizing to the liver in half of the patients. Increased gastric fluid may prevent proper coating of stomach with barium. Gastric and duodenal ulceration may be seen. CT may show mucosal fold thickening and metastatic liver lesions. Localization of the primary gastrinoma as a hypervascular lesion on a triphasic CT scan commonly seen in the duodenal wall or pancreas (Fig. 8.2.26)

may be difficult as functioning tumours can be too small to be easily missed and may require multi-modality investigation by endoscopic ultrasound, angiography, selective portal venous sampling or occasionally even an explorative laparotomy.

FIG. 8.2.26 Gastrinoma. Patient with recurrent peptic ulcer disease was investigated with CECT which reveals multiple hyperperfused nodular lesions within the gastrinoma triangle as seen within the retrohepatic-suprapancreatic location (A, F), within the medial wall of the gastroduodenal junction (B, large arrow), two lesions along the lateral wall of the 1st part of the duodenum (B, small arrow and F) and hypervascular nodules suggesting metastases in the left lobe of the liver (D, E, F). Histopathology from the gastroduodenal wall lesion and liver lesion confirmed the diagnosis of gastrinoma. Corrosive ingestion Corrosive gastritis usually occurs from accidental or suicidal ingestion of caustic substances like bleach, lye, household cleaners. Although acute ingestion of chemicals typically affects the oesophagus first, they may erode the gastric mucosa when ingested in large quantity and typically affect the gastric antrum when consumed in the upright position. The stomach is not affected by alkaline agents as gastric acid can neutralize these substances but acidic corrosives, can severely

denude the stomach. The damage depends upon the concentration, type and quantity of ingestion of the harmful material. In the initial stages post ingestion, there is mucosal necrosis with sloughing which is seen as mucosal irregularity and oedema on fluoroscopy or CT. Severe full thickness tears may lead to gastric wall perforation and cause pneumoperitoneum or peritoneal fluid. In later stages, healing by fibrosis and stricture formation can result in a deformed stomach with scarring and contraction. Radiation gastritis With refinement in radiation therapy techniques and portals, radiation gastritis is a less commonly observed entity. The acute effects post irradiation may be non-specific like mucosal thickening which can ulcerate if radiation doses are severe. Chronic fibrosis can cause a strictured or contracted stomach. Emphysematous gastritis Emphysematous gastritis is rare, life-threatening gastritis due to infection with gas-producing organisms, often encountered in the elderly with uncontrolled diabetes mellitus. Patients with emphysematous gastritis are acutely ill and may present with abdominal pain, hematemesis, tachycardia, fever and shock. Gastric insults like caustic ingestion, alcohol abuse, trauma, gastroduodenal surgery or gastric volvulus disrupt the gastric mucosal barrier and allow for subsequent infection with gas-producing organisms such as Escherichia coli, Staphylococcus aureus, Clostridium perfringens. Abdominal radiographs may demonstrate mottled gas outlining the stomach. Entrapped foci of air between gastric rugae must be differentiated from air within the wall and needs CT to elucidate this. Intramural gas in emphysematous gastritis may have a streaky, bubbled, or mottled appearance which should maintain a constant relationship to the stomach with positional changes. CT is very sensitive to localise even a small amount of gas in the wall of the stomach as well as additional complications, including portal venous gas and pneumoperitoneum. Water-soluble contrast material should be used rather than potentially injurious barium-based agents for fluoroscopic examinations. Intramural dissection of orally administered contrast material or frank extravasation may be seen. Treatment involves fluid support, correction of electrolyte and metabolic abnormalities, and broad-spectrum antimicrobial therapy. Surgery is necessary in the event of perforation; otherwise, it is avoided until sepsis is controlled, as there is a very high risk of secondary complications. Mortality rate can be high despite optimal treatment. D IFFE R E NT IAL D IAGNO SIS FO R GAST R IC MU R AL AIR

• Benign gastric emphysema: Intramural gas without associated gas-producing infection. Patients are relatively asymptomatic. Gas enters the gastric wall following a mucosal rent caused by increased intraluminal pressure (gastric outlet obstruction) or iatrogenic trauma (instrumentation, endoscopy). Intramural gas in gastric emphysema typically appears long, thin and linear rather than bubbly and mottled, as noticed in emphysematous gastritis. There is also no associated thickening of the gastric folds. • Gastric pneumatosis: rare form of pneumatosis intestinalis with multiple gas-filled blebs or cysts in the gastric wall.

Gastric polyps Gastric polyps could arise from the mucosa or submucosa or even be extrinsic and these encompass a broad spectrum of pathologies of varied histology, neoplastic potential and management. Although asymptomatic in most cases, polyps especially when large can cause bleeding, anaemia, obstruction or abdominal pain. Broadly, gastric polyps could be epithelial, mesenchymal and hamartomatous. Epithelial polyps include hyperplastic, fundic gland and adenomatous subtypes. The fundic gland polyps are the most common (77%) variety of gastric polyps which can be seen as sporadic ones or associated with proton pump inhibitor (PPI) use. These are sessile polyps located in the gastric fundus and body, usually very small (1–8 mm) and typically seen in middle-aged women. These polyps are identified in stomach in about 40% patients of familial adenomatous polyposis coli. Due to the low malignant potential, fundic gland polyps do not warrant polypectomy although a biopsy is warranted to exclude dysplastic change but large polyps greater than 1 cm are often resected to avoid tissue sampling error. In double-contrast barium studies, hyperplastic polyps on the dependent gastric surface (posterior wall) typically appear as smooth, round filling defects in the pool of barium (Fig. 8.2.27), vis-à-vis polyps on the non-dependent surface (i.e. the anterior wall) which are seen as ring shadows etched in white due to trapping of the barium between the edge of the polyp and adjacent mucosa.

FIG. 8.2.27 Gastric polyps. Multiple sharply demarcated rounded filling defects in the barium pool consistent with polyps. (Source: Courtesy of Dr Govind R Jankharia. Picture by Jankharia, Mumbai.) Differential Diagnosis for Sessile Gastric Polyp: Hyperplastic polyps seen as ring shadows on double-contrast studies must be differentiated from shallow ulcers on the dependent (posterior) gastric wall and from unfilled ulcers on the nondependent (anterior) wall. With flow technique, however, shallow ulcers on the dependent wall should fill with barium, while ulcers on the non-dependent wall should fill with barium on prone compression views. If the polyps are pedunculated, the stalk may be seen en face as an inner ring shadow overlying the head of the polyp, producing the ‘Mexican hat’ sign, which is typically demonstrable with pedunculated polyps in the colon. Hyperplastic polyps by themselves are not premalignant, but occur more commonly in patients who have other risk factors for malignancy like atrophic gastritis, post gastric resection and bile reflux gastritis. When associated with H. pylori infection, 80% of hyperplastic polyps resolve spontaneously once the infection is controlled. They are usually sessile or pedunculated, are less than 2 cm in diameter, and typically occur in the antrum. The size cut-off for

polyp resection is debatable, with some authors preferring a minimum 2 cm size for polypectomy, while others recommend resection of all polyps larger than 0.5 cm. Furthermore, the risk of adenocarcinoma in the surrounding non-polypoid tissue is greater than in the polyp itself and hence, multiple biopsies from the adjoining mucosa, rather than polyp itself is recommended. Adenomatous polyps are true neoplasms and premalignant, with tubular, villous and tubule-villous histologic subtypes. Adenomas are usually solitary, greater than 1 cm and commonly encountered in the antrum. They could be sessile or pedunculated, and usually show a lobulated contour. Villous adenomas show a frond-like morphology seen as feathery or serrated margin on imaging. Malignancy is seen in 50% of adenomas greater than 2 cm size especially when of the villous variety. Due to the premalignant potential, it is recommended to perform a complete removal of the adenoma, with further examination of the entire gastric mucosa for abnormalities, all of which should also be sampled. Further, follow-up by endoscopy after resection is necessary at 6 months (for incompletely resected polyps or high-grade dysplasia) or at 1 year (for all other polyps). Hamartomatous polyps result from disordered growth of tissues indigenous to the site of origin; these are classically mucosalbased but can develop from any of the embryonic layers. Examples include Peutz-Jeghers and juvenile polyps, as well as hamartomatous polyps without specific eponyms. These can be either sporadic in nature or may be associated with various polyposis syndromes like Peutz-Jeghers syndrome, juvenile polyposis syndrome, CronkhiteCanada and Cowden syndrome. Of these, the Peutz-Jeghers polyps have malignant potential, and the average age of patients presenting with gastric carcinoma is estimated to be 30 years. Current guidelines, therefore, recommend that gastric Peutz-Jeghers polyps larger than 1 cm should be resected endoscopically, and patients should receive annual surveillance; whereas polyps less than 1 cm must receive surveillance once every 2 to 3 years. Juvenile polyps are typically solitary pedunculated hamartomatous lesions in the antrum and range from 3 mm to 20 mm. When found alone, they are believed to be benign incidentalomas; however, when multiple juvenile polyps are seen, a syndrome of juvenile polyposis should be considered. Juvenile polyposis is an autosomal dominant disorder which carries a life-time gastric malignancy risk of greater than 50%, and therefore endoscopic screening is recommended every 3 years from the age of 18 years. Mesenchymal polyps include inflammatory fibroid polyp, GISTS, leiomyomas and granular cell tumours. These arise from the mesenchyme and typically have a more nodular rather than polypoidal morphology. In general, syndromic polyps carry a higher risk of adenocarcinomatous transformation as compared to sporadic polyps but the gastric specific data is unavailable.

Gastric cancer Although on the decline, gastric carcinoma remains the fourth most commonly diagnosed cancer worldwide and the second most lethal cancer following lung cancer. There are wide variations in the geographic distribution, epidemiological trends, presentation and location of gastric carcinoma. The incidence continues to remain high in the Far East than the Western World. High-risk countries include Japan, Korea and China whereas low-risk countries include India, Australia and North America. More than 60% of cases occur in developing countries and men have approximately twice the predisposition as women. It is the third most common cancer in males and fifth most common cancer in females worldwide. The median age at diagnosis is 71 years and 5-year survival is approximately 25% for advanced gastric cancers. Only 24% of gastric cancers are localized at the time of diagnosis, 30% have metastatic lymph nodes and another 30% have distant metastatic disease. Survival rates are predictably higher for those with localized disease, the 5-year survival rate being 60%. The decline in incidence is limited to non-cardia gastric cancers while the number of newly diagnosed cases of perigastric and GE junction adenocarcinoma has increased six folds since the 1980s. These proximal tumours are thought to be biologically more aggressive and more complex to treat. Aetiology and risk factors A host of factors are implicated as causes of gastric carcinoma. Widely diverse geographic disparities suggest both genetic and environmental contributions. Gastric carcinoma is more common in the Asian subcontinent than in the western countries. Gastric carcinomas are also seen as a part of the hereditary non-polyposis syndromes such as Peutz–Jegher’s Syndrome and familial adenomatous polyposis. Mutations of E-Cadherin gene are also a cause of hereditary diffuse gastric cancer. Diets poor in fruits and vegetables, rich in smoked or poorly preserved foods, salt nitrates and nitrites, infection with H. pylori and smoking are considered as significant risk factors for developing carcinoma stomach. Chronic atrophic gastritis, previous gastric surgery, gastric polyps, obesity and low socioeconomic status are all associated with increased risk of gastric carcinomas. AE T IO LO GY O F GAST R IC C ANC E R • Incidence greater in the Asian subcontinent (highest Japanese population) as compared to Western countries like Europe and the USA. • Diet: reduced intake of fruits and vegetables, increased smoked or preservative food, increased intake of salt, nitrates and nitrites. • Infection with H. pylori. • Smoking, irradiation.

• Low socioeconomic status. • Obesity and gastro-oesophageal reflux associated with Barrett’s oesophagus, cardio oesophageal junction and proximal gastric cancers. • Atrophic gastritis, pernicious anaemia, gastric polyps, partial gastrectomy, and Ménétrier disease. • Genetic (1%–3%): Mutations of the E-cadherin gene associated with diffuse gastric cancers. • Hereditary non-polyposis syndromes like Peutz-Jegher’s syndrome and familial adenomatous polyposis. Segmental distribution of Gastric Adenocarcinoma Fundus/Cardia: 30% Body: 30% Antrum: 30% Entire stomach: 10% Patients with gastric carcinoma usually have non-specific symptoms that often lead to delays in diagnosis. Most common symptoms at the time of diagnosis are upper abdominal pain, fatigue and weight loss. Other frequently found symptoms are dysphagia, early satiety, nausea and vomiting which may occur due to gastric outlet obstruction. Anaemia is a common finding in the elderly. Advanced disease may manifest as a lump in the abdomen, hepatomegaly from liver metastases, abdominal distension due to ascites from peritoneal disease, jaundice and lymphadenopathy. On the odd occasion, one may come across an asymptomatic patient who is incidentally discovered with gastric cancer on a screening endoscopy. Pathology Malignant tumours of stomach can be divided into four major subtypes on the basis of cellular origin: epithelial, mesenchymal, neuroendocrine and lymphoma. Malignant epithelial tumours constitute the majority of gastric neoplasia and nearly 90% of them are adenocarcinoma. 2010 WHO classification recognizes four major histologic patterns of gastric cancers: tubular, papillary, mucinous and poorly cohesive (including signet ring cell carcinoma), plus multiple uncommon histologic variants. The signet ring cell carcinoma (defined by the presence of signet ring cells in over 50% of the tumour) accounts for nearly 10% of gastric cancers and its prognosis is controversial. Most authors in the past have recorded a worse prognosis with signet cell cancers whereas recent studies have stated it to have similar prognosis as other subtypes but it still remains a diagnostic challenge as even 18-F-FDG does not show significant expression in these tumours. The Borrmann classification divides gastric carcinoma based on gross appearance into four subtypes: Type I (polypoid and fungating lesions), Type II (polypoid lesions with central ulcerations), Type III

(lesions with ulcerated and infiltrating margins) and Type IV (linitis plastica). However, the simplest and most widely accepted classification is the Lauren classification which divides histological classification of gastric carcinoma into the diffuse, intestinal and mixed types. Diffuse type is seen in young patients and is associated with E. Cathedrin gene mutation. There is deep infiltration of gastric wall with marked desmoplasia and more gland formation. These tumours present as linitis plastica and tend to be poorly differentiated or of the signet ring variety. Intestinal type is related to environmental factors, secondary to chronic atrophic gastritis, H pylori infection and occurs in high-risk areas. These are more differentiated and show an expansile growth pattern with recognizable gland formation similar to colonic mucosa. Those cancers having features of both intestinal and diffuse types are considered mixed. Lauren classification

Intestinal Type Pathological Characteristics

Route of Dissemination Site

Demographics Prognosis Etiopathogenesis

Diffuse Gastric Type

Tumour cells exhibit adhesion, are arranged in tubular or glandular formation and are frequently associated with intestinal metaplasia

Lack of adhesion by tumour cells which infiltrate the stroma as single cells or small subgroups, resulting in a population of noncohesive, scattered tumour cells.

Lymphatic or vascular invasion

Peritoneal dissemination

Lesions scattered in distant locations, typically gastric antrum

Gastric body

Elderly male

Younger females

Better overall prognosis

Rapid progression and poorer prognosis

Environmental factors like H. pylori and diet.

Less affected by environmental factors than the intestinal type, although HP infection may also be implicated in the development of diffuse gastric cancer.

Eradication of H. pylori infection reduces incidence of chronic atrophic gastritis, but the risk of intestinal metaplasia or gastric cancer is not prevented Pathway: Chronic inflammation → Atrophic gastritis → intestinal metaplasia → dysplasia → gastric carcinoma

Intracellular mucin may displace the nucleus resulting in signet appearance

Active gastritis considered as major risk factor Chronic inflammation → Gastric carcinoma

Intestinal Type Gene expression

CDH1, CDX-2, MSI, HER2

Diffuse Gastric Type CDH1

Biomarkers of lauren classification Certain genes or proteins exhibit varying degrees of expression in intestinal gastric cancer, compared with diffuse gastric cancer and may serve as biomarkers representing two different pathogenetic mechanisms. However, the specific role of such biomarkers to prognostic gastric cancer is still unclear. CDH1 mediates cell adhesion and its expression is significantly greater in intestinal gastric cancer than in the diffuse type, expression of CDH-1 is lesser in less differentiated cancers. However, in patients with family history of diffuse gastric carcinoma, who exhibit CDH1 mutation, endoscopy should be strengthened, or preventive total gastrectomy may be recommended, as CDH1 mutation carriers have a lifetime risk of 70%– 80% of developing diffuse gastric cancer. On the other hand, Caudal type homeobox-2 (CDX-2) shows higher expression in intestinal gastric cancer compared with the diffuse type, and is considered as a positive prognosticator based on majority of the studies. Microsatellite instability (MSI) may be seen in about 20% of gastric carcinomas and is more common in the intestinal type compared with the diffuse type of gastric cancer, but its role as a prognosticator is controversial. Human epidermal growth factor receptor 2 (HER2) also shows higher expression in the intestinal type and Trastuzumab is the drug used for the treatment of tumours exhibiting positive HER2 expression. Despite the vast biological heterogeneity of gastric cancers, detecting expression of drug-related genes prior to treatment may enable selection of efficient chemotherapeutic agents to design optimal treatment regimens for gastric cancer. Patterns of tumour spread Dissemination of gastric cancer can occur by multiple routes like direct invasion of adjacent organs; lymphatic dissemination; subperitoneal dissemination along the perigastric ligaments, mesentery, or omentum; transperitoneal seeding; and/or hematogenous dissemination. Direct Invasion: Gastric carcinomas especially the diffuse variety show a propensity to spread through direct contiguous invasion of adjacent peritoneal reflections and also to adjacent organs (which is referred to as stage T4b). Initial growth of tumour occurs by penetration of gastric wall, extension within the wall longitudinally and through the wall. Spread via the perigastric ligaments can occur as follows: the liver via the gastrohepatic/hepatoduodenal ligament, into the colon via the gastrocolic ligament, the spleen across the gastrosplenic ligament and into the pancreas via the lienorenal or hepatoduodenal ligament. Direct contiguous extension can also occur into the diaphragm, parietis, adrenal, kidney, small bowel and

retroperitoneum. Direct tumour seeding is also known along laparoscopic and percutaneous biopsy tracts. It must be noted that longitudinal extension along the gastric wall rostrally into the oesophagus or caudally into the duodenum does not classify for T4b disease. Transperitoneal Dissemination: In more than 50% patients of gastric cancer who have had a curative (R0) surgical resection, the most common route for disease recurrence is transperitoneal, which can occur via penetration of the peritoneal layers and disseminate into the peritoneal cavity through ascitic fluid. This form of disease dissemination often renders the disease surgically incurable. Peritoneal metastases may present as ascites, discrete or plaque-like soft tissue nodularity along the peritoneum or bowel serosa and irregular enhancing and thickened peritoneal lining. Ascites permits disease spread to the dependent portions of the peritoneal cavity (like the rectouterine or rectovesical pouch, right paracolic gutter) or to locations where a large amount of peritoneal fluid is absorbed, typically subdiaphragmatic surface and omentum. Involvement of the bowel surface predisposes to bowel obstruction which is often the clinical manifestation and identifying the small peritoneal deposits can be quite challenging. Mucinous gastric adenocarcinomas can reveal calcification within the peritoneal deposits. Of noteworthy mention is that diffuse histologic type of gastric adenocarcinoma can manifest with peritoneal metastases without an easily identifiable primary gastric lesion. This finding can lead to a retrospective diagnosis of gastric cancer. Spread of tumour to the ovaries (Krukenberg’s tumours) is commonly associated with the signet cell type. Lymphatic dissemination: Although lymphatic dissemination depends upon location of the primary tumour, the pathway is not completely predictable as it is multidirectional and complex. As per the Japanese Gastric Cancer Association Classification, the perigastric nodal stations on CT can be identified as in Fig. 8.2.28. The regional lymph nodes comprise perigastric nodes (stations 1–6, i.e. right cardiac (1), left cardiac (2), lesser curvature (3), greater curvature (4) (comprising 4sa-short gastric, 4sb-left gastroepiploic and 4sd-right gastroepiploic), suprapyloric (5), and infrapyloric (6) lymph nodes and extraperigastric nodes (stations 7–12, i.e. left gastric artery (7), common hepatic artery (8), celiac axis (9), splenic hilar (10), splenic artery (11), and hepatoduodenal (12) lymph nodes. Stations 13 to 16 include nodes posterior to the pancreatic head/retroduodenal (13), mesenteric root (14), transverse mesocolon (15) and para-aortic (16) locations. Other stations include paraoesophageal nodes in the diaphragmatic hiatus (17), paraoesophageal nodes above the diaphragmatic hiatus (18), paraoesophageal nodes in the lower thorax (110), supra-diaphragmatic nodes separate from the oesophagus (111) and posterior mediastinal nodes separate from the oesophagus and diaphragmatic hiatus (112) respectively. Differences between the Japanese Gastric Cancer Association Classification and AJCC TNM staging are enlisted below.

Nodes Superior mesenteric vein node (station 14) Infradiaphragmatic, paraoesophageal, and supradiaphragmatic lymph nodes (stations 19, 20, 110 and 111)

Japanese Gastric Cancer Association Classification Regional

8th AJCC TNM Staging Metastatic

Regional (if the Metastatic tumour involves the oesophagus)

FIG. 8.2.28 Nodal stations on CT. 1. Right cardiac nodes; 2. Left cardiac nodes; 3. Nodes along the lesser curvature; 4. Nodes along the greater curvature; 5. Supra-pyloric nodes; 6. Infra-pyloric nodes; 7. Nodes along the left gastric artery; 8. Nodes along the common hepatic artery; 9. Nodes around the celiac axis; 10. Nodes around the splenic hilus; 11. Nodes along the splenic artery; 12. Nodes in the hepatoduodenal ligament; 13. Retropancreatic (peri-duodenal); 14. Root of mesentery; 15. Middle colic; 16. Para-aortic; 17. Paraesophageal (at the diaphragmatic hiatus); 18. Paraesophageal (above the diaphragmatic hiatus). Irrespective of the primary tumour location, the lymph node stations most commonly affected include the lesser curvature (station 3), greater curvature (station 4), and left gastric (station 7) stations. Further, tumours located at the proximal third of the stomach are more likely to disseminate to the paracardial (stations 1 and 2), celiac (station 9), splenic hilar (station 10), splenic artery (station 11), and

para-aortic (station 16) stations. On the contrary, lesions of the lower third of the stomach are more likely to involve the common hepatic artery (station 8) and superior mesenteric vein (station 14) stations. Tumours situated in the middle third of the stomach demonstrate a mixed pattern of nodal involvement. When single regional node is involved, the affected perigastric node is located on the same side as the tumour in 83%–92% of cases but the distribution is not always predictable. Skip lymph nodal metastasis refers to the presence of a metastatic lymph node in an extraperigastric location without perigastric nodal involvement, and this phenomenon is observed in 5%–14% cases and more commonly observed in advanced cancers involving the upper and middle third of the stomach. Staging The TNM Staging by the American Joint Committee on Cancer (AJCC) is the most widely accepted method for staging gastric carcinomas. T-staging Various imaging modalities like upper gastrointestinal endoscopy, EUS, CT scan and PET CT are routinely used for preoperative Tstaging of gastric carcinoma. Pathological staging in specimens not subject to CT–RT is considered the gold standard for T-staging of gastric carcinoma. T- stage indicates depth of invasion and is an independent prognostic factor for local recurrence and survival. The 10-year survival rate of T1 lesions is 80%, T2 lesions is 50%, T3 and T4 lesions is 30%. Nodal staging (N) This has been elucidated above in the section of lymphatic dissemination. Metastasis (M) According to AJCC, nodal spread along the left supraclavicular, left para-aortic, hepatoduodenal, retropancreatic and mesenteric regions are considered distant metastatic disease. Most common organ for metastatic disease is the liver which usually shows hypovascular metastasis with or without ring enhancement, hence a routine scan during portal venous phase is adequate (Fig. 8.2.29A). Other sites for metastasis include peritoneum, omentum, ovaries (Krukenberg’s tumour) (Fig. 8.2.29B) and rectovesical pouch (Blumer’s shelf tumour). Ascites is seen in advanced disease and there could be mucinous deposits resulting in pseudomyxoma peritonei (Fig. 8.2.29C). Extra-abdominal sites of metastases include bones (Fig. 8.2.29D) and lungs.

FIG. 8.2.29 Metastases. A. Diffuse concentric mural thickening due to gastric adenocarcinoma (M) showing infiltration of the pancreas (P), extensive bilobar hepatic metastases (arrows) and tumoral invasion of the main portal vein (TIV). B. Bilateral enhancing solid- cystic adnexal (ovarian) masses in a case of mucinous adenocarcinoma stomach, consistent with Krukenberg’s neoplasms with minimal free fluid. C. Sclerotic bone metastases in the skull base and frontal bones. D. Mucinous adenocarcinoma stomach (M) with pseudomyxoma peritonei – plaque like peritoneal deposits along the peritoneal recesses, transverse mesocolon, coating the serosal surface of the bowel loops (B), anterior pararenal space.

Imaging findings in gastric cancer The imaging appearance of gastric adenocarcinoma varies according to the size and stage of the tumour. Upper GI contrast examinations Mucosal pattern and distensibility are useful for identification on barium studies. Double-contrast barium studies may demonstrate early gastric cancer as mucosal irregularity with disruption of the normal areae gastricae and may be associated with a protruding lesion (seen as intraluminal filling defect) or ulcerative/excavating lesion (seen as collection of barium) (Fig. 8.2.22). The imaging appearance

varies depending upon the radiographic view and the wall involved (dependent vs non-dependent). When viewed en face (frontal view), an ulcer along the dependent wall is seen as collection of barium as opposed to a ring like appearance with barium surrounding the lesion (filling defect) when it lies on the non-dependent wall. As described earlier in the section on gastric ulcer, the lesion localization on the gastric wall may be confirmed by rotating the patient and visualization in the supine and prone positions. If a ring shadow is seen with the patient supine suggesting an anterior wall lesion, it may be filled when the patient is made to lie prone on the fluoroscopy table, and vice versa for posterior wall lesions where the barium will flow into it on the supine position. When viewed in profile (lateral view), a malignant ulcer filled with barium typically projects beyond the gastric wall, similar to the appearance seen on CT scans. Rigidity of the wall in the form of reduced or lack of focal or diffuse distensibility are highly suggestive for a malignancy. In cross-sectional imaging like CT or MRI, a varied imaging spectrum comprising asymmetric nodularity or thickening, contoural variations like presence of polypoidal growth, ulceration or lobuloinfiltrative margins, contrast enhancement pattern, lack of luminal distensibility or gastric outlet obstruction are utilized as morphologic indicators. Although CT historically has been not very encouraging in detection of early gastric cancer (T1 disease), the accuracy rates in differentiating T1 and T2 tumours have improved in recent years to 65%–82% with use of adequate gastric distention, better image resolution of scanners, thin reconstructions, multiplanar imaging, and three-dimensional reconstructions with surface shaded volume-rendered display. Thickening: Asymmetric focal nodular thickening more than 1.5 cm is suspicious for malignancy. Signet ring cell cancers typically cause infiltrative mural thickening of a scirrhous variety resulting in lack of distensibility (linitis plastica) (Fig. 8.2.30). These tumours arise from the distal stomach and can extend proximally into the fundus or cardia. Certain mimickers of pathology for a novice radiologist on a CT scan are apparent focal nodular thickening of the gastro-oesophageal junction as seen on the axial images due to oblique course of the wall which this must be confirmed on multiplanar reconstructions before raising suspicion; also pseudothickening of the gastric fundus is a common incidental finding which can be verified by imaging on adequate luminal distension.

FIG. 8.2.30 Linitis Plastica. 60-year-old male presenting with early satiety and weight loss. Endoscopic biopsy revealed gastric adenocarcinoma. The CECT shows reduction in gastric distensibility, secondary to diffuse transmural circumferential mural thickening involving the cardia, fundus, body and proximal antropyloric region reaching rostrally up to the GE junction (A). A solitary 9 mm deep ulcer is noted in the greater curvature (B). Multifocal nodular extraserosal-perigastric extension and fat stranding suggesting infiltration, including contiguous invasion with enlarged nodes in the gastrohepatic fold (A, dashed arrow). Lesion enhancement: Typically gastric carcinomas reveal enhancement on the early arterial phase whereas those lesions with significant fibrous component show an increasing enhancement on the delayed phase (Fig. 8.2.31). Mucinous tumours are known to be more eccentrically located, hypoenhancing as compared to normal gastric wall (corresponding to the mucin pool) and may show the presence of associated multiple, punctate calcifications (9.5%) (Fig. 8.2.32). The calcification may be peripheral/central, punctate, septate, linear or amorphous in nature.

FIG. 8.2.31 T4 gastric cancer with perigastric infiltration. Hyperenhancing circumferential transmural infiltrative thickening involving the stomach (dashed arrows) is depicted on the coronal plane (images from anterior to posterior), with subperitoneal infiltration involving the supramesocolic omentum (A), Transverse mesocolon (B, C), small bowel mesentery along the mesenteric cuff (D) and anterior pararenal space.

FIG. 8.2.32 Mucinous adenocarcinoma stomach. K/C/O mucinous adenocarcinoma stomach. The CT study reveals an asymmetric heterogeneously enhancing transmural infiltrative plaque like gastric lesion showing exuberant calcification, involving the fundus, cardia, and body, predominantly involving the lesser curvature (A), with regional calcified (B) lymphadenopathy and hypoenhancing liver lesion (proven metastases on PET-CT). Follow up CT after chemotherapy and palliative radiotherapy therapy showed further increase in the extent of calcification. Gastric mural identification and T staging: Dynamic contrastenhanced CT scan with optimal gastric distension, use of negative oral contrast and multiplanar reconstructions gives high accuracy in T staging of gastric cancer. The normal gut signature is identified as 1–3 mm high-attenuation inner mucosa; surrounded by a hypoattenuating variable thickness submucosa, and the muscularis propria, subserosa, and serosa, appear as a single, slightly high-attenuation outer layer. The mural layers are identified best on the arterial phase but also seen on the venous phase. With greater luminal distension, only two layers may be identified with stretching of the normal hypoattenuating submucosa, whereas in some instances, only a single layer may be discernible or trilayer stratification may be appreciable in focal areas of the stomach. Gastric wall thickness varies from 5 mm to 10 mm depending upon adequate distension to underdistension, respectively, but the wall thickness differs depending on the location, and normal gastric antral wall often measures 5 mm in thickness. Some studies infer that antral wall thickness greater than 10 mm is the optimal cut-off point for differentiating benign from malignant conditions, with a sensitivity of 81.8% and a positive predictive value of 95.5%. CT may be useful in identifying the degree of mural involvement in terms of involvement of the submucosal stripe (T2 lesions) vis-à-vis

only mucosal affection in T1 lesions which may be difficult to identify (Fig. 8.2.33). T3 tumours involve the subserosa with an intact serosal lining (visceral peritoneum) and can be associated with mild whiskering of the perigastric fat, whereas T4a lesions reveal an irregular nodular breach of the serosal layer with definite perigastric extension and band like fat stranding. However, as the subserosa and serosa are seen as a single enhancing layer on cross sectional imaging, differentiating T3 from T4a tumours may be challenging and can be better appreciated on endoscopic ultrasound (EUS). Also, fat stranding is not necessarily because of tumour infiltration as desmoplasia and inflammation also produce the same response. T4b lesions refer to frank infiltration of viscera adjoining the stomach.

FIG. 8.2.33 T1 Gastric carcinoma. 79-year-old woman with T1 gastric adenocarcinioma. Endoscopy showed a superficial mucosal based lesion along the lesser curvature, which was biopsy proven gastric adenocarcinoma. Fig A: Preoperative CT revealed no mural thickening or hyperenhancement along the lesser curvature. Patient underwent wedge resection. Fig B: Followup CT 3 months later shows the staple line at the operative bed, with no recurrent lesion. Intramural extension to duodenum or oesophagus is not considered invasion of an adjacent structure, but is classified using depth of greatest invasion in any of these sites. Any gastric cancer with an epicentre more than 2 cm distal to the GEJ is staged by means of gastric cancer classification, even if the tumour crosses the GEJ.

The role of MRI in T staging of gastric carcinoma is limited due to respiratory and cardiac motion-related artefacts. However, fatsuppressed 3D T1WI post-Gd acquisitions can demonstrate T1 lesions better. Perigastric extension via ligaments As described earlier in the section on anatomy, as the peritoneum folds and covers the abdominal viscera, it condenses to form ligaments which along with the mesentery and omentum, constitute potential interconnecting subperitoneal spaces between the parietal and visceral peritoneum, acting as potential pathways for bidirectional disease spread. Tumour can extend as linear sheets along the perigastric ligaments form the stomach to adjoining viscera, depending upon location of the primary tumour (Fig. 8.2.34). Local spread of cancer across the subserosal connective tissue into the perigastric ligaments, greater or lesser omentum, without perforation of the visceral peritoneum, is classified as T3 tumour.

FIG. 8.2.34 Perigastric infiltration. 36-year-old woman with T4 signet cell gastric adenocarcinioma. CT shows a transmural infiltrative hyperperfused gastric antropyloric mass (dashed arrows) invading the perigastric tissues with loss of fat planes with the pancreas (P), infiltrating the greater omentum (Fig B), transverse mesocolon (TMC) and hepatoduodenal ligament (HDL) in Fig C. S: Stomach, C: Colon. Up to 50% of tumours penetrating the muscular layer or beyond have peritoneal disease at the time of presentation. Diffuse histologic subtype can manifest with peritoneal metastases without an easily identifiable gastric lesion. Lymphatic spread (Fig. 8.2.35)

Predictors for Nodal Metastasis on CT: • Short axis diameter >6 mm for perigastric nodes and >8 mm for non-perigastric nodes • Central necrosis, Loss of fatty hilum • Clustered perigastric nodes (>3) regardless of size • Round shape • Heterogenous enhancement

FIG. 8.2.35 Nodal involvement in gastric cancer. Gastric carcinoma (dashed arrow) presenting with nodal involvement in the gastrohepatic fold and hepatoduodenal ligament (A), supra- and infrapyloric, periduodenal locations (B) and at the splenic hilum (C). The sensitivity of CT for lymph node staging ranges from approximately 63%–92%. Certain pitfalls of cross-sectional imaging include the variable nodal drainage pattern with skip metastases, presence of metastatic disease in normal-sized nodes, and enlarged nodes which could be reactive rather than metastatic. Although morphologic appearance and enhancement can help in differentiating benign from malignant lymph nodes. PET/CT is a useful adjunctive tool to identify distant nodal spread. The CT imaging appearances corroborating with the TNM Staging are enumerated below:

TNM Definition Stage Tumour (T): T1a Tumour invades lamina propria or muscularis mucosae T1b Tumour invades submucosa

CT Appearances

Focal enhancement and/or thickening of the inner mucosal layer compared normal mucosa Mucosal thickening and enhancement Hypoattenuating submucosal stripe remains visible T2 Tumour invades Loss of submucosal hypoattenuating muscularis propria stripe but smooth outer gastric wall T3 Tumour penetrates Mildly blurred but generally smooth subserosal connective outer gastric wall, with a few small tissue without invasion linear areas of stranding, Nodular or of visceral sheet like soft-tissue thickening peritoneum/adjacent within perigastric ligaments structures T4a Tumour invades serosa Nodular or irregular serosal surface, (visceral peritoneum) infiltration of surrounding peritoneal fat T4b Tumour invades Direct invasion into adjacent organs adjacent and structures structures/organs Node (N): N0 No regional node involvement N1, Regional node Short axis: >6–10 mm, rounded, N2, involvement perinodal fat stranding, clustered N3 nodes, heterogeneous enhancement Metastases (M) M0 No distant metastatic disease M1 Distant metastasis Distant (nonregional) lymph nodes involving distant nodes, —for example, peripancreatic, non-direct extension mesenteric root, retroperitoneal and into other organs, or para-aortic nodes peritoneal carcinomatosis Peritoneal carcinomatosis involving ascites, peritoneal nodules, plaques, fat stranding, thickening, and/or enhancement Post therapy Imaging is a crucial tool in postoperative surveillance of cases with gastric malignancy to identify local recurrence (Fig. 8.2.36). Intratumoural calcification maybe develop usually due to dystrophic calcification caused by degenerative changes of the tissue, such as

necrosis or haemorrhage. This is often seen in mucinous adenocarcinomas, mucinous cystic carcinoma both de-novo or may develop posttherapy, and may be increased in extent as compared to the primary scan.

FIG. 8.2.36 Operated gastric antral carcinoma with recurrence at the gastrojejunostomy site. Operated case of gastric antral carcinoma presented a year later with gastric outlet obstruction. A hypoenhancing ulceroproliferative mass (M) with associated mural thickening is seen at the gastrojejunostomy site (identified by hyperattenuating staple line in A) which shows infiltration of the anterior parietis (C), extensive perigastric infiltration with conglomerate necrotic nodes in retrogastric location, mesentery, encasing the SMA, SMV (C) with splenic V occlusion (D) and retroperitoneal nodes encasing the IVC and aorta (C). Nodes are shown in white arrows.

Gastric lymphoma Extranodal lymphomas can arise from sites with primary lymphoid tissue (like the spleen, thymus, Waldeyer ring), from organs or tissues lacking lymphoid tissue (like brain, soft tissue), or from organs constituting significant lymphoid tissue component (like the gastrointestinal tract). Gastrointestinal lymphoma may be primary or secondary. The secondary type of lymphoma is typically multifocal

whereas primary lymphoma usually involves one site. The most common extranodal manifestation of non-Hodgkin lymphoma affects the gastrointestinal tract, comprising up to 20% of all cases, which is exceedingly rare in Hodgkin disease, with only isolated cases reported in literature. Primary gastric lymphoma represents 1%–5% of gastric malignancies and about 50%–70% cases of primary gastrointestinal lymphoma. Normally gastric mucosa is devoid of lymphoid tissue, but chronic H pylori infection is associated with the lymphoid tissue proliferation in the lamina propria. Most low-grade primary gastric lymphomatous disease arises from this mucosa-associated lymphoid tissue (MALT) and are therefore categorized as MALT lymphomas also referred to as Extranodal Marginal Zone B-Cell Lymphoma (ENMZCL) while the other common form of gastric lymphoma is of the diffuse large B cell variety (DLBCL) which is of high grade. High-grade lymphomas are known to be transformed from the low-grade tumour but can also arise de novo. Whereas the low-grade tumours are associated with a 5-year survival rate of 75%–91%, the 5-year survival rate for high-grade MALT lymphomas of less than 50% makes it crucial to diagnose these tumours at the earliest. Gastric lymphomas are often the superficial spreading variety confined to the mucosa and submucosa. Double-contrast studies may reveal ulcerative, polypoidal, or infiltrative patterns, which mimin the appearance of gastric carcinomas. However, the diagnosis of lymphoma may be hinted by the presence of multiple polypoidal tumours, especially when they exhibit central ulceration (‘bulls- eye’ appearance), giant cavitating lesions, or extensive infiltration with gastric fold thickening. The preservation of gastric distensibility helps to differentiate this entity from linitis plastica. As Endoscopic ultrasonography (EUS) clearly demonstrates the layers of the gut, the thickening of the intermediate anatomic layers (submucosa, muscularis propria), extramural infiltration, and lymph node involvement can be best visualized by this imaging technique. Three different EUS patterns have been described in gastric lymphomas: giant rigid gastric folds, sometimes giving a polypoid appearance, localized or diffuse hypoechoic infiltration and thickening with superficial stellate-shaped ulcerations. EUS is considered superior to CT for the staging and the assessment of the T and N parameters in lymphoma but is not sensitive to demonstrate the extraluminal or distant nodal extent (M). Also, EUS is useful for local disease evaluation following therapy. The most common CT patterns of gastric lymphoma are the presence of diffuse or segmental wall thickening of 2–5 cm with low contrast enhancement and extensive longitudinal extension of the tumour due to submucosal spread (Fig. 8.2.37). Low-grade tumours reveal less visible mural thickening, shallow lesions and abdominal adenopathy as opposed to high grade tumours which reveal more pronounced mural thickening and thus CT can also help in reasonable assessing the tumour grade. Tumoural enhancement is usually

homogeneous, but low-attenuation areas of necrosis may occasionally be seen in the high-grade lesions (24,38). Unlike patients with ENMZCL, the majority of patients with DLBCL have abdominal lymphadenopathy at CT. FDG avidity has been reported in 97% of primary gastric DLBCLs, and PET/CT may also provide a more accurate assessment of lymph node involvement.

FIG. 8.2.37 Gastric Lymphoma. Case of Hodgkin’s lymphoma post remission on surveillance. CECT (A–B: Axial sections, C: Coronal reconstruction, Fig D: sagittal reconstruction) revealed well circumscribed sessile mural mass (M) showing mild homogeneous enhancement with broad base along the greater curvature of the body of the stomach with whiskering of the perigastric fat (B) in close contact with the pancreatic body and tail (D), without glandular infiltration. Multiple enlarged non-necrotic nodes in the gastrohepatic, periportal location, mesentery and para-aortic regions (not shown here). A right lower lobe pulmonary nodule is seen in C. MRI is comparable to CT in identification but is often not the investigation of choice due to costs, longer scanning times and propensity for artefacts from movement and peristalsis.

Mesenchymal tumours Mesenchymal tumours of the stomach include gastrointestinal stromal tumours (GISTs) which are the most common subtype, non-GIST sarcomas, lipomas, leiomyomas, schwannomas, glomus tumours,

hemangiomas, inflammatory fibroid polyps (IFPs), inflammatory myofibroblastic tumours (IMFTs) and plexiform fibromyxomas. Mesenchymal masses are typically well-circumscribed, bulge into the lumen with an intact overlying mucosa, and when bulky and arising from the muscularis propria, as in GIST, typically show an exophytic growth pattern. Many of the gastric mesenchymal have a distinctive histologic appearance; however, immunohistochemical stains are currently employed for confirmation of particular tumours. Immunoreactivity to c-KIT (CD117) or DOG1 is used to confirm GIST and desmin positivity helps to diagnose a leiomyoma. Positivity for S100 protein is useful to confirm schwannomas. Detection of ovoid cells and hypervascularity favours a glomus tumour, and reactivity to smooth muscle actin is useful as a marker. A spindle cell tumour with intratumoural plasma cells and immunoreactivity to anaplastic lymphoma kinase is compatible with an inflammatory myofibroblastic tumours (IMFT) while Chromogranin A and synaptophysin are immunomarkers for carcinoid tumours. Barium studies of a mesenchymal tumour would reveal a broadbased elevation along the wall without disruption of the rugal pattern or these may be stretched/effaced by the submucosal pathology (Fig. 8.2.38).

FIG. 8.2.38 Mesenchymal Tumour on Barium. An irregularly marginated broadbased lesion along the greater curvature of the gastric body with effacement of the overlying gastric rugae (white arrow) favours a submucosal lesion, associated with focal mural indrawing (white dashed arrow). (Source: Courtesy of Dr Govind R Jankharia. Picture by Jankharia, Mumbai.)

Gastrointestinal stromal tumours (GIST) Gastrointestinal stromal tumours are the most common subepithelial tumours of the gastrointestinal tract with spindle or epitheliod cells, these were initially labelled histologically as leiomyosarcomas but they actually arise from the interstitial cells of Cajal in the myenteric plexus and immunohistochemistry identification of activating mutations of the KIT gene enabled labelling these tumours as a distinct entity. In about 90% cases, these tumours typically express a type III receptor tyrosine kinase (RTK), KIT (CD117) and in another 5%–10%, mutation of the platelet-derived growth factor receptor alpha (PDGFRA) gene is detected. • Mutations in KIT can involve exon 9, 11, 13 and 17 and exon 11 mutation occurring in more than 60% cases is more often identified in gastric GISTs. • Majority of the mutations of PDGFRA and succinate dehydrogenase (SDH) gene also occur in GISTs of gastric origin.

• Deletions of the exon 11 are associated with aggressive biology as compared to point mutations of the same gene. • Exon 11 mutant GISTs show a dramatic response to Imatinib whereas exon 9 mutant or SDH deficient varieties are inherently resistant (primary resistance). However, the exon 11 mutants can exhibit resistance to therapy after 6 months which is referred to as secondary resistance. GISTs are most commonly seen within the stomach (60%–70%) and small bowel but can be seen anywhere in the gastrointestinal tract and less commonly in the peritoneal cavity. These tumours have a spectrum ranging from absolutely benign to malignant lesions, depending on the anatomic location, tumour size, and mitotic frequency. Benign tumour biology is exceptionally common in gastric GIST, where benign lesions outnumber malignant ones by a ratio of 3– 5:1. Clinical features of GISTs vary on location and tumour size and can be non-specific like early satiety, bloating, vague abdominal pain or palpable lump. Occasionally, they may present as upper gastrointestinal bleeding when they ulcerate the mucosa. Majority of GISTs are exophytic and hence grow to a large size till clinical presentation and yet do not typically cause luminal obstruction. Imaging features are varied, depending upon the size and aggressiveness of tumour. Primary GISTs are typically large, hypervascular enhancing masses on contrast-enhanced CT with small lesions appearing well homogeneous in attenuation but can appear markedly heterogeneous secondary to necrosis, haemorrhage, or cystic degeneration. Calcification has also been reported in tumours with necrosis. Other common features include ulceration and fistulization. Although displacement of organs and vessels is a common feature, the more aggressive form of GIST can at times invade adjoining organs, and identification of organ of origin may be difficult due to dominant exophytic location with respect to the gut. Unlike adenocarcinomas, metastases from GISTs are uncommon but when present, metastases involve the liver and peritoneum by hematogenous spread and peritoneal seeding respectively and nodal dissemination is very rare. The metastatic lesions mimic the appearance of the primary tumour. Response of GISTs to imatinib Treatment with imatinib mesylate results in decreases in the size of GISTs, but this response often takes several months before achieving satisfying traditional tumour response criteria, like the RECIST. Response to Imatinib is characterized by rapid transition from a heterogeneously hyperattenuating pattern to a homogeneously hypoattenuating pattern along with resolution of the enhancing tumour nodules and a decrease in neovascularity (Fig. 8.2.39). Typically, the overall tumour attenuation decreases significantly with the development of myxoid degeneration (the term ‘cystic degeneration’ to be avoided in description) and, occasionally,

haemorrhage or necrosis. Paradoxically, tumours may enlarge during treatment (due to intratumoural haemorrhage or myxoid degeneration) but if there is an overall decrease in tumour enhancement despite enlargement of the tumour, it is considered as pseudoprogression. On the other hand, demonstration of increase in enhancing nodules despite stable lesion size favours tumour progression. The overall change in lesion morphology as assessed with CT often correlates with the standardized uptake value (SUVmax.) on an 18F-FDG PET and a PETCT can be informative when CT criteria are equivocal to assess response.

FIG. 8.2.39 Gastric GIST before and after Imatinib. A. Heterogeneously enhancing broadbased mass lesion along the anterosuperior wall of the stomach causing severe luminal compromise, showing few areas of ulceration. B. CT obtained 1 year following therapy with Imatinib shows small relatively hypoenhancing residual component. Although surgical treatment is the primary therapy of choice for primary GISTs, despite an Ro resection, there are chances of recurrence which are known to occur in a median time of 2 years after surgery. Patients are kept on surveillance and development of GIST recurrence has to be treated as per guidelines for metastases as per the National Comprehensive Cancer Network (NCCN). Imatinib therapy is known to cause fluid overload which may manifest as ascites, pleural effusion, pericardial effusion, or extensive subcutaneous oedema. Consequently, development of new ascites on imaging should not be mistakenly interpreted as indicating new peritoneal disease, when the primary disease is otherwise stable or resolving.

Leiomyomas The distinction between GISTs and leiomyomas is clinically significant because leiomyomas are benign and GISTs show varied tumour aggressiveness and can be associated with a risk of progression and metastasis. In the stomach, GISTs far outnumber leiomyomas which are more commonly seen in the oesophagus. Leiomyomas are almost always identified in the gastric cardia as homogeneous, lowattenuation masses with an endoluminal growth pattern, when larger than 2 cm in diameter, these lesions also may demonstrate central ulceration, mimicking a GIST.

Neuroendocrine tumours (carcinoid) The most frequent site of carcinoids is the gastrointestinal tract (67% of cases) with small bowel being the most common location followed by gastric carcinoid tumours which are rare, (accounting for only 0.3%–1.8% of all gastric malignancies). These tumours usually originate from enterochromaffin-like cells (Kulchitsky cells) in the gastric mucosa and are therefore epithelial in origin but as the bulk of the tumour is usually submucosal, they must be included in the imaging differential diagnosis of a submucosal gastric tumour. There are various histological types of gastric carcinoid (I to III), with type I being the most common variety and type IV described as neuroendocrine cancer (NEC). These tumours show avid contrast enhancement on CT scan. It is imperative to differentiate the type of carcinoid as type I and II resection and surveillance, whereas type III carcinoids and NEC warrant gastric resection. The various types of carcinoids have been described in Table 8.2.2.

TABLE 8.2.2 Carcinoids Type I Incidence 70%–80%, women Associations Chronic Atrophic gastritis Pathology 30%

The appropriate imaging modality highly depends on the tumour grade. According to the recent ENETS guidelines, 18F-FDG PET/CT is only recommended in G3 tumours. Whereas for tumours of low grade like G1 and G2, SSR (somatostatin receptor)-binding PET ligands (e.g. 68Ga-Dotatate or 68Ga-Dotatoc) are recommended. However, there is data favouring the combination of both imaging modalities. It has been shown that FDG positivity is associated with an inferior prognosis.

Nerve sheath tumours (schwannomas) These arise from the myenteric plexus and commonly affect the stomach (60%–70%) and most often in the body of the stomach, exhibiting S-10 protein on immunohistochemistry. These show an exophytic or intramural growth pattern, typically manifest as hypoattenuating subepithelial masses despite a large size with minimal

enhancement during the arterial phase and delayed enhancement during the equilibrium phase. Absence of haemorrhage, necrosis, or cavitation is a useful feature of schwannomas, this feature can be used to distinguish schwannomas from the more heterogeneous appearance of GISTs. Malignant nerve sheath tumours may demonstrate necrosis and heterogeneous enhancement. A diagnostic approach to gastric submucosal tumour is illustrated in Table 8.2.3.

TABLE 8.2.3 Approach to Submucosal Gastric Lesions

Typical Imaging Features: • Lymphoma: Low grade (MALT): Mural thickening, homogeneous, nodes Malignant: Bulky, infiltrative, multifocal, multiple nodes • Adenocarcinoma: Hyperenhancing, focal mass like or infiltrative with perigastric extension, nodes • Carcinoid: Avid postcontrast enhancement • GIST: Low-grade lesions: well-defined, homogeneous Malignant: Bulky, infiltrative, heterogeneous enhancement, ulceration, necrosis • Leiomyoma: Well-defined, smoothly marginated, low attenuation, homogeneous enhancement • Schwannoma: Homogeneous attenuation with minimal enhancement in the arterial phase and delayed enhancement in the equilibrium phase on CECT • Ectopic Pancreas: Sharply defined nodule 8 was a significant independent prognostic predictor of overall survival. In another study by Kim and colleagues with 321 patients, primary tumour SUVmax greater than 5.74 was found to be a poor prognostic indicator of progression-free survival. Likewise, FDG activity in metastatic lymph nodes can also provide prognostic information with pretreatment nodal SUVmax being an independent risk factor for recurrence-free survival as well as overall survival.

Multimodality diagnostic and therapeutic approach to gastric cancer (from an oncosurgeon’s perspective) Diagnosis and staging Oesophagogastroduodenoscopy is the modality of choice to detect and diagnose carcinoma stomach owing to its high specificity and advantage of obtaining a tissue biopsy. Double-contrast barium studies are used less commonly now, however, these were widely used in the past for detection of gastric carcinoma. Once the diagnosis is achieved, the disease staging is performed using various investigations as follows: Staging of gastric cancer 1. CT scan A comprehensive CT of the chest, abdomen and pelvis with contrast is mandatory and central to staging and planning out treatment strategy. The CT defines • nature of the tumour with respect to size, location and its relation to the surrounding structures.

• It conclusively identifies infiltration or abutment of the surrounding structures and offers complete anatomical detail of the tumour (T stage) • Identifies lymph nodes and helps map out lymph nodal involvement (N stage) • Identifies peritoneal, liver, omental disease along with retroperitoneal nodes, para-aortic nodes or disease elsewhere in the body like bones, lungs etc. (M stage) 2. PET-CT scan 18-F-FDG PET-CT scan is an adjunct to staging. Due to normal background uptake of FDG, the role of PET CT in detection and T staging of carcinoma stomach is inconsistent. However, detection of FDG avid nodes and indeterminate lesions in the liver, lungs, bones, peritoneum, may help in understanding the nature of these lesions. However, diffuse cancers and some histological variants like signet ring carcinoma and poorly differently carcinomas show little or no FDG uptake. 3. EUS – Endoscopic Ultrasound Endoscopic ultrasound is an invasive investigation - aimed to define the nature of very small mucosal lesions and the nature of lymph nodes. It is the most accurate imaging technique for preoperative T. staging of gastric carcinoma with accuracy rate of 78%–94 %. Tumours are hyper- or hypoechoic and disrupt the normal stratified mural pattern of the stomach. Small perigastric lymphnodes can be evaluated. EUS also enables biopsy to arrive at a histological diagnosis. 4. Staging and diagnostic laparoscopy Diagnostic laparoscopy with peritoneal washings is recommended in • Locally advanced gastric cancers to rule out peritoneal metastases • Prior to commencement of Neoadjuvant chemotherapy • Determine peritoneal carcinomatosis index (PCI) in select patients being considered for cytoreductive surgery

Treatment strategies for gastric cancer Treatment of Gastric Cancer is based on the TNM staging based on well-standardized protocols. Accurate TNM staging based on the abovementioned diagnostic modalities is fundamental for an accurate staging. Treatment is usually defined on basis of a multidisciplinary team consensus between a surgeon, medical oncologist and a dedicated gastrointestinal radiologist.

Classification of gastric cancer based on stage The local staging (T stage) of stomach cancer depends on the invasion of the tumour across the gastric wall. The risk of lymph nodal metastases in gastric cancer is largely dependent on the T stage. Hence greater the depth of infiltration into the gastric wall (T stage), greater are the chances of regional lymph node metastases. The risk of lymph node metastases in T1a gastric tumours is minimal. 1. Very Early Gastric Cancer: T1a tumours – These tumours are confined to the mucosa and do not extend into the submucosa (T1b). The tumour does not extend beyond the lamina propria or the muscular mucosa 2. Early Gastric Cancer: T1b tumours – Tumours which extend into but not beyond the submucosa. The presence or absence of regional lymph node metastases does not matter. Hence Early Gastric Cancer is defined as T1b, N0/N+ 3. Locally Advanced Gastric Cancer: T3/T4, N0/N+ tumours 4. Metastatic disease (cancer which has spread into distant sites): M+ disease. Endoscopic therapy Endoscopic therapy should be explored for T1a tumours as these are very superficial lesions, which do not extend into the submucosa. Options include Endoscopic Mucosal Resection (EMR) or Endoscopic Submucosal Dissection (ESD) and lesions eligible for this treatment should be • well-differentiated tumours • 3 cm), irregular margins and heterogeneity of echotexture. Identification of peri-lesional nodes permits accurate nodal staging and is useful during follow-up.

FIG. 8.3.1.14 EUS showing layers of small bowel wall with hypoechoic submucosal mass. The increasing demand to shift from invasive or surgical interventions to minimally invasive alternatives has driven the development of multiple EUS-guided interventions, and EUSguided tissue sampling is perhaps the most useful contribution of this technique. EUS-guided endoscopic resection can also be done for mucosal tumours. The technique requires training and familiarity with the orientation and is usually the domain of the endoscopists. Other limitations of EUS remain the availability of the technique and the shallow depth of field of view.

Computed tomography Cross-sectional imaging has now become the mainstay of bowel imaging as they allow visualization of the entire bowel along with luminal, mural and extramural manifestations in a single examination. With recent advancements, like superior detectors, thinner collimation and reduced scan time, MDCT (multi-detector computed tomography) has now emerged as the first line investigation for most bowel conditions because of its wide availability, rapid execution, superb spatial and temporal resolution

and high-quality multiplanar reconstructions. Modern postprocessing techniques, such as volume-rendered images, shaded surface displays, virtual enteroscopy and the introduction of artificial intelligence (computer-aided detection) have increased the sensitivity of CT and enhanced the confidence of radiologists in picking up smaller lesions with greater accuracy. However, like any other imaging technique, CT has its fair share of drawbacks. High-radiation dose that CT entails is of significant concern especially in young patients or patients with chronic bowel conditions who would require multiple serial scans during their treatment course. Other demerit is poor mucosal delineation and subtle alterations in mucosal morphology, which are best demonstrated on barium studies. Types of enteric contrast agents: (Table 8.3.1.3). TABLE 8.3.1.3 CT Enteric Contrast Agents Neutral Agents Negative Agents (Near Water (Negative CT Attenuation, 0–30 Attenuation) HU) • Air • CO2

• Water, milk • Methylcellulose • PEG • Mannitol, sortibol • Low density (0.1%) barium suspensions (VoLumen)

Positive Agents (High CT Attenuation, >50 HU) • Barium preparations • Gastrografin

Collapsed bowel loops may give false impression of bowel wall thickening, thus mimicking pathologies or may hide one. Enteric contrast agents are necessary to adequately distend, otherwise, usually collapsed bowel loops, for better evaluation. Choice of enteric contrast agent depends on the information being sought. Neutral enteric contrast agents, with their inherent low CT attenuation (0–30 HU), provide better evaluation of mucosal, submucosal pathologies and bowel wall enhancement patterns and are best for routine CT enterography/enteroclysis. Positive agents, due to their high CT attenuation, obscure GI bleeds, mucosal and mural details. They have fewer indications; that is in evaluation of site of small mechanical obstruction, bowel perforation, anastomotic leaks, sinus/fistula patency, differentiating bowel from adjacent masses, interloop collections or lymphadenopathy. Negative contrast agents like carbon dioxide are being used in virtual enteroscopy.

Water as enteric contrast agent is cheap, easily available, can be consumed in large quantities and better tolerated; however, due to its rapid intestinal absorption, distension achieved by water is highly variable and sometimes inadequate. Better bowel distension is achieved by mannitol and methylcellulose as they retain water in bowel lumen. Milk as neutral contrast is preferred in paediatric patients as hyperosmolar agents like mannitol can cause dehydration. PEG can cause watery diarrhoea in some patients. Commercially available neutral agent, VoLumen (Bracco Diagnostics, Princeton, NJ) is a 0.1% w/v barium sulphate suspension in sorbitol and produces better distension than many other neutral agents. Usually 1–2 L of oral contrast produce adequate luminal distension; however, volume to be administered should be adequately tailored according to the safety profile of the specific agent, to achieve good luminal distension with minimal side effects. Smaller volumes, depending upon patient tolerance, are recommended in patients with history of bowel resection. CT enterography Patients are advised to completely restrict solid food intake for about 6 hours prior to examination. To assure better compliance, they should be well-briefed about the procedure. They are encouraged to drink at least 1.3–1.5 L of neutral oral contrast over a period of 45–60 minutes immediately prior to the study. An intravenous assess is secured with 18G or 20G cannula and saline flush is given to check patency. Slow injection of 1 mL of Buscopan (hyoscine butylbromide) is given immediately before the scan to relax bowel smooth muscles and decrease peristalsis. Scan techniques include routine plain and ‘enteric phase’ imaging performed 45–50 seconds after giving ~1.5–2 mL/kg of iso or low osmolar intravenous contrast at the rate of 4 mL/s. Multiphase CT with arterial and delayed phases is indicated while evaluating occult GI bleeds or vascular malformations. Slice thickness of 0.9 mm is adequate with reconstruction interval of 0.45 mm. CT enteroclysis CT enteroclysis is a semiinvasive imaging technique that differs from CT enterography only in the mode of enteric contrast administration. CT image acquisition remains the same. It combines the advantages of enteroclysis (good luminal distension) with cross-sectional imaging in a single examination. Large volume of enteric contrast is pumped directly into the small bowel at high rates. This volume challenge to bowel ensures better and reliable luminal distension than CT enterography, thus aiding in better evaluation of mucosal lesion and mural enhancement patterns.

Fluoroscopic phase: Under fluoroscopic guidance and without conscious sedation, a long (~120–150 cm length), small calibre 9–12F balloon catheter (Freka tube) is inserted via the nasal route, advanced into the duodenum till its radioopaque tip crosses the midline to the left. With its tip at duodeno-jejunal junction, the balloon is inflated using 30 mL air so as to prevent reflux of enteric contrast into the duodenum. About 1.5 L of neutral enteric contrast is then infused into bowel via an automatic pump or hand-held injector at around 80 mL/s, keeping in mind not to cause discomfort to the patient and ensuring that the bowel does not go into spasm, resulting in segmentation or in paralytic atony. IV Buscopan (1 mg) can be given to relax peristalsis. The patient is then transferred onto the CT table. CT phase: Another 1 L of oral contrast is given at 100 mL/s followed by single ‘enteric’ phase contrast-enhanced CT just like CT enterography. Once the CT examination is over, the balloon is deflated, the refluxed enteric contrast in stomach is aspirated and the catheter is withdrawn. A good CT enterography examination with adequately distended bowel loops can demonstrate luminal, mural as well as extraluminal pathologies. Better patient tolerance and noninvasive nature has made CT enterography a preferred imaging choice in modern noninvasive small bowel evaluation. A good CT examination of the bowel can help in detecting abnormal bowel loops positioning, intussusception (Fig. 8.3.1.15), intraluminal, mural (Figs. 8.3.1.16 and 8.3.1.17) and extramural pathologies. Arterial phase images are particularly useful in evaluating the small bowel arterial supply for stenosis, strictures, thrombosis and arterio-venous malformations (AVMs) (Figs. 8.3.1.18 to 8.3.1.20).

FIG. 8.3.1.15 Intussusception: Target/Doughnut sign: Axial CT section showing concentric rings appearance due to bowel-in-bowel configuration with intervening hypodense mesenteric fat ring. Sagittal CT section of the same patient showing bowel-inbowel configuration with intervening mesenteric fat.

FIG. 8.3.1.16 (A) Unenhanced coronal CT image showing mural thickening involving IC junction, caecum and ascending colon with adjacent fat stranding and discrete abdominal lymphadenopathy. (B) CECT coronal CT image shows mural stratification with hyperenhancing mucosa, oedematous thickening of submucosa and enhancing serosa, ‘Target-water’ sign. This was a case of acute Crohn’s disease.

FIG. 8.3.1.17 Crohn’s disease: Axial and coronal CECT sections showing multiple circumferential short segments enhancing mural wall thickening with resultant luminal narrowing and dilated intersegmental bowel loops (SKIP lesions) and abdominal lymphadenopathy. MIP images of the same patients show prominent mesenteric vasculature giving the appearance of a comb (COMB sign).

FIG. 8.3.1.18 Median arcuate ligament syndrome: Axial and sagittal reformatted images of arterial phase show focal narrowing of the superior aspect of the proximal celiac trunk forming a hooked or ‘J’ appearance caused by inferiorly placed median arcuate ligament. Volume-rendered image shows focal narrowing with hooked appearance of celiac trunk.

FIG. 8.3.1.19 Gossypiboma: CT topogram showing coiled radio-opaque marker in LLQ of abdomen with small air lucencies superimposed on this area giving a ‘mottled’ appearance. Oblique reformatted axial and coronal CECT images of the same patient showing intraluminal retained surgical sponge in distal jejunum showing classical spongiform or mottled appearance and hyperdense marker at one end, with upstream small bowel obstruction.

FIG. 8.3.1.20 Small bowel GIST: Axial and coronal CECT sections showing an ill-defined exophytic heterogenously enhancing mass arising from one of the jejunal walls, having internal nonenhancing necrotic areas and cavitation. This lesion is seen to communicate with the bowel lumen with resultant few foci of intralesional air. No significant bowel obstruction, lymphadenopathy or ascites are seen.

MR imaging of small bowel Until recently, despite excellent inherent soft tissue resolution, MR imaging had limited role in GI tract evaluation. The major hurdle being longer acquisition time, resulting in image degradation from motion artefacts due to respiratory movements and bowel peristalsis. With advancements in MR hardware and development of faster breath-hold imaging sequences, scan times have reduced considerably with minimal motion artefacts and superior image quality. When combined with good luminal distention and intravenous administration of gadolinium-based contrast media, MR provides exceptional luminal, mural and extramural details along with vascular and functional information. Increasing awareness of radiation hazards associated with high-radiation dose in CT has furthered MR enterography to the forefronts of GI imaging especially when imaging paediatric, pregnant patients or patients with chronic bowel pathologies who require sequential imaging during their disease course. Advantages of MR over CT are lack of ionizing radiation, superior soft tissue contrast, dynamic information with respect to bowel motility and relatively safer intravenous MR contrast profiles. Limitations of MR include limited availability, higher cost, longer scan time, lower spatial and temporal resolution as compared to CT and known

contraindications to MR such as claustrophobia, metallic implants and pacemakers. Gadolinium-based contrast agents, especially gadodiamide, are contraindicated in patients of chronic kidney disease or renal insufficiency with eGFR < 30 mL/min/1.73 m2 due to risk of fatal nephrogenic systemic fibrosis.

Patient preparation and enteric contrast agents For adequate bowel cleansing, patients are advised to take liquidbased diet for a day with four bisacodyl tablets in the evening prior to imaging. Preprocedural fasting of 4–6 hours is advised. All this minimizes food residue and debris in small bowel which may mimic luminal pathology while interpreting the scan. Bowel distension is necessary for evaluating the intraluminal and mural pathologies as collapsed small bowel segments can mimic pathological mural thickening or hide underlying pathologies. MR imaging of small bowel makes use of enteral contrast agents to provide homogenous and adequate intestinal distension and increase contrast between lumen, bowel wall and extraluminal soft tissue. Properties of a good enteral contrast agent include easy availability, low cost, least side effects and high contrast between lumen and bowel wall. Depending on the signal intensity on various sequences, MR enteric contrast agents can be divided into positive (bright on T1w images), negative (dark on T2w images) and biphasic (dark on T1w and bright on T2w images) contrast agents. Positive contrasts like gadolinium chelates, ferrous and manganese ions and food items like blueberry juice are not commonly used as enteric contrast due to high cost, unavailability and poor distinction of mural enhancement postintravenous contrast injection. Negative contrast agents include superparamagnetic iron oxides (SPIOs) and ultrasmall SPIOs (USPIOs). They are used in MR pancreaticocholangiography to suppress the high signal from bowel luminal contents. High signal intensity of pathology or inflammation in bowel wall and surrounding fat stands out against accompanying luminal low signal intensity on T2W images. However, negative contrasts are not preferred for bowel imaging as, apart from gastrointestinal side effects like nausea, vomiting and diarrhoea, the associated susceptibility artefact can mask the hypointense signal from normal bowel wall and hide low signal intensity lesions like carcinoids on T2W images. Biphasic agents are the most commonly used enteric contrast agents in MR and include osmotic agents like mannitol, polyethylene glycol, low-density barium sulphate (VoLumen) and nonosmotic agents like water, locust gum resin and methylcellulose. Osmotic agents retain water within the lumen producing better luminal distension than nonosmotic agents; however, this may lead to mild diarrhoea postexamination.

On T2W images, there is marked contrast between the high signal intensity of the lumen against dark appearing normal bowel wall, thus aiding detection of transmural ulcers, sinuses and fistula. On fat-suppressed postintravenous contrast T1W images, their inherent low signal intensity provides outstanding contrast between low signal intensity lumen, intermediate signal intensity of normal bowel wall and high signal intensity of enhancing mural/extramural inflammation or neoplasm. Enteric contrast may not be required in patients with suspected high-grade obstruction because retained intestinal fluid adequately distends the loops proximal to obstruction, and additionally administering large volumes of fluid may cause patient discomfort, vomiting or even bowel perforation. Similar to CT imaging, MR imaging of the small bowel includes two techniques of small bowel distension: MR enterography (MRE) with oral administration of the enteric contrast and MR enteroclysis, wherein the enteric contrast is infused directly into the small bowel via a naso-jejunal tube inserted under fluoroscopic guidance. MR Enterography: Patient is encouraged to drink about 1.5–2 L of biphasic enteric contrast over a period of 45–60 minutes immediately prior to scan. Some authors recommend staged imaging, one after 20 minutes when proximal jejunal loops are maximally distended and other at after 45–50 minutes for imaging distal jejunal and ileal loops. Practically, single time imaging after 45 minutes of enteric contrast ingestion is preferred for better patient compliance and time management of MR scanner. Breathhold 2D T2W FSE image of the whole abdomen is acquired first to assess for adequate bowel distension (Fig. 8.3.1.21). MR Enteroclysis: Under fluoroscopic guidance and without conscious sedation, a long (~120–150 cm length), small calibre 8–12F balloon catheter is inserted via the nasal route, advanced into the duodenum till its radio-opaque tip crosses the midline to the left. With its tip at duodenojejunal junction, the balloon is inflated using 30 mL air so as to prevent reflux of enteric contrast into the duodenum. IV Buscopan (1 mg) is given to relax peristalsis and patient is shifted into the MR scanner. Approximately 1.5–2 L biphasic enteric contrast is either infused manually or via MR compatible continuous automated infusion pump at a rate of 80–120 mL/minute. Lower infusion rate may result in suboptimal distension of small bowel loops while higher infusion rates may result in reflex hypotonia of the bowel wall smooth muscles and may be falsely interpreted as functional hypomotility of small bowel. Automated infusion produces more reliable and controlled bowel distension at

the added cost of the pump. Some authors advice increasing the infusion rate to about 200 mL/minute once the contrast reaches caecum to induce intentional hypotonia so as to maintain the desired small bowel distension throughout the scan. Dynamic breath-hold T2W coronal images of the whole bowel are taken continuously to monitor the dynamic passage of enteric contrast and obtain functional information on bowel motility.

FIG. 8.3.1.21 Normal MR enterography: (A) Coronal unenhanced b-TFE (balanced turbo field echo) image showing good bowel distension with biphasic enteric contrast (mannitol). Notice sharp contrast between high luminal signal of enteric mannitol and low signal of bowel wall. (B) Coronal postcontrast fat-suppressed T1W spoiled gradient echo image showing normal enhancement of bowel wall against a low signal intensity of lumen. Despite offering better luminal distension, and thus better evaluation of bowel pathologies, MR enteroclysis is not preferred in routine bowel imaging primarily due to shortcomings of its fluoroscopic phase which is cumbersome, time-consuming, causes patient discomfort and exposes to ionizing radiations. MRcompatible automated infusion pumps are added expense and not widely available. Furthermore, better luminal distension does not

translate to MR enteroclysis being unquestionably better than MR enterography. Although few authors promote MR enteroclysis as the preferred investigation in evaluating bowel pathologies, studies by Schreyer et al. and Negaard et al., comparing the two techniques in patients of Crohn’s disease, show no significant difference in their diagnostic accuracy and reproducibility. From the point of evidence-based medicine, level of evidence supporting superiority of MR enteroclysis is low to moderate. MR enteroclysis is a stressful and poorly tolerated procedure and should be avoided in routine small bowel imaging with low pretest probability. It should be considered in cases where MR enterography is nondiagnostic, in patients with a high pretest probability of low-grade proximal bowel obstruction needing better bowel distension and in those unable to take contrast orally. MR enterography is now indicated as the investigation of choice for follow-up of chronic bowel conditions, like inflammatory bowel disease, infections like tuberculosis and polyposis syndromes, especially in the young and pregnant, and those requiring infliximab or steroid therapy, due to the multiple scans involved in the prolonged follow-up in such cases and due to superior soft tissue contrast with better delineation of mural and extramural complications. Image degradation due to motion artefacts related to bowel peristalsis is a major issue in MR imaging of GI tract. Reducing peristaltic movements offers better image optimization, especially during image acquisition by half-Fourier acquisition single-shot turbo spin-echo (HASTE) and postcontrast fast gradient echo sequences. Ten milligrams intravenous Buscopan is given just before starting oral enteric contrast and an additional dose of same strength is given just after injecting intravenous contrast agent. Alternatively, one can administer 0.25 mg hyoscyamine (Levsin) intravenously once prior to the start of the examination as it has a slower onset and longer duration of action. Excellent soft tissue resolution of MR is sufficient to demonstrate luminal, mural or extramural pathology alone. This is of significant value in paediatric and pregnant patients or in patients with deranged renal function. However, administration of intravenous contrast agent helps in detection and better characterization of the pathology. Subtle findings like mucosal hyperenhancement in early Crohn’s disease are better appreciated after giving IV contrast. Bowel wall enhancement patterns and differential enhancement of masses can be assessed. Collections, lymph nodes and vascularity patterns become more conspicuous on postcontrast images. Most commonly used gadolinium-based intravenous MR contrast is Gadodiamide (0.2 mmol/kg at a rate of 2–3 mL/s). Protocols for GI tract MR imaging

Dedicated torso coils (surface coils) with large area of anatomic coverage are routinely used in abdomino-pelvic imaging. When using surface coils for abdominal imaging, some form of intensity correction algorithm should be used for homogeneity optimization of the acquired images. Phased array surface coils along with parallel imaging provide optimized signal and speed of image acquisition. For routine evaluation of small bowel, MRE can be performed using single breath-hold rapid MR sequences based on steady-state precession like true fast imaging with steady-state precession (TrueFISP), balanced fast field-echo (b-FFE), balanced steady-state free precession (SSFP), balanced turbo field-echo (b-TFE) and fast imaging employing steady-state acquisition (FIESTA); depending on the vendor-specific acronyms. These are ultrafast and relatively motion insensitive sequences. Images acquired by steady-state precession sequences show excellent luminal signal homogeneity and visualization of normal and diseased bowel wall. Images are sometimes degraded by chemical shift and susceptibility artefacts when air is present in bowel lumen. Mesenteric vasculature and lymph nodes are well visualized in these sequences. Coronal and axial FISP images are obtained first which allow for rapid overview of the abdomen and assess luminal distension. If distension is found adequate on FISP images, then rapid image acquisition in axial and coronal planes is done using breath-hold single-shot fast spin-echo sequences, which can acquire a single image in less than 1 second, thereby minimizing motion artefacts. These are also known by various acronyms across different MR manufacturers such as HASTE, rapid acquisition with relaxation enhancement (RARE), and single-shot turbo spin-echo (SSTSE). These are heavily T2WI sequences and provide adequate contrast between endo-luminal high signal intensity of biphasic enteric contrast and low-intermediate signal intensity of the bowel wall with an excellent depiction of abnormal bowel wall thickening and alteration in mucosal fold morphology, transmural ulcers, sinuses and fistulas. HASTE or RARE images are, however, susceptible to intraluminal flow artefacts due to peristalsis seen as intraluminal flow voids. Spasmolytics help in reducing these artefacts. Another drawback is poor mesenteric detail as half-Fourier technique results in selective spatial filtering (‘k-space’ filtering), resulting in loss of finer details of tissue with low T2 relaxation times. Knowledge of these artefacts and correlation of HASTE images with corresponding FISP images is important to avoid misinterpretation.

Respiratory triggered or breath-hold fat-suppressed T2W images are particularly helpful in evaluating mural and extramural inflammatory changes and nature of bowel wall thickening. Oedematous mural thickening due to acute inflammation appears hyperintense while fibrotic mural thickening due to chronic inflammatory process shows low signal intensity on fat-suppressed T2W images. Fat suppression of T2W images improves the conspicuity of high signal intensity of mural or mesenteric oedema against dark background. Unenhanced T1W images are best for evaluating the abdominal anatomical structures. Two-dimensional or three-dimensional T1W spoiled gradient echo sequence can be used in coalition with chemical shift imaging to get ‘In phase’ and ‘Out phase’ images. Alternatively, T1 Dixon sequence (acronyms 2-point Dixon, LAVADixon, m-Dixon) provides four separate set of images in a single breath-hold: In phase, out phase, water only and fat only images. ‘Water only’ images provide baseline precontrast uniformly fatsuppressed images with high SNR that can be compared to postcontrast images for assessing normal and pathological mural enhancement. Postcontrast images can be acquired in axial and coronal planes using 2D or 3D fat-suppressed T1W gradient echo sequences following intravenous contrast injection. Different vendors use differently named sequences. Volumetric interpolated breath-hold examination (VIBE), fast low angle shot magnetic resonance imaging (FLASH) and T1W high resolution isotropic volume examination (THRIVE) are few acronyms for three-dimensional gradient echo sequences. 2D gradient echo images are thicker in slice thickness but provide sharper images with better contrast than 3D gradient echo images. Thinner slice thicknesses of 3–4 mm used in three-dimensional gradient echo sequences provide better anatomical coverage. Two sets of gradient echo fat-suppressed T1W images are obtained in coronal plane, 30 and 70 seconds after contrast injection, followed by imaging of whole abdomen in axial plane at 90 seconds. 3D Dixon is an excellent sequence for dynamic contrast imaging (DCE). Dynamic imaging is started immediately after contrast administration without any delay. Sequential images are acquired in rapid succession with a temporal delay of ~50–10 seconds for the next 5–7 minutes followed by high-resolution T1W routine postcontrast images. DCE-MR is useful in detecting vascular malformations (like angiodysplasia of bowel), hypervascular lesions (like neuroendocrine tumours), mesenteric vascular thrombosis, active bowel inflammation with early mucosal enhancement and assessing bowel wall enhancement patterns. Fat-suppressed postcontrast images increase the conspicuity, thus aiding detection of bowel wall thickening (type, pattern and

length of segment involved), luminal or mural lesions (polyps or tumours), perienteric inflammation and better delineation of associated complications such as abscess, sinus-fistula formation and lymphadenopathy. Image subtraction sets, generated by digitally subtracting precontrast images from corresponding postcontrast images, better delineate the areas of enhancement and are particularly helpful in detecting unequivocal enhancement and further characterizing the areas of abnormal enhancement. In recent years, diffusion weighted imaging (DWI) has become an integral part of standard MRE and complements the conventional sequences in evaluating patients with bowel neoplasms and inflammatory conditions. DWI uses diffusion of water protons at cellular level to form images. Increase in cellularity (tumour, hypercellular metastases or inflammatory infiltrates) leads to restricted diffusion of water protons. Diffusion weighted images can be acquired either by breathholding, single-shot technique or a free-breathing, multipleaveraging technique and can be combined with respiratory triggering. Single-shot breath-holding sequences are fast and provide good anatomic details. However, they have poor signal to noise ratio (SNR) and are more prone to susceptibility and pulsation artefacts. Free-breathing DWI sequences are relatively slow but allow more accurate ADC calculation, multiplanar reconstruction and better SNR. Bowel pathologies stand out as they appear bright against relatively dark background. Due to their wide range of contrast, colour-coded DWI images allow better distinction between lumen, wall and extraluminal structures. DWI also permits quantitative analysis by calculating apparent diffusion coefficient (ADC) of various tissues. ADC is a measure of diffusivity of water protons and so areas of restricted diffusion have low ADC values. For calculating ADC values, DWI images acquired at two or more ‘bvalues’ is required. Commonly recommended b-values in abdominal imaging are 0, 400 and 600 s/mm2. Higher b-values increase diffusion weighting of images but decrease SNR and anatomic details (Fig. 8.3.1.22).

FIG. 8.3.1.22 Coronal T2W SSTSE image showing iso to mildly hyperintense shortsegment circumferential mural thickening involving caecum and ascending colon with loco-regional lymphadenopathy. Corresponding DWI image shows high signal intensity within the mural thickening and adjacent lymph nodes with low ADC values suggestive of restricted diffusion. Notice high target to background signal on DWI images making the pathology and affected lymph nodes stand out. DWI imaging has been found helpful in detection and staging of GI tumours. Most GI tumours are hypercellular and show restricted diffusion and appear bright on DWI images. Exceptions to this are carcinoids and highly necrotic or cystic tumours. Small lesions that may have been overlooked on CT and conventional MR sequences can also be picked up on DWI images. Metastatic lymph nodes also show restricted diffusion with reduced ADC values. Although there is considerable overlap in ADC values of benign inflammatory and malignant lymph nodes, morphological alteration with ADC value less than 1.0 × 10–3 mm2/s are highly suggestive of metastatic lymphadenopathy. Combined with postcontrast images, DWI imaging has high diagnostic accuracy in detecting small peritoneal and serosal deposits. ADC values are helpful in monitoring response to treatment, and this has a very high negative predictive value in differentiating tumours that respond to treatment from those that do not. ADC values are helpful in monitoring response to treatment. Substantial

increase in the posttreatment ADC values compared to pretreatment ADV values indicate favourable response. Distinguishing between tumour recurrence (low ADC) and postradiation oedema (high ADC) is also facilitated by ADC values. DWI is also helpful in evaluation of inflammatory bowel diseases aiding in detection, demonstrating their complications such as abscess, sinus, fistula formation and monitoring their response to treatment. DWI does not require intravenous contrast administration making it extremely useful in evaluating pregnant females and patients with renal insufficiency. With on-going advancements and researches in MR hardware and software, MRE is the future of GI imaging due to its lack of ionizing radiations and excellent soft tissue resolution. Functional information provided by DWI images and quantitative data from ADC values may help in management of patients of inflammatory bowel disease and neoplasm in detection, staging and monitoring of treatment response.

Nuclear medicine in small bowel imaging Cross-sectional imaging modalities like CT and MR provide exceptional anatomical details of the pathologies; however, these modalities rely solely on attenuation or morphological characteristics of the pathological tissues and do not provide any information about the functional or metabolic status of the disease process, thus underestimating the total disease burden. Positron emission tomography Positron Emission Tomography (PET) is a modern noninvasive molecular imaging modality that provides functional information of a tissue by determining metabolic activity at cellular level. In PET imaging, a cyclotron-generated positron-emitting radiopharmaceutical agent is injected into the patient. Within the tissue, emitted positron annihilates with electron and produces a pair of high-energy gamma photons travelling exactly in opposite directions which are detected by the symmetrically opposite detectors in the ring of PET scanner, and this localizing information is later used for image generation. Functional imaging in PET is based on a simple fact that hypermetabolic tissues, such as neoplastic tissue, exhibit increased demand for glucose. A radioactive analogue of glucose, 18-fluoro-2deoxyglucose (18FDG) is most commonly used in PET as it closely parallels normal glucose uptake. Neoplastic cells concentrate more

amount of FDG as compared to normal tissues due to overexpression of GLUT receptors on its cell surface. Once inside the cell, phosphorylated FDG cannot be broken down by glycolysis and hence remains trapped allowing sufficient time for imaging. Radioactivity in a given voxel can be measured and expressed in terms of SUV (standardized uptake value). High FDG uptake can also be seen in benign hypermetabolic states like inflammation and infections and does not always imply malignancy. However, PET still plays a crucial role in management of oncology patients by aiding in detection, staging, monitoring response to treatment and restaging. In recent years, modern chemotherapeutic agents and better surgical options have considerably improved the outcomes of small bowel malignancies, emphasizing the importance of accurate radiological staging in guiding patient treatment. As PET imaging relies on the metabolic activity, it can detect disease process in tissues that are morphologically normal yet. It can detect previously undetected loco-regional and distant metastasis, changing the stage of the disease process and thus the patient management. One of the major drawbacks of PET imaging is accurate localization of the detected abnormal FDG uptake. Fusing of PET imaging with cross-sectional imaging modalities like CT and MR resulted in hybrid PET-CT and PET-MR scanners, which offer accurate anatomical localization and characterization of abnormal FDG activity foci. PET is sensitive in detecting small bowel malignancies but its specificity decreases due to nonspecific FDG uptake by bowel. This nonspecific intestinal FDG uptake is not uncommon and may result from swallowed secretions, peristalsis, secondary to metabolic activity of smooth muscles or mucosal, loco-regional lymphocyte concentration or gut flora. Bowel loops distended with large volumes (~1.3–1.5 L) of neutral enteric contrast agents, like in CT enterography, show less overall FDG uptake with lower SUVs on PET. Morphological characterization of abnormal FDG uptake foci can be done on diagnostic helical CT images obtained during PETCT. Small bowel neoplasms comprise primary adenocarcinomas, lymphomas, mesenchymal stromal tumours, carcinoids and metastases. PET-CT can detect primary bowel lesions, establish local extent and invasion, detect and characterize locoregional/distant lymph nodes and metastatic deposits. In heterogenous neoplasms like GISTs, PET-CT can guide biopsy from metabolically active tumour areas showing maximum FDG avidity, thus increasing yield and reducing resampling. PET-CT is superior to CT in evaluation of early response of neoplastic tissue to various treatment modalities (chemotherapy/radiotherapy/surgery),

restaging and recurrence, because metabolic changes precede morphological changes. Carcinoid tumour is a type of neuroendocrine tumour, which account for almost one-third of small bowel tumours. These do not show FDG uptake and therefore go undetected on routine FDGPET. However, neuroendocrine tumours are characterized by overexpression of somatostatin receptors on their cell surface, and this property is exploited in radioimmunoscintigraphy. Newer radiopharmaceutical agents such as Ga-68-labelled-somatostatinanalogues like Ga-68-DOTANOC and 11C-labelled amine precursors like L-dihydroxy-phenylalanine and 5-hydroxy-Ltryptophan (5-HTP) have greater affinity for these neoplasms aiding their detection on PET imaging. Small bowel metastases are not as uncommon as previously thought. They arise mainly from primary tumours of breasts, lungs, stomach, colon, ovaries, uterus and primary melanoma and show increased FDG uptake similar to their parent neoplasms on routine PET imaging. Nuclear scintigraphy Scintigraphy (from Latin ‘scintilla’, meaning ‘spark’) or Gamma scan is an imaging technique under nuclear medicine wherein patients are injected with specific radiopharmaceuticals that travel to a specific organ or tissue, and the emitted gamma radiation is captured by external gamma cameras to form two-dimensional images in contrast to three-dimensional images provided by SPECT and PET. Nuclear scintigraphy currently has a limited role in small bowel imaging. Tc-99-labelled RBC scan is indicated for detecting and localizing occult GI bleeds. It is indicated when routine imaging techniques and endoscopy fail to detect GI bleeds, either due to small volume or slow bleeding rate, but clinical suspicion is high. It can detect bleeds as small as 3 mL with minimum detectable bleeding rate of 0.04 mL/minute. Indium-111-tagged WBC scan is being increasingly used for detecting and localizing sites of inflammation/infection with high sensitivity and specificity. It is of great help especially when routine contrast imaging is either unequivocal or contraindicated. Somatostatin receptor scintigraphy (SRS) or Octreotide scan is particularly useful in detection of primary or metastatic gastro-entero-pancreatic neuroendocrine tumours. SRS imaging in NET can be used to monitor response of the tumour to therapeutic somatostatin and radionucleotide therapy. Meckel’s diverticulum usually has ectopic gastric and pancreatic mucosa. 99m Technetium-pertechnetate scan has limited sensitivity and specificity in detecting Meckel’s diverticulum.

99mTc-pertechnetate is taken up by the mucin-secreting cells of normal and ectopic gastric mucosa, thus aiding in its detection.

Capsule endoscopy ‘The discomfort of internal GI examination may soon be a thing of the past’: Iddan. Due to its length and complex looped anatomy, most of the small bowel was inaccessible by conventional flexible endoscopic techniques and thus remained a grey area for gastroenterologists until the last decade. Only the most proximal jejunum and few centimetres of terminal ileum were accessible via push enteroscopy and colonoscopy with ileoscopy, respectively. Invasive intraoperative endoscopy was the only end resort for complete endoscopic evaluation of the small bowel. Introduced in clinical gastroenterology in 2001, capsule endoscopy (CE) is a revolutionary diagnostic tool for noninvasive direct endoluminal visualization of the entire small bowel using tiny swallowable wireless pill camera. Capsule consists of batterypowered tiny cameras coupled with light source (few light emitting diodes) and radio-transmitter. Bowel preparation (usually 10–12 hours prior fasting and use of laxatives) improves visualization and diagnostic yield. Similar to ECG, about eight sensors are attached over patient’s abdomen which are connected to a portable batteryoperated recorder worn by patient around his waist. Once swallowed, pill camera starts acquiring images of the GI tract at an average rate of 2–3 images per second until its battery lasts (~8–12 hours). Images acquired by pill camera are transmitted via high frequency radio-telemetry to the sensor arrays, which further sends this data to recorder which processes and stores them for later viewing. The sensors also help in rough localization of the acquired images. The recorded images are transferred to the computer workstation where they are analysed by a gastroenterologist. The capsule is excreted naturally usually after 8–72 hours. The most common indication of CE is occult GI bleed and suspected early Crohn’s disease. Many studies have found CE superior to barium, CT or MR enterography in detection of mucosal pathologies. Other potential indications of CE are evaluation of patients with polyposis syndromes, NSAID-induced intestinal damage, chronic abdominal pain, chronic diarrhoea and recurrent low grade bowel obstruction with nondiagnostic imaging. It can also be used to assess the bowel transit time. The major advantage of CE is noninvasive small bowel evaluation without sedation or exposing patient to harmful ionizing radiation. Disadvantages of CE are lack of definitive anatomical localization of the pathology, inability to take biopsies or provide therapeutic

intervention and capsule retention in cases of stricture or obstruction. 8. 3.2

INFLAMMATORY BOWEL DISEASE Aditi Chaitanya Gujarathi-Saraf, Sanjay Desai

Introduction Inflammatory bowel disease (IBD) involves ulcerative colitis (UC) and Crohn’s disease (CD) affecting the gastrointestinal tract. CD started to gain attention in India after mid-1980s, when colonoscopy, biopsy and CT scan were made widely available. CD is also known as regional enteritis. It is a chronic immunemediated inflammatory condition of the gastrointestinal tract. It shows phases of remission and relapse. Any part of the gastrointestinal tract can be involved in the disease process from the oral cavity to the anus; however, most common site is terminal ileum. Multiple skip lesions are seen at one time commonly. Radiology plays an important role in assessment of CD with use of barium studies, ultrasonography, CT enterography (CTE) and MR enterography (MRE). Barium studies such as enteroclysis and small bowel followthrough have been used traditionally. CTE is the mainstay for evaluation of CD. It has replaced barium studies due to its crosssectional ability to assess intraluminal as well as extraluminal bowel pathologies. It also helps in assessing complications of CD such as fistulae, abscess, intestinal obstruction and parts of bowel inaccessible to endoscopy. MRE has emerged as an alternative imaging technique to CTE and has largely replaced CTE as the primary cross-sectional imaging investigation of choice due to lack of ionizing radiation and better efficacy to differentiate acute from chronic disease.

Epidemiology The peak age of onset is typically between the ages of 15 and 30 years with no gender predilection. A second peak is observed between the ages of 60 and 80 years.

The incidence of IBD is increasing worldwide and varies geographically. CD incidence varies between 0.6 and 6.3 cases/100,000 population. Worldwide prevalence ranges from 10 to 70 cases/100,000 population. Highest incidence is found in the developed countries of Europe, the United Kingdom, Scandinavia and North America. The incidence is, however, rising in Japan, South Korea, Singapore and India. The incidence in India has been reported to be 6.02/100,000. It is common in white population than Africans or Asians, with a sevenfold increase in incidence of the disease among Jews. This geographical variety points towards the chances of hereditary predisposition. Urban areas have a higher incidence than rural, and high socioeconomic classes have a higher incidence than lower socioeconomic classes. CD can run in families. The risk of developing the disease is 4.5%–16.6% with a positive family history. The disease is 30 times more frequent in siblings than in the general population. Smoking increases the risk for CD four times. Flowchart 8.3.2.1 shows the risk factors for CD.

FLOWCHART 8.3.2.1 Risk factors of Crohn’s disease.

Clinical features CD can present in two forms, acute and chronic. The acute form mimics appendicitis with right lower quadrant pain secondary to jejunoileitis. Diarrhoea is commonly seen sometimes with bleeding. In chronic cases, often an inflammatory mass can be palpated in right iliac fossa. The clinical features have been listed in Table 8.3.2.1. TABLE 8.3.2.1 Clinical Features of Crohn’s Disease Acute Abdominal pain Diarrhoea Low-grade fever

Chronic Diarrhoea Weight loss Intestinal obstruction Nutritional deficiencies Fistula and abscess

Aetiopathogenesis The exact aetiology of CD is not known. The small intestine is involved in nearly 80% of cases, most common site being the terminal ileum. The proximal colon is involved in with (50% of cases) or without (15%–20%) involvement of the small intestine. Radiologically, there are four subtypes of CD: 1) Active inflammatory type 2) Fibrostenotic type 3) Fistulizing/Perforating type 4) Reparative or regenerative type The radiological and pathological findings usually correlate. Lymphoid hyperplasia and lymphoedema are the earliest changes caused by the disease process that occur in the submucosa. This is followed by a transmural inflammation. There is mucus membrane permeability causing an antigen-induced cell mediate inflammatory response. This releases cytokines like TNF and Interleukin 2. This causes defect in suppressor T cell and granuloma formation. Mucosal erosions lead to formation of aphthoid ulcers. The bowel wall is thickened by a combination of fibrosis and inflammatory infiltrates in the fibrostenotic type. The fistulizing type is manifested as formation of abscesses, fistulas and sinus tracts. Flowchart 8.3.2.2 shows pathogenesis of CD.

FLOWCHART 8.3.2.2 Aetiopathogenesis of Crohn’s disease.

Extraintestinal manifestations of Crohn’s disease Extraintestinal manifestations (EIMs) are seen in 25%–40% of patients suffering with IBD. Primary manifestations of the disease affect skin, eyes, liver and joints. Nearly all the patients with IBD

will develop some secondary effect outside of the gastrointestinal tract lumen. These can be divided into three categories on the basis of causative factor: 1) Related to disease activity and respond to therapy directed at the bowel disease (e.g. arthritis, iritis); 2) Not related to underlying bowel disease (e.g. sclerosing cholangitis, ankylosing spondylitis); and 3) Occur as a result of impaired intestinal function (e.g. cholelithiasis, renal stones). Musculoskeletal and dermatologic manifestations occur most commonly followed by hepato-pan-creatobiliary system, ocular, renal and pulmonary manifestations. Table 8.3.2.2 shows a system-wise list of EIMs and also lists these manifestations. TABLE 8.3.2.2 Extraintestinal Manifestations (EIMs) of Crohn’s Disease Systems Hepatobiliary

Manifestations Fatty liver, sclerosing cholangitis, chronic hepatitis Musculoskeletal Arthritis, sacroiliitis, osteoporosis Ocular Iritis, uveitis, conjunctivitis Dermatologic Erythema nodosum, dermatitis Haematologic Anaemia, thromboembolic disease Renal Urolithiasis, nephrotic syndrome Cardiovascular Endocarditis, myocarditis, vasculitis Pulmonary Bronchitis, pulmonary embolism Various complications of CD are listed in Flowchart 8.3.2.3.

FLOWCHART 8.3.2.3 Complications of Crohn’s disease. Crohn’s disease associated with malignancies Adenocarcinoma There is an increased prevalence of small bowel adenocarcinoma in patients with long-standing CD. The most common site affected is distal ileum. Another important site is the surgically bypassed bowel followed by site of fistulae. Lymphoma Patients with CD have nearly four times increased risk of developing non-Hodgkins lymphoma. This is attributed to a longstanding treatment with immunomodulating drugs (such as azathioprine and 6-mercaptopurine). Diagnostic modalities There are various diagnostic modalities available for evaluation of CD. Purpose of imaging studies: • Detect early changes of CD. • Demonstrate exact extent of involvement and presence of skip lesions. • Follow up patients to know stability of the disease or malignant change.

• Differentiate between active inflammatory disease, mixed active and fibrostenotic disease, and fibrostenotic disease to decide medical versus surgical treatment. • Detection of complications of CD. These can be divided into imaging and endoscopic modalities. Endoscopy is the gold standard for diagnosis and evaluating response to CD. Endoscopic techniques include ileo-colonoscopy and video capsule endoscopy. However, because of its invasive nature, endoscopy is typically reserved to detect treatment response in patients who are clinically symptomatic. Multidetector computed tomography is the most commonly and widely used cross-sectional imaging technique and has become the investigation of choice for noninvasive evaluation of the small bowel. It is not only effective in demonstrating mural abnormalities but also detects extraluminal abnormalities such as fistulae, abscesses and sinus tracts. CT scan can be performed in three ways while evaluating CD. First is conventional CT abdomen and pelvis with positive oral contrast. This technique should be reserved for postoperative patients in order to detect leak of contrast through a bowel segment. Routine CT should otherwise be avoided as the use of positive oral contrast hinders the assessment of bowel wall enhancement. The other two ways of CT evaluation include CTE and enteroclysis. In enterography, patient is asked to drink 1500–2000 mL of neutral oral contrast over a period of about 1 hour. In enteroclysis, a tube is placed in the distal duodenum and neutral contrast is mechanically through a naso-jejunal tube. In CT enteroclysis and enterography, the oral contrast is neutral contrast – with a Hounsfield density similar to that of water. Water, methylcellulose, mannitol, polyethylene glycol and 0.1% barium sulphate suspension (VoLumen, E-Z-EM, New York) can be used. The advantage of these techniques over conventional CT is excellent demonstration of mural abnormalities. Intravenous (IV) contrast is administered at a rate of 3–5 mL/s. Dual phase scan is performed and includes a late arterial phase (scan time to start, 35–40 seconds) and venous phase (70 to 80-second delay from contrast injection). CTE is used in acutely ill and symptomatic patients as the technique is better tolerated by patients. CT enteroclysis combines the advantages of conventional enteroclysis and cross-sectional imaging in a single technique as it provides optimal and uniform distension of the lumen, thus allowing better assessment of mural

abnormalities. However, this technique is not well tolerated by patients and thus should be used selectively. The lack of ionizing radiation, higher soft tissue contrast and providing functional information makes MR enteroclysis the ideal technique for evaluating CD. It provides excellent information on disease activity, assessment of therapeutic response and assessment. However, unlike CTE, it takes longer time and need patient cooperation. Also, bowel peristalsis can hinder image quality. CD has a relapsing–remitting nature. This causes frequent reevaluation of disease. Thus, noninvasive, well-tolerated and inexpensive examinations should be performed. These examinations should do justice to clinical suspicion of the disease activity as well as provide morphological, extent and functional information for an effective management of the disease. As CD presents at a younger age, aims to reduce radiation exposure should be kept in mind. Ultrasonography requires scanning the bowel with a highfrequency transducer meticulously with graded compression and with the use of oral contrast agents like polyethylene glycol (PEG). It can be used as a preliminary diagnostic tool prior to invasive test. Most important role of USG is in management of CD as it is well tolerated by patients, noninvasive, widely available and inexpensive. It is used to assess the site and extent of the lesions and to detect intraabdominal complications such as abscesses and stenoses. Recent advances in contrast-enhanced ultrasound show a promising role in differentiating fibrotic versus active inflammatory stricture. Recommendations: Initial investigation: Endoscopy and CTE. For follow up: US with Doppler, MRE (preferred over CTE). Relapses: MRE or CTE with or without endoscopy. Complications: MRE and CTE if acutely ill noncooperative patients. Table 8.3.2.3 shows commonly used modalities, their advantages and disadvantages.

TABLE 8.3.2.3 Advantages and Disadvantages of Imaging Modalities Endoscopic Advantages Modalities Ileocolonoscopy • Assessment of disease activity and biopsy • Visualization of complications – strictures, bleeding and malignancy

Video capsule endoscopy

Imaging Modalities

• Useful for detecting mucosal lesions • Good tolerability and safety • Negative predictive value is more than 96% for CD

Advantages

Disadvantages • Cannot detect extraluminal complications and extraintestinal manifestations • Cannot be performed in inaccessible areas • Cannot detect extraluminal complications and extraintestinal manifestations • Obstructing stricture-major contraindication for the use of capsule • Risk of retention of capsule Disadvantages

Endoscopic Modalities Barium examinations

Ultrasonography

CT scan

Advantages

Disadvantages

• Evaluation of bowel motility, differentiation of true obstruction from pseudoobstruction • Demonstration of complex fistula • Can be used in patients with chronic kidney disease when CTE and MRE are contraindicated

• Cannot detect extraluminal complications and extraintestinal manifestations

• Wide availability • No ionizing radiation • Can detect disease activity and response to treatment with the use of colour Doppler

• Operator dependent • Limited study due to bowel gas, obesity

• Enterography can demonstrate mural abnormalities, wall thickening and extraluminal abnormalities • Extraintestinal manifestations can be seen

• Ionizing radiation • Requires good bowel distension • Cannot differentiate mixed disease from active disease

Endoscopic Modalities MRI

Advantages • No ionizing radiation • Can differentiate inflammatory versus fibrous stenosis • Evaluates each bowel segment at multiple times, which may help in differentiation of stricture from peristalsis • Better assessment of abscesses and fistulas than CT

Disadvantages • Time consuming • Requires good bowel distension • High cost

Radiological findings These can be divided according to the stage of the disease. 1) Active inflammatory disease Active inflammatory disease is characterized by the presence of superficial and deep ulcers, transmural inflammation with granuloma formation and mural thickening. Barium findings Barium examination can be done by two methods: standard small bowel series and enteroclysis. Mesenteric border is always affected more in early active CD than the antimesenteric border. The normal undulating fold pattern on the mesenteric border will become ulcerated, effaced, flattened and foreshortened, whereas there is relative sparing of the antimesenteric border, giving rise to the pseudodiverticulosis sometimes associated with the disease. Earliest finding of active disease is the presence of aphthous ulcers. These appear as punctate collections of barium of 1–3 mm in size surrounded by radiolucent halo. In this phase, there is obliteration of intestinal folds due to submucosal oedema predominantly on the mesenteric side. The thickened folds are seen as asymmetric macronodules of size >1 cm.

As the disease progresses, aphthous ulcers enlarge to form satellite, serpiginous or linear areas of ulceration. Advanced CD is characterized by transmural deep fissuring ulcers. The classical cobblestone appearance is a result of deepening of aphthous ulcers, which coalesce to form transverse and longitudinal ulcers separated by residual areas of oedematous mucosa. An inflammatory cellular infiltrate with focally pronounced oedema and granulation tissue can give rise to localized mucosal elevations or inflammatory polyps. These lesions are common in the colon but infrequent in the small bowel. Inflammatory pseudopolyps usually occur in small numbers in an area of mucosa that is denuded of folds. Occasionally, a bowel segment contains many inflammatory pseudopolyps (≤1 cm), separated from one another by curving lines of barium occupying the crevices between the elevations. When seen in profile, the polyps appear as notches demarcated by protrusions of barium. The diameter of these bowel segments is not reduced. This is called the nodular pattern of CD to underscore. Ultrasonography findings Abdominal ultrasound has a sensitivity ranging from 67% to 96% and specificity ranging from 79% to 100% in diagnosing CD. The most common finding in active CD is presence of wall thickening. A cut-off value of >3 mm has a sensitivity and specificity of 88% and 93%, respectively. Wall thickening manifests as concentric thickening with variable echogenicity depending on the active inflammation and presence of fibrosis. In active inflammatory stage, the bowel is usually fixed with sluggish or absent peristalsis. On colour Doppler, the actively inflamed wall shows high flow due to hyperaemia. On spectral Doppler, there is increase in blood flow in mesenteric vessels (superior and inferior mesenteric arteries). Along with this, there is increase in pulsatility index (PI) and decrease in resistive index (RI). There is increase in portal vein velocity too. Associated mesenteric findings include homogenous echogenic halo surrounding the mesenteric border of the bowel secondary to creeping fat that separates the bowel loops. Peribowel and mesenteric nodes appear rounded and hypoechoic with maintained echogenic hila. There is increase in the nodal vascularity on colour Doppler owing to hyperaemia. Studies are being undertaken regarding the use of contrast enhanced ultrasound (CEUS) to detect the vascularity of the affected bowel wall suggesting presence of active disease. Ripolles et al. compared findings of CEUS with endoscopy. They concluded

that CEUS has 96% sensitivity and 73% specificity in the prediction of a moderate or severe grade of inflammation. Another prospective study was carried out by Romanini et al. They did quantitative analysis of bowel wall enhancement in IBD patients by CEUS and compared the results with the vascular density of a biopsy sample from the same intestinal tract. The results showed higher enhancement peak, a shorter time to peak enhancement, a higher regional blood flow and regional blood volume in patients with active inflammation. The cut-off values for peak enhancement (>40.5%) and regional blood flow (>54.8 mL/minute) were concluded by this study in order to differentiate between active and inactive disease. In spite of these positive results, the actual role of CEUS in assessing activity of CD is currently controversial. Computed tomography findings Active inflammatory disease is present when there is wall hyperenhancement, wall thickening (>3 mm) causing luminal narrowing with surrounding mesenteric fast stranding, distension of vasa recta and lymphadenopathy in absence of proximal bowel dilatation. Wall findings 1) Wall hyperenhancement: Wall hyperenhancement is the hallmark of active disease. It can be identified as increased enhancement on postIV contrast scans in an optimally distended bowel segment. In early acute phase of CD, the only imaging finding can be mucosal hyperenhancement seen only on the arterial phase images. A simple way to identify hyperenhancement is to compare with adjacent bowel loops. It is important not to confuse pathologic hyperenhancement with the normal greater enhancement of the jejunum relative to the ileum on arterial phase images or normal greater enhancement of a collapsed bowel segment. Hyperenhancement may be classified as layered or stratified and shows two patterns, bilaminar and trilaminar. Mucosal hyperenhancement is seen in the bilaminar pattern without enhancement of outer wall of bowel. In the trilaminar pattern, the presence of mural stratification gives rise to a ‘target’ or ‘double-halo appearance’ of the wall. Target sign is attributed to the presence of brilliantly enhancing mucosal layer with hypoenhancing submucosal layer due to oedema. Sometimes, an outer layer of serosal hyperenhancement can also be present.

Bilaminar pattern is more commonly seen on CT than the trilaminar appearance due to lower soft tissue contrast resolution of CT (Fig. 8.3.2.1). 2) Wall thickening: Bowel wall thickening can be symmetric or asymmetric. It can be mild (3–4 mm), moderate (5–10 mm) or severe (>10 mm). However, the most common and consistent feature of CD is more than 1.5–2 cm. In the early phase of CD, wall thickening can be subtle or absent. However, as the disease progresses, bowel wall thickening becomes more evident on venous phase images. Wall thickening usually begins on the mesenteric side of the bowel and involves the antimesenteric side as the disease progresses.

FIG. 8.3.2.1 A 34-year-old patient came with long standing dirroahea and abdominal pain. Routine CT abdomen shows active inflammatory small bowel Crohn’s disease Axial (A) and Coronal (B) images show wall thickening with mild luminal narrowing of the distal ileum and the descending colon. Acute mesenteric findings In the acute inflammatory CD, distension of the vasa recta, mesenteric hyperaemia, fat stranding and increased attenuation of the mesenteric fat are commonly encountered findings. 1) Vasa recta distention/engorgement:

In active inflammatory stage, there is dilatation of the vasa recta (arteries arising from the mesenteric arcades and extending towards the small bowel). This is classically described in radiology as the ‘comb sign’. Dilated vasa recta are detected on CT as short, parallel, hyperenhancing linear structures perpendicular to the long axis of the affected bowel segment. Coronal maximum intensity projection (MIP) images are useful in identifying the comb sign as one can visualize the mesentery, dilated arteries and the small bowel accurately. 2) Adenopathy: Enlarged homogenously enhancing mesenteric lymph nodes are typically observed in patients with active inflammatory stage. Lymph nodes are considered to be enlarged if the short axis diameter is more than 1.5 cm. Between 1.5 and 2 cm, the nodes are likely to be inflammatory. However, if more than 2 cm and multiple, malignancy should be suspected. 3) Fibrofatty proliferation of mesentery: This is characterized by deposition of fat surrounding the diseased bowel loops along the mesenteric border. This leads to displacement of the small bowel loops and their separation. Fat deposition and proliferation occur as a result of perivascular inflammation and can be seen in up to 50% of patients with CD (Fig. 8.3.2.2).

FIG. 8.3.2.2 (A) Axial and (B) coronal CTE images showing bilaminar type of bowel wall enhancement, wall thickening without upstream dilatation, distension of vasa recta consistent with an active inflammatory CD. This patient was 28 year old and presented with right iliac fossa pain. MR enteroclysis findings 1) Aphthous ulcers: In high clinical suspicion of CD, presence of aphthous ulcers has a good diagnostic accuracy for CD. An aphthous ulcer may be seen on HASTE images as a nidus of high signal surrounded by a rim of intermediate signal intensity. Deep ulcers and cobblestone appearance of mucosa are seen in advanced active inflammatory disease. The enteral contrast material outlines the deep ulcers which then appear as linear, hyperintense protrusions into the bowel wall on HASTE sequences. Sensitivity of MRI in detecting bowel ulcers is between 75% and 90%. Presence of longitudinal and transverse ulcers within the bowel wall gives cobblestone appearance. It is described as patchy, sharply demarcated hyperintense areas in the diseased bowel segment. Pseudopolyps are identified as hyperenhancing papillary, nodular defects protruding though the bowel wall. 2) Wall hyperenhancement:

Similar to CT, hyperaemia secondary of active inflammation is seen at mucosal hyperenhancement on T1W postcontrast images. Trilaminar pattern or ‘Target sign’ is more commonly and accurately seen on MR than CT due to its better soft tissue resolution. Pattern of enhancement has a good correlation with the presence of active inflammation. 3) Wall thickening: Wall thickening on MR HASTE sequences is seen as thickened, blunted and distorted valvulae conniventes of the jejunal loops. Wall thickening more than 3 mm is considered to be abnormal and when present has a sensitivity of 83%–91% and specificity of 86%–100% for CD. Linear hyperintense areas in the thickened folds is secondary to the presence of oedema within the folds in active disease. Fat-suppressed sequences excellently demonstrate these acute findings due to suppression of intramural fat. Aphthous ulcers in combination with distorted, thickened valvulae conniventes have high diagnostic specificity for CD (Fig. 8.3.2.3).

FIG. 8.3.2.3 MR enteroclysis showing hyperenhancement of thickened wall, enhancing with Comb’s sign. Acute mesenteric findings Perienteric acute inflammation is identified as hyperintense signal on T2 fat-suppressed (HASTE) images in the mesenteric fat adjacent to affected segments of small bowel. On postcontrast

images, there is particularly increased enhancement of the mesenteric fat around an acutely inflamed bowel segment. Fibrofatty proliferation along the mesenteric border of affected bowel segment associated with separation of bowel loops surrounding this region is a diagnostic feature of CD on MRI. Distended vasa recta are seen on MRE as short, parallel, hypointense linear structures, perpendicular to the affected bowel showing hyperenhancement on postcontrast T1 images. Note: Hyperenhancement of wall, presence of aphthous ulcers, thickened wall, enhancing mesenteric lymph nodes and Comb’s sign when seen together are highly specific for the presence of active inflammatory CD. 2) Fibrostenotic disease As the name suggests, presence of wall thickening causing stricturous luminal stenosis and resultant proximal bowel obstruction are the classical findings of fibrostenotic disease. The dilatation is usually more than 3 cm. There should not be any signs of active inflammation on imaging studies. The fibrotic strictures are caused by chronic mural deposition of extracellular matrix (collagen) protein predominantly in the submucosa. The incidence of strictures is approx. 21% of patients with CD. These strictures have a high recurrence rate of 85% postsurgical resection. Barium findings Fibrostenotic stricture is seen on small bowel enteroclysis as narrowed segment coated with barium. On fluoroscopy, a true stricture will not change its calibre with peristalsis in contrast to the peristaltic segment which dilated as the peristaltic wave propels. A persistent stream of barium in the narrowed long-segment bowel loops is termed as ‘string sign’. The upstream/proximal bowel remains dilated in spite of a peristaltic wave. Strictures may be single or multiple. Multiple strictures are often seen in patients with advanced disease and are seen as skip lesions. Ultrasonography findings The sensitivity of ultrasound to detect stenosis is 70%–79% of patients with CD without the use of PEG as oral contrast. The accuracy increases with the use of PEG so that one stenosis can be detected in >10% and two stenoses in >20% of patients, as compared to ultrasound without oral contrast agents. Thus, the sensitivity increases to 90% for detection of a single stenosis and >75% for detection of multiple stenoses. On ultrasound, strictures are seen as mural thickening with apposing luminal surfaces of the stenotic segment. There is

resultant proximal small bowel dilatation with to-and-fro peristaltic movements. Aneurysmal dilatation of proximal bowel can be seen occasionally (Fig. 8.3.2.4).

FIG. 8.3.2.4 Ultrasonographic image showing aneurysmal small bowel dilatation in a 42 year old female. Computed tomography findings Narrowing of the involved bowel segment is a gradual process and progresses over time resulting into stricture formation. Causes of luminal narrowing include proliferation of smooth muscle in the bowel wall and/or transmural fibrosis. The upstream bowel dilatation can be graded as mild if less than 4 cm, moderate if between 4 and 6 cm and severe if more than 6 cm. Homogeneously enhancing bowel wall thickening suggests irreversible fibrosis; thus, demanding the need for surgery to relieve obstruction. It is of utmost importance to differentiate true obstruction due to stricture from bowel peristalsis. Presence of proximal bowel dilatation more than 3 cm, transition point at the level of stricture and collapsed distal loops with faecal residue in the proximal small bowel (small bowel faeces sign) as a result of delayed bowel transit

and stasis favour the diagnosis of true obstruction. It is challenging to differentiate acute versus chronic luminal narrowing. No matter what, whether acute or chronic, the presence of a stricture is a crucial finding and must be communicated to gastroenterologists, as small bowel endoscopy in this scenario can result in capsule retention (Fig. 8.3.2.5).

FIG. 8.3.2.5 Fibrostenotic inflammatory small bowel Crohn’s disease in a 34-year-old patient with small bowel obstruction. Axial (A) and coronal (B) postcontrast-enhanced CTE images show bilaminar hyperenhancement, severe wall thickening, and marked upstream bowel dilation. MR enteroclysis findings Chronic fibrotic strictures demonstrate low signal on both T1 and T2-weighted sequences. Fibrotic strictures usually show minimal inhomogeneous contrast enhancement. Asymmetric bowel fibrosis and shortening secondary to ulceration of the mesenteric side of the bowel lead to the formation of pseudosacculations on the other side. These changes are well-visualized on coronal images along the mesenteric plane. CTE is preferred over MRE when patients present with acute small bowel obstruction. However, obstruction may be long standing. In such cases, it is a diagnostic challenge to differentiate acute from chronic strictures. MR is a problem-solving tool in this

due to its excellent soft tissue contrast resolution, as acute strictures are associated with inflammatory oedema of the bowel wall and show the target sign with signs of inflammation or hyperaemia in the surrounding mesentery. The clinical significance of this is choice of medical versus surgical treatment for acute versus chronic strictures, respectively. Acute strictures require medical treatment, whereas chronic strictures often require surgical resection or stricturoplasty. Recent advances in MR fluoroscopy may demonstrate fixity of the diseased segment with proximal dilatation of the bowel in case of acute obstruction. 3) Fistulizing or penetrating disease Fistulizing or penetrating disease presents as sinus tracts, fistulae, abscesses and rarely perforation. Penetrating disease presents frequently when underlying mixed disease is present. Abscesses develop in approx. 20% of patients with CD. Abscesses form either in the mesentery or may extend into adjacent retroperitoneum. Fistulae are abnormal communications between two epithelial surfaces or an epithelial surface and the skin, with incidence of 6%– 33% of patients with CD. Deep ulcers may lead to the transmural extension of inflammation with resultant formation of abscesses or fistulas. The different types of fistulae are enteroenteric, enterocolic, colocolic and perianal fistulae, commonest being ileocaecal, ileosigmoid and enteroenteric. They can be single but are often multiple. An enterocolic fistula can cause malabsorption as a result of bacterial overload. Barium findings Fistulae are seen as abnormal communications opacified by barium between the skin and hollow viscus or between two segments of bowel. Ultrasonography findings Fistula is seen as a linear band of variable echogenicity between two epithelial surfaces or an epithelial surface and the skin. It can entero-vesical or entero-enteric fistula. It may contain air or fluid within. Presence of air can lead to ring down artefact. The sensitivity and specificity of detecting fistulae is 87% and 90% on USG as postulated by Gasche et al. Abscesses are seen as fluid-filled lesions with variable echogenicity depending on the contents. Computed tomography findings

On CT, sinus tracts are small, linear or tubular transmural tracts extending outside the lumen into the mesenteric fat. Sinus tracts are commonly associated with tethering or acute angulation of the involved bowel loop with structure formation as well. Fistulae usually appear as enhancing linear extraluminal tracts, which may or may not be fluid-filled. A simple fistula extends from one bowel segment to another or to the adjacent organ or structure. Complex fistulae have multiple ramifications extending to organs/structures. Associated interbowel inflammatory mass or abscess may be seen (Fig. 8.3.2.6).

FIG. 8.3.2.6 A case of 38 year old man with penetrating disease: A. Coronal postcontrastenhanced CTE image shows bilaminar terminal ileal wall thickening. There is an inter-bowel abscess (arrow) with air foci within. MR enteroclysis findings Sinus tracts or fistulae are seen as linear hyperintense fluid-filled tracts on HASTE sequence. Associated tethered bowel showing acute angulation is often seen. Surrounding mesentery shows inflammatory changes and lymphadenopathy. The sensitivity of MRE for detection of fistulae is approx. 83.3% and the specificity is 100%.

Multiplanar imaging of the bowel is of utmost importance to avoid missing fistulae due to partial volume averaging. Sinus tracts and fistulas can be lined by oral contrast material appearing hyperintense on HASTE images. A ‘star appearance’ can be seen in adjoining affected mesentery as a result of desmoplastic reaction. Acutely inflamed fistulas demonstrate intense enhancement secondary to hyperaemia and high vascularity. Accurate detection of any intraabdominal abscess has clinical significance as the antitumour necrosis factor agents such as infliximab is contraindicated in the presence of intraabdominal abscess (Fig. 8.3.2.7).

FIG. 8.3.2.7 Fistulizing disease- Fistulous communication between a ballooned segment of proximal ileal loop to distal ileal loop. 4) Quiescent or inactive disease Barium findings These are usually normal since the mucosa is normal. Ultrasonography findings No abnormality is usually detected; however, sometimes a mildly thickened wall showing no vascularity Doppler imaging is seen.

Computed tomography findings It is seen on cross-sectional imaging as absent to minimal bowel wall enhancement. The bowel wall is usually normal or sometimes can be thickened. With no signs of active inflammation, such segments of bowel are labelled as ‘burnt out disease’. In longstanding quiescent CD submucosal fat deposition, pseudosacculation, surrounding fibrofatty proliferation are commonly seen. The hallmark of the disease is asymmetric fibrosis and pseudosacculation of the antimesenteric border of the affected segment of bowel (Fig. 8.3.2.8).

FIG. 8.3.2.8 Known case of CD after immunosuppressive therapy. Quiescent disease. Axial (A) CTE image show mild wall thickening (arrow). The mucosa was normal at endoscopy. Acute mesenteric changes are characteristically absent. The only commonly seen finding is the fibrofatty proliferation of mesentery. MR enteroclysis findings Mucosal atrophy and the presence of regenerative polyps are the hallmarks of this stage. Narrowed bowel segment may be seen without any signs of inflammation or obstruction. Mucosal denudation with focal areas of normal mucosa is seen. Reparative polyps can be seen as filling defects without mural oedema.

Mixed fibrostenotic and active inflammatory disease Mixed fibrostenotic and active inflammatory small bowel CD is said to be present when there is bowel wall hyperenhancement, wall thickening and luminal narrowing with upstream bowel dilatation (>3 cm in diameter). Presence of mucosal hyperenhancement in an active disease does not necessarily exclude fibrosis which can coexist in a mixed disease and which can lead to obstruction. The coexistence of mixed disease is controversial (Fig. 8.3.2.9).

FIG. 8.3.2.9 This was a 42-year-old patient, known case of CD, on treatment since few years who presented with small bowel obstruction. CTE images showed a mixed fibrostenotic and active inflammatory small bowel Crohn’s disease: Axial (A) and coronal (B) postcontrastenhanced CTE images show bilaminar hyperenhancement, moderate wall thickening, and marked upstream bowel dilation.

MRE disease activity indices Several studies are in progress to develop and to standardize MRE criteria for disease activity in CD which will be beneficial for clinical use. MRE findings are compared to endoscopic findings and the MRI scores are derived to assess activity. These are magnetic resonance

index of activity (MaRIA) and activity index score (AIS). Rimola et al. did a comparative study using ileocolonoscopy as a reference standard and compared the disease activity with MRE based on various imaging features. The various features used to assess the presence of active inflammation are bowel wall thickness, mural oedema, mucosal ulceration and relative contrast enhancement (RCE). The MaRIA is derived as follows: MaRIA = (1.5 × wall thickness in mm) + (0. 02 × RCE of bowel wall) + (5 × mural oedema) + × (10 × ulceration) RCE = (wall signal intensity postenhancement) – (wall signal intensity preenhancement)/(wall signal intensity preenhancement) Mural oedema = T2 hyperintensity relative to the psoas muscle signal Mural ulceration = deep depressions in the mucosal surface The AIS is derived as follows: AIS = 1.79 + (1.34 × wall thickness in mm) + (0.94 × mural T2 score) Mural T2 score = ranges from 0 to 3, interpreted as equivalent to adjacent normal bowel wall signal to marked increased signal, nearly equivalent to the lumen

Emerging role of MRI in treatment response Endoscopy is the gold standard for evaluating response to CD therapy. However, due to the invasive nature of the procedure, serial use of endoscopy to evaluate treatment response is not well tolerated by the patients. Thus, endoscopy is reserved for evaluating disease activity in patients who are clinically symptomatic. Mucosal healing on endoscopy is defined as resolution of visible mucosal inflammatory changes in areas of prior inflammation. Greatest advantage of MR enteroclysis is its noninvasiveness. MRE has emerging role in evaluating treatment response. A study by Ordas et al. suggested that MRE has 90% accuracy for detecting ulcer healing and 84% accuracy for evaluating endoscopic remission. A good treatment response on MRE is defined as resolution of wall thickening, mural oedema and mucosal hyperenhancement on postcontrast images, which usually correlates with mucosal healing at endoscopy.

Emerging role of diffusion-weighted imaging MRI in Crohn’s disease Diffusion-weighted imaging (DWI) has a promising role in CD and can be used in future along with a routine MRE to differentiate active from inactive disease. Active inflammation is associated with low apparent diffusion coefficient (ADC) values. As the disease becomes inactive, the ADC values increase. Hordonneau et al. suggested a cut-off value of 1.9 × 10−3 mm2/s to differentiate active versus inactive disease. This had a sensitivity and specificity of 85.9% and 81.6%, respectively, for ileum. In another study by Hazim Ibrahim Tantawy, a cut-off ADC value of 1.65 × 10−3 mm2/s was used for differentiating active and inactive disease. This showed sensitivity was 88.7%, and the specificity was 80%. Thus, DWI is considered a promising technique for the detection of inflammation in patients with CD and can be used for assessing treatment response and deciding appropriate management in future.

Extraintestinal manifestations of Crohn’s disease in abdomen: What to look for beyond bowel? The abdomino-pelvic manifestations are described below. As one scans for CTE, careful and cautious effort should be made to examine the rest of the abdomen to look for EIMs. Hepatic and pancreato-biliary complications Hepatic and pancreato-biliary manifestations of CD include cholelithiasis, portal vein thrombosis, primary sclerosing cholangitis (PSC) drug-induced hepatotoxicity and drug-induced pancreatitis. Cholelithiasis is common in CD with an incidence of 13%–34%. It is especially seen with ileal disease due to interruption of the enterohepatic circulation attributed to impaired bile salt absorption. Portal vein thrombosis is a rare complication that can occur due to coagulation abnormalities secondary to chronic bowel inflammation. PSC is the most serious complication of CD. It is an idiopathic, chronic, fibrosing inflammatory disease of the bile ducts that leads to bile duct obliteration, cholestasis, multiple stricture formation

and biliary cirrhosis. Approximately, 5%–10% of PSC patients have CD; however, only 2% of CD patients develop PSC. PSC may not coexist with patients with symptomatic CD and can develop either years before or after the development of bowel symptoms. Patient with CD presenting with elevated liver function tests should rise a high suspicion for PSC as liver transplantation is the only curative treatment for this disease. Magnetic resonance cholangiopancreatography (MRCP) is the investigation of choice for patients with PSC. However, irregular ductal dilatation resulting in the classic beaded appearance and underlying cirrhosis should raise a high possibility of PSC. Drug-induced pancreatitis is a common side effect of 6mercaptopurine or azathioprine therapy. Pancreatitis can also be secondary to gallstones, duodenal involvement by CD or CDassociated granulomatous inflammation of the pancreas. Urological complications The most common urological complications that occur are obstructive uropathy and enterovesical fistulas. The incidence of developing obstructive uropathy is approximately 6% in patients with CD in acute inflammatory phase. It is more common on right side and occurs due to either acute inflammatory change encircling a portion of the ureter or a prior inflammatory episode resulting in fibrotic narrowing of the ureter leading to proximal hydronephrosis and hydroureter. Enterovesical fistulae are a rare, but serious, complication, with an incidence of 3.5% of CD. This occurs as a result of an adjacent inflamed loop of bowel. A linear enhancing tract can usually be seen extending from a bowel loop to the bladder. If a directly enhancing tract is not well appreciated, the presence of ectopic gas in the bladder, focal bladder wall thickening adjacent to an inflamed loop of bowel or the tethering of a bowel loop towards the bladder should all raise suspicion for the presence of a fistula. Patients with CD are also prone to uric acid and oxalate stones. There is fat malabsorption due to diseased bowel causing luminal calcium to bound to free fatty acids. Lack of free calcium leads to increased oxalate absorption, hyperoxaluria and formation of renal oxalate stones. Differential diagnosis of Crohn’s disease It is important to differentiate CD from UC as the management and prognosis of these two diseases are different. It is also important to differentiate CD from intestinal tuberculosis (ITB) because these two diseases closely resemble each other in their clinical presentations. In India, where ITB is

endemic, this diagnostic dilemma is a bigger problem. Moreover, in India, the incidence of CD is also rising. Histopathology is inconclusive in majority of the cases, thus adding to the diagnostic dilemma. A few differentiating points in radiology may aid in the differentiation of these diseases. These are enlisted in Table 8.3.2.4.

TABLE 8.3.2.4 Differentiating Features of Crohn’s Disease, Ulcerative Colitis and Tuberculosis Radiological Findings Location

Crohn’s Disease Any part of GI tract, commonly ileum Extent Long segment Skip lesions Common Extraintestinal Common manifestations Malignant Highly common change BARIUM FINDINGS Mucosal pattern Smooth Polyps Rare Cobblestoning Common Fistulae Very common Ulcers Aphthous ulcers ULTRASOUND FINDINGS Wall thickness Severe Wall Hypoechoic echogenicity Anatomic layers Lost CT FINDINGS Mural Present in acute stratification phase and absent in chronic Wall thickness Marked, eccentric stricture Mesenteric Mesenteric involvement inflammation with vessel engorgement – comb sign Ascites Abscesses Mesenteric nodes

Small, homogenous

Ulcerative Tuberculosis Colitis Colon, Caecum more backwash than ileum ileitis Diffuse Short segment Rare Rare Common Rare Rarely seen

Not seen

Granular Common Rare Rare Collar button

Nodular Not seen Not seen Common Longitudinally oriented

Moderate Hypoechoic

Moderate Heterogenous

Preserved

Preserved

Present

Absent

Moderate

Moderate, concentric stricture No Mesenteric mesenteric inflammation involvement without vessel engorgement Not seen

High density ascites Small, Large, homogenous necrotic, conglomerate

The factors for diagnostic differentiation include clinical, endoscopic, imaging, serological tests, immunological tests and histological features. Management The management changes according to the stage of the disease and presenting complaints of the patient. Medical management Steroids and 5-aminosalicylic acid are mainly used to induce remission in active diseases and are less useful for maintenance. Next line of drugs are the immunosuppressive agents. Azathioprine inhibits cell-mediated immunity and is used for maintenance. Antibiotics are given to control sepsis. Monoclonal antibodies like infliximab are used against severe refractory cases which act against TNFα. Surgical management Surgery is not to cure disease but to correct complications. Indications: Failure of medical treatment Intestinal obstruction Fistula formation Bleeding Perforation Malignant change It involves ileo-caecal resection, segmental resection, temporary ileostomy and stricturoplasty. Flowchart 8.3.2.4 summarizes the medical and surgical treatment.

FLOWCHART 8.3.2.4 Medical and surgical treatment of Crohn’s disease.

Prognosis Conclusion CD is a chronic relapsing and remitting inflammatory disease resulting in morbidity over time. The main aim of medical management of CD is suppressing disease activity, bowel inflammation and symptomatic control in order to provide a good quality of life by achieving disease remission and avoiding complications (Flowchart 8.3.2.5). Timely assessment of severity, extent, activity and extraintestinal complications of CD is of utmost importance in order to decide appropriate treatment. Surgery for CD is reserved for complicated diseases, not responding to medical treatment as the recurrence rate of CD is high after surgery.

FLOWCHART 8.3.2.5 Management of a suspected case of abdominal tuberculosis. Endoscopy is the current gold standard for initial diagnosis and evaluation of response to treatment in CD. Barium studies have a limited role in this era due to the availability of cross-sectional imaging and are reserved for patients in whom IV contrast is contraindicated. CTE is the imaging investigation of choice due to its noninvasiveness. It has advantages over endoscopy as it can detect luminal as well as extraluminal and EIMs of CD. The advantages of MRI are attributed to its excellent soft tissue contrast resolution, thus providing high sensitivity in the diagnosis of CD and assessing the inflammatory activity. The ability of MRE to differentiate active versus inactive disease and active inflammatory versus fibrotic stricture on serial examinations has clinical significance to optimize treatment protocols and make appropriate therapeutic decisions. MRE is an ideal imaging method for evaluating CD, offering both structural and functional information without ionizing radiation.

Small bowel tuberculosis Tuberculosis is endemic in many developing countries. Any portion of the gastrointestinal tract could be affected by tuberculosis; however, terminal ileum, ileo-caecal junction and caecum are the most common sites of affection. Ileo-caecal junction is the third most common extrapulmonary site of tuberculosis. Associated

pulmonary involvement is common; however, it may be absent in 50%–60% of the cases. The bacteria affect the intestinal mucosa leading to inflammation and subsequently granuloma formation, ulceration and necrosis. The sources of infection are: i) Dissemination of primary pulmonary tuberculosis. ii) Swallowing of infected sputum with active pulmonary tuberculosis. iii) Haematogenous spread from a focus in chest or miliary tuberculosis. iv) Spread from infected adjacent organs like fallopian tubes. v) By lymphatic spread from infected mesenteric lymph nodes. vi) Dissemination through bile from tubercular granulomas of the liver.

Presentation/clinical features ITB is a disease of young with slight female preponderance. Intestinal involvement is common in children, whereas adults commonly have peritoneal and nodal involvement. The symptoms may be acute, chronic or acute on chronic. Most patients have constitutional symptoms, with nonspecific signs. Hence high degree of clinical suspicion is necessary especially in endemic areas. The most common clinical presentations are weight loss, low-grade fever, chronic cough, malaise, anorexia and night sweats, which have been attributed to activated macrophages releasing cytokines, that is IL-1 and TNF. Additional features are diarrhoea, constipation and rectal bleeding. Occasionally, there is significant clinical, radiological and even histopathological overlap with malignancy. High clinical suspicion, endoscopic and radiological features should prompt stool and tissue staining for acid fast bacilli (AFB) and histological evaluation in line of tuberculosis. Though histological and pathological findings are definitive for diagnosis, these have been shown to have a low diagnostic yield with sensitivity as low as around 20%–25%. The ulcers due to tuberculosis are relatively superficial and rarely penetrate the muscularis and are transversely oriented. Blood in stools and perforation are also seen in ITB, although free perforation is less frequent than in CD, which is its close differential. Radiological features Concentric wall thickening of the ileo-caecal region is the most common radiological feature in small bowel tuberculosis, accounting for almost 64% of all GI TB. Possible explanation for this is stasis of bowel contents in this region and abundance of lymphoid tissue. Duodenal involvement with wall thickening

accounts for approximately 2% of ITB commonly involving the third and fourth parts. Isolated jejunal tuberculosis is rare and is commonly associated with peritonitis. Intestinal involvement by tuberculosis is morphologically classified as ulcerative, ulcerohyperplastic and hyperplastic varieties. Radiological investigations and their common findings A) Chest radiograph: It may be normal or may show concurrent pulmonary tuberculosis as hilar lymphadenopathy or lung parenchymal tuberculous lesions. B) Radiograph of abdomen: i) Nonspecific signs of obstruction is the most common finding. ii) Calcified nodes may also be seen. C) Ultrasound abdomen and pelvis: Increased bowel wall thickness, commonly in the IC region. i) ‘Pseudo kidney’ sign seen on USG due to pulling up of the involved small intestine ii) in the right subhepatic region. iii) Other associated findings as loculated intraabdominal fluid, septae within the ascites, lymphadenopathy (discrete or matted) with caseation necrosis or calcification. Caseation and calcification are highly specific findings for tuberculosis. iv) USG can also guide in fine needle aspiration cytology (FNAC) of the abdominal nodes. D) Barium meal: i) ‘Chicken intestine’ – It is due to hypersegmentation of the barium in the region of involvement. ii) ‘Hourglass stenosis’ – It is due to stiffness of the involved segment with luminal stenosis. E) Barium enema: i) ‘Fleischner’ sign or ‘inverted umbrella’ – Ileo-caecal valve thickening with narrow of the terminal ileum. ii) ‘Goose neck deformity’ – distorted normal ileo-caecal angle with the dilated ileum appearing suspended from the distorted caecum. iii) ‘Stierlin sign’ – absence of barium in the ileum, caecum and ascending colon, with a normal appearing column of barium on either side. This is due to the

narrowed terminal ileum rapidly emptying into the distorted caecum. iv) ‘String sign’ – narrowing due to stenosis of the terminal ileum. v) ‘Purse string’ – streak of barium in the narrowed terminal ileum with the barium-filled prestenotic dilated ileum. Sterline and Purse string can also be seen in CD and hence are not specific. vi) ‘Conical caecum’ – small caecum pulled out of the iliac fossa and hepatic flexure pulled down. F) CT scan abdomen and pelvis: CTE is commonly done for almost all abdominal pathologies. Small bowel tuberculosis may show a solid mass or may be multisegmental with symmetric mural thickening commonly involving the ileo-caecal area and rim-enhanced lymph nodes. i) Circumferential wall thickening of the bowel, commonly the terminal ileum, IC junction and caecum are common findings. More advanced disease reveals clumped bowel loops. Other parts of the small bowel may also show wall thickening and narrowing, common in the ileal region – skip lesions. ii) Complications as bowel perforation, abscess and subacute-acute obstruction may also be seen. iii) High attenuation ascitic fluid (25–45 HU) due to high protein content, enhancing septae (better appreciated on USG), peritoneal thickening, enhancing peritoneal nodules may also be seen. iv) Lymphadenopathy: commonly the mesenteric, para-aortic nodes appear enlarged along with periportal and pancreatico-duodenal nodes. Hypodense areas most likely representing necrosis may be noted within the enlarged nodes. v) Mesenteric thickening seen as fat stranding may also be seen. vi) Diffuse peritoneal thickening with postcontrast enhancement is also common. G) MRI abdomen and pelvis Though MRI is not an investigation of choice for bowel pathologies due to artefacts caused as a result of bowel motion, use of glucagon or hyoscine butyl bromide to reduce bowel movements and fast imaging techniques have considerably improved the quality of images. The abnormal bowel walls show asymmetric wall thickening.

i) The involved segment appears hypointense as compared to normal walls on T1WI and heterogeneously hyperintense on T2WI. ii) Fluid-sensitive T2W sequences (fat saturated T2 sequences) are helpful in picking the areas of active inflammation seen as hyperintense signal, more prominently when negative oral contrast agents as superparamagnetic iron oxide are used. iii) T1W-contrast MRI may help in mucosal enhancement recognition due to superior contrast between enhancing bowel wall and lumen. 2.5% mannitol administered orally helps in adequate bowel distension and acts as a negative contrast in T1W postcontrast sequences. iv) Cine MRI sequences can show bowel peristalsis which can help diagnose subtle strictures. v) DWI with B-values of 0, 400, 800 shows restriction of active infection. vi) The fibrotic lesions appear hypointense on T1 and T2WI. Also MRI is helpful for perianal abscess and fistulas which are common in CD and hence aiding to differentiate the two. H) FDG PET CT Performed after IV administration of Fluorodeoxyglucose (FDG) with or without iodinated contrast. Commonly combined with CTE and is useful to diagnose active infections and response to treatment by evaluating the metabolic activity of the lesion. The active lesions show increased metabolic activity, which decreases in response to treatment. It also picks up multifocal lesions. However, it has low specificity, and physiological uptake of FDG is a major limiting factor. Capsule endoscopy is a newer investigation with limited data available regarding its utility in ITB. Laparoscopy: usually combined with therapeutic procedures in cases of complications such as obstruction and perforation. It also has the advantage of direct visualization of the bowel, peritoneal thickening, septations and nodes. Therapeutic procedures such as adhesiolysis can also be performed. Differential diagnosis • Crohn’s disease • normal omentum and peritoneum • fistulas and abscesses are common

• Small bowel carcinoma (adenocarcinoma) • eccentric caecal wall thickening • evidence of metastatic disease • Small bowel lymphoma • very thick (>2 cm thickness) bowel wall • lack of stricturing • associated lymphadenopathy +/– hepatosplenomegaly Differences in Small bowel Tuberculosis and Crohn’s Disease Small Bowel Tuberculosis Skip lesions are less common Malformation of IC junction and caecum commonly associated Lymph node calcification and central necrosis Asymmetric wall thickening with irregularity Fleischner sign on barium No creeping fat Positive chest findings in 50% Omental and peritoneal thickening Short-segment involvement Concentric stricture Mural thickening without stratification No vascular engorgement in the mesentery High density ascites

Crohn’s Disease Skip lesions common Abscess and fistula formation are common Mildly enlarged lymph nodes. Calcified lymph nodes are uncommon Circumferential bowel wall thickening Cobblestone appearance on barium Creeping fat – abnormal quantity of fibrofatty proliferation of mesenteric fat is common Negative chest findings Omentum and peritoneum are normal Long-segment involvement Eccentric stricture Mural thickening with stratification in acute inflammation Hypervascular mesentery Ascites is not a common feature

8. 3.3

IMAGING OF SMALL BOWEL ISCHAEMIA

Avinash Nanivadekar, Komal Ninawe

Introduction Mesenteric ischaemia or small bowel ischaemia is defined as reduced blood supply to the small bowel. A complex and rare condition that is difficult to diagnose owing to its nonspecific clinical presentation, with high mortality rates as per the cause, duration and injury to the bowel. This specific condition and its various subtypes lead to about 0.09%–0.2% of emergency surgical interventions. At the same time, the mortality rates reported internationally are in the range of 30% and 90%. This profound range of mortality can be a result of various factors including the disease itself being rare as well as a very complex, which may lead to delay in diagnosis. At the same time the nature of the imaging findings, being subtle and nonspecific also may lead to difficulty in specific diagnosis adding to further delay. The best approach to the condition lies inadequate consideration of both clinical and imaging findings, on parts of the clinician and the radiologist. A high index of suspicion also provides a necessary impetus to early diagnosis. Computerized Tomographic Angiography (CTA) followed by a complete imaging study, proves the investigation of choice in the diagnosis of mesenteric ischaemia. Management of mesenteric ischaemia depends on its severity, cause, patient’s conditions and comorbidities. The initial step in management is always to ensure the haemodynamic stability of the patient which includes fluid resuscitation to prevent its aggravation. Intravenous infusion of blood thinners like heparin, vasodilators like papaverine and antibiotics to prevent inflammation and sepsis is considered as a vital component of treatment. Further, in patients with acute mesenteric ischaemia with complications of peritonitis, bowel infarction or necrosis, perforation or pneumoperitoneum, emergency laparotomy should be done. It provides direct visualization of the bowel for resection of the nonviable segment and to reestablish the blood flow to the ischaemic region. Revascularization techniques include thrombectomy, embolectomy, angioplasty or bypass. In patients without signs of peritonitis or other complications, endovascular treatment is done for the restoration of blood flow to the ischaemic segment of the bowel. The only disadvantage of endovascular treatment is that viability of the bowel cannot be assessed. Endovascular treatment is also commonly used in patients with chronic mesenteric ischaemia. The advantages of endovascular treatment include fast recovery with short hospital stay and lesser complications though early recurrence of symptoms

might be seen. Nonocclusive causes of ischaemic bowel are managed by treating the cause of reduced intestinal perfusion. Intravenous infusion of vasodilators like papaverine is considered vital in such patients. Mesenteric ischaemia due to venous occlusion needs long-term anticoagulation therapy with intravenous heparin or warfarin in acute cases followed by conversion into oral form after 48 hours. In this chapter, we are going to discuss the role of CT in diagnosing mesenteric ischaemia, its causes and radiological findings in acute cases, chronic cases, arterial, venous and nonocclusive ischaemia. Though other imaging modalities like plain X-rays, ultrasonography, colour Doppler studies also play a vital role, CTA and complete CT study remain the gold standard to triage the severity of ischaemia and plan therapy based on this one important modality.

Anatomical considerations Three major arteries supplying the small and large bowel are the coeliac artery, superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) (Figs. 8.3.3.1–8.3.3.3). 1. Celiac artery – It arises from the anterior aspect of the aorta at the level of the T12 vertebral body. It is one of the major branches of the abdominal aorta. It supplies blood to the distal esophagus to the superior portion of the duodenum. 2. Superior mesenteric artery (SMA) – It arises from the anterior aspect of the abdominal aorta, inferior to the celiac trunk at the level of L1 vertebra. It supplies blood to the third and fourth part of the duodenum through the inferior pancreaticoduodenal branch, jejunum and ileum through the jejunal and ileal branches through the anastomotic arcade vasa recta and transverse and ascending colon up to the splenic flexure through the middle and right colic branches. 3. Inferior mesenteric artery (IMA) – It arises at the level of L3 from the abdominal aorta. It supplies the large intestine from the splenic flexure, descending colon, sigmoid colon and upper part of the rectum through the left colic, sigmoid and superior rectal branches. 4. Internal iliac arteries, middle and inferior rectal arteries – They supply the distal rectum.

FIG. 8.3.3.1 CT volumetry window of the aorta and its main branches, namely coeliac trunk and superior mesenteric artery and the aortic bifurcation.

FIG. 8.3.3.2 CT angiography window, sagittal section showing the aorta and its main branches, namely coeliac trunk, superior and inferior mesenteric arteries.

FIG. 8.3.3.3 Superior mesenteric artery and its branches. The venous drainage runs parallel to the arterial system to drain the respective bowel loops. The superior and inferior mesenteric veins drain into the splenic vein and form the main portal vein. Collateral pathways can be found between the mesenteric and systemic venous system.

Pathophysiology and types of mesenteric ischaemia Mesenteric ischaemia is a broad term that may refer to a variety of both acute and chronic conditions. Acute mesenteric ischaemia is more common than its chronic form (Fig. 8.3.3.4). It can result from occlusive or nonocclusive obstruction of the specific arteries supplying the mesentery. It also can result from obstruction of the venous outflow of the small intestine. The incidence of mesenteric ischaemia increases with age and is said to be the highest in elderly patients especially with those having known cardiovascular comorbid conditions. Nonocclusive cases result from hypoperfusion which may be caused by low cardiac output or mesenteric arterial vasoconstriction. However, in younger patients, who present with this condition, venous thrombosis is one of the main causes. The estimated prevalence of each aetiology leading to mesenteric ischaemia is about mesenteric arterial embolism (50%), mesenteric arterial thrombosis (15%–25%), mesenteric venous

thrombosis (5%) and mesenteric ischaemia resulting from hypoperfusion (20%).

FIG. 8.3.3.4 Types of mesenteric ischaemia. Regardless of the cause of injury, ischaemic injury occurs when there is inadequate oxygen delivery to the cell leading to impairment of the basic cellular functions. In nonocclusive mesenteric ischaemia, however, the injury can also occur by reperfusion of the tissues following the ischaemic insult which further exacerbates the intestinal injury. The increased vascular permeability following a vascular insult leads to the activation of the inflammatory cascade. These inflammatory cells release reactive oxygen species, proinflammatory chemokines and protein kinases, which further injure the tissue. The further dysfunction of this intestinal barrier leads to bacterial infiltration of the intestinal mucosa and submucosa after such an injury. In their animal models, João SA et al. labelled a bacterium with 99m-Tc which was fed to the animal prior to induction of an ischaemic reperfusion injury. This labelled bacterium was later traced to serum, lung, liver and mesenteric lymph nodes in a time-dependent manner. The damage to the tissue is proportional to the decrease in blood flow to the mesentery and may range from minimum lesions due to reversible ischaemia up to definitive transmural injury, leading to necrosis and perforation.

Clinical features In acute conditions, the clinical features are vague and are mostly nausea, vomiting, bloating and diarrhea. The presence of peritonitis on physical examination is an indicator of irreversible ischaemia and bowel necrosis. In chronic cases, the patient shows signs such as early satiety, postprandial abdominal pain, gradual weight loss and ‘food fear’.

Aetiology of mesenteric ischaemia 1. Arterial embolic or thrombotic occlusion: The most common cause of arterial occlusion is arterial thrombosis and emboli in the mesenteric arteries. It usually affects older individuals but can also be seen in young patients with atrial fibrillation. Such emboli commonly originate from the left atrium, left ventricle or left-sided cardiac valves and are predisposed by severe atherosclerotic disease. Other uncommon causes include SMA dissection, aortic dissections involving the SMA, and aneurysms. About 20% of cases with mesenteric emboli might also have emboli in organs like kidneys and spleen. Proximal SMA occlusion is most commonly seen. It occurs from a predisposing atherosclerotic disease of SMA, with acute thrombosis formation. The patient may have a gradual progression of occlusion and typically present with a syndrome of abdominal pain up to 3 hours after taking meals, also known as ‘abdominal angina’, leading to hesitancy in eating and weight loss. Arterial occlusion leads to bowel ischaemia or transmural infarction, which is characterized by dilated small bowel with a classic ‘paper-thin wall’ appearance. It occurs due to the loss of bowel wall tissue, vasculature and muscular tone. Characteristic CT findings include focal bowel dilatation with mural stratification and thinning of the bowel wall, hypoenhancing or nonenhancing bowel wall due to decreased or absent arterial supply, referred to as ‘pale ischemia’, mesenteric fat stranding and ascites (Figs. 8.3.3.5–8.3.3.14). 2. Venous occlusion: Venous occlusion occurs due to inflammatory or infectious pathologies like appendicitis, diverticulitis, pancreatitis, inflammatory bowel disease or neoplasia. The classic features of venous occlusion include circumferential bowel wall thickening, hypoenhancing or nonenhancing bowel wall, bowel wall oedema, fat stranding and fluid collection. In cases of venous occlusion, the arterial supply to the bowel remains unaffected. Due to the normal inflow (arterial supply) but obstructed outflow (venous drainage), resulting in increased hydrostatic pressure and hence resulting in circumferential thickening of the bowel wall due to wall oedema. The small bowel wall may thicken up to 15 mm, the normal thickness being 2–3 mm. This hypodense wall oedema being formed in

the submucosal layer of the bowel, between the two hyperdense muscular layers – mucosa and muscularis propria, give a ‘halo’ or ‘target’ sign. Extravasation of fluid in the mesentery due to increased hydrostatic pressure leads to the accumulation of mesenteric free fluid and fat stranding. It is rarely seen in cases of mesenteric ischaemia due to arterial occlusion (Figs. 8.3.3.15–8.3.3.21). 3. Nonocclusive mesenteric ischaemia (NOMI): As the name suggests, in nonocclusive ischaemia, there is no obvious arterial or venous occlusion. It occurs in states of low flow such as cardiogenic or haemorrhagic shock, sepsis or arrhythmia, reflex splanchnic vasoconstriction. The classic CT features include mural thickening and enhancement of the bowel, luminal dilatation, ascites, flat inferior vena cava – a group of features known as ‘shock bowel’. In such states with reduced blood flow, the blood is diverted to the critical organs such as the heart and brain. This leads to hypoperfusion of the intestines and increased vascular permeability thus leaking of plasma and red blood cells in the bowel wall and mesentery. Imaging appearance of NOMI may be overlapping with infections, inflammation or traumatic enteritis, hence it becomes difficult to diagnose on CT. Relevant clinical history can prove to be a key factor in making a diagnosis. Adrenal glands also show hyperenhancement in some cases. Catheter/CT angiography findings include narrowing and irregularity of SMA branches, decreased filling of intramural vessels and spasm of mesenteric arcades (Figs. 8.3.3.22–8.3.3.26).

FIG. 8.3.3.5 A 71-year-old presented with abdominal distension and decreased urine output. The CT scan reveals concentric mural thickening and hypoenhancement of the terminal ileum, caecum, ascending colon with surrounding mesenteric fat stranding.

FIG. 8.3.3.6 In the same patient, the axial section of CT scan reveals concentric mural thickening and hypoenhancement of the terminal ileum, caecum, ascending colon and proximal transverse colon with surrounding mesenteric fat stranding (red arrow).

FIG. 8.3.3.7 In the same patient, the jejunum and ileal loops show diffusely thinned out and nonenhancing walls with multiple air foci within that is pneumatosis intestinalis.

FIG. 8.3.3.8 In the same patient, the jejunum and ileal loops show diffusely thinned out and nonenhancing walls with multiple air foci within (red arrows), that is pneumatosis intestinalis and multiple small mesenteric air foci in the midabdomen suggesting pneumoperitoneum due to ileal perforation.

FIG. 8.3.3.9 On the arterial phase, the CT scan of the same patient shows a long-segment proximal superior mesenteric artery thrombosis (red arrows).

FIG. 8.3.3.10 On the MIP images, the CT scan of the same patient shows a long-segment proximal superior mesenteric artery thrombosis (red arrows) with its reformation distally through collaterals from the inferior mesenteric artery and complete thrombosis of the coeliac artery with development of collaterals.

FIG. 8.3.3.11 SMA thrombus in different patients, resulting in arterial mesenteric ischaemia.

FIG. 8.3.3.12 SMA thrombus in another patient, resulting in arterial mesenteric ischaemia.

FIG. 8.3.3.13 SMA thrombus resulting in arterial mesenteric ischaemia.

FIG. 8.3.3.14 Complete thrombosis of the ileocolic artery and its branches, resulting in arterial mesenteric ischaemia of the ileal loops.

FIG. 8.3.3.15 A 38-year-old patient presented with abdominal pain and distension, the CT scan reveals diffuse segmental dilatation of the proximal jejunal loops (red arrows) with few air foci within (pneumatosis intestinalis) and loss of mucosal folds of these bowel loops with no enhancement of the mesenteric borders. Distal jejunal loops are collapsed with postcontrast enhancement.

FIG. 8.3.3.16 CT scan of the same patient reveals diffuse segmental dilatation of the proximal jejunal loops (red arrows) with few air foci within (pneumatosis intestinalis) and loss of mucosal folds of these bowel loops with no enhancement of the mesenteric borders. Distal jejunal loops are collapsed with postcontrast enhancement. A large collection due to jejunal perforation with few areas of hyperintensities depicting haemorrhages along with moderate ascites and surrounding mesenteric fat stranding is also seen.

FIG. 8.3.3.17 Circumferential wall thickening of collapsed distal jejunal loops with postcontrast enhancement in the same patient.

FIG. 8.3.3.18 The portal venous phasesagittal view of the same patient reveals a central filling defect in a dilated superior mesenteric vein (red arrow).

FIG. 8.3.3.19 It is a volume-rendered image of the same patient showing the SMV thrombosis with a filling defect in the portal vein.

FIG. 8.3.3.20 Thrombosis of the portal vein.

FIG. 8.3.3.21 Portal vein thrombus with extension into the superior mesenteric vein, resulting in venous mesenteric ischaemia.

FIG. 8.3.3.22 Nonocclusive mesenteric ischaemia (NOMI) in the jejunum.

FIG. 8.3.3.23 CT scan of a 45-year-old patient showing wall thickening with hypoenhancement of the ascending colon, hepatic flexure and proximal transverse colon (red arrow) with mild surrounding fat stranding. Also, a collapsed IVC can be seen depicting a hypotensive state – Flat IVC adjacent to a contrast-filled aorta with a small diameter.

FIG. 8.3.3.24 CT scan of the same patient in a soft tissue window reveals multiple air foci within the jejunal loops – pneumatosis intestinalis along with few air foci along the small bowel mesenteric arcade, suggesting pneumoperitoneum.

FIG. 8.3.3.25 A CT scan of the same patient shows the presence of porto-mesenteric gas (red arrows), along with pneumatosis, which is a confirmatory sign of mesenteric ischaemia.

FIG. 8.3.3.26 Aetiology and characteristic radiological findings in different types of mesenteric ischaemia.

Biochemistry Ischaemic bowel proves as a diagnostic challenge for a physician as most of the patients present with only abdominal pain, sometimes diarrhea and vomiting. These symptoms tend to overlap with any other causes of the acute abdomen like appendicitis, pancreatitis and cholelithiasis. Clinical history, physical examination and laboratory values can suggest a bowel pathology but still are nonspecific. Lactic acid levels if elevated can be indicative of anaerobic metabolism in cases of ischaemic bowel, but it is not a specific marker as it can be seen in other pathologies also. A recent preliminary study with D-dimer and other biomarkers, such as serum alpha-glutathione S-transferase (alpha-GST), intestinal fatty acid-binding protein (I-FABP) and cobalt-albumin binding assay (CABA), may play a confirmatory role in the diagnosis of mesenteric ischaemia. However, none of these markers are currently used as a part of standard clinical practice and further research is needed to assess their reliability.

Investigations A complete overview to approach in diagnosis and treatment of different clinical scenarios of mesenteric ischaemia must include the various clinical signs, relevant clinical history and high index suspicion from the treating physician and the radiologist. A multipronged approach that employs a combination of biochemical tests, radiological investigations and indicated surgical interventions is deemed to be the most useful (Fig. 8.3.3.27).

FIG. 8.3.3.27 Interdisciplinary approach to investigations and management of mesenteric ischaemia. 1) Abdominal radiographs: The clinically vague presentation and a broad spectrum of differential diagnosis make radiological investigations a major part of the diagnosis of the condition. Conventionally, abdominal radiographs have been used for diagnosis. However, they are neither specific nor sensitive, and may further delay diagnosis. About 25% of patients with mesenteric ischaemia would show normal radiographs. In the elderly, the presence of bowel dilatation (ileus) and a gasless abdomen and thumbprinting of the small bowel or right half of the colon can be seen in younger patients as prominent findings of acute mesenteric ischaemia. Hepatic portal venous gas is of the rare but important findings in the case of bowel necrosis secondary to acute mesenteric ischaemia. 2) Doppler ultrasound: Doppler ultrasound is not routinely used in suspected acute cases. Moreover, the applied pressure leading to pain is already a limiting factor in the initial evaluation of patients with suspected acute mesenteric ischaemia. In chronic cases, it forms a useful tool in screening with B-mode and Doppler waveform analysis. It can demonstrate proximal mesenteric vessel thrombosis in Doppler mode and can be used in detecting proximal superior mesenteric and celiac artery stenosis with 85% sensitivity and 90% specificity. Peak systolic velocity with cut-off values of 295 and 400 cm/s for the SMA and 240 cm/s for the celiac artery provides overall accuracy for ≥50% and ≥70%, respectively. 3) Conventional angiography: Catheter-based angiography was once considered the gold standard in the diagnosis of mesenteric ischaemia. One of its advantages is the provision for diagnosis and treatment in a single sitting. In recent times, with advances in technology CTA has become the first-line imaging technique, and angiography transitioned to complementary diagnostic roles with an option of

endovascular treatment for revascularization candidates. It has a sensitivity range of 74%–100% and specificity of 100%. In chronic conditions, the endovascular therapy approach has surpassed open repair because of its high efficacy and a lower rate of significant complications. 4) CECT with angiography: Due to round-the-clock availability of the CT scan, noninvasive nature and its relative inexpensiveness, CTA has now been used as the primary diagnostic method. It has been suggested to have a sensitivity of 96% and specificity of 94%, for both acute and chronic forms. However, the risks related to the contrast medium such as nephrotoxicity and hypersensitivity must always be kept in mind. The American college of radiology (ACR) explains that ‘CTA uses a thin-section CT acquisition that is timed to coincide with peak arterial or venous enhancement. The resultant volumetric dataset is interpreted using primary transverse reconstructions as well as multiplanar reformations and 3-D renderings’. a) CT technique: About 0.9–1.4 L of oral fluid is given 2–3 hours prior to the scan so as to distend the bowel lumen, allowing for characterization of the degree of mucosal enhancement and enabling visualization of the vascular tree with multiplanar thick maximum intensity projections (MIPs) or volume renderings (Fig. 8.3.3.28). A fundamental decision for CT scanning in patients with suspicion of bowel ischaemia is whether or not to administer positive versus neutral oral contrast material. The following table compares the two methods (Table 8.3.3.1). These images are then reformatted into 1 mm axial, 0.5 mm sagittal and coronal images. MIP, 3D reconstruction with volume rendering techniques (VRTs) are used along with angiography to study and conclude a diagnosis. The appropriateness criteria for mesenteric ischaemia can be enumerated as follows (Tables 8.3.3.2 and 8.3.3.3).

FIG. 8.3.3.28 CECT protocol.

TABLE 8.3.3.1 Administration of Oral and Intravenous Iodinated Contrast in CTA Positive Oral Contrast CT number ≥50 HU MIP and VRT Unsatisfactory for 3D reconstruction Features It can help rule out anastomotic bowel leaks, fistulas and in cases of small bowel obstruction to see the transition point. It helps differentiate between haematoma, abscess and free fluid.

Neutral Oral + Intravenous Contrast Range (–20) to (+20) HU Satisfactory It allows evaluation of the bowel wall thickness, vascularity, enhancement of the affected bowel segment as hypo/hyper and active intraluminal extravasation of the intravenous contrast, in cases of active GI bleeding. It resembles the body fluids and hence makes it difficult to differentiate from abscess, haematoma or free fluid.

TABLE 8.3.3.2 The Criterion for Initial Imaging of Acute Mesenteric Ischaemia American College of Radiology ACR Appropriateness Criteria VARIANT 1: INITIAL IMAGING FOR ACUTE MESENTERIC ISCHAEMIA Appropriateness Relative Procedure Category Radiation Level 1 CTA abdomen and pelvis with IV Usually appropriate contrast 2 CT abdomen and pelvis with IV Maybe appropriate contrast 3 Arteriography abdomen Maybe appropriate (disagreement) 4 MRA abdomen and pelvis without and Maybe appropriate O with IV contrast (disagreement) 5 Radiography abdomen Maybe appropriate 6 US duplex Doppler abdomen 7 CT abdomen and pelvis without and with IV contrast 8 CT abdomen and pelvis without IV contrast 9 MRA abdomen and pelvis without IV contrast

Maybe appropriate Usually not appropriate

O

Usually not appropriate Usually not appropriate

O

TABLE 8.3.3.3 The Criterion for Initial Imaging for Chronic Mesenteric Ischaemia American College of Radiology ACR Appropriateness Criteria VARIANT 2: INITIAL IMAGING FOR CHRONIC MESENTERIC ISCHAEMIA Procedure Appropriateness Relative Category Radiation Level 1 CTA abdomen and pelvis with IV Usually appropriate contrast 2 MRA abdomen and pelvis without and Usually appropriate O with IV contrast 3 Arteriography abdomen Maybe appropriate (disagreement) 4 CT abdomen and pelvis with IV contrast Maybe appropriate 5 MRA abdomen and pelvis without IV contrast 6 US duplex Doppler abdomen 7 CT abdomen and pelvis without IV contrast 8 CT abdomen and pelvis without and with IV contrast 9 Radiography abdomen

Maybe appropriate

O

Maybe appropriate Usually not appropriate

O

Usually not appropriate Usually not appropriate

Imaging features of mesenteric ischaemia on MDCT A) Characteristic features: 1. Bowel wall enhancement: The normal bowel loops show uniform, homogenous enhancement in the portal and venous phases. Decreased blood flow to the bowel, due to arterial or venous occlusion causes hypoenhancement or no enhancement of the bowel loops. It is referred to as ‘pale ischemia’ and has a specificity of 9%. When the perfusion is restored, it may result in bowel wall hyperemia, causing hyperenhancement, as seen in shock bowel (Fig. 8.3.3.29). 2. Bowel wall thickening/thinning: The thickening or thinning of the bowel wall depends upon the aetiology and is the most sensitive indicator of mesenteric ischaemia (96%). However, thickening it is the least specific as it is also seen in inflammatory and infective conditions and up to 15 mm in acute cases. Long-standing obstruction of the arterial supply results in microvascular capillary damage. Prognosis is good in cases of bowel wall thickening as it is a reversible change. In chronic cases, the destruction of the intramural vessels and tissue with loss of muscular tone leading to a ‘paper-thin’ bowel wall. This is an irreversible finding (Fig. 8.3.3.30). 3. Bowel dilatation: The luminal dilatation of the bowel can be seen in both bowel obstruction and ischaemia of arterial origin. It occurs due to interruption of peristalsis when transmural infarction sets in. Focal bowel dilatation is due to spastic contraction, in cases of early ischaemia and is reversible. However, dilated fluid-filled bowel loop due to fluid exudation is suggestive of irreversible ischaemia or infarct. 4. Mesenteric oedema or fat stranding: Venous occlusion, obstruction or strangulation causes increased mesenteric venous pressure, resulting in accumulation of fluid in the mesentery resulting in surrounding mesenteric fat stranding or ascites. 5. Pneumatosis and porto-mesenteric gas: It refers to the presence of air within the bowel. It marks the end stage of the disease process. Pneumatosis seen in addition to porto-mesenteric gas marks a 100% specificity for bowel ischaemia. ‘Band-like’ pneumatosis can be commonly seen in transmural bowel infarction and ‘bubble-like’ pneumatosis can be in cases of partial mural ischaemia (Figs. 8.3.3.31–8.3.3.32) (Table 8.3.3.4). B) Miscellaneous features:

1. Intramural haemorrhage: Intramural haemorrhage is a nonspecific finding and can be seen in various bowel pathologies. However, haemorrhage limiting to the mucosal layer of the bowel is considered as a reversible change and its advancement to the submucosa, muscularis propria and transmural layers is considered as irreversible (Fig. 8.3.3.33). 2. Flat bowel: Flattening of the dependent posterior segment of the affected bowel loop (Figs. 8.3.3.34–8.3.3.35). 3. Flaccid bowel loop: The affected segment of the bowel loop loses its muscular tone and becomes flaccid and immobile. This depicts an advanced stage of ischaemia (Fig. 8.3.3.36). 4. Small bowel faeces sign: It is a nonspecific sign seen in various conditions including ischaemia. Its results from undigested fluid leading to obstruction and secondary bacterial infection. The resulting absorption of water proximal to the obstruction leads to this sign (Fig. 8.3.3.37). C) CT findings and reversibility/irreversibility of symptoms: The presence of various CT findings and their clinical correlation with the severity of the disease progression can be enumerated as follows (Figs. 8.3.3.38 and 8.3.3.39).

FIG. 8.3.3.29 A sagittal section of CT scan showing hyperenhancement of the bowel wall in the ischaemic and stenotic segment.

FIG. 8.3.3.30 CT scan showing dilated fluid-filled bowel loop with paper-thin walls and surrounding fat stranding, mesenteric fluid and ascites suggesting an irreversible change of ischaemia.

FIG. 8.3.3.31 CT scan of a 70-year-old patient presenting with generalized abdominal pain showing hypoenhancing ascending colon and caecum with thinned out walls in the venous phase with focal pneumatosis intestinalis.

FIG. 8.3.3.32 Arterial phase CT of the same patient reveals submucosal oedema of the nonenhancing bowel loops with focal hyperenhancement. Mild ascites with mesenteric fat stranding is seen in the pelvic fossa regions. TABLE 8.3.3.4 Summary of Characteristic CT Findings in Different Types of Mesenteric Ischaemia Sr. CT No. Findings 1.

Bowel wall thickening

2.

Bowel wall thinning Bowel wall enhancement

3.

4.

Bowel dilatation

5. 6.

Mesenteric fat stranding Ascites

7.

Vasculature

Venous Arterial Mesenteric Ischaemia Mesenteric Ischaemia Paper-thin bowel walls

Circumferential thickening and oedematous -

Hyperenhancement of mucosa and Hypoenhancing/nonenhancing serosa with walls in pale ischaemia. nonenhancement of the submucosa Hyperenhancing in areas of and muscularis reperfusion propria – target/halo sign Collapsed bowel Focal luminal dilatation loops – Shock bowel Present Less common Can be variable.

Less common Arterial filling defects, narrowing, dissection or aneurysms

Nonocclusive Mesenteric Ischaemia (NOMI) Mural/diffuse wa thickening Mural hyperenhanceme

Diffuse bowel dilatation Present

Present

Present

Venous filling defects with an enlarged diameter

Flat IVC with vasoconstriction o mesenteric arteri

FIG. 8.3.3.33 A coronal section of the CT scan showing multiple foci of intramural bleed/haematoma in the bowel loop.

FIG. 8.3.3.34 Axial sections of CT scan of two different patients showing flattening of the posterior dependent wall of the affected segment of bowel (blue arrows) with transmural infarct. Both the patients had mesenteric ischaemia.

FIG. 8.3.3.35 Axial sections of CT scan of two different patients showing flattening of the posterior dependent wall of the affected segment of bowel (blue arrows) with transmural infarct. Both the patients had mesenteric ischaemia.

FIG. 8.3.3.36 An axial section of CT scan showing flaccid and immobile bowel loop with loss of its muscular tone.

FIG. 8.3.3.37 Axial section of CT scan showing a dilated bowel loop filled with faeces (small bowel faeces sign).

FIG. 8.3.3.38 Schematic representation of the mucosal layers of the bowel wall affected in different stages of mesenteric ischaemia.

FIG. 8.3.3.39 Table showing characteristic CT findings with the extent of severity of disease owing to its reversible or irreversible criteria. 8.3.4

SMALL BOWEL OBSTRUCTION Swati Mody

Introduction Abdominal distension is one of the commonest presentations at the GI emergency facility. It is often associated with other features like vomiting, obstipation and electrolyte imbalance. Along with clinical findings, imaging plays a key role in: • Diagnosis of intestinal obstruction. • Differentiating obstruction from close clinical mimics (constipation, pseudoobstruction, paralytic ileus). • Finding the site/cause of obstruction. • Differentiating partial from complete obstruction. • Identifying surgical red alerts like closed loops/strangulations. • Recognizing other complications arising from obstruction (bowel wall ischaemia, perforation). Apart from an acute emergency, small bowel obstruction can also present as recurrent episodes of subacute obstruction – often partial and self-limiting. Imaging in such cases

helps identify the aetiology – sometimes medically correctable.

Aetiopathogenesis with radiological correlation The normal gastrointestinal tract is an elongated, hollow tubular structure, which allows smooth passage of orally ingested food mixed with fluid secreted by its mucosal cells and ingested air. The passage is facilitated by propulsive movements of the GI wall musculature. Luminal narrowing along the course of the GI tract initiates the pathophysiology of the clinical situation of bowel obstruction. Any of multiple aetiologies may be responsible for the narrowing. A specific form of obstruction occurs when there are two sites of luminal narrowing at a short distance from each other, leading to the formation of what is aptly called a ‘closed loop’.

Simple obstruction

Closed loop obstruction

Imaging features of small bowel obstruction – recognizing the signs Small bowel obstruction accounts for around 4% of all patients presenting to the emergency department with abdominal pain. Selection of the correct imaging modality for evaluating small bowel obstruction depends upon the clinical scenario and the particular information needed therein. With the increasing availability of scanners even in remote areas of the country, CT scan has become the preferred modality as a one-stop shop to determine the presence, level, cause and complications of obstruction. Radiographs and ultrasound also retain their place in certain selected situations – for example, for follow-up of conservatively treated patients, as a screening tool in patients with equivocal clinical features and as a first-line approach in paediatric patients. Barium studies – once the cornerstone of GI imaging – are losing their popularity in favour of CT scan due to significant differences in the amount of information yielded. MRI is not primarily used in cases of small bowel obstruction.

Plain radiographs Principle The differential contrast provided by lucent air and opaque fluid/soft tissues make radiographs a good mode of demonstrating distribution of air in the abdomen, bowel diameter and air-fluid levels. In order to demonstrate the supernatant-dependent relationship of air-fluid levels and the straight line at their interface, it is imperative to image the abdomen with its long axis perpendicular to that of the image receptor. The upright position is by far the most popular projection for this purpose. It is usually

recommended to leave a margin of few minutes between propping up a supine patient and acquiring the radiograph, in order to allow for the differential gravitation of air and fluid. In moribund patients, modifications like lateral decubitus position are useful. Lateral radiograph of the presacral region helps demonstrate the presence or absence of air within the rectum. Gaseous distension of rectum makes proximal structural obstruction less likely. Results of conventional radiography are diagnostic in 50%–60%, equivocal in 20%–30% and normal, nonspecific or misleading in 10%–20%. Signs Bowel dilatation Intraluminal air is used as a surrogate marker for bowel diameter. The usual norms for calling small bowels dilated are beyond a diameter of 3 cm, allowing for differences in patients’ body habitus. Mucosal folds often form linear impressions within the gas shadows. In patients with largely fluid contents within bowels, air trapped between the mucosal folds is visualized as closely spaced, parallel and lucent lines. Lack of dilated, air-filled bowels in the peripheral portions of the abdomen on an erect film suggests (though does not confirm) the level of obstruction proximal to the ileo-caecal junction. Air-fluid levels These represent a surrogate sign of stagnation and hence help differentiate gaseous distension of nonobstructed bowels from true obstruction. Few (two to three) small airfluid levels may be seen even in a normal radiograph – in the regions of pyloroduodenum (epigastrium) and terminal ileum (right iliac fossa). The number and distribution of air-fluid levels help differentiate the dilated small bowel (smaller, central, more numerous levels) from large bowel (larger, peripheral, fewer levels). Air-fluid levels more than 2 in number, wider than 2.5 cm and differing more than 2 cm in height from one another within the same small bowel loop are said to predict high-grade small bowel obstruction. Changes in the number of air-fluid levels and degree of gaseous distension of bowels on serial radiographs aid monitoring response to treatment. A caveat to be remembered is radiographs of patients with diarrhoea may also show airfluid levels due to profuse intraluminal secretions (Fig. 8.3.4.1).

FIG. 8.3.4.1 Erect radiograph of the abdomen showing shadows of multiple gas filled, dilated bowel loops in central abdomen with mucosal folds and horizontal air-fluid levels (arrows). Source: (Image courtesy: Dr. Chirag Sondarva, Consultant Radiologist, Parth Imaging Centre, Rajkot). Pneumoperitoneum Presence of free gas in the peritoneal cavity in the absence of recent peritoneal surgery or penetrating trauma is pathognomonic for gastrointestinal perforation. Air, being lighter rises to the most nondependent portion of the peritoneal cavity in any given position. This principle forms the basis of including both domes of diaphragm on an erect radiograph. Air collected in subdiaphragmatic regions forms a sharp contrast to the denser diaphragm. On the right lateral decubitus projection, the liver helps squeeze out air from under its lateral surface to line the left lateral (nondependent) peritoneal wall. Supine radiographs form a challenge for the radiologist, due to the lack of perpendicularity between the abdominal axis with that of the image receptor. Certain signs, however, help suspect extraluminal air. They include Rigler’s sign (gas on both sides of the bowel wall), the falciform ligament sign (gas outlining the falciform ligament), the football sign (gas outlining the peritoneal cavity), the inverted-V sign (gas outlining the medial umbilical folds), the right-upper-quadrant gas sign/lucent liver sign (localized gas in the right upper quadrant) and cupola sign (air accumulation underneath the central tendon of the diaphragm in the midline). Certain mimics of the ‘gas under the diaphragm sign’ of pneumoperitoneum include subdiaphragmatic abscesses and an anatomical variant called the Chilaiditi syndrome which involves the interposition of a colonic loop between the liver and diaphragm. Merits • Rapid • Easy availability • Portability • Low radiation dose • Low cost • Easy interpretation for non-Radiologists Demerits • Cause of obstruction remains undiagnosed. • Closed loop obstruction remains undiagnosed. • Evaluation of bowel wall ischaemia can only be made after pneumatosis sets in. • No evaluation of bowel motility.

Ultrasound Principle A real-time evaluation, ultrasound affords the evaluation of the bowel wall, lumen and motility. High-frequency transducers are usually favoured, especially in lean and moderately built patients. Signs Dilated and fluid-filled bowels Anechoic fluid within the dilated (proximal) bowel lumen often has few internal echogenic particulate contents, representing incompletely digested contents. Diameter of more than 3 cm and length of 10 cm are considered significant. In addition, the collapsed state of large bowel is corroborative (Fig. 8.3.4.2).

FIG. 8.3.4.2 Ultrasound image of a significantly dilated and fluidfilled small bowel loop. Note echogenic floating foci with distal dirty shadowing representing intraluminal air. Source: (Image courtesy: Dr. Kiran Parmar, Parth Imaging Centre, Rajkot). To-and-fro peristalsis Normal small bowel peristaltic movement is propulsive. Fluid in one segment gets displaced to the next, with the development of a constrictive wave at the site of the previous distension. With obstruction, a short, forward wave of fluid shows rapid backflow into the same segment, keeping the loop persistently dilated. This ineffective pattern of motility is aptly termed ‘to-and-fro’, ‘dysfunctional’ or ‘whirling’ movement. Ischaemic bowel A dilated and aperistaltic segment of small bowel with thickened wall (more than 3 mm) should raise the possibility of wall injury by ischaemia. However, a CT scan would be confirmatory. Ascites Mild and clear interbowel fluid is often a reactive phenomenon in cases of small bowel obstruction. However, larger volumes of fluid with rapidly moving internal echoes should alert the sonologist to the presence of ongoing ingress of turbid intraperitoneal contents – indirectly suggesting bowel perforation. Mesenteric inflammation Echogenic, thickened mesentery is a tell-tale sign of underlying inflammatory pathology – often the site of transition. Merits • Allows assessment of motility

• Rapid • Easy availability • Portability • No radiation • Low cost Demerits • Gaseous distension of bowels obscures the visibility of peritoneal cavity deep to it (Fig. 8.3.4.3). • The entire length of small bowel is not sonologically assessable, obviating visualization of transition site and hence the cause of obstruction. • Similar limitations towards diagnosing complications. • Closed loop obstruction is not diagnosed.

FIG. 8.3.4.3 Ultrasound shows near complete obscuration of the peritoneal cavity due to gaseous distension of bowel loops. Source: (Image courtesy: Dr. Kiran Parmar, Parth Imaging Centre, Rajkot).

CT scan Principle Probably the next best thing to laparotomy/laparoscopy in terms of visibility, CT scan has become the investigation of choice for suspected small bowel obstruction wherever available. Cross-sectional imaging and multiplanar reconstruction allow visualization of the entire gastrointestinal tract in all orthogonal planes. The limitation of visibility faced on ultrasound, posed by overlap of subjacent bowels is completely obviated. Bowels can be linearly traced up to and beyond the transition site. A complete overview of bowel lumen, walls and surrounding mesentery is afforded – all possible bearers of the cause of obstruction. The addition of IV contrast provides additional details including neoplastic/inflammatory pathologies at the transition site, bowel wall viability and state of mesenteric vasculature. Signs Bowel dilatation and air-fluid levels In an already established case of small bowel obstruction, the dilated (>2.5 cm from outer wall to outer wall) and fluid-filled bowel loops are fairly unmistakable. Distension of bowels by fluid makes oral contrast unnecessary. As the patient is scanned in supine position, air-fluid levels are oriented with air in anterior (nondependent) portions of small bowels. In early cases, however, bowel dilatation may be seen just proximal to the transition site with few, if any, air-fluid levels. Similarly, distal bowels may not be completely collapsed until their contents are evacuated. High-grade obstruction is suggested by a 50% difference in calibre between the proximal dilated bowel and the distal collapsed bowel (Fig. 8.3.4.4).

FIG. 8.3.4.4 Axial section through mid-abdomen showing dilated and fluid-filled small bowel loops with air-fluid levels. Collapsed descending colon (arrow) corroborates obstructive dilatation of small bowels. Source: (Image courtesy: Dr. Nilesh Shingala, Parth Imaging Centre, Rajkot). The transition site Probably, the key information surgeons need from any good diagnostic study is regarding the exact site of obstruction. Commonly referred to as the transition site or point, it forms the junction between proximal dilated and distal collapsed bowel loops. The ‘transition’ may be abrupt or gradually tapered, depending on the cause. The anatomical location of the transition site (jejunum or ileum) can be estimated by gauging the length of small bowel proximal and distal to it. In patients with numerous dilated bowel loops, tracing the transition may be slightly challenging – an endeavour which may be aided by tools like using triangulation on a workstation, retrograde tracing from ileo-caecal junction and spotting the small bowel faeces sign (read below). Sometimes multiple areas of bowel narrowing may be present (e.g. with multilevel strictures, adhesions, serosal deposits). Hence the importance of carefully scouring the entire length of small bowel even after a transition site is found. Two or more sites of narrowing may give rise to the distinct entity of closed loop obstruction – an entity for which CT scan is the only diagnostic imaging modality. Passage of orally administered iodinated contrast beyond the transition site on delayed images (up to 24 hours from start of oral intake of contrast) indicates partial bowel obstruction. Absence of a definite transition site may be explained by possibilities including alternate diagnosis like paralytic ileus and low-grade, partial obstruction. The small bowel faeces sign Prolonged hold-up of partially digested intraluminal contents along with increased intraluminal fluid secreted by small bowel mucosa due to stretching and multiple air foci together give the appearance similar to faecal matter. As this phenomenon commonly initiates just proximal to the site of luminal narrowing, the small bowel faeces sign is a useful pointer towards the transition site in moderate to high degree of obstruction – especially in the presence of multiple dilated loops. Similar findings may sometimes be seen in terminal ileum of patients with chronic constipation (Fig. 8.3.4.5).

FIG. 8.3.4.5 Coronal reformat in a case of short segment ileocolic intussusception. Note the mottled pattern of air foci interspersed with fluid and particulate matter within the most dilated segment of terminal ileum (thick arrow) just proximal to the transition site (thin arrow). Source: (Image courtesy: Dr. Nilesh Shingala, Parth Imaging Centre, Rajkot). Signs of complications – recognizing the surgical candidate Perforation Due to its cross-sectional capability, CT has very high sensitivity in spotting even a small pneumoperitoneum as in early perforation. Additional findings include peritoneal fat stranding and interbowel fluid. Bowel wall ischaemia A dreaded complication of closed loop obstruction, a good contrast-enhanced CT study shows well the lack of wall enhancement in strangulated bowel loops. Presence of lowdensity fluid within bowel lumen accentuates wall enhancement and by corollary, the lack of it. In advanced cases, air foci may be seen within bowel walls (pneumatosis) as well as within the mesenteric/portal venous systems (portal pyaemia). It is important for the radiologist to distinguish between intraluminal gas closely abutting bowel wall and intramural gas.

Imaging features of specific aetiologies of small bowel obstruction Intraluminal causes 1. Gall stone ileus Intestinal migration of a gall stone large enough to occlude small bowel lumen is relatively uncommon, complicating about 0.5% of gallstone disease. The diagnosis may be suggested on an erect radiograph, by a combination of a round or oval calcific density and multiple air-fluid levels. Finding the gall stone at the site of transition on CT scan confirms the suspicion (Fig. 8.3.4.6).

FIG. 8.3.4.6 Large gall stone with calcified centre and soft rim (arrow). Few dilated and fluid-filled proximal bowel loops also visualized. Source: (Image courtesy: Dr. Rahul Ranjan, Professor, Department of Radiodiagnosis, Rama Medical College, Kanpur). 2. Bezoar While more common in the stomach, an ill-defined, heterogenous soft tissue structure with linear strands and air foci at the transition site should raise the possibility of undigested contents like a hairball (trichobezoar) or vegetable residue (phytobezoar). Only around 1.1% of cases present as acute surgical small bowel obstruction. 3. Ingested foreign body Often of high density, foreign bodies are suspected by their geometric configuration in the correct clinical setting. CT scan with 3D volume rendering may help define the shape of a radiolucent foreign body. Presence of intestinal obstruction forms the 1% of cases of ingested foreign bodies which require surgical intervention. 4. Pica The compulsive eating of nonfood items may result in impaction of the ingested solids with resultant acute or subacute obstruction, at the level of small bowel or large bowel. Ileum has been found to be the commonest site of impaction. The presence of multiple closely placed hyperdense rounded structures often interspersed with air foci within bowel lumen may give a clue to this aetiology. 5. Intussusception Invagination of a small bowel loop into adjacent, more distal loop with resultant luminal occlusion is one of the commonest causes of obstruction in paediatric patients. The forward propulsive movement of peristalsis may cause a transient and reversible intussusception even in normal subjects. Hence, a worthwhile exercise to repeat scan after a 30 minute interval when a clinically unsuspected intussusception is found on ultrasound. However, when the walls of involved loops are thickened, the reverse excursion of the intussusceptum is hampered. With an increase in wall oedema, the constrictive effect at the mouth of intussusception increases. This forms the transition site of bowel obstruction. Wall thickening in toddlers may be attributed to the enlargement of lymphoid aggregations in distal ileal wall (Peyer’s patches) reactive to subclinical infections. In adults, however, the presence of an intussusception (5% of all intussusceptions) should prompt the search for a pathology acting as the ‘lead point’, for example a neoplasm which facilitates the forward propulsion of the intussusceptum into the intussuscipiens. A variety of benign/malignant masses as well as venous malformations may be implicated as the pathological lead point. An inverted Meckel’s diverticulum as the lead point would appear as a central core of fat attenuation surrounded by a collar of soft tissue attenuation.

Presence of multiple or recurrent small bowel intussusceptions may alert the radiologist to the possibility of underlying celiac or Crohn’s disease. While the most commonly encountered form of intussusception in clinical practice is ileocolic, other forms include jejunoileal, ileoileal, ileoileocolic and colocolic. Meckel’s diverticulum and rarely appendix may form the intussusceptum at times. On ultrasound and CT scan, an intussusception is diagnosed by recognizing the presence of a bowel loop within another. On short axis, the ‘multiple concentric ring sign’, the ‘crescent in doughnut sign’, on long axis, the ‘sandwich sign’ and ‘hayfork sign’, make it fairly unmistakable due to the distinctive appearance of the gut signature of the intussusceptum and surrounding mesenteric fat. Additionally, mesenteric lymph nodes may be identified within the lumen of the intussuscipiens. Ultrasound is believed to have a sensitivity of 98%–100% and specificity of 88%–100% for the diagnosis of intussusception. Absence of blood flow at the apex of an intussusception at Doppler US predicts a low rate of reduction. It, however, does not have any significant correlation with bowel viability (Figs. 8.3.4.7 and 8.3.4.8).

FIG. 8.3.4.7 Axial CT scan image showing bowel-within-bowel appearance in right lower abdomen, s/o intussusception (arrow). Source: (Image courtesy: Dr. Nilesh Shingala, Parth Imaging Centre, Rajkot).

FIG. 8.3.4.8 Coronal CT scan of the same patient as Fig. 8.3.4.7 showing short segment intussusception of terminal ileum (thin arrow) into caecum with proximal small bowel dilatation. Also note the small bowel faeces sign in terminal ileum just proximal to the site of intussusception (thick arrow). Source: (Image courtesy: Dr. Nilesh Shingala, Parth Imaging Centre, Rajkot). Ultrasound-guided hydrostatic reduction of ileocolic intussusception is now the first-line therapeutic approach in paediatric patients. The procedure involves per rectal instillation of fluid in the form of a continuous infusion. Alternately, air can be pumped in under pressure but poses a limitation to visibility on ultrasound. The transit (reduction) of the intussusceptum is then monitored under image guidance, with complete reduction being the end point. At times, however (e.g. in long-standing cases with significant wall oedema), the intussusception is resistant to reduction by this method. Continued/forceful infusion of fluid into bowel lumen in such patients invites the risk of perforation. Hence the so-called ‘Rule of three’ – at most, three attempts at reduction of up to 3 minutes each, with instillation from a height of 3 feet above the level of the patient. However, this ‘rule’ is now more of a guideline, with many institutes making more than three attempts at reduction. Recurrent intussusceptions or failed attempts may be dealt with by a repeat attempt at reduction after few hours. However, prolonged persistence of intussusception increases risk of bowel wall gangrene. Presence of large volumes of peritoneal fluid with internal echoes should raise suspicion of bowel wall perforation, making image-guided reduction unadvisable in favour of surgery. Involvement of long segments of bowel (e.g. extension of ileocolic intussusception up to splenic flexure) may also not be amenable to hydrostatic reduction. A few recent studies have concluded that duration of symptoms, age at presentation and recurrence after hydrostatic reduction are no contraindications to nonoperative management. They document the success of hydrostatic reduction even after the third and fourth recurrences. Ultrasound combines the advantages of real-time assessment and lack of ionizing radiation. Use of saline is much safer in the event of intraprocedural bowel perforation. However, the pressure generated by the fluid column is less than that generated by the traditionally used barium suspension. The latter was initially utilized for fluoroscopic reductions but has now fallen out of favour for fear of barium peritonitis in case of perforation. Nonionic iodinated contrast is also utilized to circumvent this limitation of barium when performed under fluoroscopy guidance.

Intramural causes 1. Stricture Chronic fibrotic scarring and contracture may result in focal luminal narrowing. This may be a sequel of recent or remote infective, inflammatory or ischaemic injury to the bowel wall. Short segment, unifocal involvement favours postinfective scarring. Narrowing due to chronic inflammatory pathology like Crohn’s disease may be multifocal (skip lesions). Depending on the inciting event, ischaemic stricture may be unifocal or multifocal, involving a short or long segment of the bowel (Fig. 8.3.4.9).

FIG. 8.3.4.9 Irregular circumferential wall thickening in terminal ileum and ileo-caecal junction secondary to Koch’s enteritis (arrow). Resultant low-grade/subacute small bowel obstruction. Source: (Image courtesy: Dr. Malay Dhebar, Parth Imaging Centre, Rajkot). Radiation enteritis may rarely cause small bowel obstruction by a combination of bowel wall thickening and mesenteric adhesive changes. 2. Intramural haemorrhage Bowel wall thickening (usually unifocal, short segmental involvement more likely than long) which appears hyperdense on noncontrast CT scans favours intramural haematoma – either in the posttraumatic setting or in patients on anticoagulant therapy. 3. Neoplasm Neoplastic involvement of small bowel is much less common than that of large bowel or stomach. However, irregular, eccentric wall thickening (or circumferential with more pronounced involvement on one side) alerts the radiologist to the possibility of a neoplasm. Degree of wall thickening is generally greater than that with other benign conditions. Additional findings like extraserosal fat infiltration, enlarged locoregional lymph nodes and hepatic metastases when present are corroborative. Extraluminal causes 1. Adhesions and bands The commonest of all causes (50%–80% of all cases), bowel luminal narrowing by peritoneal adhesions is presumed by the absence of a demonstrable structural lesion at the transition site. At times, thick adhesions may be seen as curvilinear bandlike structures across peritoneal fat. Presence of multiple transition sites in almost linear (spatial) relation to each other strengthens the case for a peritoneal band. History of prior surgical intervention is much more common than that of peritoneal infection (Figs. 8.3.4.10 and 8.3.4.11).

FIG. 8.3.4.10 Twisted mesentery and ileal loops (white arrow) around a central pedicle (black arrow) consisting of mesenteric vessels and a thin band. Dilated jejunal loops proximal to the site of twist/narrowing. Source: (Image courtesy: Dr. Hitesh Bhalodia, Parth Imaging Centre, Rajkot).

FIG. 8.3.4.11 Same patient as Fig. 8.3.4.10. Thick linear band (white arrow) extending from umbilicus to an air-filled diverticulum (black arrow) represents vitellointestinal band attached to Meckel’s diverticulum. Congenital peritoneal bands can cause obstruction by direct compression or by forming the central pedicle/axis around which small bowel volvulus occurs. Source: (Image courtesy: Dr. Hitesh Bhalodia, Parth Imaging Centre, Rajkot). 2. Extrinsic mass Compression by extrinsic primary peritoneal or secondary (serosal) neoplastic lesion is commoner than primary intramural small bowel neoplasm. 3. Hernia A common occurrence is the entrapment of bowel loops within a hernial sac. This may lead to simple or closed loop obstruction, depending on whether the narrowing is only at the afferent limb or also at the efferent limb. External hernias are much commoner and easily

clinically recognizable than the relatively rare internal hernias. Apart from the classical sites of inguinal and umbilical hernias, incisional hernias may occur variably depending on the incision site – often multiple and complex. Depiction of the precise number, sizes and locations of anterior abdominal wall defects helps a surgeon plan surgery including preoperative determination of the size of mesh (Figs. 8.3.4.12–8.3.4.13).

FIG. 8.3.4.12 Axial CT scan showing herniation of a short segment of bowel through anterior abdominal wall defect at umbilicus (white arrow). Another hernial sac lies just lateral to it (black arrow), with bowel loop entrapped between muscle layers of anterior abdominal wall – an uncommon but not impossible occurrence. Resultant proximal small bowel obstruction. Source: (Image courtesy: Dr. Brijesh Sumaria, Ujjwal Imaging Centre, Jamnagar).

FIG. 8.3.4.13 Axial CT in a case of multiple complex ventral hernias. Note the sharp transition site (white arrow) within the hernial sac with small bowel faeces sign proximal to it (black arrow) – as opposed to the usual transition at the hernial neck. This may be due to coexistent stricture or displacement of bowel loops from neck to sac due to peristaltic movement. Source: (Image courtesy: Dr. Brijesh Sumaria, Ujjwal Imaging Centre, Jamnagar). Internal hernias form an uncommon but potentially serious subset of the spectrum due to lack of a clinically identifiable site and the high propensity to form a closed loop obstruction. The earliest signs of bowel wall ischaemia include wall hyperdensity on noncontrast scan, submucosal oedema followed by hypoenhancement and adjacent mesenteric haziness. Further delayed signs include bowel wall pneumatosis and portal pyemia. Any/all of these signs are red alerts signalling the need for urgent surgical intervention (Fig. 8.3.4.14).

FIG. 8.3.4.14 Oblique coronal reformat of venous phase imaging in a case of closed loop (arrows) obstruction shows loss of normal enhancement along mesenteric border of the involved loop with adjacent mesenteric fluid and the presence of small air foci in the involved bowel wall. Source: (Image courtesy: Dr. Komal VadgamaJogi, Usmanpura Imaging Centre, Ahmedabad).

Mimics of small bowel obstruction Paralytic ileus Cessation of peristaltic movements causes stagnation of intraluminal contents within small bowels. This, coupled with ongoing secretions produces luminal dilatation and air-fluid levels, closely simulating mechanical obstruction on imaging. Two clues which help make the distinction, however, are absence of peristaltic movements on ultrasound and absence of a transition point on CT scan with persistent bowel distension up to rectum (Figs. 8.3.4.15 and 8.3.4.16).

FIG. 8.3.4.15 Axial CT scan of a patient recently operated for cholecystitis with persistent postoperative abdominal distension. Dilated and fluid-filled ascending/descending colon (arrows) favour paralytic ileus rather than adhesive obstruction. Source: (Image courtesy: Dr. Pooja Patel, Parth Imaging Centre, Rajkot).

FIG. 8.3.4.16 Sagittal reformat of the same scan shows markedly distended rectum (arrow) – a sign conventionally used on plain radiography to make the distinction. Source: (Image courtesy: Dr. Pooja Patel, Parth Imaging Centre, Rajkot). Large bowel obstruction Pattern of bowel dilatation is distinct from that of small bowel obstruction in showing peripheral distribution. Air-fluid levels are larger, more peripheral and less numerous than with small bowel obstruction. Pseudo-obstruction (ogilvie syndrome) Marked dilatation of the colon without mechanical obstruction in an elderly, moribund patient also poses a confounding picture on conventional imaging. CT scan would help document the lack of a transition site up to the rectum. 8.3.5

POSTOPERATIVE SMALL BOWEL IMAGING Abhishek Jain, Gayathri Achuthan, Rajan Patel

Introduction Being aware of the imaging findings of alterations in the small bowel anatomy and related complications following abdominal surgeries is the key to the correct diagnosis. The radiologist needs to differentiate whether a finding is an expected postoperative change or relates to a complication to prevent misdiagnosis. Communication with the surgeon for detailed surgical history is of utmost importance; however, pertinent surgical history may be incomplete or even unknown at the time of diagnostic imaging, thus expertise in appreciation of postoperative anatomy and associated intestinal alterations is important. Abdominal surgeries can alter the anatomy of the small bowel in a few defined patterns. Major surgical interventions performed on any segment of small bowel include surgical resection, surgical repair, the formation of enterostomies or mucous fistulas and an enterotomy. Some seldom performed surgical procedures are the creation of ileal reservoirs and ileoanal pouches. Another recent surgical development is small bowel transplantation being used for limited adult and paediatric indications.

Technique A plain abdominal radiograph is usually performed in the postoperative period as a screening tool or first-line investigation for obstruction and perforation, but overall sensitivity and specificity of plain X-rays are low (sensitivity approximately 70% for highgrade obstruction). Furthermore, a plain radiograph lacks in the depiction of anatomical details and complications. Gastro-intestinal (GI) water-soluble contrast studies are to look for specific complications like intestinal leak and adhesive small bowel obstruction. Nonpassage of the contrast in the colon on an abdominal X-ray taken 24 hours after administration of the contrast is highly suggestive of the failure of nonoperative management. CT enteroclysis/enterography is the preferred investigation to evaluate small bowel integrity, postoperative small bowel anatomy and related complications. Many factors specific to the patient and institution are considered, before choosing between enteroclysis (intubation and infusion method) and enterography (the oral approach). MRI enterography is used for specific indications like suspected recurrence of cancer or inflammatory bowel disease.

Normal postsurgical imaging findings It is imperative to distinguish between expected and abnormal postoperative findings, particularly in the early postoperative period. It is important to be aware of the time and type of surgery performed. Some common postoperative findings normally observed are (Fig. 8.3.5.1): • Fat stranding in the intraabdominal fat and abdominal wall. • Small volume pneumoperitoneum and free fluid usually noted up to 4–6 days. In laparoscopic procedures, more volume of free gas and emphysema are expected, extending into the chest. • Peritoneal and bowel oedema is usually noted adjacent to the surgical site. • Adynamic ileus/pseudo-obstruction: No transition point is noted. • Mild reactive pleural effusion and atelectasis in lung bases.

FIG. 8.3.5.1 Abdominal radiograph demonstrates postoperative adynamic ileus. Dilated large (asterisk) and small (circle) bowel loops with surgical clips and drain in the right iliac fossa. Small pneumoperitoneum is seen under the left hemidiaphragm (white arrow).

Postoperative small bowel-related complications

Postsurgical small bowel-related complications: 1) Anastomosis-related complications: • Anastomotic leak or perforation (Fig. 8.3.5.2) • Anastomotic stricture or stenosis • Blind pouch syndrome

• Afferent loop obstruction 2) Herniation • Internal hernias • External hernias 3) Adhesions and obstructions 4) Primary disease-related complications • Neoplastic or inflammatory bowel disease recurrence

FIG. 8.3.5.2 Coronal and axial sections of the CECT abdomen demonstrate thick walled sinus tract (blue arrows) with air foci within, extending from postoperative drain site and communicating with the pelvic abscess (asterisk). Postoperative small bowel complications can be classified as related to anastomosis, hernias (abnormal bowel position), related to adhesions and primary disease-related complications. 1. Anastomosis-related complications Anastomosis generally follows eneterectomy with or without formation of external ostomy. Anastomosis is a frequently done gastro-intestinal procedure for establishing continuity of the bowel after resection, for bypassing an obstructed bowel segment and for making an enteric reservoir. Surgically, the types of intestinal anastomoses are end-to-end, end-to-side or side-toside anastomosis (Fig. 8.3.5.3). An end-to-end anastomosis is preferred provided there is minimal disparity in luminal size of small bowel segments and serves to avoid small bowel stasis syndromes. Performing a side-to-side anastomosis in close proximity to the closed ends of bowel segments serves as a functional end-to-end anastomosis and increases the anastomotic surface. To compensate for size discrepancies for the parts to be joined, an end-to-side anastomosis is used and a side-to-side anastomosis is indicated for large anastomosis in the setting of a narrow lumen (Fig. 8.3.5.4). When an end-to-side anastomosis is performed, the end of the proximal lumen is anastomosed to the side of the distal intestinal segment, thus distal segment peristalsis prevents stasis.

FIG. 8.3.5.3 Types of anastomosis. (A) End-to-end anastomosis. (B) End-to-side anastomosis. (C) Side-to-side anastomosis.

FIG. 8.3.5.4 Coronal section of CT abdomen demonstrate side-toside ileo-transverse anastomosis (white arrows) in an operated case of ileo-caecal carcinoma. A. Anastomotic leak or perforation Patient with history of GI surgery presenting with abdominal pain or GI bleed is investigated with abdominal radiograph, water-soluble contrast studies and CT with positive intraluminal contrast agent. Anastomotic dehiscence can be identified by the presence of pneumoperitoneum on abdominal radiographs. Contrast studies performed with water-soluble contrast media may demonstrate an intestinal leak, although CT can demonstrate contrast leak along with other complications like abscess formation, phlegmon formation and anastomotic obstruction.

Although few studies suggest water-soluble contrast agents are superior to CT in detecting anastomotic leaks; however, the most recent studies suggest CT with positive intraluminal contrast agent to be superior and is the modality of choice. Most sensitive evidence of anastomotic leaks on CT are intraabdominal free fluid, intraabdominal free gas and perianastomotic stranding; however, the identification of highly specific finding of positive contrast leak outside the bowel lumen helps radiologist in correctly identifying anastomotic perforation (Fig. 8.3.5.5). Although the overall sensitivity of CT for the detection of anastomotic leakage remains low, diagnostic performance can be improved by using an intraluminal contrast agent and ensuring that it reaches the anastomosis. Other less sensitive imaging predictors of anastomotic leak include perianastomotic gas, bowel wall thickening, focal collection, reduced bowel wall enhancement and obstruction at anastomosis. Anastomotic leaks may be complicated by enterocutaneous, enteroenteric and enterovesical fistula formation, and often follows abscess formation. Error in diagnosis can occur if inadequate contrast is used and secondary to a limited understanding of postoperative anatomy.

FIG. 8.3.5.5 Axial and sagittal sections of CT abdomen demonstrate anastomotic perforation and positive contrast leak after right hemicolectomy. Leak of positive oral contrast (white arrow) at the anastomotic site (black arrow) with peritoneal collection and pneumoperitoneum (curved arrow). B. Anastomotic stricture/stenosis: Causes for stricture are not clearly understood and probably depend on the type of surgery as well as the technique of surgery performed. Symptomatic gastric stenosis is noted in 3%–5% of cases after gastrojejunostomy. It develops secondary to prolonged exposure of anastomosis to an inappropriately large volume of gastric acid resulting in ongoing inflammation, ulceration and stricture formation. Another type of obstruction is stenosis of Roux loop in Roux-en-Y gastric bypass. Several studies also suggest an increase in the incidence of strictures with the use of stapler versus handsewn anastomosis, both for gastrojejunostomy and colorectal anastomosis. In case of ileal pouch anal anastomosis, a metaanalysis revealed an incidence of anastomotic strictures of 9.2%. The symptoms are abdominal pain, distension, nausea and vomiting; these reflect the degree of luminal stenosis. Upper GI contrast studies can detect anastomotic strictures and show contrast material hold-up, prestenotic bowel dilatation and can demonstrate perianastomotic fistulae. CT abdomen is now the preferred investigation due to proper delineation of the anastomotic abnormality as well as extraluminal structures. CT findings are focal bowel wall thickening at the anastomosis and distended proximal bowel loops filled with fluid, air-contrast level or desiccated stool (Fig. 8.3.5.6).

FIG. 8.3.5.6 Sagittal and coronal sections of the CECT abdomen demonstrate anastomotic stricture and obstruction. Bowel wall thickening is noted at the site of ileo-ileal anastomosis (surgical clips, white arrow) with upstream dilatation of small bowel loops (asterisk) and air-fluid levels in a patient of recurrent Crohn’s disease. Thick walled abscess (black arrow) is seen adjacent to anastomosis with air within it, secondary to anastomotic site infection. Strictures can be managed with either dilatation (manual or endoscopic) or operation, depending upon the location. C. Blind pouch syndrome (Fig. 8.3.5.7) With the reduced application of side-to-side anastomosis in gastro-intestinal tract surgeries, the prevalence of blind pouch syndrome has decreased. During side-to-side anastomosis, local dysmotility secondary to the division of the circular muscle can result in stasis that leads to subsequent dilation of the proximal anastomotic segment and formation of a blind intestinal pouch. Occasionally, it can also be encountered in an incorrectly performed end-to-side anastomosis and end-to-end anastomosis.

FIG. 8.3.5.7 Blind pouch syndrome in end-to-side anastomosis. (A) Proper anastomosis of end of proximal small bowel segment with side of distal small bowel segment, resulting in flow of intestinal contents in peristaltic direction (arrows) into the patent bowel. (B) Improper anastomosis between side of proximal bowel loop and end of distal bowel loop, resulting in flow of intestinal content with peristalsis (arrows) into the blind loop. Clinically, it classically presents as abdominal pain and distension, episodic diarrhoea and a history of previous intestinal anastomosis. CT scan and upper GI contrast studies accurately confirm the diagnosis, seen as a distinct saccular enteric structure, with surgical clips in the vicinity. Complications include inflammation, ulceration, intestinal bleeding and perforation. Surgically it is corrected via segmental pouch resection and a restorative end-to-end anastomosis. D. Afferent loop obstruction An afferent loop is the bowel loop for biliopancreatic drainage in various gastric or pancreaticogastric operations. Afferent loop syndrome (ALS) is the chronic mechanical obstruction of the afferent loop seen in 0.3%–2% of gastroenterostomies, both in Billroth II surgery (Fig. 8.3.5.8) and Whipple or Roux-en-Y procedures (Figs. 8.3.5.9 to 8.3.5.10).

FIG. 8.3.5.8 Billroth type II surgery. Gastrojejunostomy (black arrow) between the remnant stomach (S) and jejunum with closure of duodenal stump (dashed arrow). A, afferent loop; E, efferent loop.

FIG. 8.3.5.9 Roux-en-Y gastric bypass surgery (RYGP surgery) stomach is bypassed using gastrojejunal anastomosis (dashed arrow) and jejunojejunal anastomosis (solid black arrow). Gastric pouch (GP), Biliopancreatic limb (BP), Roux loop of jejunum (R), Common channel (C).

FIG. 8.3.5.10 Whipple procedure demonstrating the three classic anastomotic sites, end-to-side choledochojejunostomy (red arrow), end-to-side pancreatico-jejunostomy (solid black arrow) and end-toside gastrojejunostomy (dashed arrow). Stomach (S), Jejunum (J). Multiple scenarios can lead to ALS including anastomotic stricture, adhesions, retrograde intussusception, internal hernia, recurrence of neoplasm, inflammatory disease recurrence, due to preferential gastric emptying into the afferent loop due to abnormal surgical anastomosis or secondary to efferent loop obstruction resulting in fluid accumulation in the afferent loop (Fig. 8.3.5.11).

FIG. 8.3.5.11 Axial and coronal sections of the CECT abdomen demonstrate afferent loop (asterisk) obstruction secondary to tumour recurrence. Distended afferent small bowel loops (asterisk) and collapsed efferent loop (transverse colon, black arrow) due to mass lesion at the anastomotic site (white arrow) in a patient of anastomotic site recurrence of carcinoma appendix after hemicolectomy and ileotransverse anastomosis. Afferent loop obstruction may develop years after primary surgery and may not be clinically evident, although the classic presentation is of abdominal pain and bilious vomiting with pain relief following vomiting.

Abdominal radiographs are mostly nonspecific, although the obstructed afferent loop may be seen as dilated fluid-filled loop. Gastro-intestinal contrast studies can be helpful in the diagnosis of this condition by showing nonfilling of the afferent loop or preferential filling of dilated afferent loop; however, normally in about 20% of cases, nonobstructed afferent loops are also not filled. After oral contrast administration, retention of contrast and preferential filling in a dilated afferent limb for at least an hour is another finding suggestive of ALS. CT is the most preferred imaging tool in establishing the diagnosis and delineating the site, degree and cause of ALS. A fluid-filled tubular or C-shaped structure containing small air bubbles crossing the midline between the aorta and the superior mesenteric vessels, with valvulae conniventes projecting into the lumen, in symptomatic patients after the gastro-pancreatic procedure is characteristic. Acute afferent loop obstruction can present with acute pancreatitis or biliary dilatation due to back pressure changes. Chronic complications of ALS may include strangulation, malabsorption, intestinal bleeding and perforation. CT can readily identify complications as well as helps prevent misdiagnosis of pancreatic pseudocyst. 2. Hernias (altered bowel positions) A. Internal hernias An internal hernia after abdominal surgery is the herniation of the small bowel into the abnormal aperture/abnormal closed space created by the operation. Two mechanisms can be identified for internal hernias following abdominal surgeries: firstly, mesenteric defect/hole created during reconstructive anastomosis of the gastro-intestinal tract; and secondly, small bowel can enter closed space generated secondary to adhesive peritoneal bands. Internal hernias are a frequent cause of obstruction following abdominal surgeries including Roux-en-Y reconstruction, Billroth II reconstruction, perineal hernia after pelvic surgeries and after gynaecological procedures. Clinically, internal hernias may present as nonspecific intermittent abdominal pain or strangulated obstruction (the most common presentation). Basic aim of imaging is to diagnose the cause of obstruction, to delineate the complex anatomy of internal hernias related to prior abdominal surgeries, to identify hernial orifice and to identify features suggesting progression to strangulation, thus guiding the surgical or medical management. Along with axial and coronal reformations, multiplanar reconstructions (MPR) play a crucial role. On CT, additional MPR images in the intestinemesentery plane demonstrate hernial orifice as an area where the mesentery of the closed loop converges, and plane vertical to the intestine-mesentery plane shows hernial orifice as a round or oval configuration of the converged mesentery. Pathophysiology and identifying progression to strangulation: Internal hernias can rapidly lead to volvulus, strangulation and perforation. CT findings closely correlate with pathophysiological findings in internal hernias and can demonstrate severity of strangulation to guide the management. Firstly, it begins with mesenteric vein occlusion, mesenteric as well as bowel congestion (seen as dilated mesenteric veins, mesenteric fat stranding and ascites); then as venous and capillary pressure increases (impending strangulation), it leads to fluid-filled dilated bowel loops as well as intramural and intramesenteric haematoma (seen as increased bowel wall and mesenteric attenuation on precontrast CT). As the congestion advances, signs of strangulation, bowel wall necrosis as well as ischaemia develop: trilaminar enhancement of bowel walls, poor or absent enhancement of bowel walls, twisting or whirl sign of dilated mesenteric vessels, thrombosis of mesenteric vessels and pneumatosis intestinalis/pneumoportalis. Few basic CT findings allow a radiologist to identify postoperative internal hernia (Fig. 8.3.5.12): • Identification of closed loop of the small bowel: Seen as C-shaped or U-shaped segment with obstruction at two points (demonstrating beak sign) with mesenteric vessels converging at a point and radial configuration of the mesentery. • Dilatation of the bowel loops proximal to the closed loop and collapsed distal loops.

• Clustering of small bowel forming a sac in case of a small enclosed space. Different types of postoperative small bowel internal hernias and their specific CT findings are as follows: a) Roux-en-Y gastric bypass: Roux-en-Y reconstruction is commonly used in gastric or biliary surgeries as well as in bariatric surgeries and liver transplants. In adult patients with prior history of abdominal surgery, Roux-en-Y surgery is the most frequent cause of acquired internal hernias. Surgically, two types of Roux-en-Y reconstruction are done, one with antecolic Roux loop and the other with retrocolic Roux loop. Four types of internal hernias documented following Roux-en-Y gastric bypass are as follows (Fig. 8.3.5.13): via defect in transverse mesocolon in retrocolic Roux limb (meso-colic window), via small bowel mesenteric defect posterior to Roux limb (Petersen’s defect), via meso-jejunal mesenteric window at jejuno-jejunal anastomosis (most common type) and secondary to an adhesive peritoneal band. Specific CT findings which are useful in identifying these acquired hernias are swirling of the mesenteric vessels in the upper abdomen, whirl sign, clustering of dilated bowel loops in upper abdomen, presence of the jejunal anastomosis to the right of abdomen and presence of small bowel loops other than duodenum, posterior to the superior mesenteric artery. MPR is useful in determining subtype of internal hernia following Rouxen-Y reconstruction. Herniation through meso-jejunal mesenteric window demonstrates a specific CT finding of deformed and displaced Y-limb (proximal jejunal loop) surrounding the hernial orifice. Stretched Roux limb around the hernial orifice is specific for Petersen’s hernia. b) Billroth II gastrojejunostomy: Billroth II gastrojejunostomy is done after total or subtotal gastrectomy and afferent limb is the duodenum. After this surgery, retro-anastomotic internal hernia is documented in which small bowel loops herniate through the gap between the transverse colon and gastrojejunostomy. Swirling of jejunal loops and mesenteric vessels is noted in the periumbilical region on CT in retro-anastomotic hernia. c) Perineal hernia: A perineal hernia is defined as herniation of the abdominal contents via defect in pelvic floor at the incisional site, seen as an uncommon complication after conventional abdominoperineal resection, pelvic exenteration, hysterectomy and rectal resections. Perineal hernias are more common in females and are usually detected within 1 year of surgery. Although they are often asymptomatic, they may present with perineal pain or as bulging masses at buttocks. The CT features include sac-like clustering of small bowels in the presacral retroperitoneal space, often resulting in closed loop obstruction.

FIG. 8.3.5.12 Multiplanar reformatted image of the CECT abdomen demonstrates closed loop obstruction secondary to internal hernia in an operated case of intestinal obstruction. C-shaped configuration of distended clumped up proximal small bowel loops (asterisk) in left lumbar region with stretched mesenteric vessels (curved arrow) giving rise to balloons on strings sign and whorled pattern of mesenteric vessels (whirl sign, white arrow). Rest of the small bowel loops are collapsed.

FIG. 8.3.5.13 Line diagrams illustrating types of internal hernias after Roux-en-Y anastomosis with antecolic Roux loop (A) and retrocolic Roux loop (B). (1) Hernia occurring through a defect in the mesentery posterior to the Roux loop, also known as Petersen’s defect. (2) Hernia occurring through a defect in the mesentery at the mesojejunal window. (3) Hernia occurring through a defect in the transverse mesocolon. (4) Hernia occurring through an aperture secondary to adhesions. B. External hernias An incisional hernia is defined as herniation of peritoneal fat with or without bowel loops through any gap in the abdominal wall in the area of a postoperative scar. After any abdominal surgery, incisional hernias can develop with an incidence approaching 20% and are being increasingly encountered due to increased life expectancy as well as high prevalence of risk factors such as obesity, diabetes, malnutrition, increased intraabdominal pressure and chronic respiratory disease. Incisional hernias are common with open abdominal surgeries than laparoscopic procedures. Stomal and parastomal hernias are subtypes of incisional hernias and represent protrusion of the abdominal contents through any defect in the abdominal wall in the vicinity of the stoma or at the stomal site. It mostly occurs within a year of abdominal surgery, and its occurrence also depends on site of stoma placement as well as size of

fascial opening. Parastomal hernias are common, with an expected prevalence of 33%– 78%, depending on whether evaluated clinically or via CT (Fig. 8.3.5.14).

FIG. 8.3.5.14 Sagittal and coronal sections of the CECT abdomen demonstrate type 3 parastomal hernia at the colostomy site (white arrow) in an operated patient of carcinoma rectum. Herniation of omentum and ileal loops (curved arrow) at the colostomy site in left iliac fossa. Recent study has classified parastomal hernias based on CT findings: Type 0 – Peritoneum follows the bowel forming the stoma, with no sac. Type 1a – Bowel forming the enterostomy with a sac 5 cm. Type 2 – Sac containing omentum. Type 3 – Intestinal loop other than the bowel forming the stoma. Type 0 and type 1a are considered expected findings and are not considered true hernias. USG is used as first line investigation of suspected abdominal wall hernia as it can differentiate hernia from other abdominal masses like cyst, haemorrhage, abscess and neoplasm. USG provides added advantage of dynamic evaluation, as patient can be examined in standing position as well as while exerting in case of small hernias. USG have limited value in detecting complications such as incarceration, obstruction and strangulation. Absence of peristalsis of herniated bowel contents, bowel wall thickening, fluid in herniated sac, absence of Doppler signals in herniated sac and signs of mechanical obstruction with presence of peritoneal fluid – these are the USG signs of complicated hernias. CT scan with contrast is an excellent modality to evaluate hernias in postoperative period. CT scan comprehensively visualize the operated abdominal wall and deeper intraabdominal structures. After abdominal surgeries, abdominal wall seromas are seen as fluid attenuation nonenhancing collections, abdominal wall haematomas are noted as high attenuation collection, and infection with abscess formation are noted as collections with irregular peripheral walls. CT is the main stay modality to determine size of abdominal wall defect, incarceration, strangulation, bowel obstruction, peritonitis, fistula formation, secondary infection and hernia recurrence, thus helps in choosing between conservative, interventional or operative treatment (Fig. 8.3.5.15). Arterial phase imaging can provide useful information regarding active bleeding. Depending on the size of abdominal wall defect, location of defect and presence of complications, open or laparoscopic repair with or without prosthetic mesh can be performed.

FIG. 8.3.5.15 Sagittal and axial sections of the CECT abdomen demonstrate strangulated incisional hernia (black arrow). Herniation of small bowel loops in the supraumbilical region with dilated afferent loops (asterisk) and collapsed efferent loops (white arrow) in an operated patient of intestinal obstruction. 3. Adhesions and obstructions A. Adhesions and simple adhesive small bowel obstruction Peritoneal adhesion or just adhesion is defined as the fibrous tissue which connects surfaces or organs within the peritoneal cavity that are normally separated, often as a result of pathological healing after surgery. Postoperative adhesions are the leading cause of small bowel obstructions, accounting for 60% of cases. Nonobstructive subtypes of adhesions are also known in which patients may present with abdominal bloating or pain after abdominal surgery. Intermittent or low-grade obstruction secondary to adhesions can lead to such symptoms. CT enterography has low sensitivity for low-grade obstructions, although CT enteroclysis or dynamic MRI may prove to be useful for better demonstrating the transition point. Other less sensitive CT features that may be present indicating presence of adhesions include: closely opposed small bowel loops to anterior peritoneum, thickened anterior peritoneum, acute angulation of bowel loops, kinking of bowel loops and wispy lines in the mesentery (Fig. 8.3.5.16). In appropriate clinical setting, such cases may be treated with adhesiolysis.

FIG. 8.3.5.16 Coronal and sagittal sections of the CECT abdomen demonstrate adherent clumped up ileal loops (asterisk) to the anterior abdominal wall with wound dehiscence and enterocutaneous fistula formation in a patient with ileal resection and ileo-ileal anastomosis secondary to the abdominal Koch’s. Leak of positive oral contrast (white arrow) at site of wound gapping. Thickened terminal ileum (blue arrow) and necrotic mesenteric lymph nodes (curved arrow) noted. Clinically significant overt or high-grade small bowel obstruction after a history of prior abdominal surgery needs imaging primary for the following indications: • To rule out causes of obstruction other than adhesive small bowel obstruction, as adhesions are mostly diagnosis of exclusion. • Identifying the need for urgent surgical exploration. • Recognizing and preventing complications from bowel obstruction. Helical CT scans with water-soluble contrast agents are the preferred imaging technique for diagnosing small bowel obstruction and have approximately 90% accuracy in predicting strangulation and the need for urgent surgery. The commonly noted CT findings pointing towards adhesive small bowel obstruction include a narrow zone of transition without an identifiable lesion (such as a mass, wall thickening or adenopathy), traction of bowel loops, stretching of the bowel loops and the presence of cord-like structure containing mesenteric fat bridging two peritoneal surfaces (fat-bridging sign) (Fig. 8.3.5.17). Along with clinical judgement, certain radiological signs which indicate need for urgent surgery include: signs of bowel ischaemia/strangulation, signs of peritonitis and signs of closed loop obstruction. However, further risk of developing adhesions increases as the number of surgeries increases.

FIG. 8.3.5.17 Axial sections of the CECT abdomen demonstrate adhesive obstruction and contained perforation in a patient operated for small bowel obstruction. Dilated proximal small bowel loops (asterisk) with narrow zone of transition (white arrow), traction of bowel loops and positive fat-bridging sign (red arrow). Collection with air-fluid level (black arrow) is noted at the site of obstruction secondary to contained perforation. B. Closed loop obstruction and strangulation Closed loop obstruction is when a segment of bowel is obstructed/incarcerated at two points along its course, often adjacent to each other. It forms a segment of bowel with no outlet, thus predisposes bowel segment to twist on itself, resulting in development of volvulus compromising the vascular supply and subsequent ischaemia as well as strangulation. Although incarceration commonly leads to strangulation; however, incarceration may resolve spontaneously as well. Postoperative adhesions are the most common cause of closed loop obstruction, less frequently internal or external hernias can also result in it. Other rare causes reported include posttraumatic or spontaneous closed loop obstruction. Remnant salpinx after ovarian resection can also cause closed loop obstructions along with peritoneal adhesive bands. CT findings of closed loop obstruction include (Fig. 8.3.5.18): • Findings of mechanical small bowel obstruction along with identifying contagious points of transition. • Clumped up dilated bowel loops forming beaked configuration at the site of obstruction, referred to as beak sign. • Whorled pattern of mesenteric vessels in the middle of the obstruction (whirl sign) reflects degree to which the mesentery is rotated. Although CT has low sensitivity for this sign, a recent study suggests more likelihood of the need for surgical intervention in the presence of this sign. • U/C configuration of incarcerated distended bowel loop. Multiplanar reformatted image plays an important role in identifying bowel configuration and diagnosis of closed loop obstruction. • Clumped up dilated small bowel segments forming a closed loop tethered by stretched mesenteric vessels (balloons on strings sign). • Often signs of strangulation are noted at the time of diagnosis, including altered bowel wall enhancement, mesenteric oedema and ascites.

FIG. 8.3.5.18 Axial section of the CECT abdomen demonstrate Ushaped configuration (white arrow) of small bowel loop in closed loop obstruction with positive beak sign (curved arrow) and encapsulated peritoneal collection (black arrow) in a patient operated for carcinoma ovary. Clinically, it is difficult to diagnose closed loop obstruction and differentiating it from simple small bowel obstruction. Delay in treatment is a major prognostic factor for increased morbidity and mortality, thus CT plays an important role in determining appropriate management (medical vs surgical). Teaching points • Late postoperative complications after gastro-intestinal tract surgery can be classified into procedure-related and disease-related categories. • The most commonly encountered procedure-related complications are adhesions and internal hernias. • Prompt recognition of signs for urgent surgical intervention in postoperative cases and early intervention is vital for patient survival. • Computed tomography provides extensive details of postoperative anatomy and is the most useful investigation when complications are suspected.

8.4: Colon Kulbir Ahlawat, Ravi Chaudhary, Arvind Pandey, Anuj Bahl, Navni Garg, Sonam Shah, Sonali Sharma 8. 4 .1

EMBRIOLOGY AND ANATOMY OF COLON Sonali Sharma

Embryology of colon A deep understanding of the development and the embryology of the colon is essential to understand the variety of the developmental anomalies related to the aberrations in the normal embryological processes (Table 8.4.1.1).

TABLE 8.4.1.1 Key Points to Remember Regarding the Embryology of the Colon KEY POINTS • Colon is derived from the midgut and the hind gut. • The prearterial segment gives rise to the postpapillary duodenum, jejunum and major part of ileum. • The postarterial segment gives rise to terminal ileum, caecum, appendix, ascending colon and major part of the transverse colon. • The anomalies of the stage of physiological herniation, are rare and include situs inversus, inverted duodenum and extroversion of the cloaca. • Anomalies of the reduction phase of the physiological hernia are relatively more common than the ones that originate from the stage of physiological hernia and include nonrotation, malrotation, reversed rotation, internal hernia and omphalocele. • Anomalies of this stage of fixation are common and include mobile caecum, subhepatic or undescended caecum, hyperdescent of the caecum, and persistent colonic mesentery • Appendix develops as an appendage due to growth discrepancy between the caecal apex and the caecal base and its position is due to the asymmetric growth of the lateral wall of the caecum and hindrance of the growth of the medial wall by the ileum and its vascular pedicle, leading to the shift of the appendix towards the ileocaecal valve across the midline of the caecum. • Phrenicocolic ligament fixes the splenic flexure to the left upper quadrant and seals the disease from the left paracolic gutters from reaching the left upper abdomen. • Sigmoid colon maintains its mesentery or sigmoid mesocolon at its posterior aspect and is prone to volvulus. • Enteric nervous system (ENS) is called the second brain due to its autonomy. • In contrast to the neural crest-derived cells of the enteric plexuses, interstitial cells of Cajal (ICCS), which serve as the ‘pacemakers of the intestine’, arise from intestinal mesenchyme. • While rotation anomaly of the prearterial segment may be an isolated entity but, the rotation anomaly of the postarterial segment is invariably associated with the anomaly of the prearterial segment. Broadly the development of the colon can be summarized in three stages:

First Stage: Physiological Herniation Second Stage: Return of the Midgut to the Abdomen Third Stage: Fixation of the Midgut The rate of growth of the embryo exceeds the growth rate of the yolk sac during the third and the fourth weeks of development. During the fifth week there is development of the omphalomesenteric duct or the Vitello intestinal duct or the yolk stalk which serves as a connection between the extraembryonic and the intraembryonic coelom (Fig. 8.4.1.1).

FIG. 8.4.1.1 Cross-section at the end of fourth week of embryonic development. The midgut at this point is divided into two equal length segments and the loop has its axis at the superior mesenteric artery (SMA). The apex is marked by the yolk stalk or the omphalomesenteric duct. There is a periarterial segment and the postarterial segment of the loop, the former starting at the foregut–midgut junction and ending at the apex. The postarterial segment lies between the apex and the midgut–hindgut junction. Eleventh week marks the beginning of the return of the postarterial segment of the gut, which continues to rotate in front and then to the right of the SMA. By the twelfth week the colon completes a 270-degree anticlockwise rotation with prior 90 degrees during herniation, and a further 180-degree counterclockwise rotation during the reduction of the postarterial segment. The prearterial segment gives rise to: Postpapillary duodenum, jejunum, ileum (major part) The postarterial segment gives rise to:

Terminal ileum, caecum, appendix, ascending colon, transverse colon (major part) There is a switch over to the hind gut at the junction of the proximal two-thirds and the distal one-third of the transverse colon where there is also a switch over in the arteries supplying the segments, with SMA (middle colic) supplying the proximal segment and the inferior mesenteric artery (IMA, left colic) supplying the distal segment. The fifth week also marks the development of a small swelling in the proximal postarterial segment which represents the caecal bud. There is the herniation of the midgut at the sixth week of development called the physiological herniation of the gut. At this time there is growth of the liver, and the right lobe pushes the prearterial segment downwards and to the right. The series of events represent a 90-degree counterclockwise rotation when viewed enface (Fig. 8.4.1.2).

FIG. 8.4.1.2 Events of development (CCcounter clockwise). The anomalies of this stage (stage of physiological herniation) are rare and include situs inversus, inverted duodenum and extroversion of the cloaca.

With growth of the peritoneal cavity and no further significant growth of the liver, there develops a free space within the peritoneal cavity for the reduction of the midgut hernia at about the tenth week of development. Eleventh week marks the beginning of the return of the postarterial segment of the gut, which continues to rotate in front and then to the right of the SMA. By the twelfth week the colon completes a 270-degree anticlockwise rotation with prior 90 degrees during herniation, and a further 180-degree counterclockwise rotation during the reduction of the postarterial segment (Fig. 8.4.1.2). There occurs the fixation of the gut in this final sequence of events which start towards the later part of the first trimester. Anomalies of the reduction phase of the physiological hernia are relatively more common than the ones that originate from the stage of physiological hernia and include nonrotation, malrotation, reversed rotation, internal hernia and omphalocele (Fig. 8.4.1.3).

FIG. 8.4.1.3 Primary arterial supply to the gut.

Development of the appendix

There is a discrepancy in the growth rates of the base of the caecum and the apex of the caecum which leads to the formation of an appendage called the appendix. Further till the fifth month of gestation there is a progressive gradual resorption of the dorsal mesentery. Gradually, fusion of parts of the primitive mesentery occurs, with fixation of the duodenum, and the ascending and descending parts of the colon to the posterior abdominal wall in their final position. Anomalies of this stage of fixation are common and include mobile caecum, subhepatic or undescended caecum, hyperdescent of the caecum and persistent colonic mesentery (Fig. 8.4.1.3). The mesentery of the transverse colon (mesocolon) persists with its partial fusion with the greater omentum leading to the formation of the gastrocolic ligament. The distal end of the transverse mesocolon condenses to form the phrenicocolic ligament, which suspends the transverse colon near the splenic flexure fixing it to the diaphragm in the left upper abdomen. It also prevents the spread of pathologies from the left paracolic gutters to the left upper abdomen. The sigmoid colon continues to maintain it dorsal mesentery or sigmoid mesocolon at its posterior aspect. The length of the mesentery is short relative to the variable length (sometimes very long) of the colon to which it is attached. This discrepancy leads to the sigmoid volvulus.

Colonic blood supply basics Colon is formed from the midgut and the hind gut with the junction of the proximal two-thirds and distal one-third of the transverse colon being the point of demarcation between the two. The midgut development continues beyond the opening of the papilla, to form the duodenum beyond the papilla, ascending colon and the proximal two-thirds of the transverse colon. This segment is supplied by the Superior Mesenteric Artery with corresponding venous and lymphatic drainage (Fig. 8.4.1.4).

FIG. 8.4.1.4 Embryological development summary of the colon with diseases related to interruption at various steps – A comprehensive flowchart. The distal third of the transverse colon, descending colon, sigmoid colon, rectum and the anal canal above the dentate line all are derived from the hind gut and supplied by the Inferior Mesenteric Artery with corresponding venous drainage and lymphatics (Fig. 8.4.1.3).

Nervous system of the colon

Enteric nervous system (ENS) functions independent of the CNS and is thus referred to as the ‘Second Brain’ and it regulates many aspects of gastrointestinal physiology including peristalsis, sphincter tone, glandular secretions, smooth muscle activity and microcirculation. The neuroenteric ganglion cells migrate from the neural crest to the upper end of the alimentary tract and then follow vagal fibres caudad during the first trimester. The ENS is composed of two types of ganglionated plexuses: the Auerbach (myenteric) plexus, which is located in the outer muscular layer and regulates gastrointestinal tract motility and function of extraluminal organs, and the Meissner (submucosal) plexus, which regulates enteral secretory activity. In contrast to the neural crest-derived cells of the enteric plexuses, interstitial cells of Cajal (ICCS), which serve as the ‘pacemakers of the intestine’, arise from intestinal mesenchyme. Nerve supply

Sympathetic innervation: L2–L5 roots, inferior and superior mesenteric plexus and coeliac ganglia. Parasympathetic innervation: The Vagus nerve and sacral spinal cord (S2–S4 spinal nerves).

Common anomalies related to development Great details of the various disorders are beyond the scope of this book. A short review is written (Table 8.4.1.2).

TABLE 8.4.1.2 Other Anomalies Associated With Abnormal Intestinal Rotation and Fixation The anomalies of rotation and fixation may be associated with multiple other anomalies listed below. COMMON ANOMALIES Duodenal atresia (11%) – most common Meckel’s diverticulum (11%) – second commonest Omphalocele (9%) Other stenosis or atresia (5%) Hirschsprung’s disease (2%). LESS COMMON ANOMALIES Cardiac and orthopaedic anomalies Biliary atresia Pancreatic anomalies Microcolon Esophageal webs Tracheoesophageal fistula PROXIMAL COLON DUPLICATION These include three anomalies: Mesenteric cysts Diverticula Long colon duplication

Nonrotation It is commonly known as malrotation and occurs due to an arrest of the first 90 degrees rotation of the midgut which causes the prearterial segment to lie to the right of the hernial sac and SMA and the postarterial segment to the left. The dorsal mesentery lies in the midline and is shared by both the pre and the postarterial segments. This makes the bowel loops imbalanced and mobile and prone to volvulus. The twisting of the midgut loop can occur mostly at the level of the duodenojejunal junction and less commonly at the level of the midtransverse colon. There is a disruption of the normal SMA to SMV relationship, with the SMV seen to the left of the SMA in this pathology.

Reversed rotation In this there is a reversal of the sequence of return of the midgut with postarterial segment returning first and lying posterior to the SMA with the duodenum and the small bowel lying anterior to the colon. Abnormal mesenteric bands may form leading to obstruction.

Omphalocele Failure of the midgut to retract into the abdominal cavity with retention in the hernial sac.

Incomplete rotation and malfixation anomalies The colon may fail to complete its final 180-degree rotation and lie in the right upper quadrant. Incomplete resorption of the mesentery may lead to abnormally mobile colon segments due to centrally placed dorsal mesentery. It is interesting to know that the rotation anomaly of the prearterial segment may be an isolated entity but, the rotation anomaly of the postarterial segment is invariably associated with the anomaly of the prearterial segment.

Incomplete attachment of the caecum and mesentery Caecum is an intraperitoneal organ either almost completely invested with peritoneum or at least invested by it in its lower half. It is fixed by a small mesocaecum. In 5% individuals the caecum rests directly on the iliacus muscle and the psoas major muscle due to lack of the peritoneum. Also, an abnormally mobile caecum and ascending colon may be seen in about 10%–22% individuals usually due to a long mesentery. Thus varied locations of the caecum may be seen. This is a fixation anomaly and may lead to a volvulus.

Hyperrotation This exclusively affects the postarterial segment with normal mobility and position of the prearterial segment. The caecum may lie in the left upper quadrant.

Internal herniations

Errors in the resorption of the dorsal mesentry, may lead to development of abnormal fossae through which the loops of the bowel may herniate (Fig. 8.4.1.5). Few common ones are detailed below:

FIG. 8.4.1.5 Types of internal hernias. (A) Paraduodenal. (B–F) Of Winslow. (C) Intersigmoid. (D) Pericaecal. (E) Transmesenteric. (F) Retroanastomotic. Fossa of landzert It formed the incomplete fusion of the mesentry of the descending colon. The bowel loops may herniate under the colon and in front of the IMA. This leads to the left paraduodenal internal hernia. Fossa of waldeyer or mesentericoparietal fossa A defect in the small bowel mesentery leads to herniation of the loops in the left upper quadrant, beneath the SMA to the right. This is called the right preduodenal hernia and is less common the left preduodenal hernia. Defect in the sigmoid mesocolon and transverse colon mesentery

Anatomy of colon – a brief insight

Work on the anatomy of the colon dates back to the 16th century with the pioneering work of Andreas Vesalius. The versatile and ever evolving radiological procedures have further added to this knowledge over the past few decades, improving our understanding of this organ. There are no two opinions on the vital functions of absorption of nutrients, water and electrolytes and transmission and storage of residue performed by this organ. The colon is a long tubular conduit with variable length in different individuals, measuring approximately 120–200 cm (Table 8.4.1.3).

TABLE 8.4.1.3 Important Points to Know About Colon Anatomy HIGHLIGHTS • Ascending colon and the descending are retroperitoneal and relatively immobile, while the transverse colon. Caecum and the sigmoid colon are intraperitoneal segments with long welldeveloped mesentery in the sigmoid colon. • Appendices epiploic are exclusive to the colon and not seen in the small intestine as well as rectum and beyond. • Caecum is the widest part of the colon and the sigmoid colon is the narrowest part, and hence caecal masses present later as opposed to the sigmoid masses which cause obstructive symptoms earlier in the course of the disease. • Ileocaecal valve is a site of physiological narrowing, which may simulate a malignant stricture. However, it is transient and may be evaluated postsmooth muscle relaxant and gas insufflation which relieve the narrowing. • Transverse colon is the longest segment and the most mobile segment of the colon. • Sigmoid colon is attached to the pelvis by its long and wellformed mesentery, giving it a looping potential making the evaluation difficult at colonoscopy and making the sigmoid colon prone to volvulus. • Sigmoid colon is prone to diverticulosis due to narrow lumen and sharp angulation of rectosigmoid and increased intraluminal sigmoid pressure. • Appendix when intraperitoneal is more symptomatic. • Griffith’s Critical Zone and Sudeck’s Point are important watershed zones prone to ischaemia. • Thick meandering artery called the Arc of Riolan plays a critical role in providing collateral circulation between middle colic artery and the ascending branch of the left colic artery. • The marginal artery of Drummond is called the central anastomotic artery, runs along the entire medial aspect of the colon and provides the collateral circulation between the SMA and the IMA. • Large bowel has a rich supply of lymphatics. • Paediatric colon measures about 60 cm with lack of haustra particularly over the first 6 months. How to identify the large bowel? Large bowel is differentiated from the small intestine structurally due to its unique longitudinal muscular bands called taenia and

characteristic macroscopic saccular appearance and haustral pattern and Appendices Epiploic (Fig. 8.4.1.6).

FIG. 8.4.1.6 Appendices epiploicae and taenia coli. The saccular appearance is attributed to the shorter length of the longitudinal muscle fibre bands or taenia, which are about onesixth shorter in length than the length of the colon per se. Also the haustral pattern or segmented appearance seen in the colon is characteristic, wherein the haustra are separated by the semilunar cresentric incomplete folds known as plicae semilunaris which may be better visualized when appropriate colonic distension is obtained by barium or air insufflation. The colon also has circumferential folds extending around the luminal surface called the plicae circularis, also seen in the small intestine where they represent folds of the mucus membrane. Thus, the plicae circularis are not exclusive to the colon. The longitudinal muscle bands called the taenia coli run along the serosal surface of the colon, and arrange into three muscle bands namely taenia liberis, taenia omentalis and taenia mesocolica, that are located 120 degrees from each other, and run from the caecum to proximal rectum. Taenia omentalis runs posterolaterally and is attached to greater omentum, taenia mesocolica runs posteromedially and is attached to mesocolic taenia and taenia liberis is boundless and runs anteriorly. At the rectosigmoid junction, taenia expands to cover the rectum. At the level of the sacral promontry there is gradual transition between

the colon and the rectum, with confluent muscle fibres giving the rectum a Taenia Free appearance. It is worthwhile here to mention briefly the Appendice epiploicae which are exclusive to the colon and not seen in the small intestine as well as rectum and beyond. These are fatty appendages which perform the fat storage reserve function and are located along the serosal surface of the colon. Inflammation of these is now a disclosed entity frequently encountered in the radiological practice.

Segments of the colon The colon is divided into the caecum including the vermiform appendix, ascending colon, transverse colon, descending colon and the sigmoid colon (Fig. 8.4.1.7).

FIG. 8.4.1.7 Segments of colon. The ascending colon and the descending colon are retroperitoneal, while the caecum, transverse colon and the sigmoid colon are intraperitoneal. The caecum is the widest part of the colon measuring 7.5 cm in diameter while the sigmoid colon is the narrowest part measuring 2.5 cm. It is due to this reason that the caecal masses acquire a very large size before causing obstructive symptoms and present later in the course of disease while the sigmoid colon masses present earlier in the course of the disease with obstructive symptoms. At the posteromedial aspect of the caecal wall two elliptical folds form the orifice for the ileocaecal valve which is formed by the circular muscle layers of terminal ileum and has a

typical nipple like appearance. Some authors have suggested that an intact ileocaecal valve is advantageous in patients of short bowel syndrome by increasing the absorption of the nutrients. The ileocaecal valve appears mostly incompetent on the Barium Enema. However, a competent valve is known to prevent colonic decompression in patients of high-grade colonic obstruction. The Vermiform Appendix is a blind-ended tubular appendage arising from the caecal wall at its base posteromedially. It lies mostly intraperitoneally (95%). It is more commonly directed medially towards the ileum, retro caecally or alternatively in the lesser pelvis. Apart from these commonest locations, the appendix may be subcaecal (31%), transverse retrocaecal (2%), paracaecal, preileal (1%) and ascending paracaecal retroileal/postileal (0.5%). Appendix lacks taeniae, haustra, plicae semilunaris and appendices epiploicae and is located at the site of confluence of the three taenia. The appendix can be variable in length ranging 2–20 cm. It is interesting to note that clinically an intraperitoneal appendix is more symptomatic due to inflammation of the parietal peritoneum as opposed to a retrocaecal appendix. The ascending colon is short measures 10–20 cm and lies within the anterior pararenal space. The ascending colon is a (secondarily) retroperitoneal structure covered only on its ventral and lateral surfaces by the posterior peritoneum, with the mesocolon fused with the retroperitoneum. The ascending mesocolon is not a real mesentery because it is not formed by two peritoneal layers suspending the colon. The ascending mesocolon follows the course of the ileocolic vessels and marginal vessels along the mesocolic side of the colon. As the ascending colon reaches the liver, it turns 90 degrees at the curve called the hepatic flexure to continue across the upper abdomen to the left side to form the transverse colon up to the spleen where it curves to form the splenic flexure. The colon is completely wrapped by the peritoneum at the site of junction of the hepatic flexure and the transverse colon. Transverse colon is the longest part of the colon measuring about 40–50 cm in length. Transverse colon is the most mobile part of the colon due to its well-developed mesentery and may even reach up to the pelvis. It is attached to the diaphragm by the phrenicocolic ligament. Transverse colon is an intraperitoneal segment of the colon. The greater omentum is fused to the taenia mesolica at the inferior surface of the transverse colon. Beyond the splenic flexure the colon turns inferiorly to continue as the descending colon which is (secondarily) retroperitoneal, immobile and measures approximately 25–45 cm. The descending colon reaches the left iliac fossa where it continues as the S-shaped sigmoid colon which has the caudal end at the level of S3 vertebra.

The sigmoid colon is attached to the pelvis by the sigmoid mesocolon and is completely invested by the peritoneum. The sigmoid mesocolon has long length and is tortuous and these features make the sigmoid colon prone to volvulus. The sweep of the sigmoid colon into the pelvis can range from gentle to an omega loop to a redundant coiled appearance. These variations and looping tendency in the sigmoid colon make it a difficult part to evaluate at colonoscopy. Why is sigmoid colon the commonest site of diverticulosis in the large bowel? It is an interesting fact the rectosigmoid region acts as a functional sphincter due to sharp angulation in this region along with narrow luminal diameter thereby increasing the transit of residue across this region and thereby increasing the intrasigmoid pressure making it prone to diverticulosis.

Blood supply of the colon Arterial supply The colon is supplied by the SMA and the IMA which are branches of the abdominal aorta. The SMA gives rise to 12–20 jejunal and ileal branches and then continuing as the ileocolic trunk shifting further to the right towards the caecum. The ileocolic artery is a relatively constant artery with not many variations in the course. The SMA gives rise to the right colic artery (RCA) and the middle colic artery (MCA) which may show variations (Fig. 8.4.1.8).

FIG. 8.4.1.8 Distribution of superior mesenteric artery.

The IMA bifurcates into an ascending branch and a descending branch. The descending branch runs caudally and supplies the descending colon (Fig. 8.4.1.9). In the pelvis it gives 2–6 sigmoidal arteries and becomes the superior haemorrhoidal artery also called the superior rectal artery. The anterior branch ascends and contributes to the formation of the Arc of Roilan.

FIG. 8.4.1.9 Distribution of inferior mesenteric artery. It is interesting to know that while most of the blood supply off the colon is segmental, the sigmoidal arteries form an arcade that is similar to the small bowel vasculature and have multiple anastomosis.

Venous supply It corresponds to the arteries. Collateral circulation in the colon – a protective mechanism The marginal artery of Drummond is called the central anastomotic artery, runs along the entire medial aspect of the colon and provides the collateral circulation between the SMA and the IMA. A watershed zone called the Griffiths Critical Zone is seen at the junction of the proximal two-thirds and the distal one-third of the transverse colon which is the site between the blood supply by

the SMA and the IMA branches is also the site where the midgut joins the hind gut. Another area of diminished blood supply is called the Sudeck’s point which is located near the rectosigmoid Junction. It is a point of anastomosis between the IMA and the internal iliac artery. There is another thick meandering artery called the Arc of Riolan that plays a critical role in providing collateral circulation between middle colic artery and the ascending branch of the left colic artery when either the SMA or IMA is occluded. The vasa recta supply the colonic lumen.

Lymphatics The colon has a rich lymphatic supply, typically divided into: Epiploic – on the bowel wall under the peritoneal lining and in the appendices epiploicae. Paracolic – along the marginal artery of Drummond and vascular arcades. Intermediate – along the primary named colic vessels. Principal – along the superior and the inferior mesenteric vessels.

Nerve supply The sympathetic supply of the right colon originates from lower thoracic segments. They synapse with preaortic, coeliac and superior mesenteric ganglia. Parasympathetic supply is from the right Vagus nerve branch and the coeliac plexus. The sympathetic nerves supplying the left colon and rectum arise from L1 to L3.

Paediatric colon anatomy The large intestine measures about 60 cm in length. The muscularis is very poorly developed. The ascending and descending colon are relatively shorter than the transverse colon. The normal haustra and appendices epiploic are not present, giving the paediatric colon a very smooth outline. The haustra appear over the first 6 months of birth. 8. 4 .2

IMAGING TECHNIQUES FOR COLON Navni Garg, Ravi Chaudhary

Plain abdominal radiograph Plain abdominal radiograph is usually the first imaging investigation requested in patients suspected of bowel obstruction and/or perforation. They aid in differentiating small bowel obstruction from large bowel obstruction (LBO). Specific signs on a plain radiograph prompt the radiologist towards considering particular aetiology. Various indications of abdominal radiograph are enlisted in Table 8.4.2.1. TABLE 8.4.2.1 Indications of Abdominal Radiograph (ACR Guidelines) 1. Evaluation and follow-up of abdominal distension, bowel obstruction or nonobstructive ileus 2. Constipation, especially assessment of faecal load in children 3. Evaluation for necrotizing enterocolitis, particularly in the premature newborn 4. Evaluation of congenital gastrointestinal abnormalities 5. Follow-up of the postoperative patient, including detection of inadvertent retained surgical foreign bodies 7. Evaluation of ingested or other introduced foreign bodies 8. A scout radiograph prior to a planned imaging examination, that is fluoroscopy 9. Evaluation of the placement of medical devices 10. Evaluation for pneumoperitoneum 11. Evaluation of possible toxic megacolon 12. Evaluation of unstable patients after blunt trauma to the abdomen 13. Evaluation for suspected retained video endoscopy capsule and determination of location of patency capsule 14. Evaluation of colon transit time using the simplified radiodense marker colon transit test The abdominal radiography usually involves a supine radiograph (anteroposterior projection) and should include the diaphragm superiorly and ischial tuberosities inferiorly. An additional horizontal beam (upright, decubitus, or cross-table lateral) projection may be done where obstruction/perforation is suspected to detect small amounts of pneumoperitoneum and evaluate air–

fluid levels. Some institutions prefer to perform an upright chest radiograph to detect small amount of intraperitoneal free gas. Horizontal beam radiographs should always be performed after placing the patient in upright or decubitus position for at least 5 minutes before exposing the radiograph. The size of the film or image receptor varies with the size of the patient. In adults, a 14 × 17 inch film is usually appropriate. Radiographs are usually taken at end expiration, wherever possible using low kVp (60–75 kVp). However, technical parameters are usually varied according to patient size. Few of the important indications are discussed here: Colonic obstruction: In LBO (Fig. 8.4.2.1), there are gasfilled dilated colonic loops >6 cm in calibre located in periphery of abdomen with the presence of haustrations. Dilated caecum is seen as dilated (>9 cm) round gas shadow in right iliac fossa (RIF). It can be open or closed loop depending on the patency of ileocaecal valve. Ileocaecal valve is competent in approximately 75% cases, leading to closed-loop LBO with progressive colonic distension and high risk of perforation. Common site of perforation in such cases is caecum because it requires least amount of pressure to distend. An incompetent ileocaecal valve will decompress the large bowel into the small bowel. In cases of colonic obstruction, lung bases and right hypochondrium should be reviewed carefully as the presence of any lesions would prompt the radiologist towards considering malignant obstruction. Colonic pseudo-obstruction (Ogilvie syndrome): It is secondary to sympathetic innervation of colon and mimics LBO. There are a number of causes implicated including inflammatory, infectious, posttraumatic and metabolic to name a few. Symptoms mimic LBO including nausea, vomiting, abdominal distension although there is lack of abdominal tenderness commonly seen in LBO. Abdominal radiograph reveals dilated caecum, ascending and transverse colon, gas may distend sigmoid colon and rectum. Prolonged caecal distension for more than 2–3 days needs intervention in the form of decompression or surgery as there are high chances of perforation. Lateral decubitus radiograph normally leads to distension of suboptimally distended distal colonic segment in pseudo-obstruction though not in LBO. If ambiguity still persists, computed tomography (CT) should be done which helps to delineate zone of transition. Neostigmine with parasympathetic stimulation and colonic decompression are treatment of choice.

FIG. 8.4.2.1 Supine (A) and upright (B) abdominal radiographs reveal dilated bowel loops along periphery with air–fluid levels suggesting large bowel obstruction due to sigmoid colonic stricture. No rectal air appreciated. Adynamic ileus is generalized dilatation of small and large bowel loops and is different from pseudo-obstruction as there are no chances of perforation in ileus. Frank distension of rectum implies ileus. Air–fluid levels not seen in pseudo-obstruction or ileus and favour obstruction. Colonic volvulus: Volvulus occurs when the colon along with its mesentry twists around itself leading to closed-loop obstruction. Sigmoid, being intraperitoneal and mobile is the most common site followed by caecum. In sigmoid volvulus, absence of rectal gas with three dense lines, representing the sigmoid walls, seen converging to the site of obstruction (Frimann–Dahl sign) is considered diagnostic. There are multiple fluid levels with gas distended colonic loop in right abdomen and absent haustra. In comparison, single fluid level with gas distended colonic loop in left upper abdomen or right lower abdomen showing haustrations is seen in caecal volvulus (Fig. 8.4.2.2). Colonic perforation: Caecum, appendix, transverse colon and sigmoid colon are intraperitoneal whereas ascending and descending colon are retroperitoneal. Perforation in respective parts results in pneumoperitoneum or pneumoretroperitoneum. Free intraperitoneal air lines the under surface of diaphragm, inferior edge of liver, falciform

ligament and collects in spaces between the bowel loops forming geometrical shapes. Cupola sign (supine view) is accumulation of air underneath the central tendon of the diaphragm, Rigler’s sign (any view) is visibility of both sides of bowel wall, Silver’s sign (supine) refers to air outlining the falciform ligament, Inverted V sign (supine) is seen when free air outlines the lateral umbilical ligaments and Football sign (supine) is seen in massive pneumoperitoneum where a large amount of free air lines the abdominal cavity. Chilaiditi syndrome, linear atelectasis at lung bases, pneumomediastinum, subdiaphragmatic lipomatosis and subcutaneous emphysema may give false impression of pneumoperitoneum and lead to interpretative errors. Retroperitoneal air usually doesn’t rise to the peak of diaphragmatic dome and is located medially or laterally rather than beneath the apex of diaphragmatic leaf. It usually lines the kidneys and assumes reniform shape. Colitis: Inflammatory/infective (pseudomembranous)/ischaemic colitis leads to large bowel wall thickening due to oedema seen as thickened haustra projecting into the lumen called as thumbprinting. Chronic colitis leads to atrophy of mucosa leading to absence of haustral markings in the diseased segment referred to as lead pipe colon. Colonic neoplasms: Plain radiographs may show LBO, calcified liver metastases, lung and bony metastases.

FIG. 8.4.2.2 Supine (A) and upright (B) abdominal radiographs reveal caecal volvulus in right lower qudrant.

It is important to rationalize the use of radiographs and perform alternative radiation free modality like ultrasound wherever possible.

Ultrasonography (USG) USG is often the first modality used for imaging patients with abdominal pain. It is an inexpensive and widely available modality for abdominal imaging. However, limitations such as operator experience, patient’s body habitus, bowel gas–related artefacts and patient cooperation preclude the wide use of this noninvasive modality for imaging of colonic pathologies. Imaging technique and interpretation: USG evaluation of colon includes measurement of wall thickness, evaluation of integrity of gut signature (Fig. 8.4.2.3), mural vascularity and any ancillary findings. One of the important aspects of USG imaging is its real-time (dynamic) nature which helps in assessing peristalsis (reduced in most pathologies), compressibility (reduced in pathology), and also postValsalva response (in assessing hernia). Examination includes the use of a curvilinear probe (3.5–5 MHz) for evidence of any bowel thickening and/or any ancillary findings such as any masses, lymphadenopathy, inflamed fat and fluid collections. This is followed by use of a higherfrequency probe (7–12 MHz) for high-resolution imaging of suspected diseased segment and length of bowel involved. Graded compression can be used for better assessment wherever possible as it separates the bowel loops and removes the gas obscuring the underlying bowel. Transvaginal/Transrectal USG can be performed for better assessment of bowel loops located deep in pelvic cavity. Depending on the luminal distension, colonic mural thickness varies from 3 to 5 mm.

FIG. 8.4.2.3 On USG, colon displays gut signature. The innermost hyperechoic ring is referred to as mucosa (white arrowhead) with corresponding hypoechoic muscularis mucosa (black arrowhead), hyperechoic submucosa (white arrow), hypoechoic muscularis propria (black arrow) and, most peripherally hyperechoic serosa (*) surrounding it. Destruction of gut signature is harbinger of some malignant process, more so if length of bowel involved is short. However, aggressive inflammatory processes may also cause focal disruption of gut. Normally diseased bowel segment is better appreciated on USG due to reduced motility and thickened walls are larger and easier to see. Further, colour Doppler can be used to assess mural vascularity however due to low blood flow in the mural vessels and artefacts due to peristalsis, it may not always be possible to document hyper- or hypovascularity. Mural hypervascularity is usually seen in inflammatory or infectious diseases whereas hypovascularity in thickened bowel is suspicious of ischaemia. Contrast-enhanced ultrasonography (CEUS): CEUS is predominantly used in IBD for quantification of vascularity which correlates with inflammatory markers, such as Creactive protein (CRP). The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology have specified indications for the use of CEUS in IBD cases: a) Estimation of disease activity by quantifying bowel wall vascularization which correlates with endoscopic severity

b) Differentiation between fibrosis and inflammatory strictures in CD c) Characterization of suspected abscesses and their differentiation from phlegmons d) Confirming and following the route of a fistula Limitation of CEUS is bowel motility which leads to suboptimal imaging quality and only limited segment is evaluated at a time. Ultrasound elastography: Ultrasound elasticity imaging is based on strain, deformation and elastic moduli that have been clinically developed and approved for the evaluation of different tissues. One where shear waves generated by an ultrasound transducer produces acoustic radiation force impulse (ARFI) and other one is real-time ultrasound elastography (RTE). ARFI differentiates low-grade fibrosis from high-grade fibrosis. At experimental levels on animal models, it can differentiate between fibrotic and inflammatory stricture. RTE can be used to reliably distinguish fibrotic from nonfibrotic tissue. Use of elastography to discriminate inflammatory from fibrostenotic stenosis in CD in future remains questionable, considering stenosis in CD usually involves a combination of inflammatory and fibrotic components. Crohn’s disease (CD): USG findings include circumferential bowel wall thickening most commonly involving the terminal ileum and caecum (Fig. 8.4.2.4), though any part of bowel may be involved. Gut signature is usually preserved though loss of mural stratification may be seen in some cases with histological inflammatory changes. There is echogenic creeping fat and hypertrophied mesenteric fat seen adjacent to involved bowel. Luminal narrowing is seen in cases with gross inflammatory bowel wall thickening or fibrotic strictures. Inflammatory and fibrotic strictures can be differentiated as the former shows’ loss of gut signature whereas the latter shows preserved mural stratification with a prominent echogenic submucosal layer due to collagen deposition.

FIG. 8.4.2.4 USG abdomen showing Crohn’s colitis with thickened bowel wall with blurred stratification (arrow) and increased fibrofatty proliferation (*). On colour Doppler, inflammatory strictures usually show mural hypervascularity, known as Comb sign (Fig. 8.4.2.5). Intramural ulcers, sinus tracts, fistulas and perienteric abscess may also be seen though require an experienced operator. Perianal USG is helpful in detecting perianal fistulas and abscesses. Ulcerative colitis (UC): UC affects the colon in a retrograde contiguous manner, mucosal inflammation beginning in the rectum and proceeding proximally. USG findings include bowel wall thickening, preservation of gut signature, loss of haustra coli and hypervascularity. Hyperechoic thickening of the submucosa may be seen during active inflammation due to oedema. Colonic dilatation (>6 cm) with decreased wall thickness (4 mm are other warning signs of bowel ischaemia. Colour Doppler can also be used to assess mural perfusion. USG-guided tap of intraperitoneal free fluid can be done to detect any blood, seen in cases of bowel gangrene. Newer techniques: Sonocolonography involves retrograde instillation of water into the colon before USG examination and enables better visualization of colonic lumen, wall and adjacent connective tissues and aids in detection of colonic

polyps. Gianetti et al. studied the role of strain elastography in colonic diseases and concluded that it acts as an adjunct to grey scale imaging. It can be used to differentiate benign and malignant tumours of colon on the basis of desmoplastic reaction, qualitatively assess bowel wall stiffness in patients with chronic diseases and for their follow-up.

FIG. 8.4.2.7 USG abdomen showing ischaemic colitis with nonstratified thickened sigmoid (S) walls with barely visible colour flow (only one pixel) and associated altered pericolic fat (white arrows).

FIG. 8.4.2.8 Transabdominal ultrasound (A) with convex probe reveals colocolic anastomosis along transverse colon, confirmed on CT (B) with inflammatory polyp (not shown) as its lead point.

FIG. 8.4.2.9 USG abdomen in case of caecal carcinoma reveals an eccentric hypoechoic mural thickening of caecum with loss of stratification. White arrow shows slightly eccentric intraluminal air.

Contrast enema Even with the advent of advanced imaging techniques, contrast enema continues to provide relevant information to clinicians and surgeons. The aim is to obtain good-quality images with various

projections and least radiation exposure. Various indications and contraindications of contrast enema are enlisted in Table 8.4.2.2. TABLE 8.4.2.2 Indications of Contrast Enema (ACR Guidelines 2018) • Diverticular disease • Inflammatory bowel disease • Colon cancer screening • Incomplete colonoscopy • Distal intestinal obstruction syndrome or meconium ileus equivalent in cystic fibrosis patients • Evaluation of questionable findings on other imaging examinations such as computed tomography • Colonic volvulus • Assessing integrity of rectal anastomosis prior to colostomy or ileostomy closure • Assessment of possible colonic fistulae • Diseases involving the colon with familial inheritance pattern • Perioperative evaluation of the colon for surgical planning and follow-up • History of previous colon polyp or neoplasm • Bowel fistulas CONTRAINDICATIONS: • Unexplained pneumoperitoneum or pneumoretroperitoneum • Acute colitis, including toxic megacolon • Combative, uncooperative patient • Recent endoscopic intervention, needs 7 days gap Technique Patient is advised to consume low-residue diet for previous 2 days and laxative a day before the examination. In our centre, two scout views are taken before contrast administration: AP abdomen and left lateral pelvis to check for adequate bowel preparation and rule out any obstruction/perforation. This is followed by introduction of a rectal tube lubricated with lidocaine jelly through the anal opening, taped to the sides and connected to an enema bag hanged on an IV pole. Either barium or water-soluble contrast can be used. Water-soluble contrast is used in patients with suspected colonic obstruction or volvulus, early postsurgical patients where perforation/leak is suspected or where Blind-ending colonic segments (e.g. rectal remnant following the Hartmann procedure or

J-pouch) are present. It is also recommended in patients with distal intestinal obstruction syndrome/meconium ileus equivalent in patients with cystic fibrosis to demonstrate the level of the obstruction and possibly be therapeutic. Repeat enemas with water-soluble contrast agents over several days may be required to mobilize the tenacious stool plugs. Water-soluble contrast contains 300–370 mg of iodine/mL, equivalent to 60%–76% density. It may be diluted with water to 20%–30%, depending on the indication. For visualization of water-soluble contrast, kilovoltage of 70–80 kVp should be used during image acquisition. Contrast enema can be performed as single contrast or double contrast study. Single contrast study allows real-time imaging of colonic leaks and fistulas in inflammatory bowel diseases (IBDs) and postoperative patients whereas double contrast study provides better mucosal information in patients with failed colonoscopy for screening of colorectal malignancy. Single contrast study involves use of 20% w/v of barium. A kilovoltage of 100 kVp or greater should be used (depending on patient size) during image acquisition. Barium is allowed to flow and patient is turned to facilitate the passage of barium till it reaches the caecum and the ileocaecal valve (and possibly the appendix). Spot radiographs are taken intermittently to demonstrate each loop of colon with adequate barium coating and distension (Figs. 8.4.2.10–8.4.2.13). Manual or mechanical compression should be applied as appropriate to all accessible segments of the colon during fluoroscopy. Images should include (ACR Guidelines): i. Frontal and oblique views of the entire filled colon ii. An angled-beam view of the sigmoid colon iii. A lateral view of the rectum (whenever possible, the lateral rectal view should include an image obtained after the enema tip has been removed) iv. Postevacuation images should be obtained when possible and should always be obtained in the evaluation for leak v. Dedicated spot radiographs may be taken for any abnormal areas seen.

FIG. 8.4.2.10 Single contrast barium study showing normal lateral view of rectum.

FIG. 8.4.2.11 Single contrast barium study showing normal AP and oblique views of rectosigmoid.

FIG. 8.4.2.12 Single contrast barium study showing normal supine view of entire colon.

FIG. 8.4.2.13 Single contrast barium study showing normal post evacuation film. Double contrast study involves use of 80% w/v of barium followed by air insufflation (Fig. 8.4.2.14). A kilovoltage of 90 kVp or greater is used for image acquisition. Contrast is allowed to flow in left side down position so that barium reaches proximal sigmoid, descending colon and splenic flexure followed by Trendelenburg position for movement of barium into splenic flexure. Then patient is turned to prone position so that barium reaches mid transverse colon. At this point, excessive barium is evacuated by lowering the enema bag and room air is insufflated slowly and intermittently to prevent air bubble formation. Following radiographs are taken after rolling the patient (ACR Guidelines): i. Spot images of the rectum, sigmoid colon, flexures and caecum ii. Large-format images, including prone and supine views of the entire colon iii. An angled-beam view of the sigmoid colon iv. Lateral view of the rectum, either cross-table lateral or vertical beam, preferably with the enema tip removed v. Both lateral decubitus views of the entire colon using a horizontal beam (a wedge filter is recommended)

vi. Erect or semierect flexure views vii. Postevacuation views, when possible viii. Additional dedicated spot radiographs for any abnormal areas seen

FIG. 8.4.2.14 Normal double contrast barium study after air insufflation. In patients with colostomy or colonic mucous fistula, fluoroscopic contrast enema is performed when disease is suspected involving a colostomy site or to delineate the anatomy in preparation for colostomy revision/takedown. A Foley’s catheter, red rubber catheter or cone colostomy tip is inserted into the stoma. The balloon is inflated under care inside the stoma and under strict fluoroscopic guidance to avoid injury. Low-density barium or water-soluble contrast should be instilled into the ostomy through the Foley’s catheter under fluoroscopic observation. The examination should attempt to rule out any leak or answer the clinical question. Appropriate spot radiographic images should be recorded. Interpretation A systematic approach is essential while interpreting contrast enemas. Surface patterns: Normally the colonic surface is smooth and featureless. Innominate grooves (areae colonicae) are collections of barium within the crevices of normally

collapsed colon and disappear after colonic distension. Reticular pattern may be seen in conditions causing colonic ulcerations or oedema, granularity in UC, nodularity in lymphoid hyperplasia (small and discrete nodules), lymphoma (confluent and larger nodules) and cobble stoning in CD. Diverticula, stalks of pedunculated polyps and menisci at the edge of elevated lesions may appear as abnormal lines on the surface. Fold patterns: Inter haustral folds are straight and oriented perpendicular to the long axis of the bowel. Coiled spring appearance is seen in intussusception due to barium coating the mucosal folds of outer loop giving appearance of concentric rings. Serpentine folds may be seen in mucosal/submucosal vascular and inflammatory processes. Endometrial implants or intraperitoneal metastases on the serosal surface may extend into the bowel wall and result in desmoplastic reaction causing pleating of the overlying mucosa into thin folds. Protruding lesions: A protrusion on the dependant surface displaces barium from the barium pool and is seen as a filling defect. Protrusion on non-dependant surfaces is coated with barium and is seen as etched in white. Polyps, pseudo-polyps (UC), submucosal and extrinsic masses, plaques (pseudomembranous colitis) present as protruding lesions within the lumen and may appear as filling defect or etched in white depending on their location. Depressed lesions: A depressed lesion is one that extends beyond the normal contour of bowel like an ulcer or diverticulum. A depression on dependant surface traps the barium and is seen as focal barium collection. When located on the nondependant surface, there is coating of sides of the lesion resulting in ring shadow. Apthoid ulcers (CD, viral infections and amoebiasis), linear ulcers (CD and drug use), collar button ulcers (UC), exoenteric masses (lymphomas, metastatic melanomas and gastrointestinal stromal tumour), intraluminal tracks, fissuring (CD) cause depressed lesions within the lumen. Contour abnormality: Tapering refers to smooth, gradual narrowing of a bowel loop and may be seen due to benign scarring in chronic inflammatory diseases. Shouldering refers to abrupt change in calibre of a bowel loop and is seen in malignant entities. Thumbprinting is seen in ischaemic colitis due to submucosal oedema and fold thickening projecting into the lumen. Sacculations are outpouchings on the antimesenteric border due to healing and scarring on the mesenteric border in chronic CD, ischaemia and diverticulitis. Spiculation and angulation of bowel wall may occur due to extrinsic desmoplastic process. Circumferential

lesions cause annular stenosis and are seen in benign strictures caused by radiation, ischaemia or diverticulitis or in malignancies such as primary tumours (apple core sign) or metastases. Lead pipe colon is ahaustral, smooth walled colon seen in chronic UC.

Immunoscintigraphy Scintigraphy using radionuclides is a noninvasive technique for visualizing active disease in small as well as large bowel and can be used in patients with IBD who do not tolerate colonoscopy/ileoscopy. In these studies, white blood cells (WBCs) separated from the patient’s blood are labelled with radionuclide and then reinjected into the patient. Radiotracer-labelled WBCs accumulate at sites of active inflammation and infection. Imaging is performed at serial intervals for any bowel or intraabdominal activity. Earlier indium-labelled WBCs were used for detection of active bowel inflammation; however due to limited availability, high radiation dose and inferior image quality it could not gain wide acceptance. Lately selective agents such as technetium-99m hexamethylpropylene amine oxime-labelled white blood cells (Tc99m HMPAO WBC) are being used for diagnosis of IBD, extent of disease, assessment of disease activity, progression, response to treatment and follow-up. Easy availability, lower radiation dose and superior imaging quality make this agent suitable for screening patients as well as a problem-solving tool in patients with equivocal tests or failed colonoscopy. However, these techniques fail to differentiate between inflammatory and infectious bowel diseases and findings need to be correlated with clinical information and other relevant tests. The role of immunoscintigraphy using different monoclonal antibodies and their fragments against tumour-associated antigens has also been studied in the past but none of the studies have been able to demonstrate substantial clinical utility of this technique in imaging of colorectal cancers (CRCs).

Angiography/arteriography Colonic bleeding may occur due to ischaemic colitis, radiation colitis, IBDs, postpolypectomy procedure, colonic cancers, vascular ectasias, though diverticulosis remains the most common cause. Though colonoscopy remains the initial modality for evaluating colonic bleed, angiography remains a rescue for unstable patients with massive bleeds where bowel preparation for colonoscopy is not possible. Selective angiography can detect a bleeding rate as low as 0.5 mL/min and allows embolization of the source in the same setting. However inability to detect aetiology and nonactive bleeding sites remain its drawbacks. Also it cannot be performed in

patients with allergy to contrast media and/or deranged renal function.

CT perfusion CT perfusion is a newer functional imaging technique that provides an insight into regional perfusion, shunting and microvascular function. A limited plain abdominal and pelvic CT covering the area of interest is performed followed by intravenous administration of 100 mL of iodinated contrast through 18-gauge cannula at rate of 5 mL/second through pressure injector. After 5 seconds following the start of contrast, dynamic CT is performed at 1 second interval using cine acquisition mode. With this dynamic contrast-enhanced CT technique, iodinated contrast agent kinetics are used by perfusion software to assess blood volume, blood flow, mean transit time and vascular leakage (permeability surface product). Sairah et al. performed CT perfusion for assessment of colorectal wall perfusion and vascularization and reported that proximal colon has higher blood flow as compared to distal colon. They concluded that CT perfusion can be used to assess bowel wall perfusion but has certain limitations due to patient motion, respiratory motion, bowel peristalsis leading to slice misalignment. In colonic cancers, CT perfusion allows quantification of tumour vascularity and provides a surrogate measure of tumour hypoxia and angiogenesis. It can be used as an adjunct to other cross-sectional studies for tumour phenotyping, intratumoral heterogeneity, selection of individualized treatment, prognostication, assessment of treatment response, surveillance and investigation of suspected disease relapse. There is a difference in colonic wall blood flow (10−40 mL/min per 100 tissue) as compared to CRCs (50–200 per 100 tissue). Sun et al. and Kim et al. reported that CT perfusion can be used to differentiate well, moderately and poorly differentiated CRCs as they have difference in mean blood flow.

CT colonography CT colonography (CTC) was first described in 1994 by Vining et al. CTC is a reliable, minimally invasive investigation to rapidly evaluate entire colon for clinically relevant lesions at the lowest feasible radiation dose. It is a reasonable alternative technique in patients who refuse or cannot undergo colonoscopy, which is still the gold standard. Indications 1. Screening identifies individuals who have CRC or adenomatous polyps without signs or symptoms of the disease. Individuals without other risk factors are at average

risk. The American Cancer Society (ACS) recommends screening beginning at age 45, whereas the United States Preventive Services Task Force (USPSTF) recommends screening beginning at age 50 in average-risk individuals. Individuals with a single first-degree relative (mother, father, sister, brother or child) who have had colorectal neoplasia before age 60 or multiple first-degree relatives with colorectal neoplasia diagnosed at any age are defined as being at moderate risk. Average- and moderate-risk individuals should be screened by CTC. The diagnostic accuracy of CTC nearly equals that of colonoscopy in CRC screening of asymptomatic adults at average risk. Person with longstanding history of IBD or who are from families with defined genetic syndromes are at high risk and should not be considered for screening by CTC. European Society of Gastrointestinal Endoscopy (ESGE)/European Society of Gastrointestinal and Abdominal Radiology (ESGAR) do not recommend CTC as primary test in screening or individuals at averageor high-grade risk to develop CRC and/or with positive first-degree family history of CRC. However, CTC may be used as CRC screening test on an individual basis, after adequate patient information about its characteristics, benefits and risks. 2. Use of CTC as surveillance tool in patients with previously diagnosed colorectal neoplasia – belonging to the high-risk category. It is also performed in patients with previously diagnosed colonic polyps and not resected in order to assess stability of lesions – considered low risk. 3. Diagnostic CTC examinations are performed on symptomatic individuals presenting with abdominal pain, diarrhoea, constipation, gastrointestinal bleeding, anaemia, intestinal obstruction and weight loss. 4. Characterization of colorectal lesions indeterminate on optical colonoscopy. 5. Following incomplete colonoscopy, that is failure to intubate the caecum, patient discomfort or intolerance to the procedure, poor bowel preparation, redundant colon, colonic spasm, acute angle flexures and tortuosity and colonic obstruction caused by neoplastic or nonneoplastic stenosis, increased risk for complications during colonoscopy (advanced age, anticoagulant therapy, sedation risk). 6. For surgical planning of CRC to localize the tumour or to look for synchronous lesions. 7. Future indications include sigmoid colonic stoma evaluation, patients with deep pelvic endometriosis and in

chronic diverticular disease to differentiate between inflammatory versus neoplastic stenosis. Contraindications Relative contraindications or conditions that require caution while performing a CTC examination include, symptomatic acute colitis, acute diarrhoea, acute diverticulitis, recent colorectal surgery, recent deep endoscopic biopsy or polypectomy/mucosectomy, known or suspected colonic perforation, abdominal wall hernia with entrapment of colonic loops and symptomatic or high-grade small bowel obstruction. CTC is not indicated in routine follow-up of IBD patients, hereditary polyposis or nonpolyposis cancer syndromes and pregnant or potentially pregnant patients. Methodology Bowel preparation: First and foremost, step is bowel cleansing. Colon preparation is done by means of a lowresidue diet and cathartic cleansing, with oral administration of polyethylene glycol (PEG)-wet preparation; magnesium citrate or sodium phosphate-dry preparations. Low-volume (2 L) PEG-based solutions are preferred and addition of simethicone promotes discharge of colonic bubbles and improves mucosal surface visualization. Due to its safe and quick laxative action, it is preferred in old patients or those with poor general condition. The main contraindications are bowel obstruction, bowel perforation, paralytic ileus, toxic colitis and megacolon. Sodium phosphate in combination with bisacodyl (dry preparation) is better tolerated by patients and promotes reduced amount of residual fluid in the colonic lumen. It is contraindicated in serum electrolyte imbalances, advanced hepatic dysfunction, renal failure, recent myocardial infarction, unstable angina, congestive heart failure, ileus, malabsorption and ascites. Magnesium citrate is another dry preparation which has a better safety profile and negligible risk of electrolyte imbalance. ESGAR guidelines recommend reduced cathartic preparation to 24 hours or less and noncathartic approach (also known as ‘prepless’ or ‘minimal prep’ CTC – without laxative but with faecal tagging) may be considered in frail and elderly patients. Faecal Tagging:

Despite proper bowel preparation, some faecal or fluid residue may be retained which need addition of oral tagging with positive contrast media (either iodine, barium or both) to distinguish polyps from faecal material and to detect lesions submerged by fluids. Barium produces heterogeneous tagging because of low water solubility and poses hindrance in same day colonoscopy if required. Iodinated agents are relatively better with greater homogeneity. Sodium amidotrizoate and meglumine amidotrizoate (Gastrograffin, Bracco) is the most frequently used for oral tagging. It has varied compliance because of unpleasant taste, hyperosmolar effects and rarely may cause anaphylactoid reactions. Oral tagging is complex and may reduce patient compliance. Neri et al. proposed ‘rectal iodine tagging’ technique. Iodinated contrast media is introduced through the same insufflation probe, immediately before CT image acquisition. This is quick, simple and immediate tagging scheme having comparable accuracy in polyp detection, tagging quality and better patient acceptance. Examination technique 1. The patient is advised to defecate prior to insertion of the rectal tube. 2. Preferably soft tip rectal tube is inserted into the rectum by a physician or a specifically trained assistant. If inflatable rectal balloons are used then a prior digital rectal examination is recommended. Inflation should be stopped if patient complains of severe pain as there are chances of perforation. Balloon should be deflated to improve visualization of distal lesions. 3. As per 2019 ACR recommendations, there is no use of antispasmodics in routine examination as there is inconclusive evidence about improved distension or patient comfort. There may be some benefits with Hyoscine-Nbutylbromide (Buscopan) in selected cases, though not licensed in several countries, including the United States. It may reduce insufflation-related discomfort and facilitate bowel evaluation, in structuring and diverticular diseases. There are no benefits seen with glucagon. It should be administered before start of insufflation. Specific contraindications to antispasmotic administration need to be assessed. 4. Bowel distension is required for better visualization of the colonic surface. It is done by mechanical insufflation using carbon dioxide or manual insufflation with room air is

acceptable as well. Automated dynamic CO2 insufflation is most preferred distension technique as it allows better colonic distension. Controlled values of flow rate and pressure reduces risk of perforation and procedure-related discomfort, as CO2 is rapidly reabsorbed and continuous low-pressure CO2 delivery reduces colonic spasm. The overall volume of gas required varies from 3 to more than 10 L. Visualization of luminal surface of each colonic segment in both decubitus or at least in one position is considered adequate distension. 5. Complete imaging of the colon and rectum should be obtained in two different patient positions (such as supine and prone, supine and right lateral decubitus or bilateral decubitus) in end expiration to reduce pressure effects of inflated lungs on the transverse colon. Addition of pillows beneath the chest and pelvis may also help in colonic distension on prone positioning. 6. Screening studies should use low-dose, nonenhanced CT technique on a multidetector CT (MDCT) scanner. There should be proper adaptation of computed tomography dose index volume (CTDIvol) to patient size, using either technique charts or automatic exposure control. As per ACR guidelines 2019, radiation output CTDIvol for routine screening CTC for an average-sized patient should be 5 mGy or less per position. In general, scans are done at 120 kVp, and require an effective 50 mAs. Dose-reduction techniques such as automatic exposure control systems, image-based noise reduction algorithms and iterative reconstruction techniques can be used. For morbidly obese patients, radiation dose should be appropriately increased to maintain diagnostic image quality. 7. Additional imaging after repositioning and reinsufflation may be required to delineate a particular colonic segment. Additional imaging (e.g. in right or left decubitus position) can be obtained if two positions fail to adequately display the colonic lumen. 8. CTC is generally performed on an MDCT (≥16 slice) scanner. A section thickness of 1–1.25 mm with a reconstruction interval of ≤1 mm is optimal. The breathhold should not exceed 25 seconds. 9. Diagnostic CTC examinations should use the same CT parameters as screening CTC examinations. There is initial low-dose noncontrast prone series followed by a supine series with IV contrast acquired in portal venous phase. IV contrast is used to characterize colonic and extracolonic structures and dose is similar to a standard abdominal pelvic CT.

10. There should be a network to transfer the data to a workstation having specialized software for CTC interpretation. Data interpretation and reading strategies: Both twodimensional (2D) and three-dimensional (3D) readings should be integrated to evaluate colonic pathologies. A standard 2D analysis is lumen tracking from one end to the other end of colon with supine and prone images scrolled simultaneously. A wide window width (bone window) and window centre close to lung window, that is 1500 HU and –200 HU are ideal for polyp visualization. Soft tissue window is required for lesion attenuation including density values, faecal tagging and enhancing characteristics. MPR should be used as a problem-solving tool as and when required. 3D-volume rendered views allow endoluminal evaluation such as endoscopy leading to better visualization of polyps. Antegrade and retrograde ‘fly through’ done along automated centre line helps in viewing both sides of haustral folds. 3D evaluation is hampered by residual fluid hence 2D evaluation is required for confirmation of pathology on 3D. There are few other advanced 3D methods of visualization including panoramic view, virtual dissection, unfolded cube projection, filet view and tissue transition projection available to overcome some of 2D and endoluminal 3D view limitations. Virtual dissection view is display of colon bisected along its long axis, opened and flattened for its internal display. It shortens interpretation time although requires expertise. There is a bit controversy about whether primary 2D followed by 3D evaluation or vice versa should be routine protocol for colonic evaluation. Pickhardt et al. reported better effectiveness and greater polyp detection in primary 3D approach in low prevalence screening population. According to the ESGAR consensus statement, both 2D and 3D reading strategies are acceptable with primary 2D interpretation usually faster (Fig. 8.4.2.15). The choice of the primary reading method is subjective and based on personal preference and experience.

FIG. 8.4.2.15 3D endoluminal view reveals sessile polyp (arrow head) just behind ileocaecal junction (arrow) and confirmed with 2D coronal view showing soft tissue density. Computer-aided detection (CAD) for CTC uses computer algorithms on the basis of features of polyps such as its shape. Use of CAD as secondary reader helps in increasing sensitivity though no significant change in specificity. Reporting CTC should be reported by radiologists with good abdominal imaging experience and well versed with technique. ESGAR consensus statement and ACR practice guideline suggest following to be part of CTC report: 1. Patient’s medical history, family history, symptoms and signs, previous rectoscopy/colonoscopy or biopsies. 2. Technical data including dose protocol, effective dose in mSv 3. IV contrast administration or not 4. Patient preparation and tagging (laxative agent, tagging regimen) 5. Patient positioning. 6. Room air and/or CO2 insufflation. 7. Use of spasmolytics 8. Overall quality and limitations of the examination if any, that is incomplete or impaired colonic visualization due to inadequate bowel preparation, untagged fluid, metal or movement artefacts; suboptimal distension, any colonic segments that cannot be adequately evaluated should be indicated.

If any colonic abnormality is found the following things need to be mentioned: A. Colonic anatomy (normal or abnormal) and features including wall thickening, diverticula, strictures, extrinsic compression, postsurgical variations. B. Polyps and/or cancer characteristics including size, maximum diameter and two- or three-dimensional measurements, density, morphology (sessile, pedunculated or flat), mobility, location, infiltration of extracolonic fat. For exact size of polyp normally 2D MPR reconstruction is used. In screening, any polyp with 6 mm size or more is considered positive, though any polyp greater than 10 mm is of greater clinical significance. ESGAR CT Colonography Working Group and NHSBCSP suggested if more than three polyps with less than 6 mm are detected with confidence, they should be reported (Figs. 8.4.2.16–8.4.2.17).

FIG. 8.4.2.16 3D endoluminal view reveals a polypoidal filling defect and 2D supine view reveals pseudolesion with inhomogeneous attenuation and trapped air locules suggesting residual stool.

FIG. 8.4.2.17 3D endoluminal view reveals colonic stenosis (arrow) along descending colon. 2D supine view shows mild shouldering which disappeared subsequently on prone view suggesting colonic spasm. Colorectal polyps are of homogeneous attenuation density and appear round, oval, or lobulated intraluminal projections. Most of the polyps enhance after intravenous contrast injections, though differentiation of adenomas from no-neoplastic – inflammatory or hyperplastic polyps is extremely difficult and requires histopathological confirmation. Pedunculated polyps have large stalk, are mobile and change position on prone and supine images, though can be easily differentiated from faecal matter by their shape and stalk attachment. Normally head of pedunculated polyps is measured. Large villous adenomas in which villi are easily recognized, sometimes contain trapped tagging material or gas which may create confusion in diagnosis. Carpet lesions are usually seen in right-sided colon while lipomas can be easily diagnosed because of their fat density. Colorectal carcinomas have varying appearances and typical apple core stenosing appearance is seen in symptomatic patients. Small carcinomas in proximity to circumference of haustrum, sessile or flat lesions are difficult to detect and need expertise. These are normally seen in asymptomatic patients or synchronous or metachronous lesions in previously diagnosed cancer patients. Pitfalls in interpretations Proper stool tagging helps in diagnosis of residual stool and is of no diagnostic challenge. However in untagged stool heterogeneous density, presence of gas bubbles, lack of enhancement and change in position on supine and prone images suggest faecal origin. Electronic cleansing is a postprocessing technique to remove tagged material and helps better visualization of soft tissue pathologies. Partial voluming, heterogeneous tagging and over subtraction are though some of its limitations. Few other pitfalls include:

• Incomplete luminal distension • Presence of thickened or complex folds • Extrinsic impression • Presence of polyps coated with contrast material Presence of the following conditions: • Diverticular disease, invasive tumour, appendiceal lesions, submucosal lesions • Anorectal lesions, such as internal haemorrhoids and hypertrophic anal papillae • Flat and carpet lesions • Nonadenomatous polyps • Intraluminal foreign bodies, such as pills and capsules • Pedunculated polyps (positional shift) • Presence of cleansing and subtraction artefacts C-RADS CTC findings have been standardized in classification known as CRADS to establish a protocol on how to describe findings in report (Table 8.4.2.3).

TABLE 8.4.2.3 CT Colonography Reporting and Data System Colorectal and Extracolonic Classification Scores Score Description COLORECTAL C0 Inadequate study C1 Normal colon or benign lesion C2 Intermediate polyp or indeterminate finding C3 Polyp, possibly advanced adenoma C4 Colorectal mass, likely malignant EXTRACOLONIC E0 Limited examination E1

E2 E3

E4

Normal examination or anatomic variant Clinically unimportant finding Likely unimportant, incompletely characterized Potentially important finding

Inadequate preparation; inadequate insufflation No polyp ≥ 6 mm; recommend routine screening with CT colonography or colonoscopy in 5 years Polyps 6–9 mm, < 3 in number; recommend CT colonography polyp surveillance or colonoscopy with polypectomy Polyps ≥ 10 mm; ≥ 3 polyps, each 6–9 mm; recommend colonoscopy with polypectomy Lesion compromises bowel lumen, shows extracolonic invasion; recommend surgical consultation Compromised by artefact; evaluation of extracolonic tissues severely limited; not used in practice by our program No extracolonic abnormalities visible; no workup indicated Examples: simple liver or kidney cyst, cholelithiasis without cholecystitis; no workup indicated Example: minimally complex or homogeneously hyperattenuating kidney cyst; workup may be indicated; dependent on specific clinical scenario Examples: solid kidney mass, aortic aneurysm; workup generally indicated, but dependent on specific clinical scenario; communicate to referring physician as per accepted practice guidelines

Table is based on data published elsewhere. The classification system consists of categories ranging from inadequate study (C0) to likely malignant colonic mass (C4). In

case of multiple lesions (either colorectal or extracolonic), the examination was scored by the most advanced finding. Positive cases were patients with a C-RADS score of C2 through C4. Patients with a score of C3 or C4 were referred for colonoscopy with polypectomy, whereas patients with a score of C2 were given choice of either colonoscopy with polypectomy or CTC polyp surveillance. Score of C1 was considered negative examination and recommended to undergo routine screening in 5 years. It is important to note that extracolonic findings with categories E3 and E4 denote potentially significant findings, further workup may or may not be indicated, as it depends on clinical scenario, previous diagnosis and prior workup history.

PET-CT and PET-CT colonography Positron emission tomography is a well-established functional imaging technique which when combined with anatomical imaging modality such as CT can provide information on morphological details as well as the metabolic activity of the lesions at the same time. PET is based on increased uptake and metabolism of glucose by rapidly dividing cells in cancers and inflammatory conditions. PET-CT involves the use of multislice helical CT for obtaining 5 mm contiguous axial cuts from vertex to midthighs. Resolution of collapsed bowel on PET is very poor, therefore distension of the intestine is required. This has given way to PET CTC which is performed after ingestion of 2.5 L of polyethylene glycol solution to distend colon followed by PET-CT scan 60 minutes after injection of 10 mCi of fluoro-deoxyglucose (FDG) radiotracer injection. Alternatively, 2 L of 0.5% methylcellulose solution can be given through a nasojejunal catheter just before the study. Diffuse colonic activity is usually physiological whereas focal activity needs attention. Liu et al. investigated the clinical significance of focal colonic FDG activity. They recommended that patients with focal colonic FDG activity and either of the following: high risk of colon cancer, prior history of colon cancer, anatomical changes at the site of FDG uptake, focal FDG activity at the site of prior anastomosis for cancer, and focal FDG activity in the same location seen in a prior FDG-PET/CT scan should undergo colonoscopy for further evaluation. PET CTC is a promising tool for staging CRC, detecting local recurrence, detecting previously unrecognized hepatic or extrahepatic metastatic disease, predicting response to chemoradiotherapy and plan radiotherapy. PET CTC without bowel preparation and faecal tagging can be useful in older patients and to reduce the chances of electrolyte imbalance. PET CTC detects nearly all polyps with >10 mm size because of FDG avidity, while 50% of 6–10 mm-sized polyps and none of 6 mm in size and advanced neoplasia. Ajaj et al. reported a sensitivity and specificity of 87% and 100%, respectively in detecting IBD-related colonic changes by MRC. Though MRC has gained access into clinical routine practice for evaluation of large bowel, it has certain drawbacks such as high cost, limited availability, high susceptibility to motion artefacts, longer examination times and limited accuracy for detecting lesions 38.5°C

1

WBC count (10,000–14,999 cells/cumm)

1

(>15,000 cells/cumm)

2

Polymorphonuclear leucocytes 70%–84%

1

>85%

2

C-reactive protein, 10–49 mg/L

1

>50 mg/L

2

TABLE 8.4.3.2 Interpretation of AIR Scores Scores 9

Probability of AA Low risk Intermediate risk High risk

Plan Outpatient treatment/discharge Admission and monitoring Emergency surgery

TABLE 8.4.3.3 Adult Appendicitis Score (AAS) Symptoms and Signs

Score

Pain in RLQ

2

Pain relocation

2

RLQ tenderness

Guarding

Women, aged 16–49 years All other patients

3

Mild

2

Moderate to severe

4

Laboratory Tests Blood leucocyte count (× 109)

Proportion of neutrophils (%)

CRP (mg/L), symptoms24 hours

1

Score Between 7.2 and 10.9

1

Between 10.9 and 14.0

2

>14.0

3

Between 62 and 75

2

Between 75 and 83

3

>83

4

Between 4 and 11

2

Between 11 and 25

3

Between 25 and 83

5

>83

1

Between 12 and 53

2

Between 53 and 152

2

>152

1

TABLE 8.4.3.4 Interpretation of Adult Appendicitis Score (AAS) Scores Probability Recommended Action 16

High risk

Surgery

Diagnosis of acute appendicitis in paediatric age group The diagnosis of acute appendicitis in the paediatric age group is even more challenging because of unreliable clinical symptoms and higher risk of perforated appendicitis. It is therefore recommended to routinely use serum inflammatory markers along with clinical scores in children to increase the probability of diagnosis. Paediatric appendicitis score The PAS (Paediatric Appendicitis Score) is derived from Alvarado score with addition of one important sign in children, that is pain in the right lower quadrant with coughing, hopping or percussion (Table 8.4.3.5).

TABLE 8.4.3.5 Paediatric Appendicitis Score Symptoms and Signs/Laboratory Test Migration of pain

Score 1

Anorexia

1

Nausea/vomiting

1

RLQ tenderness

2

Coughing/hopping/percussion pain

2

Fever

1

Leucocytosis

1

Neutrophilia/left shift of WBC count

1

Interpretation 6: appendicitis likely Inflammatory markers in serum: The strong risk factors for acute appendicitis in paediatric age group are CRP level ≥10 mg/L on admission and leucocytosis ≥16,000/mL. Role of imaging in acute appendicitis Adults The Adult Appendicitis Score (AAS) recommends imaging in patients only who fall under intermediate probability. Patients with low risk do not need further imaging and can be managed conservatively. The high-risk patients can be undertaken for surgery. This approach was considered too simplified and still led to doubts and a risk of erroneous diagnosis. The availability of point-of-care ultrasound (POCUS) aids the clinical diagnosis in emergency setting. USG is now the recommended initial imaging investigation for confirmation of suspected acute appendicitis. The advantage of ultrasound is that it rules out complicated acute appendicitis and presence of appendicoliths with high accuracy. Imaging with CT in acute appendicitis is reserved for patients with inconclusive findings on ultrasound or in patients >40 years of age with risk of underlying malignancy. MRI is an alternative to CT imaging with high accuracy without the risk of radiation and its use is based on local availability. Ultrasound and CT findings in acute appendicitis

Graded compression technique is used to localize the appendix in RIF. Initial investigation with ultrasound has an added advantage in young women with lower abdominal pain, to rule out ectopic pregnancy and other ovarian lesions. USG findings Normally appendix is identified on ultrasound as a blind ending, tubular structure in RIF. In case of acute appendicitis (Fig. 8.4.3.2), there is 1. Increased diameter of appendix (measurements mentioned under CT section) 2. It is noncompressible and distended with fluid and may show diffuse wall thickening. 3. Presence of an appendicolith within the appendiceal lumen can be identified by an oval echogenic focus with posterior acoustic shadowing. 4. There may be signs of inflammation such as periappendiceal free fluid or echogenic mesenteric fat. 5. The presence of focal defect in the appendiceal wall with or without loculated fluid collection may be indicative of perforated appendicitis.

FIG. 8.4.3.2 USG abdomen with RIF screening shows noncompressible, increased diameter of appendix (white arrows) with probe tenderness.

CT findings in acute appendicitis CT is highly accurate to diagnose or to exclude acute appendicitis and its complications and is used in patients with inconclusive findings on ultrasound. The ideal technique to perform CT for suspected acute appendicitis is with oral and intravenous contrast and scanning the entire abdomen and pelvis. However, it can be modified in patients based on the patient needs or in an emergency situation. Findings 1. Appendiceal thickening: One of the most important USG and CT finding in acute appendicitis is that of its increased cross-sectional diameter (measured from outer wall to outer wall). A diameter of >10 mm is a definite indicator of appendicitis whereas 3 mm. 3. Appendiceal wall hyperenhancement/mural stratification on contrast CT. 4. Appendicolith – can be identified as intraluminal calcific focus in one-third patients. The presence of appendicolith in cases of acute appendicitis is associated with increased chances of perforation and failure of conservative antibiotic treatment. 5. Periappendiceal inflammation changes – including fat stranding in surrounding mesenteric fat, thickening of lateroconal fascia and minimal free fluid in the right paracolic gutter or in pouch of Douglas support the diagnosis of acute appendicitis. In complicated appendicitis, additional findings of localized collection in periappendiceal region indicating abscess due to sealed perforation or findings of peritonitis with thickening of peritoneum and free fluid in the peritoneal cavity are appreciated. 6. Caecal thickening – either focal around the appendiceal lumen where the cross-sectional diameter of caecum attains triangular configuration (the arrow head sign) or diffuse

thickening which can be appreciated if the ileocaecal region is optimally distended with luminal contrast. 7. Perforated appendicitis/impending perforation is suggested on CT by the presence of a defect in the enhancing mural wall. There may be associated localized inflammatory changes near the defect or fluid collection suggesting sealed perforation or sometimes extraluminal air/fluid indicating frank perforation. 8. Periappendiceal abscess – loculated rim enhancing collection in RIF or in pelvis indicating perforated appendicitis (Fig. 8.4.3.4). TABLE 8.4.3.6 Interpretation Correlation With Appendiceal Diameter Appendiceal Diameter 10 mm

Interpretation Appendicitis is excluded. Indeterminate, additional signs of inflammation/clinical symptoms Definite appendicitis

FIG. 8.4.3.3 CECT abdomen axial (A) and coronal (B) scans depict thickened appendix (white arrows) with periappendiceal fat stranding signifying appendicitis. Mild thickening at caecal base is also seen.

FIG. 8.4.3.4 CECT abdomen axial (A and C) and coronal (B and D) scans showing features of complicated appendicitis with appendicular lump/RIF phlegmonous mass formation (A and B indicated by white arrows) and appendicular localized perforation leading to abscess formation (C and D indicated by black arrows). Management of acute appendicitis The World Society of Emergency Surgery (WSES) formed a consensus for the management of acute appendicitis in adults and children with guidelines as described below. The flowchart depicting the management can be seen in Fig. 8.4.3.5 (A and B).

FIG. 8.4.3.5 (A) Management of acute appendicitis in adults (The World Society of Emergency Surgery [WSES]). (B) Management of acute appendicitis in paediatric age group (The World Society of Emergency Surgery [WSES]). According to the above algorithms the management of acute appendicitis includes: 1. NOM/Conservative treatment – with antibiotics is indicated for patients in the low-risk and intermediate-risk group in both adults and children who are motivated, have uncomplicated appendicitis confirmed on imaging. 2. Surgical treatment – laparoscopic appendectomy is the standard of management for uncomplicated and confirmed acute appendicitis on imaging in intermediate and high-risk

groups and in low-risk groups if they choose to go for surgery instead of NOM. 3. In case of appendicular abscess, percutaneous drainage of the abscess and interval appendectomy is recommended. Recurrent acute and chronic appendicitis refers to repeated episodes of right lower quadrant pain or pain that lasts for more than 3 weeks. The pain is milder in severity than acute appendicitis and the clinical and imaging features are usually inconclusive of acute appendicitis. However, the surgical resection of the appendix is curative with the resected specimen indicative of chronic active inflammation or appendiceal fibrosis.

Appendicular tumours Primary tumours arising from appendix are rare and generally occur in older adults. Primary appendiceal tumours may be classified as follows: 1. Carcinoid or neuroendocrine tumour 2. Mucinous type of epithelial tumours 3. Nonmucinous epithelial tumours are much less common and generally present as malignant adenocarcinoma 4. Non-Hodgkin’s lymphoma may occur in appendix, as gastrointestinal tract is the most common location for extranodal site for lymphoma and is rare Carcinoid tumours of appendix The carcinoid tumours of appendix are the most common appendiceal tumours, derived from neuroendocrine cells in the appendiceal wall and belong to a group of NET (neuroendocrine tumours). The appendiceal carcinoid tumours are generally very small in size ( 5 cm) of fat stranding with slight swirling of adjoining omental vessels and may show hyperdense peripheral halo. Management is mostly conservative (Fig. 8.4.3.9).

FIG. 8.4.3.9 Omental infarction. Axial (A and B) and coronal (C) NCCT abdomen scans show focal area of fat stranding with associated slight swirling of adjoining vessels (white arrows). 8. 4 .4

INFLAMMATORY BOWEL DISEASES OF COLON Sonam Shah, Anuj Bahl Ulcerative colitis (UC) and Crohn’s disease (CD) are the two types of chronic inflammatory diseases that affect the colon. They cause multiple episodes of colonic inflammation with intervals of disease remission and complications in the long term. Inflammatory bowel disease (IBD) is no longer limited to the western population. The incidence in India and other Asian countries has increased over the past few decades. According to a study by Singh et al. India ranks second in terms of the burden of IBD patients globally with approximately 1.4 million patients. The large population-based ACCESS study (The Asia-Pacific Crohn’s and Colitis Epidemiologic Study) which included 8 Asian countries reported an average incidence of IBD as 1.37 per 100,000 in Asian population. The individual incidences of UC, CD and UIBD

were found to be 0.76, 0.54 and 0.07, respectively with the incidence of UC higher in India as compared to other Asian countries. The onset of IBD occurs in the young adult population with most cases between 20 and 39 years. The incidence of IBD is nearly equal in both sexes.

Etiopathogenesis The etiopathogenesis of IBD is highly complex and dependent on multiple factors. IBD is believed to occur in individuals who have aberrant genes which makes them abnormally susceptible to commensal bacteria which are normally present in the colon (intestinal microbiota) thus causing inflammation in the colonic mucosa. These interactions between the mucosa of the colon and colon commensals are triggered by the exposure to risk factors in the environment. The genome wide association studies have discovered 163 such genetic loci associated with IBD. Out of these, about 110 gene aberrations are linked with both UC and CD while 30 are CD specific and 23 UC specific. This explains the fact that many mechanisms of immune pathway activation are common in both UC and CD. Another interesting fact about these genetic loci, is that the majority of them are also linked to other immune mediated disorders such as type 1 DM, ankylosing spondylitis, psoriasis etc. explaining their common associations. The basic pathway for the pathogenesis of UC and CD are similar, as mentioned in the flowchart:

The commonly observed genes linked with UC and CD are mentioned in Table 8.4.4.1. TABLE 8.4.4.1 Genes Associated with UC and CD Common in Both UC UC Specific and CD HNF4A, CDH1, XBP1, ORMDL3, LAMB1, GNA12 AGR2, MUC19 IL23, STAT3, JAK2, IL12 MUC1 IL-10

CD Specific NOD2 mutation on CARD15

SCL9A3

ATG16L1

IRF5, TNFRSF14, ITGAL

FUT2

TNFSF15 HLA-DR class II When individuals with susceptibility genes are exposed to certain environmental factors, they have increased risk of developing UC or CD. The main adverse and protective factors are mentioned in Table 8.4.4.2.

TABLE 8.4.4.2 Risk and Protective Factors for UC and CD Ulcerative Colitis

Crohn’s Disease

RISK FACTORS:

RISK FACTORS:

Higher socioeconomic status (hygiene hypothesis)

Higher socioeconomic status (hygiene hypothesis)

Previous h/o enterocolitis

NSAIDs

NSAIDs use

OC pills

OC pills

Antibiotic use in childhood Smoking

PROTECTIVE FACTORS:

PROTECTIVE FACTORS:

Breast feeding

Breast feeding

Smoking Appendicectomy Immunological changes The genetic defects and the possible mechanism by which they are responsible in the pathogenesis of inflammation in IBD is listed in Table 8.4.4.3.

TABLE 8.4.4.3 Genetic Defects and the Possible Mechanism Responsible in the Pathogenesis of Inflammation in IBD Genetic Loci Aberration XBP1, ORMDL3, AGR2, MUC19 IL23, STAT3, JAK2, IL12 IL10, TNFSF15 HLA-DR class II MUC1 HNF4A, CDH1, LAMB1, GNA12 SCL9A3 IRF5, TNFRSF14, ITGAL NOD2 mutation ATG16L1 FUT2

Mechanism of Inciting Inflammation Overactivity of intestinal epithelium to bacterial proteins and TNF alpha Upregulation of IL-17 and differentiation of Th17 Increased secretion of proinflammatory cytokines Alteration in immune regulation Activates innate immune Defects in tight junctions at the intestinal mucosal level causing increased permeability to bacterial antigens. Altered epithelial permeability due to defect in Na/H exchanger Upregulates immune response Decreased tolerance to commensal bacteria by increased TLR-mediated Th-1 response Defective presentation of bacterial antigens to CD4+ T cells, and increased inflammatory cytokine production by Paneth cells Altered interaction of intestinal microbiota with intestinal mucosal epithelium

Diagnosis and approach to IBD The investigations and approach to the diagnosis of IBD in this chapter are based on the joint recommendations by ECCO (European Crohn’s and Colitis Organization) and the ESGAR (European Society of Gastrointestinal and Abdominal Radiology) group of members and published in the Journal of Crohn’s and colitis. No single investigation is considered to be of gold standard to confirm the diagnosis of UC or CD (Table 8.4.4.4).

TABLE 8.4.4.4 Investigations and Approach to the Diagnosis of IBD Mild Bloody stools/day 30 mg/L

It requires taking into account: 1. Clinical symptoms. 2. Serum and stool analysis for inflammatory markers. 3. Endoscopic findings of colon. 4. Histopathological features 5. Radiological findings. In addition, • Patients with suspected IBD may suffer from malnutrition due to malabsorption or longstanding diarrhoea and should be investigated for anaemia, hypoproteinemia, electrolyte and vit D levels. • Screening for latent TB is advised, especially before starting immunotherapy in IBD. • Infectious colitis should always be ruled out by stool analysis for toxins and parasites before making a diagnosis of IBD. Clinical presentation The presentation of UC is usually typical with episodes of loose stools or diarrhoea along with blood in stools. These episodes are intermittent and are present for >6 weeks which differentiates it from more acute severe forms of infectious colitis. The severity of symptoms is based on the extent of colonic inflammation with proctitis presenting as a mild form of UC and pancolitis with severe symptoms. Patients with predominant rectal inflammation also give a history of crampy abdominal pain relieved on defecation (tenesmus). Most of the patients report spontaneous resolution of episodes of diarrhoea whereas few may proceed to acute fulminating course with explosive diarrhoea and hypotension needing hospital admission. Extraintestinal symptoms may be seen

in less than 10% of patients associated with bowel symptoms and commonly includes joint pains, skin rash or iritis. CD can affect any part of the gut from mouth to anus and usually involves multiple segments of small and large bowel at the same time. Its presentation is thus varied but most commonly presents with diarrhoea, rectal bleeding or abdominal pain. The diarrhoea and rectal bleeding with CD occurs due to colonic inflammation and it is much less severe than that reported with ulcerative form of colitis. The abdominal pain in CD can be either mild colicky type in periumbilical region seen with small bowel or functional bowel disease or it can be localized in RIF (in ileocolonic CD) mimicking acute appendicitis. The pain of CD is attributed either to acute inflammation or even due to obstruction or stricturing longstanding CD. In case of perianal CD, patient may present with perianal fistulas or abscesses initially. Patients with CD often suffer from weight loss and appear malnourished in case of extensive small bowel disease. The severity of patient presenting with colitis can be graded as mild, moderate and severe based on the clinical presentation and physical signs.

Diagnostic algorithm for confirmation of IBD diagnosis

Inflammatory markers in serum and stool IBD can cause raise in acute phase reactants in serum with leucocytosis and elevated CRP levels. However, they are not specific for IBD and can be found elevated due to other causes. Similarly, they are not sensitive markers either with normal levels seen in mild to moderate disease. Inflammatory markers in stool Faecal calprotein: Faecal calprotein (FC) found in the stool is the most sensitive marker of intestinal inflammation. It is derived from the neutrophils and is detected in the faeces when there is mucosal breakdown due to ulceration. Faecal calprotein levels have been found to be useful for the initial diagnosis of IBD, and to diagnose relapse and also to assess treatment response. 1. Baseline FC levels of >150 ug/g is an effective cut off to distinguish IBD from functional bowel diseases in patients presenting with gastrointestinal symptoms and warrants an ileocolonoscopy for further investigation. 2. In patients on remission, an increase of FC to >250 µg/g is taken as an indicator of relapse. 3. Serial monitoring with faecal calprotein levels is used to monitor drug response with the aim of therapy to maintain FC levels less than 250 µg/g.

Endoscopic findings of IBD Patients with suspected IBD should undergo ileocolonoscopy at the time of initial investigation. The exception being severe acute colitis where sigmoidoscopy is sufficient to avoid the risk of perforation. The normal colonic mucosa is salmon coloured and glistening with visualization of small capillaries arborizing underneath and is considered as the normal vascular pattern of colonic mucosa. In early disease, the mucosa is oedematous and hyperaemic with loss of normal vascular pattern. Mild disease is characterized by congested mucosa with absence of frank ulcerations. There may be minimal fresh blood in the lumen which goes off when washed with underlying mucosa showing no ulcerations. In moderate disease, tiny erosions 75% Not passable

Interpretation (Table 8.4.4.9) TABLE 8.4.4.9 Crohn’s Disease Endoscopic Index of Severity Score 0–2 3–6 7–15 >15

Severity Remission Mild Moderate Severe

Histopathology of inflammatory bowel disease The mucosal samples derived from endoscopy are studied under the microscope to see the pattern of colonic inflammation as ulcerative or Crohn’s type, assess its severity and recognize early signs of intraepithelial neoplasia/carcinoma in situ. Ideally, for the diagnosis of IBD, multiple mucosal samples with at least one from each of five segments of colon and terminal ileum is advised. The typical microscopic features of IBD consist of widespread architectural distortion of crypts, crypt abscesses and infiltration of acute inflammatory cells in the mucosal layer. Like endoscopy, the hallmark of UC on histology is rectal involvement and continuous inflammation. In CD, these inflammatory changes are focal with background mucosa appearing normal. Noncaseating granulomas and presence of inflammatory cells across all the layers of colonic wall are other characteristics of CD. In early disease, the sensitivity and specificity of mucosal diagnosis is low with findings of crypt distortion seen in only 20%. In the absence of confirmatory findings, a repeat biopsy is recommended after an interval. In chronic longstanding disease, mucosal inflammation can be patchy due to varying treatment response. Healing on histology is defined by the absence of inflammatory cells in the mucosa. The sequelae of previous mucosal injury in the form of crypt distortion, mucosal atrophy and Paneth cell metaplasia may still be evident. Early dysplastic changes can be identified on histopathology in longstanding cases of ulcerative or Crohn’s colitis. These include overcrowding of glands, thickened mucosa, excessive lengthening and budding of crypts lined by tall, high columnar cells. Mucin in columnar cells rather than in the usual goblet cells is also a sign of colonic dysplasia. Therefore, targeted biopsies from suspicious lesions at endomicroscopy/chromoendoscopy is usually recommended for surveillance in IBD cases. Mucosal abnormalities in ulcerative colitis (Fig. 8.4.4.2) 1. Punctate mucosal ulcer – crypt abscess; 2. Collar button ulcer – extending into submucosa; 3. Polypoidal granulation tissue; 4. Inflammatory pseudo polyp; 5 and 6. Sessile mucosal polyps;

7. Pedunculated polyp; 8,9,10. Postinflammatory pseudo polyps of various configurations; 11. Mucosal bridge over an area of underlying ulceration; 12. New epithelium covering previous ulcerated surfaces.

FIG. 8.4.4.2 Various mucosal abnormalities in ulcerative colitis.

Assessment of disease extent and severity of ulcerative colitis

Assessment of disease extent and phenotype of Crohn’s disease

Patients with CD pattern on colonoscopy and histopathology must undergo small bowel assessment to look for additional lesions which can affect the plan of treatment. This can be undertaken either by capsule or cross-sectional imaging techniques. Role of radiological imaging techniques in diagnosis and management of IBD Radiological imaging techniques do not play a primary role in the diagnosis and confirmation of IBD but rather have a complementary role to endoscopy and biopsy. Imaging techniques have evolved and refined over time, starting with barium studies and plain X-rays being used to evaluate the bowel to CT and MR imaging which are the current preferred mode of imaging. Currently, the radiological imaging techniques are used in a patient with IBD for the following purposes: 1. To localize diseased segments of bowel in CD. 2. To assess extramural complications in penetrating CD. 3. To evaluate bowel proximal to the stenotic segment in case of stricturing CD. 4. To diagnose complications such as acute colonic dilatation (toxic colitis) and intestinal perforations. 5. To evaluate perianal fistulizing CD. 6. Cross-sectional imaging modalities allow for evaluation of extraintestinal associations, for example hepatobiliary manifestations or changes of sacroiliitis in IBD patients. 7. To evaluate for postsurgical complications or pouch disorders in patients undergoing bowel resection and anastomosis. CT and MR imaging Both CT and MR imaging can be used to assess small and large bowel with similar and high sensitivity and specificity. In both the imaging modalities, the affected segments of bowel appear

thickened with mural enhancement on postcontrast imaging. However, MR is preferred over CT due to the absence of radiation especially in young patients. In clinical practice, following scenarios can help to decide between CT or MR imaging: CT imaging is preferred for: 1. Initial or baseline evaluation in suspected IBD and to rule out any alternate diagnosis. 2. In acutely ill patients, CT is much faster. 3. In penetrating CD, to assess for extraluminal tracts and fistulas. 4. Local availability – CT is more widely available than MR. 5. Any contraindication to MR imaging such as claustrophobia or gadolinium allergy. MR imaging is preferred for: 1. Young and paediatric age group. 2. Follow-up of CD localized to terminal ileum or right colon. 3. Pregnant patient. 4. Fistulizing CD, better soft tissue resolution of MR enables evaluation of perianal fistulae. 5. Contraindication/allergy to iodinated contrast. Bowel preparation for CT and MR imaging The preparation for both CT and MR imaging of bowel is the same and relies on optimal luminal distension. This can be achieved with either ingestion of oral contrast (enterography) or via administration via nasojejunal tube (enteroclysis) to distend the small bowel. The large bowel can be optimally distended using water enema. To enhance assessment of bowel mucosa neutral contrast such as mannitol is administered for luminal distension. In general, 1–1.5 L of mannitol can achieve optimal luminal distension. Administration of an antiperistaltic agent, such as buscopan at the time of oral contrast administration reduces artefacts due to bowel peristalsis. Technique Once oral contrast is administered, the patient is placed on the scanner and rectal and intravenous contrast is administered. The CT is performed in portal venous or enteric phase with thin sections. The protocol for MR imaging includes T2-weighted and balanced steady state free precession gradient echo sequences (SSFP GE) sequences to assess the bowel segments for thickening. Gadolinium-enhanced sequences are used to look for enhancement

in thickened segments of bowel. In patients who are at risk of gadolinium toxicity, diffusion-weighted sequences can provide information for acute inflammation. Cine motility sequences are used to assess peristalsis across a bowel stricture and provides dynamic information about the degree of obstruction. Imaging features on CT and MRI 1. Wall thickening: The affected segments of small and large bowel are thickened in IBD. The normal wall thickness is 10 mm thickening is considered severe. Care should be taken to comment on bowel thickness in only distended segments as nondistended bowel loops may falsely appear thickened. In UC, the thickening will be predominantly distal colonic involving the rectum and the left colon. CD will involve proximal/right colon along with small bowel segments in skip pattern (Fig. 8.4.4.3).

FIG. 8.4.4.3 (A and B) Contrast-enhanced CT in UC different patients. In A, there is enhancing mural thickening of rectosigmoid colon (white arrows). In B, mural stratification with enhancing mucosa and hypoenhancing submucosa due to oedema is seen. Both findings indicate active disease (black arrows). In chronic disease, the colon appears shortened with loss of haustral pattern. The shortening is again asymmetric, more along the mesentery with sacculations or outpouchings along the antemesenteric wall (Fig. 8.4.4.4).

2. Wall enhancement: The postcontrast hyperenhancement of the thickened bowel wall is specific for acute inflammation. The mural hyperenhancement in IBD is supposed to be asymmetrical with the mesenteric wall affected more than the antemesenteric wall but homogeneous bowel enhancement is also seen in IBD like in other forms of colitis.

FIG. 8.4.4.4 Contrast-enhanced CT in different patients with Crohn’s disease: In A, asymmetric wall thickening of mesenteric side of distal ileum with comb sign (arrow) along with thickening of right colon, suggesting skip involvement. Enlarged mesenteric lymph nodes are reactive. In B, deep ulcer in right colon identified by nonenhancing area posteriorly extending from mucosa up to serosa (arrow). In C, stricture (arrow) in proximal colon with upstream bowel dilatation.

Another pattern of wall enhancement described with IBD is that of ‘wall stratification’ which occurs due to hyperenhancing mucosa against the oedematous submucosa appearing hypodense. In chronic inactive disease, the submucosa may still appear hypodense due to fat infiltration but there will be no mural hyperenhancement. The term ‘mucosal hyperenhancement used earlier in IBD has been replaced by ‘mural hyperenhancement’ due to the fact that the mucosa is practically thinned out due to ulceration and not visualized on endoscopy in IBD. 3. Bowel wall oedema: In addition to thickening and enhancement, MR imaging also detects changes in signal intensity of acutely inflamed bowel wall in the form of T2weighted hyperintense signal and is suggestive of bowel oedema. Along with T2 hyperintensity, restricted diffusion may be present on diffusion-weighted sequences in acutely inflamed bowel segments. 4. Bowel strictures: These are defined as persistently narrowed segments of bowel due to oedematous thickening and/or bowel wall fibrosis. When severe enough, the luminal narrowing may cause obstruction and upstream dilatation of bowel. These strictures can be seen in acute episodes of inflammation as well as subacute longstanding cases. 5. Mucosal ulcerations: Mucosal ulcerations which are sine-qua-non of IBD on endoscopy are rather difficult to recognize on cross sectional imaging. It may be recognized as focal mucosal defects with extension of intraluminal air or contrast within the wall. The presence of mucosal ulcerations on imaging is a sign of severe inflammation. 6. Image-based scoring criteria: Imaging-based scoring systems such as MaRIA, Clermont scores have limited clinical use at present owing to their complex nature. 7. Mesenteric changes: Along with wall thickening and enhancement, surrounding mesentery appears congested and hyperemic with prominent mesenteric vessels (comb sign). The mesenteric lymph nodes may show reactive enlargement in acute inflammatory episodes. There may be interbowel and intraperitoneal free fluid indicating serositis. In chronic cases, the mesenteric hypervascularity may subside with proliferation of fat in the mesentery as well as in perirectal region. The choice of imaging modality for small bowel is dependent on local availability but cross-sectional imaging is preferred over SBCE in stricturing CD or patients with suspected obstruction wherein there is a fear of capsule retention.

Role of ultrasound in IBD Ultrasound is a widely available and noninvasive mode of investigation. Currently, it plays a limited role in the management of IBD. 1. It is mainly used to monitor response to drug therapy in patients with ileocolonic CD who are in remission and are asymptomatic. Using high-frequency linear array probe (5– 17 MHz), bowel thickening can be assessed in terminal ileum and colon and if measures >4 mm is considered to be thickened (Fig. 8.4.4.5). 2. Normal bowel wall appears as stratified on ultrasound with five alternating layers of hyper- and hypoechogenicity and it may be lost in CD. 3. Doppler imaging may also reveal increased vascularity suggesting hyperemia in the thickened bowel segments. 4. The diagnostic value of ultrasound for mesenteric abscesses and diagnosis of enteroenteric fistulous tracts has concordance with MRE. 5. Transperineal (TPE) and transrectal ultrasound (TRUS) is an alternative to contrast-enhanced MR pelvis in the assessment for perianal fistulizing disease.

FIG. 8.4.4.5 (A and B) High-frequency transverse and longitudinal ultrasound image of oedematous thickening of right colon with heterogeneous echotexture and surrounding echogenic pericolonic fat in a patient with active UC.

Barium studies Barium studies are no longer used or preferred in the diagnosis of IBD. However, before the advent of colonoscopy and cross-sectional imaging techniques, it was used to assess mucosal changes in IBD patients. The findings on barium enema are summarized below: 1. Early mucosal oedema identified by thickened haustra (thumb printing) and loss of sharp mucosal interface. 2. Stippled appearance of mucosa when the barium fills the small ulcer pits. 3. Classic collar button or flask-shaped ulcers when deep with narrow neck and wider bases due to lateral undermining in the submucosa. 4. Cobblestone mucosa when the ulcers are multiple, deep and interconnecting with in between oedematous mucosa. 5. In longstanding disease, the colon appears shortened and featureless with loss of haustra.

Plain radiographs The most crucial and clinically relevant use of plain radiograph in IBD in current times is to diagnose acute toxic colitis and colonic perforation. (Discussed later in ‘acute toxic colitis’). Plain radiographs were used in earlier days to predict the extent of colitis based on the distal extent of faecal residue. No faecal residue indicated pancolitis, faecal residue in transverse colon was suggestive of left-sided colitis and presence of faeces in descending colon of proctitis (Fig. 8.4.4.6). This was a crude method and lead to overestimation of the disease in high number of patients.

FIG. 8.4.4.6 Erect abdominal radiograph with thumb printing and lack of stools in colon suggesting colitis. Approach to complicated Crohn’s disease Complicated CD is classified as stricturing type, penetrating type or perianal fistulizing type with different plan of management for each of the above. Stricturing Crohn’s disease Stricturing or fibrostenosing type of CD is defined by a persistent segment of luminal narrowing in a patient presenting with symptoms of intestinal obstruction. Diagnosis: Cross-sectional imaging with CT/MR has high sensitivity and specificity to diagnose small or large bowel strictures. Presence of dilated bowel loop (>3 cm) upstream to stenotic segment is an important criterion to report a definite stricture. Without upstream luminal dilatation, a probable stricture can be suggested. Both inflammation and fibrosis contribute to varying degrees in pathogenesis of strictures. The inflammatory component can be identified by CT/MRE by the presence of hyperintense mural signal on T2W MRI and contrast enhancement in the strictured segment. Chronic and fibrotic strictures usually do not enhance. The quantification of wall fibrosis in the bowel is a matter of research currently. Management: The management of stricturing CD depends on the number of stenotic segments, its location in the small or large bowel, presence of inflammatory component and whether the patient is asymptomatic or symptomatic with obstruction. The available modes of therapy include:

1. Trial of medical management using corticosteroids or biological agents – in asymptomatic patients with small or large bowel strictures and with demonstration of inflammatory component in a stricture. 2. Small bowel strictures: Endoscopic balloon dilatation has high technical success rate in symptomatic patients with short segment ( 90/min, temperature >37.8°C, haemoglobin 30 mm/h, or CRP > 30 mg/L. Patient needs to be admitted to the hospital on the same day and the first line of therapy administered immediately. Urgent investigations

1. Stool chart along with stool culture for C. difficile toxin and parasites if recent travel history to rule out infectious colitis. 2. Unprepared limited flexible sigmoidoscopy on the same day with two biopsies to exclude CMV. 3. Supine abdominal X-ray to exclude toxic megacolon (transverse colon diameter> 5.5 cm) and assess extent suggested by stool-free colon. 4. CT may be required if there is clinical deterioration and can identify small perforations and features of peritonitis which warrants urgent surgical intervention. 5. Check FBC, U&E, Mg++, LFT, coagulation profile, Ca++ and PO43−, lipid profile, CRP or ESR. Regular monitoring with clinical assessment should be performed 12 hourly. Colorectal team should be informed and surgical opinion sought after. Abdominal X-ray should be performed daily to assess for colonic dilatation. In case of clinical deterioration or no improvement by day 3 after admission, consider the need for urgent colectomy. In case of clinical improvement, patient is discharged on day 5 with conversion of intravenous steroids to oral therapy. The patient is followed up each week with plan to taper steroid dose, provide maintenance therapy and to optimise nutrition. Colorectal cancer surveillance Longstanding UC and CD have increased risk of CRC. The risk of developing CRC increases with the chronicity of the disease and with each passing decade. The ECCO-ESGAR GL 2018 recommends screening colonoscopy to exclude neoplasia 8 years the onset of symptoms. Timing of surveillance colonoscopy depends on identifying patients as low, intermediate or high risk for CRC based on risk factors described in Table 8.4.4.10.

TABLE 8.4.4.10 Timing of Surveillance Colonoscopy Risk Level Low risk

Risk Factors Extensive colitis with mild endoscopic or histological inflammation

Surveillance Every 5 years

Colitis affecting Ileum Ileum > Caecum Homogeneous Single segment (terminal ileal) Present, concentric Rare

Stratified Multiple skip lesions

Present Present

Present, usually eccentric with antimesenteric wall sacculations More common and in penetrating type of disease Uncommon Uncommon

Necrotic

Small and reactive

Uncommon

Common

8. 4 .5

DIVERTICULAR DISEASES OF COLON Sonam Shah, Anuj Bahl, Kulbir Ahlawat

Introduction

Colonic diverticulosis is an acquired condition wherein the mucosa and submucosal layer of colon herniate through the muscularis layer of the wall. These develop when the intraluminal pressure in the colon is increased causing mucosa to protrude at sites of least resistance. These areas can be found where the marginal arteries enter the colon, on the mesenteric side of taenia coli. The risk factors for colonic diverticula include advanced age, obesity, red meat, smoking and drugs such as NSAIDs, aspirin and acetaminophen. In an asymptomatic patient, the discovery of colonic diverticula on colonoscopy or cross-sectional imaging by itself requires no further treatment. Symptomatic uncomplicated diverticular disease (SUDD) refers to nonspecific symptoms of altered bowel habits or constipation with or without spasmodic abdominal pain with imaging evidence of colonic diverticula. Colonic diverticula are most commonly present in the sigmoid followed by ascending colon. The size of the diverticula can vary, larger a diverticulum is, greater are its risk of complications. Diverticula get complicated when obstructed and infected (diverticulitis) or if there is a haemorrhage from the vessels running across the diverticulum (diverticular bleed).

Diverticulitis Diverticulitis occurs when the bowel segment containing diverticula gets inflamed. The process of diverticular inflammation ensues when a diverticular opening is obstructed by inspissated stool. This leads to overgrowth of bacterial flora within the diverticulum and mucosal inflammation. Classically, patients with diverticulitis present with left lower quadrant pain as sigmoid colon is the most common site of diverticular inflammation. Fever may be present with signs of inflammation such as leucocytosis and raised inflammatory markers such as CRP. Other causes

of left lower quadrant pain needs to be ruled out via imaging when diverticulitis is suspected. CT with intravenous contrast is the recommended investigation for suspected acute diverticulitis. Imaging with CT not only confirms the diagnosis of acute diverticulitis but also guides the management. The inflammation limited to the bowel wall is termed simple/uncomplicated diverticulitis. Extension of inflammation beyond the bowel wall in the mesentery with either perforation, abscess formation or peritonitis is a complicated diverticulitis. CT findings Colonic diverticula: appear as thin-walled outpouchings perpendicular to the colonic wall. They may be filled with fluid or air and sometimes appear hyperdense due to faecal contents. Diverticular inflammation appears as segmental circumferential wall thickening with hyperenhancement. Distension of bowel loops with luminal contrast delineates the bowel wall thickening better. In an uncomplicated diverticulitis, localized fat stranding or inflammatory soft tissue (phlegmon) may be visualized in the adjacent mesentery. There will be no fluid collections or free intraperitoneal air. In a complicated diverticulitis, loculated fluid collections (abscess) may be present suggesting sealed diverticular perforation with infection. Rarely, they may also form at distant sites like in the pelvis or in the upper abdomen. Free air presents outside the colonic lumen also suggests diverticular perforation large enough and not sealed by omentum (Fig. 8.4.5.1).

FIG. 8.4.5.1 (A) CT axial sections with rectal contrast shows large sigmoid diverticulae (arrows) (B) Organized collection adjacent to sigmoid colon due to localized diverticular perforation (C). Role of colonoscopy Colonoscopy has no role in the diagnosis of acute diverticulitis. It is, however, recommended for follow-up of patients who recover from complicated diverticulitis after at least 6 weeks to rule out any underlying CRC. Management

The treatment of diverticulitis is based on CT findings (Modified Hinchey Classification) (Table 8.4.5.1). Conservative management with antibiotics is recommended for simple uncomplicated diverticulitis. Localized fluid collections require percutaneous drainage whereas frank perforation with large free air requires urgent exploratory laparotomy. TABLE 8.4.5.1 Modified Hinchey Classification Stage CT Findings 0 Mild mural thickening, no pericolic inflammation 1a 1b 2 3 4

Localized pericolonic phlegmon Pericolic abscess 10 mm lesions. Magnetic resonance imaging (MRI): MRI has the main advantage of avoiding ionizing radiation and it can be used to detect and stage rectosigmoid tumours more accurately than tumours in other areas of the colon. As per the NCCN guidelines version 2.2020 on colon cancer, in cases of iodinated contrast allergy, then contrast-enhanced MRI study of abdomen and pelvis with IV gadolinium-based contrast agent can be used, after testing for allergy. In cases with chronic renal failure (GFR 1 cm. PET-CT MRI scores over all modalities in the local staging of rectal neoplasms. The more common application of PET-CT is in

identifying nodal and distant metastases in rectal adenocarcinoma, melanoma and lymphoma. Limitations of PET include poor sensitivity in detecting small (15 mm

T4

Tumour invades peritoneum or other organs

a

Tumour penetrates visceral peritoneum

b

Tumour invades other adjacent organs or structures

REGIONAL LYMPH NODES (N) NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Regional lymph node metastasis (1–3 nodes)

a

1 lymph node

b

2–3 lymph nodes

c

Tumour deposits in subserosa, mesentery/nonperitonealized perirectal tissues (cannot be differentiated from nodes on imaging)

N2

Regional lymph node metastasis (>4 nodes)

a

4–6 node

b

>7 nodes

DISTANT METASTASES (M) M0

No distant metastasis

M1

Distant metastasis

a

Metastasis in one (1) organ

B

Metastasis in more than one organ

c

Metastasis to the peritoneum with/without other organ involvement

Once the diagnosis is confirmed and staging investigations are completed, management is usually decided in multidisciplinary team meetings consisting of Surgeon, Radiation oncologist, Medical oncologist, Pathologist and Radiologist. The treatment protocols differ in the United States and Europe (Fig. 8.5.15).

FIG 8.5.15 Treatment algorithm of rectal cancer in USA and Europe. The different types of rectal surgeries are enumerated in the Table 8.5.7 and depicted in Fig. 8.5.16.

TABLE 8.5.7 Different Types of Rectal Surgeries for Rectal Cancer Types of Surgery Transanal Endoscopic Microsurgery (TEM) Total Mesorectal Excision (TME) Low Anterior Resection (LAR) Abdomino-Perineal Excision (APE) Extra Levator AbdominoPerineal Excision (ELAPE)

Indication T1(sm1) T1(sm2, sm3), T2, T3a, T3b Post-CRT T3/T4 Tumours above anorectal junction Tumours below anorectal junction/levators not involved Tumours below anorectal junction/levators involved

FIG 8.5.16 Various surgical techniques used to treat rectal cancer. Red area – Tumour. Green line – structures removed during the surgery. (A) Transanal endoscopic microsurgery (TEM) with resection of a tumour. (B) Low anterior resection (LAR) with total mesorectal excision (TME) with sigmoid colectomy. (C) Abdominoperineal resection (APR) and TME, with resection of the sphincter complex. (D) Intersphincteric abdominoperineal resection (APR) and TME. (E) Extralevator abdominoperineal resection (ELAPE) and TME. Concept of use of neoadjuvant short course RT, long course RT with chemotherapy and chemotherapy only is a rapidly evolving field. Radiologist should be aware of the protocol used in their institution. A subset of patients (10%–23%) was found to have complete pathological response (pCR) in the postsurgical pathological

specimen. There is significant evidence of prediction of pCR on presurgical MRI. Considering the ability of MRI in prediction of pCR, Prof. Habr-Gama and her group suggested the possibility of organ preservation in these patients. Hence ‘watch and wait’ policy came into vogue. In the subgroup where MRI predicts complete response, surgery can be avoided and patients may be followed up every 8–12 weeks using DRE, proctoscopy/sigmoidoscopy and MRI. Both T2W and DWI are used in MRI for prediction of complete response as well as for follow-up for prediction of recurrence. Close follow using the above-mentioned protocol ensures early detection of recurrence and hence treatment. Thus, MRI plays an important role in personalized treatment of rectal cancer. MRI imaging MRI plays an important role in rectal cancer management: During initial staging MRI helps in: 1. Stratification of tumours so that locally advanced lesions are treated with neoadjuvant CRT before surgery and not so advanced lesions with upfront surgery. 2. Surgical planning. 3. Prognostication of tumours by identifying poor risk factors such as EMVI, MRF involvement and mucinous subtypes. In restaging after NACT, MRI helps in: 1. Response evaluation 2. Surgical planning 3. Detecting complete tumour response 4. Follow-up of patients with nonsurgical treatment Therefore good-quality high-resolution rectal MRI is required for accurate locoregional staging. Technique and protocol of MRI is summarized in the Tables 8.5.8 and 8.5.9.

TABLE 8.5.8 Technique of Rectal MRI Recommended

Optional

1.5T-3.0T magnet strength High resolution T2w sequences Small FOV images Axial and coronal images – parallel and perpendicular to the rectal tumour

Bowel preparation Spasmolytic agents Endorectal filling with gel

Not recommended Endorectal coil

For low rectal tumours coronal images –perpendicular to the anal canal Microenema IV Gadolinium contrast TABLE 8.5.9 MRI Protocol for Rectal Cancer MRI Protocol LARGE FOV FOR PELVIS T2 TSE DWI Axial Axial TR (ms) 4500– 8800– 5000 13500 TE (ms) 85– 75 100 FOV 380 × 420 × 315 (mm × 330 mm) Slice 5 5 thickness (mm) B values NA 50,400,800

SMALL FOV FOR RECTUM T1 T2 TSE T2 TSE RESOLVE TSE Sagittal Coronal DWI Axial Axial 3500– 3000– 500– 4500–6500 5500 6000 900 80–100 80–100 12– 55–60 24 190 × 180 × 180 × 240 × 240 190 180 180 3

3

3

3

NA

NA

NA

50,400,800

Anatomic and surgical landmarks It is important for the Radiologist to be aware of the key anatomical and surgical landmarks that play an important role in management of rectal cancers (see anatomy sec.).

Staging of rectal cancer It is good practice for the Radiologist to have a knowledge of DRE, endoscopy, histopathological examination (HPE) findings and history of any previous surgery. The findings of MRI should be communicated using a structured reporting template as suggested by ESGAR and SAR (see Table 8.5.10A). A) Location and morphology: Tumour location should be described both in craniocaudal and axial plane (clock face position). Measurement of the tumour height is calculated from the AV and ARJ to the most cranial portion of the tumour. The location of the tumour is categorized as low (0–5 cm from the AV), middle (>5.0–10 cm from the AV) and high (>10–15 cm from the AV) (Fig. 8.5.17). Tumours located (above 15 cm from the AV) are considered as sigmoid colon masses. Management of these tumours is different from those of rectal cancer. Morphologic pattern of the tumour (polypoid, ulcerating, circumferential or semicircumferential) and its appearance (nonmucinous vs mucinous) should also be described. Mucinous tumours usually have high signal intensity at T2-weighted MRI (see mucinous tumour section later in the chapter). B) T stage (Fig. 8.5.18): MRI has accuracy, sensitivity and specificity of 85% (66%– 94%), 87% and 75%, respectively according to a metaanalysis. Depth of tumour involvement of the rectal wall and beyond in the mesorectum decides the T category. This category is more applicable in high-rectal and midrectal cancers. 2D T2W is the principal sequence used for T staging. However it cannot differentiate between T1 and T2 tumours. EUS performs better in this situation. DWI, though can identify small tumours, does not play an important role in T staging. Although NCCN suggests neoadjuvant CRT in any tumour above T2 category, European guidelines reserve this therapy for tumours >T3b category because of high chances of local recurrence. Therefore T3 tumour substratification is recommended. An area of difficulty is to differentiate between 5 cm, which partly diminishes for lesions between 0.5 cm and 5 cm in size with sensitivity and positive predictive being 83% and 93%, respectively. It receives the most criticism in the evaluation of lesions < 0.5 cm with significantly low sensitivity and positive predictive value (43% and 76%, respectively). There is also a great degree of variation in sensitivity based on the anatomical location of the

disease. In a study by Koh et al., the detection rates ranged from 8% to 67%, depending on the region involved; only the epigastrium exceeded 60%, with the small-bowel disease being the most poorly visualized (8%–14%). The sensitivity for tumour detection in epigastrium, greater omentum and under surfaces of the diaphragms was 60%–90%, while it was 50%–70% in the retroperitoneum and pelvis, and small bowel-mesentery involvement was detected in merely 20%–50% of cases. These are noteworthy findings, as small-bowel involvement has major implications on outcome and is one of the limiting factors for complete cytoreduction. Poor soft tissue resolution of CT doesn’t allow accurate differentiation between mucinous deposits from ascites. Administration of positive enteric contrast can mask calcified serosal deposits. Dual-energy CT (DECT) DECT uses two separate x-ray energy spectra and allows characterization of tissues based on their differences in attenuation properties at different energies. Though the role of DECT in the assessment of abdominal pathologies is increasingly reported in the literature, there are very limited data available on its application in assessment of peritoneal pathologies. The combination of iodine overlay with conventional imaging has shown a better specificity in differentiating PM from benign peritoneal entities, and hence can be particularly useful in the postoperative setting. MRI MR imaging offers excellent soft tissue resolution, multiplanar capabilities and avoids exposure to ionizing radiation, making it an attractive tool for evaluation of peritoneal diseases. MRI is better suited and can be problem solving in visualization of smaller lesions (5 cm), swirling of omental vessels in torsion MULTIFOCAL, ILL-DEFINED, INFILTRATIVE LESIONS (OFTEN FORMING ‘OMENTAL CAKE’) Peritoneal Irregular thickening of the outer contour carcinomatosis of the infiltrated omentum, known primary malignancy, the most common cause of omental cake Pseudomyxoma Low attenuation deposits, scalloping of peritonei hepatic surface Tubercular peritonitis Features of dry and fibrotic types of peritoneal tuberculosis Malignant Ascites, irregular or nodular peritoneal mesothelioma thickening, stellate mesentery, bowel wall thickening Lymphomatosis Ascites without any loculation or septations and a diffuse distribution of enlarged lymph nodes, retroperitoneal and mesenteric lymphadenopathy Oedema Cirrhosis with portal hypertension MASS-FORMING LESIONS Solid Haemangiopericytoma Well-circumscribed, solid hypervascular mass; necrosis and haemorrhage indicate a malignant form Liposarcoma Predominantly fat-containing lesion with enhancing solid components Gastrointestinal The solitary lesion usually extension tumour (GIST) from gastric or small bowel GIST, multiple lesions due to metastatic spread Cystic Cystic lesions Most of the lesions are similar to mesenteric cystic lesions (refer Table 8.6.26) OMENTAL DISEASE FOLLOWING ABDOMINAL SURGERY

Pattern Differentials Contusion Hematoma Panniculitis Infarction

Abscess Gossypobioma

Pancreatitis related omental lesion

Diagnostic Clues/Associated Features Linear soft tissue density stranding and higher attenuation of omental fat Focal hyperattenuating collection Features similar to mesenteric panniculitis Four types: type 1 (ill-defined, heterogeneous, fat density lesion); type 2 (well-defined fat density lesion with rim enhancement); type 3 (well-defined heterogeneous lesion with a fat component); and type 4 (well-defined heterogeneous lesion without a fat component) Rim enhancing thick-walled collection Spongiform appearance with gas bubbles, hypodense mass with a thin enhancing capsule, calcification may be seen along the network architecture of sponge Evidence of postoperative acute pancreatitis with extrapancreatic inflammation

Peritoneal carcinomatosis/peritoneal metastasis Peritoneal carcinomatosis (PC) refers to the metastatic involvement of the peritoneum from abdominal or extraabdominal malignancies. Though PC and PM are often used interchangeably, PM is the preferred terminology keeping line with TNM staging besides implying that metastasis is a potentially treatable condition.

Aetiology and incidence Intraabdominal tumours of genitourinary and gastrointestinal origin are common causes of PM, with ovarian cancers being topmost entity comprising of about 46% of cases. The reported incidence of PM in the colorectal, advanced gastric and pancreatic malignancies is about 12%, 14% and 9%, respectively. Primary tumours of small intestine, uterus and prostate less frequently present with PM. PM can arise from extraabdominal primary malignancies (Fig. 8.6.42) in about 10% of cases with most common malignancies presenting in this way are breast (41%), lung (21%) and melanoma (9%). Incidence of PM in an unknown primary is about 10%.

FIG. 8.6.42 Peritoneal carcinomatosis in the operated case of moderately differentiated carcinoma of lower lip (extraabdominal primary) with ipsilateral nodal metastasis. Axial CT (A) and (B) showing diffuse peritoneal and subperitoneal disease after 11 months off neck surgery. (C) CT-guided biopsy of omentum. PET images (D) and (E) showing disseminated peritoneal – subperitoneal process, and extensive skeletal deposits. PM can occur in different time frames during evolution and management of primary tumours. Synchronous PM is defined as the presence of metastasis at initial diagnosis of primary cancer or presenting within 1 month of resection of primary cancer. Metachronous PM is defined as the presence of metastasis after 1 month of treatment of primary tumour. This discrimination has prognostic importance as colorectal cancers with metachronous PM have worse disease-free survival following CRS and HIPEC compared to synchronous metastasis. Besides the presence of synchronous PM increases the likelihood of metachronous metastasis. Pathophysiology The establishment of PM is considered a multistep process. Peritoneal metastases arising from different primaries not only differ in biological behaviour but also have different patterns of peritoneal spread. Organ preference of particular malignancy is considered to be a result of a complex interaction between metastatic cancer cells (‘the seed’) and organ-specific environment (‘the soil’) in accordance to Paget’s ‘seed and soil’ theory of oncogenesis. Different pathways involved in the spread of peritoneal-free cancer cells to implantation site include translymphatic, transmesothelial and superficial spreading pattern. One tumour may involve one or more of these pathways of peritoneal dissemination. In mucinous appendiceal tumours the translymphatic pathway is employed, while in gastric and colorectal cancers, both transmesothelial and translymphatic pathways are used. Three different patterns of spread of tumour from the site of implantation into the peritoneal cavity are summarized in Table 8.6.28.

TABLE 8.6.28 Patterns of Peritoneal Cancer Spread With Examples and Its Implication on Treatment Random Proximal Pattern Distribution (RPD) Key Presence of Determinants adhesion molecules

Widespread Cancer Distribution (WCD) Absence of Abundant mucus adhesion molecules production with mucus production Mechanism Adhesion Lack of adhesion Abundant mucin molecules on molecules on production by tumour cells tumour cells with tumour cells despite lead to early mucin production the presence of implantation allows distribution adhesion molecules but along the pathway hinders the cell distribution is of peritoneal fluid adherence and early random circulation leading implantation leading to to CR. leading to WCD RCD Biological Moderate- to Low aggressive Aggressive and behaviour high-grade tumours undifferentiated tumours tumours Examples Carcinoid of Pseudomyxoma Mucinous cancers the appendix, peritonei and of the ovary and nonmucinous diffuse malignant colorectal region, cancers of mesothelioma appendiceal appendix, cystadenocarcinoma stomach, colorectal region and serous ovarian cancer Implication Selective Complete peritonectomy with extended on parietal cytoreduction as per need management peritonectomy Complete Redistribution (CR)

Management of peritoneal metastasis Presence of PM was previously considered to be a terminal untreatable disease with very poor prognosis. Advances in surgical and medical oncology over last the few decades have led to the emergence of various surgical techniques and chemotherapeutic management strategies, improving overall prognosis. The current standard of care for patients with PM is a comprehensive management plan, comprising of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), which has significantly elevated patient survival, as compared to other treatment options. CRS and HIPEC have been employed in the treatment of select cases of primary malignancies (including ovarian epithelial cancer, primary peritoneal cancer gastric cancer, colorectal cancer and peritoneal mesothelioma), pseudomyxoma peritonei from appendiceal cancer as well

as in the recurrent metastasis (from ovarian and colorectal cancers and pseudomyxoma peritonei) with different success rates in terms of survival benefits. A recent systematic review concluded that only epithelial ovarian cancer management using CRS and HIPEC has a level I evidence and the rest are still under various trials to develop definitive recommendations. Various aspects of CRS and HIPEC are summarized as following: procedure (Table 8.6.29, Fig. 8.6.43), resection for CRS (Table 8.6.30) and contraindications (Table 8.6.31). Prognostic indicators affecting the outcomes of patients undergoing CRS and HIPEC are detailed in Table 8.6.32. TABLE 8.6.29 Procedure of CRS and HIPEC Technique CRS Rationale To achieve a macroscopically complete cytoreduction of the carcinomatosis Procedure Includes a combination of visceral resections and peritonectomy procedures based on the volume and distribution of the carcinomatosis (summarized in Table 8.6.30)

HIPEC To manage the microscopic disease and small tumour deposits measuring 2.5 mm or less. Includes circulation of heated chemotherapy solution in the peritoneal cavity, for 30–90 minutes at a fixed flow rate, maintaining an intra-abdominal temperature of 41°C–43°C, as hyperthermia aids in deeper penetration of chemotherapeutic agents.

FIG. 8.6.43 Cytoreductive surgery: (A) Cholecystectomy, (B) splenectomy, (C) lesser omentectomy, (D) greater omentectomy, (E) hysterectomy with bilateral oophorectomy and pelvic lymph node dissection, (F) midline abdominal incision, (G) subdiaphragmatic peritonectomy, (H) pelvic peritonectomy, (I) right hemicolectomy, (J) liver nonanatomic resection.

TABLE 8.6.30 Cytoreductive Surgery Types

Selective parietal peritonectomy Complete parietal peritonectomy PROCEDURES FOR CYTOREDUCTION Peritonectomy Visceral Resection Anterior Abdominal incisions and umbilicus Right diaphragmatic Gall bladder IVC bursectomy Liver capsule Left diaphragmatic Partial/ total gastrectomy Pelvic Splenectomy Greater omentectomy Right colon / sigmoid colon Lesser omentectomy and porta Total colectomy hepatis Mesenteric and serosal Hysterectomy and oophorectomy Sugarbaker PH, Sardi A, Brown G, Dromain C, Rousset P, Jelinek JS. Concerning CT features used to select patients for treatment of peritoneal metastases, a pictoral essay. International Journal of Hyperthermia. 2017 Jul 4;33(5):497-504. TABLE 8.6.31 Contraindications for CRS and HIPEC DISEASE-RELATED CRITERIA Absolute contraindications • Extraabdominal disease proven by histopathology • Extraperitoneal disease such as massive retroperitoneal adenopathy (N3 nodal disease) or liver metastasis except colorectal carcinoma (CRC), up to 3 resectable metastases) Extent of peritoneal disease precluding complete cytoreduction • Conditions with no established PCI cut-off • Two or more sites of segmental small bowel obstruction, requiring extensive bowel resection compromising the future quality of life • Extensive involvement of root of the mesentery • Involvement of the pancreas head, bladder trigone and pelvic sidewall involvement • Massive or diffuse involvement of the pleural space • Conditions with established PCI cut-off. i.e. >17 PCI in CRC and >12 in gastric cancer PATIENT-RELATED CRITERIA • Poor performance status score and >2 severe comorbidities • Patient age >65 years • BMI ≥ 40

TABLE 8.6.32 Prognostic Indicators Affecting Success Rate and Disease-Free Survival in Patients Undergoing CRS and HIPEC Preoperative Indicators • CT PCI • SPAAT score • Prior surgical score Tumour histopathology Intraoperative Indicators • Peritoneal Carcinomatosis Index (PCI) • Gilly peritoneal carcinomatosis staging • Dutch Simplified Peritoneal Carcinomatosis Index (SPCI) • Carcinomatosis staging by the Japanese Research Society for Gastric Cancer Postoperative Indicator • Completeness of Cytoreduction Score Harmon RL, Sugarbaker PH. Prognostic indicators in peritoneal carcinomatosis from gastrointestinal cancer. International Seminars in Surgical Oncology 2005 Dec (Vol. 2, No. 1, p. 3). BioMed Central.

Newer treatment modalities Pressurized intraperitoneal aerosol chemotherapy (PIPAC) PIPAC is a novel approach to deliver intraperitoneal (IP) chemotherapy to patients with PM. PIPAC has pharmacokinetic advantage over IP chemotherapy in terms of more homogeneous distribution, higher drug concentration within peritoneal cavity due to aerosol delivery, increased tumour drug penetration using lower dose with limited systemic absorption. Initial studies have shown promising results in PM of various origins. An ongoing prospective clinical trial expects that PIPAC-directed therapy can induce major or complete response in 50% of patients with PC of colorectal origin and 30% of patients with PC of noncolorectal. Early postoperative intraperitoneal chemotherapy (EPIC) EPIC is administered via drainage tubes inserted during surgery, given on postoperative days 1–5 with theoretical advantages of being administered when the disease burden is minimal and when adhesions have not yet formed, thus enabling a more even drug distribution. However, further studies are required to establish the potential benefits of EPIC. Combination of HIPEC with EPIC has shown to have a significantly better 5-year survival than HIPEC alone in appendiceal adenocarcinoma (62.3% for HIPEC+EPIC, 30.5% for HIPEC alone). Peritoneal carcinomatosis index

PCI is a numerical score developed by Sugarbaker to quantify disease extent. In this method, the abdomen and pelvis are divided into 13 regions by imaginary lines with each area assessed for size of lesions with lesion size score on a scale from 0 to 3 (Fig. 8.6.44). This is then calculated as PCI, which is the sum of the lesion sizes from all 13 areas with final score ranging between 0 and 39. Preoperative PCI is calculated using CT, MRI and PET/CT. Intraoperative surgeons calculate the final PCI score.

FIG. 8.6.44 CT coronal image showing abdominal segmentation for calculation of peritoneal carcinomatosis index (PCI). PCI is both diagnostic and prognostic marker. PCI is an independent quantitative predictor of both morbidity and overall survival – a higher PCI has a negative impact on both. In patients with gastric PC, the overall survival (1, 2, 3 and 5 years) showed significant difference above and below PCI of 12. CRS plus HIPEC does not seem to offer any survival benefit when the PCI exceeds 17 in PC of colorectal origin. In patients with PC of serous epithelial ovarian cancer, a univariate logistic regression analysis showed that suboptimal surgical cytoreduction (hazard ratio [HR] = 2.24; 95% CI = 1.23–4.09; p = 0.005), and PCI score >13 (HR = 2.18; 95% CI = 1.22–3.89; p = 0.012) were the factors that had a statistically significant impact on OS. It is important to note that involvement of critical sites overrides total PCI in operative decision making.

Imaging findings of PM (Fig. 8.6.45) The standard image interpretation and reporting protocol followed at our institution includes the following steps: (1) Identification of PM (2) Identification of the primary tumour (3) Identification of lesions at sites that are ‘absolute contraindications to CRS and HIPEC’ (4) Identification of lesions at sites that ‘preclude complete cytoreduction/require surgical subspecialty expertise’ (5) Identification of lesions at sites that are laparoscopic ‘blind spots’ (6) Calculation of imaging-based scoring of disease burden

(1) Identification of PM: Radiologist needs keen eye to evaluate PM as early disease can have subtle manifestations. Understanding of peritoneal and subperitoneal pathways of disease spread in the vicinity of a primary malignancy can help in identifying the early and occult disease. Some of the common manifestations of PM are described region wise as following. Peritoneal reflections: The classical feature of PM is nodular or irregular thickening with the enhancement of peritoneal reflections. In advanced cases, peritoneal nodules and plaques/sheets of soft tissue may progress to form large masses. Greater omentum: Omental involvement in early stages can be identified as discrete nodule and mistiness. As the tumour grows, it invades the subperitoneal tissues replacing the omental fat with nodularity, masses and thickening of omentum, known as ‘Omental caking’. Mesentery: Appearances of infiltration of small bowel mesentery range from stranding and nodularity in initial stages to distortion and retraction of mesenteric pleats in later stages, resulting in clumping of bowel loops. Ligaments: Ligamentous attachment of particular organ should be carefully assessed for subperitoneal pathway of disease spread. In cases of disseminated peritoneal malignancies, special attention should be given to these ligaments, namely, gastrohepatic – hepatoduodenal and gastrosplenic – splenorenal ligaments besides lesser sac in order to exclude involvement. Bowel: Nodular or diffuse thickening can occur along the serosal surface of bowel loops, which may show transmural infiltration and lead to bowel obstruction. Ascites: Though ascites can be caused by multiple causes, one should be aware that an unexplained ascites with history of an intraabdominal malignancy may be the earliest imaging sign of peritoneal involvement. Varying amounts of free or loculated ascites can be seen in different stages of disease progression. Serous ascites is often associated with diffuse and invasive nodules on the bowel and mesenteric surfaces. Haemorrhagic ascites in a cancer patient often indicates spontaneous necrosis of a high-grade tumour. Lymph nodes: Nodal involvement in the primary malignancy can locoregional or distant depending on the nodal station. Nodal characteristic largely deepened on the primary malignancy. Classic feature suggesting involvement is a rounded and hypoattenuating appearance of a node. Nodes in the mesenteric root, porta hepatis and retroperitoneal suprarenal nodes must be reported as it bears maximum prognostic implications. Enlargement (>5 mm in short axis) of cardiophrenic nodes may be seen in the peritoneal disease. Liver and spleen: Mostly the peritoneal deposits tend to involve the surface or subcapsular region of liver and spleen causing indentation of the underlying parenchyma,

described as ‘scalloping’. Occasionally, the surface deposits can infiltrate the parenchyma. In later stages, encasement and infiltration of subperitoneal–retroperitoneal organs may be seen. (2) Identification of the primary tumour: In many primary malignancies causing PM is known in advance based on other investigations. However, in absence of any known primary tumour, possible organ of origin can be predicted based on the distribution of peritoneal disease, as different primary tumours often exhibit distinct patterns of peritoneal dissemination, as detailed earlier. For example, a dominant peritoneal disease in left hemipelvis may point towards likely left ovarian/colorectal origin of PM. Similarly, distribution of hypoattenuating deposits in the pouch of Douglas, right and left paracolic gutters, hepatorenal fossa and right subphrenic space most likely favour an appendiceal mucinous carcinoma peritonei. Morphology of lesions may give clue about the primary tumour. Mucinous tumours are associated with hypoattenuating/fluid density deposits. The presence of calcification, before treatment is instituted, suggests mucin producing primary tumour or carcinoid tumour while neuroendocrine tumours show hypervascular deposits. A thorough search for extraperitoneal and extraabdominal primaries (such as breast, lung, melanoma) should also be made in case of unknown primary. (3) Identification of lesions at sites that are absolute contraindications to CRS HIPEC: Presence of extraabdominal disease, such as lung/bone/brain metastasis, supraclavicular/mediastinal lymph nodes is considered to be absolute contraindication. PET/CT should be used in preoperative assessment of patients with large tumour volumes and poor prognostic histologies to rule out extraabdominal metastases. Presence of extraperitoneal disease such as massive retroperitoneal adenopathy especially in the suprarenal location and at the level of celiac axis, and presence of liver metastasis should be documented except in colorectal carcinoma, where up to three resectable metastases is acceptable and in ovarian cancer, where the possibility of resection of liver lesions is considered. (4) Identification of lesions at sites that preclude complete cytoreduction/require surgical subspeciality expertise: Sugarbaker et al. have described concerning radiological features on preoperative CT scan that may be associated with an increased incidence of incomplete CRS and must be looked for in all reports. This list is enumerated in Table 8.6.33. These features indicate unresectability and some are signs indicating complex resections that may be technically feasible but are associated with increased morbidity and mortality. Potentially unresectable lesions are enumerated in Table 8.6.34.

(5) Identification of lesions at sites that are laparoscopic ‘blind spots’: Blind spots are the locations in which lesion can go unnoticed during the laparoscopy (Fig. 8.6.46). These sites are enumerated in Table 8.6.35. (6) Calculation of imaging-based scoring of disease burden: PCI is most commonly used scoring system. Each anatomic portion among 13 abdominopelvic quadrants is reassessed carefully for lesion size and score. PCI can be calculated using CT or MRI. MRI-based PCI has overall better performance in terms of surgical correlation. CT underestimates lesions less than 1 cm in size gives falsely lower score. However, if CT PCI score is high, there is higher likelihood of possibly untreatable disease in most of the conditions. In cases of low-grade mucinous adenocarcinoma of appendix, SPAAT (simplified assessment for appendix tumour) scoring is detailed in Table 8.6.36.

FIG. 8.6.45 Surgically important sites of peritoneal metastasis. I(a,b): Mucinous cystadenocarcinoma of ovary. Hypoattenuating deposits in porta hepatis chinking the main portal vein (→). II(a,b): Mucinous adenocarcinoma. Heterogeneously enhancing lesion with hypoenhancing core noted posterior and to the left of SMA (mesenteric root) with periodontal fat stranding (⇠). III(a,b): Peritoneal carcinomatosis with pseudomyxoma peritonei. Nodular and plaque-like low attenuating deposits along the costal and diaphragmatic pleural reflections (➢). IV: Peritoneal mesothelioma. IV(a): Sheet enhancing subperitoneal deposits coating the serosal surfaces of pelvic ileal and sigmoid bowel loops resulting in localized aggregation and cocooning of these loops (yellow arrow). IV(b,c): Confluent serial deposits along the serosal surface of splenic flexure of colon(❋).

TABLE 8.6.33 Reporting Checklist of Features That Preclude Complete Cytoreduction Small Bowel and Its Mesentery • Complete bowel obstruction or more than one site of partial obstruction (chaotic bowel pattern) • Clumped bowel loops due to mesenteric indrawing by tumour • Tumoural infiltration between leaflets of the mesentery • Larger deposits (≥5 cm) in jejunal region • Higher CT PCI >20 (excluding PMP, cystic mesothelioma or low malignant potential ovarian tumours) • Mesenteric lymphadenopathy Retroperitoneum • Paraaortic and supraceliac lymphadenopathy • Ureteric involvement leading to hydroureter • Psoas muscle invasion Pelvis • Invasion of pelvic sidewall invasion • Seminal vesicle invasion Lesser omentum • Hepatoduodenal ligament disease-causing porta hepatis infiltration and/or biliary obstruction • Larger deposits (≥5 cm) in gastrohepatic ligament or subpyloric space • Gastric outlet obstruction Ascites • Haemorrhagic ascites • Serous ascites in a gastrointestinal malignancy Adapted from Ref. 89. TABLE 8.6.34 Potentially Unresectable Lesions Two or more sites of segmental small bowel obstruction Need for total gastrectomy with total colectomy Extensive involvement of root of the mesentery Porta hepatis and hepatoduodenal ligament involvement Frozen pelvis, bladder dome involvement

FIG. 8.6.46 CT images showing laparoscopically blind spots (which can be missed in absence of imaging) include pleural deposits (A), hepatic parenchymal deposits (B), splenic parenchymal deposits (C) and bowel intraluminal deposits (D) all marked with arrows. TABLE 8.6.35 Laparoscopic ‘Blind Spots’ Intraparenchymal hepatic/splenic lesions Intraluminal deposits in gastrointestinal tract Retroperitoneal lesions Involvement of lesser sac, posterior hepatic space Pleural and pericardial involvement TABLE 8.6.36 SPAAT Score Components (Presence of Scalloping) Organ Liver

Score 1

Spleen

1

Pancreas

1

Portal vein

1

Small bowel mesenteric shortening

3

Score: can vary from 0 to 7 Score < 3: Complete cytoreduction Score ≥ 3: Incomplete cytoreduction

Posttreatment surveillance The combined CRS and HIPEC is associated with a morbidity of 30%–40% and a mortality of 0%–10%. Various patient and operative factors have been implicated in CRS and HIPEC-related morbidity and mortality, such as PCI score, bowel resection, GI/GU procedures and the surgeon’s expertise. Immediate postoperative imaging is often performed when the procedure has been long and difficult and if any complications are anticipated. Familiarity with the therapeutic approach used, normal postoperative appearances as well as the potential complications and their imaging features is of paramount importance. Key points for optimal evaluation of posttreatment imaging study include:

• Review the preoperative imaging studies to assess for completeness of cytoreduction • Knowledge of the operative details and various peritonectomy procedures is necessary to understand expected anatomical changes in the operative bed • Discuss with operating surgeons and focus on the sites of anticipated incomplete cytoreduction/complications • Use standardized imaging protocol • Ensure adequate bowel distension as collapsed bowel loops can mask subtle peritoneal nodules and mimic lesions • Delayed phase images may be required in cases such as ureteric obstruction, suspected leak and in cases of bowel obstruction • Further imaging (CEMRI/DWI MRI or PET/CT) may be performed in indeterminate cases • Evaluate key areas: Primary tumour bed, nodal dissection bed, anastomotic sites, colostomy/Ileostomy bed and incision/scar site. Visceral parenchymal deposits (hepatic or splenic) should be carefully assessed. Lower chest sections to be evaluated for pleural/pericardial fluid, nodularity and lymph nodes. Normal posttreatment appearance CRS is a complex surgery, responsible for several abdominopelvic changes in the immediate postoperative period. Ascites: Minimal to mild diffuse peritoneal fluid may be seen in almost every patient. Some patients may show loculations due to inflammation and early adhesions. Pneumoperitoneum: Pneumoperitoneum is a normal finding for a week following surgery, particularly in case of open surgery. Air can also remain trapped in the dissection bed in subperitoneum/retroperitoneum. Inflammation of bowel and bladder: Mild enhancing wall thickening most likely indicates a normal finding, in the absence of clinical features of sepsis. Abdominal wall: Subcutaneous oedema and discrete fluid collections are also often visible, particularly at the sites of an incision. Posttreatment complications (Fig. 8.6.47) Frequently seen postoperative complications following CRS and HIPEC are mentioned in Table 8.6.37. MDCT is the imaging modality of choice in the evaluation of most of these complications.

FIG. 8.6.47 Complications of cytoreductive surgery in four different patients: Sagittal (A) and (B) CT showing enterocutaneous fistula, sagittal (C) and axial (D) CT showing pelvic hematoma, axial (E) and coronal (F) CT showing bowel perforation, axial (G) and coronal (H) CT showing paralytic ileus. TABLE 8.6.37 Postoperative Complications Following CRS and HIPEC System Manifestations Gastrointestinal complications Related to the bowel (most Bowel perforation, anastomotic site leak, common and clinically bowel fistulas significant) Other GI complications Abscesses, pancreatic fistulas, biliary fistulas, chyle leak and paralytic ileus Lymphatic complications Lymphocoele Vascular complications Arterial pseudoaneurysm, arterial/venous thrombosis, hemoperitoneum, localized hematoma Tumoural recurrence Despite advances in treatment, local intraperitoneal recurrence of tumour occurs in 28%–44% of patients following CRS – HIPEC in appendiceal tumours. Recurrence rates can be much higher for other tumour histology, high-grade tumours, or patients with higher initial PCI scores. Recurrence is a direct prognostic factor reducing overall survival. Repeat CRS plus HIPEC for patients with the recurrent tumour has been advocated as the best approach to achieve improved overall survival. Hence, the early detection of the recurrent tumour on serial laboratory tests and imaging studies becomes critical. Detection of recurrence: Imaging versus tumour markers MRI has shown to detect tumour recurrence earlier and with a higher accuracy (94%) compared to serial tumour markers (including CA125, CEA,

CA 19–9) alone (67%) in patients of appendiceal neoplasm following CRS and HIPEC. Immediate measurement of CA-125 within 72 hours may be helpful to look for postsurgical normalization. Except for this immediate period, measurement of CA-125 is misleading and thus should not be used within the first 3 months postoperatively, following which its use as a surveillance marker can resume. Tumour markers do not reliably monitor disease stabilization, partial response or sustained complete response. Moreover, a progressive increase in serum tumour markers does not predict the volume of tumour recurrence or its location. Thus, imaging is essential for assessing the feasibility of secondary CRS and to differentiate between a curative or palliative approach. In addition, cross-sectional imaging is the principal diagnostic tool of recurrence in the subgroup of patients who are not biochemical secretors. Imaging of peritoneal tumour recurrence In the early postoperative period, the specificity of purely anatomic imaging as well as hybrid imaging (e.g. PET/CT) is reduced because of the frequently indistinguishable morphologic features and intense radiotracer uptake in both inflammatory tissue and the tumour. Initial postoperative imaging should be used to establish posttreatment baseline changes which include fat necrosis, fluid collections and reactive peritoneal and bowel thickening. Subsequent interval examinations should be carefully assessed for any interval changes, such as increasing peritoneal thickening, nodules or ascites that indicates disease recurrence (Figs. 8.6.48–8.6.49). Postoperative changes gradually resolve on subsequent follow-up (Flowchart 8.6.6). A pitfall of this approach is that slow-growing lesions can appear stable on close follow-up imaging.

FIG. 8.6.48 Examples of recurrence after cytoreductive surgery: (A) and (B) Recurrent peritonealbased nodules along the left paracolic gutter following a left hemicolectomy for a colonic adenocarcinoma, (C) baseline and follow-up, (D) showing pleural recurrence in case of pseudomyxoma peritonei, (E) baseline and follow-up, (F) showing lung nodule in colonic carcinoma.

FIG. 8.6.49 Examples of recurrence after cytoreductive surgery: (A) scar site recurrence in treated case of ovarian carcinoma. (B) and (C) recurrent disease (low attenuation deposit) coating the serosal surface of the terminal ileum and ascending colon, (D) and (E) recurrent disease (low attenuation deposit) along the right combined interfacial reflection coats the right ureter resulting in hydroureteronephrosis.

FLOWCHART 8.6.6 Imaging of assessment of indeterminate findings on index postoperative scan.

Peritoneal biopsy While cross-sectional imaging is the most accessible tool for the evaluation of peritoneal diseases, frequently a definitive diagnosis cannot be established based on imaging features alone. Ascitic fluid evaluation has inferior diagnostic yield compared to histopathological evaluation. In such cases of diagnostic ambiguity, tissue sampling is the best alternative for confirmation. It delivers the added benefit of molecular and genetic analyses, which are invaluable in guiding cancer therapy. Indications of peritoneal biopsy are to confirm a suspected malignancy, for microbiologic analysis, staging patients with known cancers and to differentiate viable tumour from necrotic tissue in posttreatment cases. An example of its indispensable role is in differentiating the cause of peritoneal thickening between infective aetiologies such as TB from malignancy because of profound impact on prognosis and further management. Various studies have shown that peritoneal TB needs to be considered as a differential diagnosis in patients with suspected advanced ovarian cancer with PM irrespective of CA 125 levels. Direct peritoneal sampling using laparoscopic or laparotomy techniques is considered the gold standard in the evaluation of peritoneal diseases. However, these techniques are usually reserved when image-guided biopsy

is nondiagnostic. Imaging-guided biopsy can be performed under US or CT guidance (Fig. 8.6.50). While CT guidance is superior in terms of better visualization of the mass and its relationship with adjacent structures, US guidance provides a real-time visualization and is more cost-effective without subjecting the patient to radiation. The preprocedure evaluation includes a review of clinical background, laboratory studies and imaging to determine the most feasible route of access. In addition, if multiple lesions are present, the one with the lowest risk and the highest yield is selected. The biopsy needle is selected based on the required tissue volume and composition. Core needle biopsies provide larger tissue samples (14-to-20gauge needles) with preserved tissue architecture, whereas fine-needle aspiration biopsy (FNAB) samples individual cells, which lack organization. FNAB is performed using smaller needles (20–25 gauges), causing less tissue trauma with rapid analysis, which permits intraprocedural determination of sample adequacy; conversely, the small tissue quantum has limited diagnostic value. Authors prefer biopsy over cytology in peritoneal lesions. Authors advocate use of coaxial method in which introducing needle is placed into the target lesion with repeated sampling performed through same tract to obtain multiple cores. Potential advantages of coaxial technique over noncoaxial technique are shorter duration for procedure and lower rates of complications.

FIG. 8.6.50 Peritoneal biopsy. Ultrasound-guided omental thickening biopsy (A). CT-guided biopsy of peritoneal thickening (B), mesenteric lesion (C) and omental thickening (D). Peritoneal biopsies can be performed under local anaesthesia depending on patient comfort and cooperation, after obtaining written informed consent. Patient positioning is determined as per the accessibility of the target lesion and patient comfort. The anterior approach is most commonly

used with its chief limitation being the intervening abdominal viscera. This can be minimized by hydrodissection to create a path of access. When US guidance is used, probe pressure can displace intervening bowel, fix a mobile mesenteric mass and also minimize the distance to the lesion. Organ transgression should be minimized and solid organs such as liver, spleen and kidneys can be safely transgressed if necessary. Hollow organs have a variable risk when transgressed with the stomach being the safest due to its thick wall and relative sterility. A posterior approach is usually reserved for lesions in the mesenteric root. The needle is passed through quadratus lumborum and psoas muscles, which makes alterations in the needle trajectory difficult. A potential advantage to the posterior approach is in the scenario of a haemorrhagic complication, it is contained within the retroperitoneum, which is prone to autotamponade. Biopsies can be performed with either coaxial or noncoaxial techniques, coaxial approach is preferred for CT guidance and direct puncture for US-guided procedures. The coaxial technique has the advantage of a single path, minimizing tissue damage and patient discomfort; however, the fixed trajectory might lead to a repeated sampling of the same intralesional site. The most commonly reported complications are pain and haemorrhage along the biopsy path. Other rare but critical complications include intraperitoneal or retroperitoneal hematomas and intraabdominal abscess especially if the bowel has been transgressed. A recent study by Derek et al. demonstrated that percutaneous omental biopsies are very accurate (99% sensitivity), safe without significant complications and more sensitive than paracentesis cytology.

SECTION 9: Hepatobiliary System O U T LINE 9.1. Radiological techniques in hepatobiliary imaging 9.2. Normal anatomy and variants 9.3. Normogram and normal values 9.4. Approach to radiologic diagnosis 9.5. Radiological signs – hepatobiliary system 9.6. Embroyology and congenital anomalies of the hepatobiliary system 9.7. Hepatobiliary system: Congenital anomalies 9.8. Paediatric hepatobiliary lesions 9.9. Imaging in portal hypertension and cirrhosis with emphasis on LI-RADS 9.10. Diffuse liver disease 9.11. Focal liver lesions 9.12. Vascular pathologies of liver 9.13. Hepatic infections 9.14. Liver transplant imaging 9.15. Imaging in biliary diseases 9.16. Paediatric pancreatic pathologies 9.17. Imaging in pancreatitis 9.18. Imaging in solid pancreatic masses 9.19. Cystic pancreatic masses 9.20. Role of imaging in pancreatic transplant

9.21. Paediatric splenic abnormalities 9.22. Imaging of spleen and splenic pathologies 9.23. Abdominal trauma 9.24. Biliary interventions 9.25. Transarterial therapy for liver tumours 9.26. Interventions in portal hypertension 9.27. Interventional management of Budd–Chiari syndrome 9.28. Portal vein embolization: Principle, technique and current status 9.29. Postliver transplant complications and interventions

9.1: Radiological techniques in hepatobiliary imaging Samarjit Ghuman, Seema Sud, Deeksha Rastogi, Swapnil Sheth, T.B.S. Buxi 9 .1 .1

PLAIN RADIOGRAPHY FOR HEPATOBILIARY IMAGING Introduction The diagnostic imaging techniques for hepatobiliary imaging can be intimidating with many techniques/modalities providing the information desired. The job of the diagnostic radiologist includes being familiar with the available choices and pick the ‘best fit’ keeping in mind the pros and cons of each modality, which includes plain X rays, Contrast studies using plain X rays and fluoroscopy, Ultrasound includiojng Doppler and Ultrasound elsastography, CT including multiphase CT and MRI and MRI elastography. Understanding the strengths and weaknesses of every modality as well as the ability to tailor each study individually will help to optimise patient cares.

Technique The abdominal radiograph is performed almost exclusively in the supine position and in the AP (anteroposterior) projection. In case of acute abdomen, an erect chest radiograph should also be performed to look for free air under the diaphragm. The standard abdominal radiograph should extend from the diaphragm to the inferior pubic rami, and includes the lateral abdominal wall musculature.

Preparation Routinely no preparation is required for abdomen radiograph done for hepatobiliary imaging.

Plain radiography for liver The radiograph has limited soft-tissue contrast, however, the liver being the largest intraabdominal organ, casts a perceptible shadow. The margins of the liver can indirectly be seen by outline of adjacent organs like lung, hemidiaphragm, pro-peritoneal fat line, kidney and gas shadows of stomach/colon. The right lobe is seen better than the left lobe of liver. The following pathologies may be visualized on the plain radiograph of the liver. Liver enlargement • An enlarged right lobe of liver causes elevation of right hemidiaphragm, depressed hepatic flexure and duodenum, depressed right kidney, bulging of the right properitoneal fat line and sometimes splaying of the lower right ribs. • An enlarged left lobe of liver causes inferolateral displacement of gastric fundus bubble and impression over the lesser curvature of stomach. • Enlarged caudate lobe causes anterior displacement of duodenal cap gas shadow. Liver mass

• If the liver mass is large enough then may cause impression over the adjacent organ outline. Calcification • Hydatid disease of liver (Fig. 9.1.1) may show eggshell, curvilinear, ring like or scattered calcification. Calcifications may be seen in granulomas or dermoids or in some hepatic tumours such as hepatoblastoma and rarely HCC. • Multiple perihepatic faint fluffy calcifications may be seen in pseudomyxoma or calcitonin-secreting metastases of medullary carcinoma of thyroid.

FIG. 9.1.1 Simulated AP radiograph (Scanogram) showing a rounded calcification (black arrow) suggestive of rim calcification in a hydatid cyst. Increased radiodensity of the liver 1. Haemochromatosis or following Lipiodol injection. Decreased radiodensity of the liver 2. Focally decreased density due to gas in liver abscess. 3. A Chilaiditi syndrome, interposition of the colon between liver and diaphragm, may resemble free gas under the diaphragm; however, haustral pattern of bowel helps in differentiation. Radiography for gallbladder and biliary tract An ultrasound is the first line investigation; however, a radiograph may be done for routine evaluation of abdominal pain. The following pathologies may be seen on plain radiograph of the biliary tree. Calculi and Calcifications • Approximately 20%—30% of GB calculi are radiopaque (Fig. 9.1.2). Mulberry calculi are usually made of pure calcium carbonate; while calculi with central lucent fissure (Mercedes Benz sign) have mixed contents. Common Bile Duct (CBD) calculi are usually radiolucent. 1. Limey bile is bile with calcium carbonate sand, which casts a layering in standing radiograph and may be associated with calculi or chronic cholecystitis. It is different from the ultrasound diagnosis of GB sludge. 2. The porcelain gallbladder is a sequelae of chronic cholecystitis with diffuse mural calcification and is a premalignant condition.

FIG. 9.1.2 AP radiograph of abdomen shows multiple faceted radiopaque calculi with internal lucency (arrows) in right hypochondrium suggesting gallbladder calculi. Gas 1. An intramural or intraluminal gas is seen in emphysematous cholecystitis, a severe form of acute gangrenous cholecystitis secondary to gas-forming organisms, usually seen in diabetics and in a setting of hepatic artery embolization (Fig. 9.1.3). 2. A branching pattern of gas in right hypochondrium suggests pneumobilia or portal vein gas. The distribution of gas along the biliary ductal system suggests pneumobilia (Fig. 9.1.4); while peripheral distribution of gas suggests portal venous gas. 3. The Rigler’s triad of ‘gallstone ileus’ consists of small bowel obstruction, pneumobilia and gall stone in small bowel usually in right iliac fossa, secondary to fistulation between biliary tree and bowel.

FIG. 9.1.3 AP radiograph showing gas around and within the walls of the gallbladder (black arrows) suggestive of emphysematous cholecystitis.

FIG. 9.1.4 AP radiograph of abdomen shows branching lucency in right hypochondrium overlying the liver shadow suggesting pneumobilia (Black arrows).

Radiography for pancreas 1. Calcification in the pancreatic bed may be seen in various conditions like chronic pancreatitis (Fig. 9.1.5), mural calcification of pseudocyst, hematoma, infarction and tumours. Phleboliths are seen in pancreatic Vascular malformations or lymphangioma. Calcification in a known case of islet cell tumour of pancreas suggests malignancy. Sunburst type of calcifications is seen in cystic pancreatic tumor like serous cystadenoma. Calcifications in chronic pancreatitis are usually along the course of the duct secondary to calculi or may be seen in the parenchyma. These are usually numerous and small or large nodular in shape. Calculi with

central lucency are seen in hereditory pancreatitis, an autosomal dominant condition. Finely granular calcification is seen in cystic fibrosis. Calcifications in chronic pseudocyst or hematoma tend to be mural and curvilinear. 2. Large pancreatic masses may cause widening of duodenal ‘c’ loop or displacement of gas shadows of stomach/bowel. 3. The plain radiograph findings in acute pancreatitis include left pleural effusion, colon cut off sign, sentinel loop sign, obscured left psoas shadow or bone infarcts. Gas in pancreatic bed could be due to emphysematous pancreatitis, pancreatic abscess, postintervention changes or fistulous communication with bowel.

FIG. 9.1.5 AP radiograph of abdomen shows multiple calcific densities in the pancreatic bed in case of chronic pancreatitis (Black arrows). 9 .1 .2

ULTRASOUND OF HEPATOBILIARY SYSTEM Introduction Ultrasonography (USG) is the initial imaging modality of choice for scanning hepatobiliary system. USG is accurate and has high sensitivity and specificity in diagnosing biliary pathologies. Table 9.1.1 shows indications of ultrasound in hepatobiliary system. The realtime nature of ultrasound lends itself to demonstrate mobility of calculi and sludge and the sonographic Murphy sign can easily be elicited during scanning. TABLE 9.1.1 Indications of Ultrasound in Hepatobiliary System 1) Method of choice to evaluate biliary tree: Biliary radicle dilatation, site and cause of obstruction 2) Gallbladder pathology: Inflammation, neoplasms and calculi 3) For assessing liver echotexture and localising collections and space occupying lesions in the liver 4) For ultrasound guided interventional procedures: Biopsy/drainage 5) Elastography technique used to assess the hepatic fibrosis 6) Doppler for Evaluation of the hepatic vasculature

The main disadvantage is operator dependence, patient’s body habitus, presence of gas which can obscure the visualization of organs, overlying bandages in a postoperative patient and incomplete evaluation in a nonfasting state.

Patient preparation USG of upper abdomen should be done after 6–8 hours of overnight fasting. Milk and fatty food should be avoided as they cause contraction of the GB and may cause the GB walls to appear thickened. History of previous surgery, especially cholecystectomy should be elicited.

Scanning technique Gallbladder and biliary tree The patient may be positioned in supine or left lateral decubitus position. The GB can be scanned from a high/lateral view, looking through the ribs in supine position or through a sub-costal view in left lateral decubitus position. Position of patient may be changed to demonstrate mobility of structures. The GB is an anechoic structure which is located in the GB fossa along the posterior and inferior aspect of the liver. It has a fundus, body and a neck. It should always be examined in at least two planes (Fig. 9.1.6A and B). The wall of the normal GB should measure 3 mm or less and pathological GB wall thickening can be due to cholecystitis or a neoplastic aetiology. Calculi appear as mobile hyperechoic foci, with distal acoustic shadowing. Other pathologies include polyps and sludge which can be differentiated on the basis of their mobility.

FIG. 9.1.6 (A) Right subcostal view showing gallbladder. (B) Short axis view for examining gallbladder wall (GB). The CBD measures less than 6 mm in diameter with increase in the diameter with patient’s age and after cholecystectomy. The CBD is usually scanned in an oblique subcostal plane with the patient in the left decubitus position (Fig. 9.1.7).

FIG. 9.1.7 Oblique subcostal view for imaging the Portal vein and CBD which are seen in the region of the hepatoduodenal ligament. The CBD (between callipers) is anterior to the portal vein (PV). The gallbladder (GB) is seen further anteriorly. Dilatation of the intrahepatic biliary radicles is readily assessed with USG and normal intrahepatic biliary radicles are usually not appreciated on USG.

Liver Ultrasound of the liver, broadly, is done to assess the size, surface (smooth, coarse or lobulated) parenchymal echogenicity (increased or decreased) vascularity and for presence and evaluation of intrahepatic masses or fluid collections. Hepatic anatomy on ultrasound The liver is divided into right and left lobes by plane of middle hepatic vein which passes through GB fossa and notch of IVC (Cantlie Line). Couinauds classification is the most commonly used system for liver segmental anatomy and described liver into eight functional segments. It is based on distribution of portal and hepatic veins. Every segment has its branch from portal vein, hepatic artery and bile duct (Fig. 9.1.8).

FIG. 9.1.8 Line diagram of liver showing Couinauds hepatic segmental anatomy. (Source: Courtesy of Robin Smithuis. Radiology assistant. NL/abdomen/liver/segmental anatomy – used with permission.)

Transducers Curvilinear transducer (3–5 MHz) is used for routine examination of liver and GB (Fig. 9.1.9).

FIG. 9.1.9 Curvilinear transducer. A high-frequency linear transducer (9–11 MHz) (Fig. 9.1.10) can be used to look for subtle irregularity of the liver surface for early Cirrhosis and fine details of GB wall.

FIG. 9.1.10 High-frequency linear array transducer. Technique of scanning liver The liver is scanned in deep inspiration, which causes inferior movement of liver, so that superior borders of the liver are well visualized. Supine position is used for the size of the liver. The measurement is made in sagittal mid clavicular position on right side, in craniocaudal dimension. It is taken from diaphragm to the lower end of the liver. It should be 120

End Time 25–35 120 Microbubble disappearance (240– 360)

FIG. 9.1.18 Time-intensity curve of lesion and normal liver parenchymal in contrast-enhanced ultrasound. Sharp upstroke followed by gradual washout. Contrast-enhanced ultrasound of a hepatic hemangioma in different phases (Fig. 9.1.19).

FIG. 9.1.19 CEUS of hepatic hemangioma. (A) Greyscale ultrasound showing hyperechoic SOL in the liver. (B) CEUS in arterial phase showing peripheral nodular enhancement. (C) Portal phase showing continuous filling of lesion. (D) delayed phase showing complete filling of the lesion. Limitations of CEUS: • The main limitations of CEUS are same as that of conventional B mode ultrasound: Beam penetration, operator dependence, breathhold etc. • Only one lesion can be studied at a time with repeat bolus required to study other lesions. • It is not advocated in lactating women as there is insufficient evidence of any side effects.

Liver elastography Liver elastography is a noninvasive method for diagnosing liver fibrosis. Liver fibrosis is induced by chronic liver disease leading to cirrhosis and liver cancer. Liver biopsy is the gold standard for diagnosing the degree of fibrosis and for staging but it is an invasive method. Elastography helps in analysing the elasticity or the stiffness of the tissue. A stiffer liver tissue indicates fibrosis or chronic liver disease.

Two main methods used are ARFI (acoustic radiation force impulse) and fibroscan ARFI is based on the principle of measuring Shear wave velocity. Short duration acoustic pulses which are generated in the tissue and these give rise to shear waves which travel, perpendicular to the ultrasound beam. These shear waves cause tissue displacement followed by recovery. This displacement and recovery depend on tissue stiffness. To monitor these shear waves US beams of low intensity are emitted continuously parallel to the main beam along with the push pulses, and these beams can gather data regarding the tissue stiffness. The shear waves cause tissue displacement and this tissue then recovers from the impulse. From this data the degree of tissue stiffness can be obtained which is displayed either as a map or quantitatively where tissue elasticity is expressed as shear wave velocity measured in meters per second. Indications and uses • Used in diagnosing degree of liver fibrosis and contributes to treatment planning and prognosis assessment in liver fibrosis. • Can be used to obtain elastographic images and values of liver lesions which may help to qualify them. Technique

• Patient in supine/slight 30 degrees left lateral decubitus position with right arm positioned overhead. Four hours fasting is ideal. • Intercostal approach is used which uses right lobe segments 7 and 8 to make measurements more reliable (left lobe unreliable). • The region of interest (ROI) should not include the major vessels and biliary structures. Measurement should be 2 cm deep and perpendicular to liver capsule. • Serial measurements (minimum 10 measurements to be taken) are taken in the same way and report is generated (Fig. 9.1.20).

FIG. 9.1.20 Liver Elastography – (A,B,C) Showing serial measurements taken and (D) showing average measurement generated. Scoring system • There are many scoring systems used of which Metavir system is most accurate. Metavir scoring (Table 9.1.3) is a semi-quantitative and has five-point scale from F0 to F4. TABLE 9.1.3 Liver Fibrosis Staging Liver Fibrosis Staging Normal

Metavir Score F0

kPa 2.0–4.5

m/s 0.81–1.22

Normal–Mild

F0–F1

4.5–5.7

1.22–1.37

Mild-Moderate

F2–F3

5.7–12.0

1.37–2.00

Moderate–severe

F3–F4

12.0–21.0+

2.00–2.64+

F0, normal; F1, enlarged fibrotic portal tract; F2, periportal/initial porto-portal septa with intact architecture; F3, architectural distortion with no obvious cirrhosis; F4, cirrhosis.

Limitations of ARFI

1) Does not replace liver biopsy for staging of liver fibrosis or cirrhosis. 2) Low specificity. 3) Liver congestion, biliary obstruction and hepatic inflammation can effect the results. 4) Difficult to distinguish normal with very mild disease and moderate with severe disease in some cases.

Fibroscan It is also known as Transient Elastography (TE) and works on the similar principle as ARFI, the difference being that B mode ultrasound image is not produced. 9 .1 .3

DOPPLER OF PORTAL VEIN Introduction The portal vein divides at the portahepatis into right and left branches. The right portal vein divides into anterior and posterior branches, and the left portal vein divides into medial and lateral branches.

Indications and uses 1. For the assessment of portal hypertension. 2. For evaluating portal venous thrombosis-benign/malignant. 3. To predict variceal bleeding in cirrhosis. 4. To evaluate flows post-liver transplantation. Technique • Low-frequency transducer (3–5 MHz) is chosen. Entire length of portal vein is examined in subcostal and right paramedian with slight oblique approach (Fig. 9.1.21). • Portal vein is observed where it crosses the hepatic artery to compare the flow with the artery. Normal portal vein diameter is less than 13 mm and is measured in quiet respiration before its bifurcation. • The sample volume cursor should be placed in the centre of the lumen midway between the portal confluence and its bifurcation into right and left branches. • The settings should be optimized for detection of slow flow. The colour Doppler sample box should be small. The pulse repetition frequency (PRF) or scale is set low to avoid aliasing and motion artefacts and the gain should be maximized till the noise artefacts do not obscure the image appear. • Doppler angle should be less than 60 degrees.

FIG. 9.1.21 (A) Line diagram showing transducer position in oblique view on right side. (B) corresponding colour flow image showing portal vein flow in red and right lobe of liver. Doppler imaging Portal vein shows a continuous, forward low-velocity flow (15–28 cm/s) on colour Doppler scanning. The flow is hepatopetal, that is, towards liver and is red in colour as it is flowing towards the transducer. It has an undulating pattern and shows respiratory variation with increase flow in inspiration. It may reflect cardiac variation and shows postprandial increase calibre and flow in healthy individuals. Normal Doppler waveform of portal vein (Fig. 9.1.22).

FIG. 9.1.22 Showing doppler ultrasound of portal vein-Portal venous waveform is monophasic with an undulating pattern with increased flow on inspiration. The sample volume should be placed in the centre of the portal vein. Portal hypertension can be defined as elevated pressure within the portal venous system resulting in impaired blood flow through the liver. Sonographic features of portal hypertension 1) Increased diameter of the portal vein (>13 mm), lack of respiratory variation in the portal vein or its tributaries. 2) Hepatofugal (flow away from the liver) flow due to raised portal pressures. The portal flow direction can be compared with the hepatic artery. When they are in opposing directions, portal flow is reversed. 3) Decreased portal velocity or volume (13 mm) abnormal liver texture and ascites are also commonly seen.

Pitfalls 1) Enlargement of the portal vein >13 mm is indicative of portal hypertension with a high degree of specificity (100%) but low sensitivity (45%–50%). Portal vein diameter may increase on deep inspiration 2) The portal vein may not always be enlarged with portal hypertension as portal flow may get diverted through lieno renal shunt, resulting in a small portal vein at the porta hepatis. 3) Portal vein flow velocity decreases with portal hypertension due to increased resistance to flow but with the presence of a recanalized paraumbilical vein, the flow velocity in the main portal vein may be increased. 4) An acute, anechoic thrombus can be missed in greyscale imaging. Hence colour Doppler and spectral Doppler are useful in these cases. 9 .1 .4

INTRAOPERATIVE PANCREATIC AND HEPATIC ULTRASOUND Intraoperative pancreatic ultrasound

Intraoperative ultrasonography of the pancreas was first described in 1980 by Lane and Glazer. It is an important technique for guidance of both open and laparoscopic surgical procedures of the pancreas. As the transducer is in direct contact with the organ of interest, with no interference with air of adjacent soft tissue, it provides good resolution. It is considered superior to CT and MRI in assessing the intraoperative tumour resectability and vascular invasion and guiding resection. Indications and uses • Intraoperative staging of tumours. • Looking for regional metastasis. • Looking for arterial and venous patency. • For identifying neuro-endocrine tumours. • Differentiating pancreatitis from a neoplasm. • For guiding biopsy. • For duct cannulation. • For guiding drainage of abscesses or cysts. • For identifying the relationship of the tumour to adjacent vessels.

Transducers for use in intraoperative US For intraoperative US during open surgical procedures, a high-frequency linear-array transducer or the hockey stick transducer (Fig. 9.1.23) are used which create highresolution detail of the exposed pancreas. The side-fire curved linear-array transducer is effective for obtaining a wider view of the pancreas and its surrounding structures and for scanning the liver.

FIG. 9.1.23 Hockey stick transducer for intraoperative ultrasound. Technique • The transducer probe is encased with a sterile probe cover or a sheath filled with coupling gel. Avoid air trapping between sheath and transducer. Normal saline can be used to avoid the artefacts near the edges of the lesion and lobulated margins of pancreas. • Overlay sweeps are given with transducer in the transverse and sagittal planes for the complete coverage of the gland. • The ultrasound is carried out with greyscale followed by colour Doppler. • Hepatic artery, portal vein and superior mesenteric artery should be evaluated especially while examining a mitotic lesion to look for vascular encasement.

• If the pancreas has not been surgically exposed, a transhepatic or transgastric approach is used in scanning, with the left lobe of the liver or the compressed stomach serving as an acoustic window. For this scanning method, a low-frequency transducer is required. Pitfalls • It may be difficult to distinguish a pancreas in cases of diffuse fatty infiltration from a background of retroperitoneal fat. In such conditions, vascular landmarks will be useful for identifying the gland. • The contours of the gland are mostly lobulated, and the clefts of the gland should not be mistaken for lesions. • Pressure exerted on the pancreas with the transducer causes vascular compression, which can be seen as vessel narrowing or occlusion. • Vascular calcifications may be seen and mislead to incorrect diagnosis of chronic pancreatitis.

Intraoperative hepatic ultrasound Intraoperative hepatic ultrasound gives the real-time visualization of the hepatic anatomy and aid for surgical planning and making decision during surgery. Indications and uses • Survey of the primary or metastatic lesions. • Guidance for resection of tumour. • To check for vascular patency after anastomosis • In liver transplantation for evaluation of vascular anastomoses and guiding harvesting phase of right lobe split liver transplantation. • For guiding intraoperative tumour ablation. • For imaging of retained stones and biliary anatomy during resection. • Extrahepatic disease extension like lymph nodes can be assessed. Transducer and technique • Side-fire T-shaped linear- or curvilinear-array transducers (5 MHz). Transducer enclosed with sterile sheath and coupling gel is required. • Continuous overlapping strokes are performed in a transverse position, from most lateral margin of the left lateral segment II towards the right side to scan the entire liver. • Only light pressure is applied to avoid venous compression. • Transducer must be appropriately positioned in the ROI and imaged including the margins. Doppler ultrasound is used for the vascular involvement and patency. • Both near and far zones must be examined when segments IV, V, and VIII are imaged. Limitations • Imaging of certain areas of the liver like high dome of right lobe and posterior subdiaphragmatic bare area of the liver is challenging. • Focal fat infiltration can appear as pseudolesions. • Margins of the segments can appear echogenic because of accumulation of air. • Small lesions just below the surface, commonly the surface metastatic lesions from colorectal carcinoma, can be missed. 9 .1 .5

MULTIDETECTOR CT OF THE HEPATOBILIARY SYSTEM AND CHOLANGIOGRAPHY

Multidetector CT of the hepatobiliary system The cross-sectional plane of the patient is denoted as the x/y plane. The plane along which the table moves is the ‘z’ plane. Multidetector CT denotes more than one detector along the Z-axis, with the latest machines having up to 320 and now even 640 rows of detectors. This provides CT with very fast, high resolution, isotropic images which can be reconstructed in any plane or even curved planes. MDCT scanners can comfortably scan the entire abdomen in 10 seconds or less, thereby allowing visualization of different phases of contrast enhancement.

Principles of contrast administration and enhancement Contrast Media (CM) after administration gets distributed from the intravascular compartment into the interstitial spaces. Intravascular arterial enhancement (for angiography) and parenchymal enhancement have different kinetics. Parenchymal enhancement is directly proportional to total iodine dose being administered and inversely proportional to weight, which is a marker of extracellular volume into which contrast redistributes. Rate of iodine administration has no effect on degree of parenchymal enhancement. As a general rule approx. 500–600 mg of iodine/kg body weight achieves adequate hepatic parenchymal enhancement. For a 60 kg adult, this translates into approx. 100–120 mL of contrast containing 300 mg of iodine per mL. Intravascular or arterial enhancement is controlled by rate at which iodine is administered (flow rate and iodine concentration of CM) iodine flux and duration for which contrast is administered longer injection also leads to better overall arterial opacification due to recirculation effects. This principle is made use of while performing abdominal CT Angiography. Higher iodine delivery rate per unit time using a higher iodine concentration contrast medium also improves conspicuity of vessels and hypervascular lesions such as HCC. For identical parameters, difference in arterial enhancement between patients is dependent on cardiac output with enhancement being inversely proportional to cardiac output. For optimal imaging and enhancement, in multiphase imaging and angiographic studies, contrast material administration and parenchymal or vascular enhancement must be synchronized with CT data acquisition. The two main methods are: Test bolus technique: A test dose of contrast is given and the time to peak enhancement is measured in a ROI placed in a target vessel this information can be used to tailor CT acquisition. Automated bolus Triggering: ROI is placed in target vessel (usually aorta at level of diaphragm) on a plain image. While CM is injected, a series of low dose scans is obtained through the ROI. When the density of contrast reaches a predefined threshold (e.g. 150 HU), at time ‘t’ the scan is automatically triggered. The trigger delay after time ‘t’ is a minimum of 2 sec, and can be programmed to any value. Bolus tracking is nowadays the method of choice for planning contrast medium administration and this technique provides more homogenous opacification. Saline chase is recommended in all multiphase protocols. Significant amount of contrast may be present in the peripheral veins after injection of IV contrast and use of saline chaser leads to better vascular enhancement and lower overall contrast dose (Fig. 9.1.24).

FIG. 9.1.24 Bolus Triggering Technique – The X-axis represents time and the y axis the HU value within the ROI placed either at the level of diaphragm or coeliac axis. The scan is triggered at the present time after the HU value crosses over the threshold density (150 HU in this Case). Using the above, a standard sequence of acquisitions and contrast enhancement techniques can be tailored to the pathology and organ of interest and pre-programmed into the scanner menu, which includes kVp, mAs, pitch, rotation time, slice thickness etc. This is known as a scan protocol. However, these can be modified as necessary. For example, rotation time can be shortened and pitch can be increased for breathless patients to reduce scan times (Table 9.1.4). TABLE 9.1.4 Standard Operating Protocol in Hepatobiliary CT • Patient 6 hours fasting • Check Serum Creatinine • Oral Water 500 mL • Wide Bore Antecubital Vein Access • Review Indication and Decide Protocol • Contrast injection and Saline Chase • Image Acquisition and Reconstruction • Viewing and Reporting

Indications for diagnostic imaging of liver and gallbladder Multidetector CT is the workhorse of hepatobiliary imaging. It plays a major role in imaging congenital, traumatic, infective, neoplastic and vascular pathologies of the hepatobiliary system. Scans can be obtained with or without intravenous (IV) iodinated contrast material administration. Multidetector CT scanners are capable of imaging multiple phases at different points of time following injection of contrast and provide dynamic imaging due to fast scan times and rapid coverage of the abdomen. Indications for liver imaging include, but are not limited to: Unenhanced Scan: Hepatic fat estimation, radio opaque biliary calculi. Single Phase Scans: Liver abscess, polytrauma, follow up of known oncologic or benign lesions, abdominal pain, suspected cholecystitis. Multiphase Studies: Evaluation of hepatic masses, imaging in cirrhosis, imaging for resectability, liver donor evaluation, malignancy of GB, hepatic venous outflow obstruction etc.

CT Angiography of Hepatic Vessels: Trauma, vasculitis, post-operative bleeding and as a part of multiphase studies. Depending on the indication, scanning protocols can be tailored to highlight the suspected pathology and provide relevant answers for further management (Table 9.1.5). TABLE 9.1.5 Scan Phases for Hepatic Imaging Phase Early arterial (CT angiography) Later arterial/portal inflow Portal/hepatic venous Equilibrium Delayed

Timing 8–10 seconds post-trigger

Visualization Arterial tree

15–20 seconds post-trigger

Hypervascular hepatic lesions

60–70 seconds post beginning of CM injection 180 seconds post beginning of CM injection 5 minutes post-trigger

Hypovascular lesions against enhanced hepatic parenchyma Some HCC in cirrhotic liver Cholangiocarcinoma, hemangioma

Scan protocols for hepatic imaging The liver has a dual blood supply, most of which is derived from the portal vein. After injection of contrast, until the portal vein provides recirculated contrast material filled blood to enhance the hepatic parenchyma, the hepatic parenchymal enhancement is relatively poor and dependent only on the hepatic artery. The hepatic arterial phase can be divided into an early arterial phase without any portal opacification, a late arterial or portal inflow phase in which there is some portal vein opacification. This is followed by a portal venous phase in which portal and hepatic veins are enhanced (also called the hepatic venous phase in some articles). In addition, an unenhanced/plain scan and an equilibrium phase can also be acquired. Tumour conspicuity of hypervascular lesions was found to be best on the late arterial or portal inflow phase (Fig. 9.1.25). The early arterial phase is seen up to 10 seconds after trigger, and provides ‘angiographic’ images of hepatic arterial anatomy. This phase is used to provide details regarding arterial anatomy and morphology. Later arterial phase 18–23 seconds, portal venous phase 60–70 seconds and equilibrium phase 180 seconds are obtained after trigger. Equilibrium phase images have been shown to increase detection of hepatocellular carcinoma in cirrhotic patients. The portal venous phase is the standard phase for routine chest/abdomen survey and follow up of hepatic abscesses and hypovascular metastases.

FIG. 9.1.25 Early arterial phase images (A) and late arterial phase images (B) in a patient with cirrhosis and multifocal HCC. Note the greater conspicuity of lesions (arrows) on the later arterial phase as compared to the early arterial phase, highlighting importance of late arterial imaging in detection of HCC. Single Phase Scan Protocol: Oncologic follow-up, Liver Abscess – For routine singlephase CT, contrast as per body weight can be injected over 40 seconds and scanning can be

done after an empiric delay of 70 seconds from the beginning of injection. This protocol provides good parenchymal enhancement and portal and hepatic vein visualization. Plain scan is optional. Dual-Phase Scan Protocol: Hepatic evaluation in patients with malignancies known to have hypervascular metastases – Neuroendocrine tumours, renal cell carcinoma, thyroid carcinoma, (.) melanoma etc. Late arterial Phase 20–22 seconds and Portal venous phase at 60–70. Plain scan optional. Hepatic Resection Protocol: For patients with known hepatic mass being evaluated for resection. Early arterial phase provides pure arterial or angiographic images. It is obtained at 8–10 seconds post trigger followed by portal venous phase at 60–70 seconds. This is required for arterial and venous anatomy and volumetric evaluation if required. Plain scan is not required. In case a hepatic mass needs characterization as well as resectability planning, late arterial and equilibrium scans may also be done. Indications for angiography are further discussed in the section on angiography. The same biphasic protocol using angiography or arterial phase images is used in patients with trauma suspected to have pseudoaneurysms, hepatic artery thrombosis or dissection in transplant recipients, evaluation of living donors and in patients in whom an angiographic ‘road map’ is required prior to intervention. Triphasic or 4 phase scan Protocol: Standard of care for patients with cirrhosis being evaluated for Hepatocellular carcinoma and for patients being evaluated for hepatic mass of uncertain aetiology. Late arterial phase scan: 20–22 seconds, Portal venous scan at 60–70 seconds and Equilibrium scan at 180 seconds. Plains scans are optional. Our institutional practice is to always do plain scans in patients who have undergone hepatic intervention. Plain scans also help to visualize siderotic and steatotic nodules. A further delayed scan is suggested by some authors at 10–15 minutes for characterization of hepatic masses of uncertain provenance. This is particularly useful in cholangiocarcinoma (Table 9.1.6). TABLE 9.1.6 Hepatic Imaging Protocols Clinical Indications Evaluation of cirrhosis for hepatocellular carcinoma Hepatic resection, liver donor vascular evaluation, suspected hepatic arterial pathology Follow-up of oncology patients, liver abscess Hepatic steatosis/liver attenuation index, suspected biliary calculi

Plain O

Early Late Portal Equilibrium Arterial Arterial Venous N Y Y O

O

Y

Y

Y

O

N

N

N

Y

N

Y

N

N

N

N

O = Optional, N = Not essential, Y = Yes/Mandatory.

Dual energy CT for liver imaging Dual-energy CT or spectra CT is based upon differential attenuation of the X-ray beam of different energies by the same material and is based on the photoelectric effect. The differential energy can either be at the level of the tube-either two tubes operating at different voltages or a single tube (consecutive or sequential scans, twin-beam with material filter, switching between two voltages) or at the level of the detector – sandwich, split and photon-counting detectors. Due to differential absorption, Dual-energy CT can detect even small quantities of material such as iodine within a voxel. The clinical applications in the liver include generation of virtual noncontrast images and increased conspicuity of enhancing or nonenhancing lesions and differentiation between tiny cysts and solid lesions/metastases (as iodine within lesion or in surrounding liver is easily visualized (Fig. 9.1.26). Other upcoming applications include quantification of liver fibrosis, liver iron content and liver fat content.

FIG. 9.1.26 Dual Energy CT images with an iodine only image (A) and Virtual non contrast images (B). The technique obviates need for obtaining plain scan. It helps in characterising these two small lesions as totally non enhancing, because the iodine images shows no iodine within the lesion. These lesions may have been difficult to qualify on standard CECT due to small size.

Perfusion CT of the liver Perfusion CT of liver is done by obtaining multiple scans through area of interest to follow contrast inflow and outflow from the liver, by monitoring tissue density over a period of time and obtaining information regarding perfusion parameters from these scans. In liver imaging, unlike other organs, the input function is derived not only from the arterial inflow, but the portal inflow as well. The CT protocol begins with a pre-contrast image, followed by a tight bolus of highdensity contrast. Dynamic sequential image acquisition after administration of CM. Two phases are seen – the first phase (40–60 seconds) which reflects hepatic blood flow and the second phase (2–10 minutes) which reflects capillary permeability. Software-based postprocession is done to generate coloured maps of blood flow, blood volume, mean transit time and permeability Clinical uses include monitoring response to treatment, prognostication of tumours based on perfusion, early diagnosis of primary or metastatic tumours, and monitoring recurrence after therapy. Challenges include high radiation dose, motion correction and reproducibility.

Indications for diagnostic imaging of the pancreas MDCT is the primary modality for imaging pancreatitis and its complications, and for determining resectability in pancreatic adenocarcinoma. MDCT is also used for suspected or confirmed neuroendocrine lesions of pancreas and is sometimes used as a primary or complementary imaging modality to MRI for Cystic pancreatic lesions. The other indications include congenital anomalies including annular pancreas and evaluation of trauma. Scan protocols for pancreatic imaging Contrast kinetics of the pancreas follows that of aorta, with an additional delay for contrast to diffuse into the pancreatic interstitium. Pancreatic adenocarcinomas are hypovascular and enhance less than the pancreatic parenchyma. Four phases can be obtained for pancreatic evaluation – plain scan, arterial phase (angiography), pancreatic phase and the portal venous/hepatic venous phase. The pancreatic phase is the time after injection when there is maximum enhancement of the pancreatic parenchyma and this precedes the venous phase. The pancreatic parenchymal phase is usually seen 35–40 seconds after contrast injection or approximately 25–30 seconds after trigger placed in abdominal aorta at 150 HU and provides maximum contrast between normal pancreas and hypovascular tumour and is thus the best phase for detection and staging of pancreatic carcinoma (Fig. 9.1.27).

FIG. 9.1.27 Early Arterial (A), Pancreatic (B), and Portovenous (C) phase images in a patient with a small hypodense lesion in pancreatic head (arrowheads). The tumour to normal pancreas conspicuity is maximum in the pancreatic phase (B) as shown above, illustrating the importance of correct phase in imaging of pancreatic adenocarcinoma. Plain Scan: Detection of chronic calcific pancreatitis, Calcification in cystic lesions and in pancreatitis with deranged renal functions or suspected haemorrhage particularly within a pseudocyst. Single Phase Scan: Usually acquired in the Portal venous Phase, for imaging pancreatitis and its complications. Our institutional protocol is to use positive oral contrast in patients with pancreatitis if they can tolerate it. Water is used in multiphase imaging Biphasic Scan: Pancreatic adenocarcinoma resectability – Pancreatic phase scan for tumour conspicuity and arterial anatomy, followed by a Portal venous phase scan for detection of hepatic metastases and evaluation of the portal and superior mesenteric veins, which may show incomplete filling or flow artefacts in the pancreatic phase. Early Arterial Phase Scan: This is akin to a pure angiographic image of the pancreatic and coeliac vasculature. It is generally combined with a portal venous phase scan for evaluation of hypervascular lesions of pancreas – Neuroendocrine tumours (Fig. 9.1.28). Arteriovenous malformations, metastases and intrapancreatic accessory spleen. It is also be indicated patients with pancreatitis with suspected intra-abdominal bleeding to rule out pseudoaneurysms. Though angiographic early arterial phase imaging has not found to add to tumour conspicuity, some institutes prefer to add this phase for details of vascular and variant anatomy if any in patients of pancreatic carcinoma being evaluated for resectability (Tables 9.1.7 and 9.1.8).

FIG. 9.1.28 Early arterial (A) and portovenous (B) images in reveal intensely enhancing lesion (arrow) of the pancreatic neck on early arterial images. The lesion appears almost isodense on the portovenous images highlighting importance of Early arterial phase imaging for pancreatic neuroendocrine tumour.

TABLE 9.1.7 Phases of Pancreatic Imaging Phase Plain Arterial (CT angiography) Pancreatic Portal/hepatic venous

Timing

Visualization Haemorrhage/altered content in pancreatitis, small calcifications 8–10 seconds post-trigger Arterial anatomy, neuroendocrine tumours, pseudoaneurysms 25–30 seconds post-trigger Pancreatic adenocarcinoma 60–70 seconds after Pancreatic adenocarcinoma (liver and beginning of injection SMV) pancreatitis

TABLE 9.1.8 Clinical Indications With Phases of Acquisition in Different Pancreatic Pathologies

Pancreatic adenocarcinoma

O

O

Y

Portal/Hepatic Venous Y

Pseudoaneurysm, neuroendocrine tumour Acute pancreatitis

O

Y

O

Y

O

N

N

Y

Chronic pancreatitis

O

N

N

Y

Clinical Indications

Plain Arterial Pancreatic

O = Optional, N = Not essential, Y = Yes/Mandatory.

Cholangiography Normal anatomy Segmental bile ducts drain an individual segment of the liver. In the right lobe, the segment VI and VII ducts unite to form the Right Posterior Sectoral duct (usually horizontal) and the Seg V and VIII ducts unite to form the right anterior sectoral duct (usually more vertical). On the AP view, the posterior ducts tend to project more laterally. These unite to form the right hepatic duct. The Right and left hepatic ducts exit from the porta to form the common hepatic duct (CHD). The common hepatic duct receives the cystic duct to form the CBD. The CBD extends inferiorly in the hepatoduodenal ligament, posterior to the duodenum, and enters the pancreas. It unites with the main pancreatic duct (MPD) to drain into the duodenum. The left hepatic duct (LHD) is anterior to the right hepatic duct (RHD). The CHD and CBD usually course ventrally as they descend inferiorly, before turning dorsally prior to entry into the duodenum and thus may not fill well in the supine position. Fig. 9.1.29A and B various variations of branching of the biliary tree may, however, be encountered.

FIG. 9.1.29 Line Diagram Showing Coronal (A) and Sagittal (B) anatomy of the biliary tree. The left sided radicles are relatively anteriorly placed thus air tends to collect in them on the supine images. Also note the anterior curve of the CBD as it descends inferiorly (RASD, Right anterior sectoral Duct; RPSD, Right posterior sectoral Duct; CBD, Common Bile Duct; RHD, Right Hepatic Duct; LHD, Left hepatic Duct; CHD, Common Hepatic Duct). MPD averages 16–17 cm in length. It has a short horizontal segment near the sphincter, then ascends cranially. Up to this segment, it drains the head. It then turns sharpl4 to course horizontally towards the tail, this transition is the neck. The remainder is the body and tail. (Approximately half and half). The left side of vertebral body can also be taken as the junction between body and tail (Fig. 9.1.30).

FIG. 9.1.30 Normal anatomy of the pancreatic duct. The main duct drains, along with the common bile duct into the ampulla of Vater. It continues superiorly through the head and then turns at the ‘shoulder’ (black arrow) in the region of the neck to continue into the body and tail. The accessory pancreatic duct drains at the minor papilla proximal to the Ampulla. CT cholangiography CT cholangiography can be used to visualise biliary pathology. Three main techniques are available. • CT Cholangiography using Intravenously administered Cholangiographic Contrast • CT Cholangiography using Orally administered Cholangiographic Contrast • CT cholangiography using Minimum Intensity projections after administration of IV contrast.

Technique for intravenous agent-cholangiography Patient fasting for 6 hours. Plain scans of the upper abdomen are obtained followed by slow intravenous infusion of 100 mL of meglumineiotroxate (Biliscopin) over 30–45 minutes. After an additional 30–45 minutes a scout film is obtained to confirm excretion into the biliary tree followed by a volumetric acquisition and multiplanar recontructions.

Indications • The primary indication is for visualization of the biliary ductal system, in preoperative evaluation of patients before hepatic resection, including prior to liver transplantation and for evaluation of variant biliary anatomy. • Post-operative biliary leaks, particularly in patients in which endoscopic access in hindered or not possible (Post gastrectomy, gastric outlet obstruction, large periampullary diverticulum etc). • Evaluation of hepatolithiasis and Choledocholithiasis.

Contraindications • Allergy to iodinated contrast material. • Deranged renal functions. • Pregnancy. Advantages • Noninvasive.

• Very high spatial resolution with isotropic voxels leading to high-quality multiplanar images. • Evaluation of contrast flow through the sphincter into the duodenum. • Visualization up to 4th order biliary radicles. • If multiphase CT acquisition done after the study, the ability to evaluate relationship of ducts to arteries and veins and provide complete pre-operative surgical road map. Disadvantages • Exposure to ionizing radiation and iodinated contrast. • Nondiagnostic in patients with bilirubin more than 3 mg/dL due to poor contrast excretion. • Nondiagnostic in patients with significantly dilated biliary tree. • Patient spends long time in department as infusion and excretion take over an hour.

Technique for oral CT cholangiography/cholecystography The patient is asked to have a late dinner and ingests 6 g of oral cholecystography contrast agent-iopanoic acid 30 minutes after dinner. MDCT Images are obtained 6–12 hours after ingestion. If GB is to be imaged, patients are given a meal containing at least 50 gms of fat, 30 minutes prior to imaging. In addition, patients are given a glass of water to drink prior to scanning to wash out contrast from the small bowel. Disadvantages • The ability of iopanoic acid to opacify the gallbladder can be hampered by many conditions that could interfere with absorption and/or excretion of contrast material into the biliary system. • Evaluation of GB may be hampered by inflammation of the GB. • Opacification of biliary tree may be suboptimal. • Large number of tablets of orally administered contrast have to be swallowed

Nonenhanced CT cholangiography using minimum intensity projection images (MinIP) This technique is also been called intravenous inverse contrast-enhanced CT cholangiography (IVICE CTC) (Fig. 9.1.31).

FIG. 9.1.31 CT ‘cholangiography’ using minimum intensity projection showing anatomy of low attenuation dilated intrahepatic biliary radicles on a background of enhanced liver with block in the region of the confluence (arrow) secondary to a cholangiocarcinoma. Note good visualisation of the anatomy of the intrahepatic ductal system.

Technique Similar to doing contrast-enhanced CT of the abdomen. Patient drinks water. A plain scan of the upper abdomen is acquired followed by IV contrast administration. Images are acquired either in the portal venous phase or as a part of a multiphase study. Administration of intravenous contrast makes the unenhanced hypodense biliary tree more conspicuous against the enhanced liver parenchyma. Thereafter, images are reconstructed in multiple planes including curved MPR and viewed as minimum intensity projections thus providing a virtual cholangiography image. This technique can also be used without IV contrast. It has been reported to have a similar diagnostic accuracy as PTC and MRCP. Curved MPR images can also be obtained. The main disadvantage of this technique is in the nonvisualization of stones having similar attenuation as bile or those that are very small in size.

Indications The predominant indication is to determine level and cause of obstruction in a patient with obstructive jaundice and dilated biliary radicles. To evaluate other disorders including congenital and neoplastic disorders of the pancreatic and biliary tree. Advantages Can be routinely used in all modern workstations as part of CT staging or imaging protocol Can be used in patients who cannot have an MRI Disadvantages Use of ionizing radiation and intravenous contrast

T tube cholangiography A ‘T’ Tube is a tube inserted into the CBD after it has been surgically handled. As the name suggests, it is shaped like a T with the shorter limbs being placed into the bile duct and the longer limb extending out through the parietal wall. It is placed to allow healing and prevent Bile leak. A T tube cholangiogram is a procedure in which dye is instilled through a surgically placed T tube and the biliary ducts are outlined (Fig. 9.1.32).

FIG. 9.1.32 Showing a normal T Tube Cholangiogram. Cystic Duct Stump (small black arrow) CBD with T tube in situ (large black arrow) Intrahepatic Biliary radicles are normally opacified with contrast noted passing into the duodenum (curved arrow).

Indications 1) To evaluate for residual calculi post-cholecystectomy. 2) To evaluate any postoperative biliary enteric anastomoses and rule out postoperative leak.

Contra-indications 1) Active Cholangitis. 2) Hypersensitivity to iodinated contrast media. 3) Pregnancy.

Patient preparation Usually, the patient is called 4 hours fasting. Usually, 4 hour fasting is required before the procedure. The T Tube is clamped to completely fill the T tube with bile and prevent air bubbles. A single dose of broad-spectrum antibiotic may be administered if patient is immunosuppressed, however, institutional practice varies and in our institute no preprocedure antibiotic is administered.

Technique Examination is usually done prior to removal of T Tube, usually around the tenth day. A preliminary supine plain image of area of interest is obtained. Dilute water-soluble iodinated contrast medium is used as a contrast medium. A small gauge needle is inserted into the T tube between the clamp and patient after cleaning the tube and contrast is injected into the biliary tree to outline the entire biliary tree. Bile is aspirated and contrast is injected into the T tube. The procedure is done under fluoroscopic guidance and filling of the biliary tree is observed. Drainage into the duodenum is confirmed At least two views of the biliary tree should be recorded on spot film. Patient position may be changed to fill unspecified portions of the biliary tree.

Delayed film at 15 minutes may be done to demonstrate emptying and distal drainage (Fig. 9.1.33).

FIG. 9.1.33 T-Tube cholangiogram showing opacification of distal CBD with a filling defect suggestive of Calculus in the lower end (arrows).

Pitfalls Contrast material should not be overly dense to prevent obscuration of stones. Adequate opacification of the CBD may not occur in the supine position due to oblique course and patient should be turned into left lateral or oblique positions. The most common confounding factor in a T tube cholangiogram is presence of air bubbles (Fig. 9.1.34). Air bubbles are perfectly round and tend to be nondependent and float superiorly on change of position. Calculi may have faceted or angular edges. Rarely, calculi may float. In case of doubt, a saline flush followed by a repeat study can be done, and bubbles will usually disappear. (Pseudocalculus defect may occur in the distal CBD due to incomplete relaxation of sphincter of Oddi, where it may show a superior meniscus.) It is usually transient and in contrast to stone, the lower edge of the pseudo calculus is never opacified. Other causes of pseudo calculus are impression of right hepatic artery and indentation by periportal lymph nodes.

FIG. 9.1.34 Tube cholangiogram showing filling defects in CBD (arrow) and left hepatic duct (arrowhead), which shows relatively poor filling due to anterior position. These filling defects disappear on change of position suggesting air bubbles with better opacification of left hepatic duct seen on left oblique position.

Complications include pain in abdomen, biliary peritonitis and Cholangitis.

Percutaneous transhepatic cholangiography (PTC) Percutaneous Transhepatic cholangiography, as the name suggests, is a method to opacity the biliary ductal system by placing a needle through the liver into a dilated biliary radicle and then injecting contrast to opacity the biliary tree (Fig. 9.1.35).

FIG. 9.1.35 Percutaneous biliary puncture using a fine needle (arrow) to opacify the biliary tree prior to percutaneous biliary drainage. Diagnostic percutaneous cholangiography is obsolete in the present imaging scenario.

Indications Historically, PTC was done as a diagnostic procedure in patients with suspected obstructive jaundice for determination of aetiology. Diagnostic PTC is now redundant. PTC, when done these days, is generally used as an initial step while performing an interventional procedure on the biliary tree, generally a percutaneous Transhepatic Biliary drainage (PTBD).

Contraindications 1) Deranged bleeding parameters. 2) Hypersensitivity to iodinated contrast.

Equipment Chiba Needle-When biliary tree is undilated or minimally dilated. In dilated systems, a thicker needle can be used. Ultrasound unit (the current standard of care). Fluoroscopy Unit.

Preparation 1. Haemoglobin, bleeding parameters and platelets are checked. 2. Prophylactic antibiotics. 3. Nil by mouth for 4 hours. 4. Arrange for analgesia/anaesthesia.

Technique

• Right, left or both sides access is decided, on the right side, usually intercostal and on the left side, the access site is usually subcostal. • After local anaesthesia, during suspended respiration, the needle is inserted into the liver, with the current practice being to do it under ultrasound guidance. • Once the needle appears to be in the biliary tree, the stilette is removed and needle connected to a syringe and bile flow is seen to confirm correct placement. • Contrast medium is injected under fluoroscopy to outline biliary tree and plan/modify procedure.

Precautions • Excessive contrast should not be injected into a dilated system. • If injected contrast disperses rapidly, needle is in a vessel. • If irregular channels are opacified, needle is in lymphatics.

Complications • Bleeding and hematoma formation. • Cholangitis. • Bile leak and peritonitis. • Septicemia. • Injury to adjacent structures (rare under ultrasound guidance). 9 .1 .6

CT ANGIOGRAPHY OF THE HEPATOBILIARY SYSTEM AND INTERVENTIONS IN HEPATOBILIARY SYSTEM CT angiography of the hepatobiliary system CT angiography for hepatic, biliary and pancreatic lesions can be performed for purely vascular pathologies, and visualization of the arterial tree, which can be seen independently from overlying or underlying structures, but in the current scenario of multi-detector CT is usually performed as part of a multiphase study which has been discussed above The basics of arterial enhancement are discussed above and re-iterated below: • Peak arterial enhancement will depend on iodine flux. To get better first pass arterial enhancement one should increase the amount of iodine injected per unit time either by increasing speed of injection or increasing concentration of iodine in contrast media. • Increasing duration of injection will lead to more sustained and broader peak of arterial enhancement due to recirculation effects. • Patients with poor cardiac output will have delay in first pass arterial contrast enhancement but will have stronger enhancement as contrast will tend to move slowly through the circulation. Indications for CT angiography in the Hepatobiliary System • Evaluation of hepatic artery Aneurysms: Second most common visceral artery aneurysm after splenic artery. • Evaluation of suspected vasculitisegPolyarteritisNodosa. • Hepatic vascular malformations including hereditary hemorrhagic telangiectasia. • Preoperative evaluation of vascular anatomy and variations in patients being worked up for hepatic resection due to tumour, GB carcinoma or in living liver donors (Fig. 9.1.36).

• Postoperative evaluation of hepatic artery in liver transplant recipients to rule out hepatic artery thrombosis or stenosis • Postoperative drop in haemoglobin or bleeding through drain in patients undergoing hepatic or biliary surgery or other interventional procedures. • Post-trauma to rule out pseudo aneurysm (Fig. 9.1.37). • Evaluation of haemobilia. • Provide a vascular ‘road map’ prior to endovascular intervention. • Evaluation of variant anatomy prior to Whipple’s procedure (Institutionalpreference). • Evaluation of suspected vascular complications of pancreatitis and pseudoaneurysms. CT angiography can both detect and help to plan therapy (choice of embolic material, extent of embolization etc). • Evaluation of suspected pancreatic vascular lesions and AV malformations.

FIG. 9.1.36 CT angiography (early arterial phase) images, providing exquisite details of the arterial tree in a liver donor. Note origin of the segment 4 artery (arrow) from the anterior division the right hepatic artery, which is a surgically important variation during right hepatectomy.

FIG. 9.1.37 CT angiography (early arterial phase) images in a patient with hepatic trauma showing well-defined arterial focus of enhancement (A). Coronal reformats reveal pseudo aneurysm arising from anterior division of right hepatic artery (B). This is confirmed on the Volume rendered images (C).

Interventions in hepatobiliary system Liver biopsy Targeted biopsy is sampling of focal liver lesions, while nontargeted biopsy is sampling of liver in case of diffuse parenchymal disease.

Indications for targeted biopsy: 1. Primary liver lesions. 2. Metastatic liver lesions of unknown primary Indications for nontargeted biopsy: 1. Assessment and progression of parenchymal disorders a. Cirrhosis–Hepatitis B, Hepatitis C, Autoimmune hepatitis. b. Nonalcoholic fatty liver. c. Hepatic steatosis. 2. Deposition disorders – Hemochromatosis, Wilson’s Disease, Gaucher’s disease. 3. Deranged liver function tests with uncertain aetiology. 4. Assessment of orthoptic liver transplant rejection. I. Contra-indications: 1. Bleeding diathesis. 2. Patient noncooperation. 3. Massive ascites. 4. Morbid obesity. II. Methods: 1. Ultrasound-guided – most commonly used modality. 2. CT guided – used when the focal lesion is not accessible on sonography. 3. Transvenous/transjugular – may be used in patients with bleeding diathesis, massive ascites and morbid obesity. III. Pre-biopsy work-up: The following laboratory requirements laid down by Society of Interventional Radiology Consensus Guidelines must be met before the procedure: • International normalised ratio P

RT

5 mm

Yes

90

350 mm

192 × 112

A>P

BF

5 2.6(IP), 1.3(OP) mm

No

70

350 mm

256 × 208

A>P

BH

61

3.9

1.3

2 mm

Yes

9

350 mm

320 × 195

A>P

BH

3.9

1.3

2 mm

Yes

34#

350 mm

320 × 195

A>P

BH

RT = Respiratory triggered, BF = Breath free, BH = Breathhold. (*) = An additional T2W with higher TE helps differentiate hemangioma from solid tumour. (#) = Increased flip angle in hepatobiliary phase gives better lesion conspicuity and T1 cholangiography.

TABLE 9.1.13 Role of Various MR Sequences in Liver Imaging MR Sequence HASTE T2FS

What to Look for Overall T2 overview Routine TE (80– 100) High TE (180– 200)

In- and opposed-phase GRE T1W

Excellent for lesion detection and primary lesion characterisation (majority of malignant lesions are isointense to spleen) To differentiate hemangioma/cystic lesion from solid tumours Intracellular fat (e.g. dysplastic nodules, HCC, liver steatosis), Intracellular iron (e.g. siderotic nodules, hemochromatosis)

FIESTA/True FISP/Balanced FFE Diffusion-weighted b=0 imaging Low b value 2500 ms (improves ADC calculation, lesion detection) and matrix lower than other sequences, in range of 128 × 128. • At least three set of DW using b-values of b = 0, lower b-values ( 3 seconds: reduces T1 effect Acquire data at multiple echo times: reduces T2* effect

Easily available

Can evaluate fat fraction from 0% to 50%

Evaluate at smallest TE to reduce T1 bias

T2* effect not considered, hence wrong quantification in iron overload T1 bias

Use the earlier low TE consecutive images to reduce T2* effect

Does not take into account T1bias, T2* effect, noise bias, spectral complexity of fat and eddy currents

Evaluate at smallest TE to T1bias,

WSM Chemical shift imaging (IP, OP, W and F only)

Can evaluate FF from 0% to 100%

PDFF Chemical shift imaging (IP, OP, W and F only) with correction for other factors

Can evaluate FF from 0% to 100%

No validated data

T2* effect, noise bias, spectral complexity of fat and eddy currents

Corrects for T1bias, T2* effect, noise bias, spectral complexity of fat and eddy currents Unaffected by technological or biological variabilities FF: fat fraction

MR spectroscopy Different protons in the body resonate at different frequencies. MRS uses this principle to quantify the signal of fat and water in the liver and hence the fat fraction can be calculated. Methylene peak of fat (CH2) resonates at a frequency of 1.3 ppm whereas water (H2O) resonates at a frequency of 4.7 ppm (Fig. 9.1.57). It is the most accurate method to quantify liver fat, however, it has its limitations. A single voxel is placed on a small part of the liver; hence it quantifies fat in that region. Multivoxel MRS results in decrease in signal to noise ratio. MRS is time-consuming and requires expertise. There are high chances of sampling error so longitudinal monitoring is not possible.

FIG. 9.1.57 MRS of the liver showing a methylene peak of fat (CH 2) (A) at a frequency of 1.3 ppm and water (H 2O) (B) at a frequency of 4.7 ppm.

Conventional in-phase (IP) and opposed-phase (OP) imaging This technique also exploits the same principle as MRS. The fact that H2O and CH2 resonate at different frequencies, the images are acquired at echo times at which water (W) and fat (F) are in-phase (W + F) and opposed-phase (W − F). The echo time for fat and water are based on the relative chemical shift between the two. The relative loss in signal on the opposed phase images can be used for volumetric liver fat detection (Fig. 9.1.58A and B). Fat signal fraction (FF) can be calculated as:

FIG. 9.1.58 In and opposed phase images of the liver showing a normal nonfatty liver with no drop in signal on the opposed phase images (A) and a fatty liver showing drop in signal on the opposed phase images (B). This approach is only valid if the range of fat signal fraction in the liver is between 0% and 50% when magnitude images are used, as the signal of the opposed phase image with 35% fat is same as the signal with 65% fat. This can be resolved with water-fat separation methods or sequences that exploit the differences in T1 between water and fat. Complex chemical shift based water separation methods (wsm) This is also based on chemical shift imaging where water and fat only images are obtained along with the in- and opposed-phased images (Fig. 9.1.59). All these images are co-registered and a fat fraction map is obtained. This method can measure fat in the dynamic range of 0%–100%.

FIG. 9.1.59 Complex chemical shift based water separation, wherein in (A) and opposed phased images (B) and water (C) and fat only (D) images are obtained at the same time. Both the conventional IOP as well as WSM don’t directly measure the concentration of fat in the liver as the MR signal is dependent on multiple factors which also need correction. Proton density fat fraction (PDFF) This sequence overcomes the limitations of water separation methods, that is, it is a chemical shift-based water separation technique which also corrects for all other factors which are responsible for the MR signal of the liver (Fig. 9.1.60). It addresses T1 bias, T2*decay, spectral complexity of fat, noise bias and eddy currents. A lower flip angle reduces the T1 bias, T2*effect is eliminated by incorporating the model into the sequence protocol.

FIG. 9.1.60 Proton density fat fraction (PDFF) image. Conclusion Various imaging techniques are available for qualitative and quantitative fat fraction evaluation of the liver by MRI. Over the years MRI has shown tremendous progress with newer techniques now available which are cost-effective and accurate. With the rise in NAFLD, there is increasing demand for robust newer sequences. Despite

these newer sequences continued technical development and validation are required for them to be widely accepted as standardized tools for liver fat quantification.

Hepatic iron quantification with mr imaging Introduction Iron overload is a systemic disorder which results in iron accumulation in various organs, with the liver being the predominant and first organ to be affected. It is characterized by increase in the plasma iron concentration with deposition of iron in the form of ferritin and hemosiderin in the affected organs. MRI has evolved as a noninvasive technique for quantification of liver iron concentration (LIC). Indication The clinical indication include an abnormal elevated level of ferritin or iron saturation, in patients of repeated history of blood transfusions, family history of hemochromatosis, help in treatment planning by grading the severity of iron overload in cases of transfusional and hereditary hemochromatosis and prevent complications of iron overload. Techniques Several sequences are available for subjective and quantitative evaluation of LIC (Table 9.1.17). In a healthy individual the signal of the liver is higher than that of the paraspinal muscles on a T2W images. T1W have limited sensitivity to iron overload, T2* with intermediate TE have moderate sensitivity and T2* with long TE are very sensitive to iron overload.

TABLE 9.1.17 The Protocol and Findings for Each Sequence for Iron Quantification Flip Parameter Breathhold Findings Angle Assessed T1W in and T2 No Low SI as opposed shortening in compared to phase in-phase spleen on inphase images T2W T2 No Low SI of shortening liver compared to spleen T2 and R2 2500 6,9,12,15,18 20 T2 No Progressive relaxometry shortening decrease in (spin echo SI of liver multi-echo) compared to spleen on increasing TE values T2* and R2* 25 Multi-echo 90 T2* Yes Progressive relaxometry 1–18 shortening decrease in (GRE multicompared to echo) spleen on increasing TE values Signal120 2,4,9,14,19 20 Liver to Yes Low SI of intensity muscle SI in liver with ratio (GRE) T1W, PD and reference to T2W with paraspinal increasing muscles TE Susceptibility 14 May vary 5 T2* Yes Progressive mapping shortening decrease in (GRE multiSusceptibility liver SI echo) compared to spleen on increasing TE values Increasing magnetic susceptibility TR

TE

The subjective sequences include: 1. Chemical shift imaging: T1W in and opposed phase. 2. Conventional T2W images. The sequences for subjective as well quantitative evaluation include: 1. T2 relaxometry. 2. Signal-intensity ratio. 3. Quantitative susceptibility mapping. Chemical shift imaging: The conventional in and opposed phase T1W images show a drop in signal in the in-phase images in cases of iron overload; however, these have significant limitations if there is associated steatosis.

Conventional T2W images: Iron is superparamagnetic, hence, causes T2 shortening and drop in signal on T2W images relative to the signal of the spleen. These two methods provide subjective information regarding iron overload, but are unable to quantify the LIC. Relaxometry: It is the quantitative measurement of LIC. They are of two types: 1. T2 relaxometry which uses a T2 spin echo sequence with multiples echoes to measure the signal decay in the liver 2. T2* relaxometry which uses single breathhold gradient echo (GRE) sequence to measure the signal decay with increasing TE (time to echo) values. R2 and R2* are the mathematical inverses of T2 and T2*relaxation. R2 and R2* are used for regulatory purposes. The sequence is based on the fact the hepatic iron deposition results in T2 shortening along with a combination of the fact that there are local inhomogeneities in the magnetic field due to ferritin and hemosiderin deposition in the hepatocytes resulting into decrease in the T2/T2* and increase in R2/R2* values. R2/R2* is measured by taking a mid-section of the liver and drawing an ROI following the liver boundaries to generate a R2/R2* values (Fig. 9.1.61). The hilar vessels are excluded in the ROI. Postprocessing algorithms are commercially available for calculating the R2/R2*values (Fig. 9.1.62) (Table 9.1.18).

FIG. 9.1.61 R2/R2* is measured by taking a mid-section of the liver and drawing an ROI following the liver boundaries to generate a R2/R2* values. The hilar vessels are excluded in the ROI.

FIG. 9.1.62 Postprocessing algorithms for calculating the R2/R2*values. TABLE 9.1.18 The Advantages and Disadvantages of T2 Versus T2* Relaxometry Time of Acquisition T2 relaxometry Long (up to 20 min), hence prone to respiratory artefacts T2*relaxometry Short, single breathhold 3D sequence, hence covers full span of the liver

Correlation Postprocessing Cost 1.5T/3.0T with LIC excellent Long: By a Expensive centralized data analysis, charged per patient Linear correlation with LIC

Short: free software available

Cheaper

Limited use in 3T machines in cases of severe iron overload (>30 g/g per dry weight)

Signal intensity ratio: This technique was introduced by Gandon and colleagues in 2004 and has been modified in 2017. The signal of the liver is compared with a reference signal, that is, the paraspinal muscles. In a healthy individual, the signal of the liver parenchyma is higher than that of the paraspinal muscles whereas in the case of iron overload this reverses. It is a multiple breathhold gradient echo sequence with increasing TE values producing different weighted images. Five sets are acquired at TE of 2 ms (T1W), TE 4 ms (proton density) and T2* at TE of 9, 14 and 19 ms. The flip angle and TR remain constant in each set. The ratio of the signal of the liver to the paraspinal muscles is calculated by placing three ROI in different locations on the liver of 1–2 cm each, away from the vessels and placing one ROI each on either side on the paraspinal muscles in each set of images. In cases of severe iron overload this technique has its limitations as the signal of the liver decays in the first acquisition. T1W opposed images are avoided as signal loss due to fatty changes cannot be differentiated from signal decay due to iron overload. This technique is performed using a body coil and not surface coils. The use of surface coils leads to reduction in signal to noise ratio and produces higher signal closer to

the coil inducing bias. The protocol for acquisition of these sequences can be obtained online for 1.0,1.5, and 3.0T magnets. The five sets of ROIs obtained are post processed using a free web-based calculator, developed by the University of Rennes. Quantitative susceptibility mapping (QSM): The presence of ferritin and hemosiderin in the liver leads to augmentation of the local magnetic field. This local magnetic field can be measured using a GRE sequence with two or more echoes. Chemical shift imaging with water-fat separation, B0 field mapping are simultaneously performed to get a quantitative susceptibility map. This technique is, however, in the research process and shall not be discussed in detail (Table 9.1.19). TABLE 9.1.19 The Advantages and Limitations of Each Quantitative Technique Technique Signal intensity ratio

Advantages

T2 Relaxometry

Limitations

Simple, easily available on all scanners

Not accurate in severe iron overload

Free postprocessing tool

Paraspinal muscles are assumed to be normal and used as reference

Postprocessing validated

Long-time of acquisition Postprocessing paid and time consuming Prone to respiratory artefacts Technically difficult Only performed on a 1.0T magnet

T2 *Relaxometry

Fast 3D acquisition so can cover large volume of liver

Postprocessing not freely available

Postprocessing available for 1.5T and 3.0T magnet QSM

Highest sensitivity

Still in research

Conclusion There are several quantitative techniques to measure LIC, each with its own advantages and limitations. The serum iron does not have a linear correlation with liver biopsy whereas the liver iron does, hence MR liver iron quantification is routinely performed in all cases of iron overload and annually in patients on long term transfusions, starting from the initiation of transfusions. MRI has now been established as a noninvasive tool to assess the distribution, detection, grade and monitor treatment response in a case of iron overload.

Magnetic resonance elastography Introduction Magnetic Resonance Elastography (MRE) is a noninvasive technique to evaluate hepatic fibrosis. It is increasingly gaining importance as hepatic fibrosis is reversible

in the early stages and is not diagnosed by routine imaging techniques. The results of MRE are comparable to liver biopsy. In fact, liver biopsy has its limitations as it is not reproducible, samples only a small part of the liver and is invasive so patient compliance is poor along with risk of complications. Indication The main indication is to detect and assess the degree of fibrosis in the liver. It is also used to monitor response to treatment, guide/replace liver biopsy, guide in treatment planning and help predict the risk of complications in liver disease. Technique It requires added software and hardware to the normal MRI machines. The hardware consists of an active pneumatic acoustic driver that generates the mechanical shear waves that is connected via a flexible polyvinyl tube to a passive driver that is placed on patient’s abdomen at the expected site of the liver and tightly strapped (Fig. 9.1.63A and B). The active acoustic driver is placed outside the MRI room. Two lines are drawn perpendicular to each other, the horizontal line at the inferior margin of the xiphisternum and the vertical line in the mid clavicular region (Fig. 9.1.64). The passive driver is placed centred at the cross section of these lines. The torso phased-array coil is placed over the driver. The shear waves are then generated with a standardized accepted frequency of 60 Hz which pass through the hepatic parenchyma. In a healthy individual the hepatic parenchyma is soft, and the waves pass slower, hence they have a short wavelength, whereas in hepatic fibrosis the liver becomes stiff and longer wavelength waves are generated. These are postprocessed by a special inversion algorithm and cross-sectional images are generated. The liver stiffness measurement (LSM) are then made in kilopascals (kPa) and a greyscale or coloured image is generated.

FIG. 9.1.63 (A) Active acoustic driver that is placed outside the MRI room. (B) Passive acoustic driver that is placed on the patient’s abdomen.

FIG. 9.1.64 The passive driver is placed on the abdomen at the intersection of lines, the horizontal line at the inferior margin of the xiphisternum and vertical line in the mid clavicular line. Patient preparation Four to six hours fasting is required, as in a patient with fibrosis, the stiffness of liver increases if patient is not fasting; however, there is no change in a healthy liver. Obesity, ascites, bowel loop interposed between the liver and diaphragm do nOt interfere with MRE, unlike ultrasound-based elastography. In a patient with iron overload, the findings may be erroneous if a gradient echo sequence is used. Sequences Depending upon the application, phase images are acquired which are based on gradient echo, spin-echo or EPI with superadded motion encoding gradients (MEGs) in the longitudinal axis. The MEG picks up cyclical micron changes in the amplitude of the shear waves. The most accepted sequence is a modified gradient echo sequence with MEGs, which generates a magnitude, phase and wave images. The protocol is listed in Table 9.1.20. Four sets of images are obtained with breathhold of 16 seconds each. These should be acquired from the widest part of the liver, avoiding the diaphragm and the most inferior part of the liver (Fig. 9.1.65). TABLE 9.1.20 MR Elastography Protocol TR/TE Matrix NEX 50/20 ms

256 × 64

1

FOV 38–48 cm

Bandwidth NEX 33 kHz

1

Acquisition Slice iPAT Time Thickness 16 seconds

2

6–8 mm

FIG. 9.1.65 Four sets of images are acquired from the widest part of the liver, avoiding the diaphragm and the most inferior part of the liver. The waves are automatically processed after the acquisition is complete and the generated images are called elastograms. These quantitative images may be displayed in grey scale or colour scale. LSM is measured by drawing the ROI. These can be drawn as an oval or geographical ROI such that the margin of the liver is not included, approximately one-half of a wavelength from the margin. Also, the portahepatis, GB and the larger vessels should be excluded (Fig. 9.1.66).

FIG. 9.1.66 ROI to generate 95% confidence map should not include the margin of the liver, the porta hepatis, gallbladder and the larger vessels. Spin echo and EPI based sequences are preferred in patients with iron overload.

Interpretation of images The stiffness of the liver is in units of kPa. The normal liver has a stiffness of 31 g, bulky ALL, connected to liver via a stalk of tissue or wide base in the subphrenic or perihepatic zone. 2. 11–30 g, small ALL, showing wide base connection to the hepatic surface or around the right posterior lobe. 3. An ALL with no connection to the liver, often seen in thorax or pelvis. 4. A tiny ectopic ALL (1 cm from confluence K4 K5

Importance of detection intrahepatic biliary variants 1. Liver transplant – knowledge of donor biliary anatomy is vital and has been discussed in details in chapter on liver transplant 2. Evaluation before biliary interventional procedures Preprocedural MRCP is often performed prior to biliary drainage procedures not only to ascertain the level of anatomical block but also identifying any anatomic variants which may lead to incomplete drainage of the obstructed bile duct 3. Before gallbladder surgeries Accessory or aberrant posterior sectoral ducts are important to identify prior to surgery in patients who undergo preprocedural MRCP. These ducts may course posterior to an inflamed gallbladder neck, parallel to and/or in close proximal to the cystic insertion and can be mistaken as the cystic duct. This information is vital to the surgeon prior to surgery to avoid inadvertent ligation or trauma to the duct.

Extrahepatic biliary tree Cystic duct The cystic duct attaches the gallbladder to the extrahepatic bile duct. The cystic duct often shows a tortuous course. The cystic duct usually joins the extrahepatic bile duct approximately halfway between the porta hepatis and the ampulla of Vater. Classical anatomy of cystic duct joining the CHD at its middle third from lateral aspect is seen in 58%–75% of cases. The point of cystic insertion is, however, variable.

Imaging anatomy

USG The normal cystic duct can be seen in up to 50% of cases as an anechoic tubular structure connecting the gallbladder and bile duct. CT The cystic duct may not always be seen on CT. When seen it appears as a tubular cystic structure with thin enhancing walls. MRI The cystic duct is best visualized on MRCP and can be traced in its entire extent from the gallbladder up to the insertion in extrahepatic system (Fig. 9.2.78). The cystic duct may also be visualized on T1weighted images when it contains concentrated, high signalintensity bile.

FIG. 9.2.78 MRCP showing cystic duct. Normal insertion of cystic duct (arrows) in CHD. The corrugated appearance is normal.

Variant cystic duct anatomy Variations in cystic duct insertion are also frequently seen (Fig. 9.2.79). Prior knowledge of the cystic duct anatomy and its variants helps in proper interpretation of disease process and avoids iatrogenic injuries.

FIG. 9.2.79 Variant anatomy of cystic duct. Pictorial representation of variants in cystic duct anatomy.

Anatomical variant 1. Parallel course of cystic duct – defined as cystic duct coursing parallel to the CHD for at least a 2 cm segment is one of the commonest variations in cystic duct insertion (Fig. 9.2.80).

FIG. 9.2.80 Parallel course of cystic duct. MRCP images in a postcholecystectomy patient showing cystic duct coursing parallel to the CHD for a length of 2 cm.

Relevance 1. The CHD can be mistaken for cystic duct and inadvertently ligated, leading to postoperative complication. Ligation or transection of long cystic duct too close to the CHD can result in strictures in the CHD. In case of long cystic duct with low medial insertion, a long stump may be left following cholecystectomy. This stump maybe prone to complications like inflammation and calculus disease contributing to postcholecystectomy syndrome. 2. Next most common variation is medial insertion of the cystic duct. 3. Low cystic duct insertion, which is seen as fusion of the cystic duct with the distal third of the extrahepatic bile duct (Fig. 9.2.81).

FIG. 9.2.81 Low insertion of cystic duct. MRCP image in a patient with choledocholithiasis showing insertion of cystic duct into the distal extrahepatic duct (arrows). Relevance – Dissection of low medial cystic duct up to its distal end may result in postoperative complications. It is advisable to leave a long remnant in such cases. 4. Short cystic duct is defined as cystic duct having a length of less than 5 mm, reported in 1.3%–2.6% of cases in previous studies (Fig. 9.2.82).

FIG. 9.2.82 –Short cystic duct. MRCP image showing a short cystic duct with length of 4 mm (arrows). Relevance – rare but important variant and increases the chance of biliary injury, especially during laparoscopic cholecystectomy.

5. Aberrant drainage of cystic duct into RHD is rare and reported in 0.3%–0.4% of patients inadvertent transaction and ligation. Other variations in cystic duct insertion are spiral course of the cystic duct and high fusion of the cystic duct with the CHD. Hepaticocystic duct is an anomalous duct draining directly into the cystic duct. Cholecystohepatic duct is a term given to a duct passing through the gallbladder fossa. Other uncommon variations are double cystic duct, absent cystic duct and cystic duct entering the RHD. CBD The RHD and LHD join in the hilar plate, in front of right branch of PV, to form the CHD. The CHD unites with the cystic duct along its right margin at an acute angle, to form the CBD. CBD is divided into supraduodenal, retroduodenal, retropancreatic and intraduodenal segments (Fig. 9.2.83). The divisions and relations of these segments are described in the table below.

FIG. 9.2.83 Segments of the CBD. MRCP image showing the supraduodenal, retroduodenal, intrapancreatic and intraduodenal segments of the CBD.

Supraduodenal This segment lies in the hepato-duodenal CBD. ligament. The portal vein is seen posterior to it and the hepatic artery proper is seen on the right of this segment. Retroduodenal This segment courses behind the superior part of part duodenum and to the right of the GDA. Retropancreatic This segment runs behind the pancreatic head to part enter the medial wall of second part of duodenum. This segment may sometimes groove in the pancreatic head or courses intrapancreatically. Only in 17% cases this segment is truly retropancreatic while in the rest it is intrapancreatic. Intraduodenal Near the middle of medial border of second part segment of duodenum, the CBD and the duct of Wirsung unite to form a common channel which opens on the major papilla.

Arterial supply of the biliary tree Arterial supply of the biliary tree has important surgical implications in liver transplantation and the development of ischaemic changes and strictures after vasculobiliary injuries. The intrahepatic and extrahepatic bile ducts are conventionally believed to be totally dependent on the hepatic arterial supply for oxygenation. There is, however, some recent evidence contribution of PV to the microvascular blood flow. The arteries supplying the CBD and CHD are posterior superior pancreaticoduodenal artery (PSPDA) from below and RHA, LHA and cystic arteries from above. The blood supply of the cystic and hilar hepatic ducts come from cystic artery and right and left hepatic arteries.

Radiology USG USG may not be able to see a normal calibre duct. However, identification of a dilated duct may be useful clue to presence of pathology. Pancreaticobiliary union is, however, not identified. CT/MRI Thin slice MDCT will identify a normal calibre CBD in its entire extent. It is excellent to identify biliary dilatation, aetiology and level of block (Fig. 9.2.84). It is, however, not the modality of choice for evaluation of anatomical variants, anomalies of pancreaticobiliary union.

FIG. 9.2.84 Normal CBD in CT. Contrastenhanced CT in venous phase showing normal CBD appearing as a thin-walled hypodense linear structure (arrows). MRI with MRCP is the modality of choice in visualization of all segments of the CBD (Fig. 9.2.85). Biliary variants, anomalous pancreaticobiliary union can be identified in most cases. Classification systems for APBDU are based on MRCP.

FIG. 9.2.85 Normal CBD on MRCP. MRCP image showing normal CBD appearing as bright fluid intensity linear structure (red arrows). The cystic duct (blue arrows) is seen inserting into CHD (yellow arrows).

The common channel The formation of this common channel between the CBD and pancreatic duct occurs in 85% cases while in the remaining 15% cases, the two ducts either open separately or form a V junction before opening (Fig. 9.2.86).

FIG. 9.2.86 Normal common channel. MRCP image showing normal common channel between the CBD and pancreatic duct (arrows) measuring 6.6 mm.

Anomalies of pancreaticobiliary union Abnormal junction of the pancreatic duct and the CBD outside the duodenal wall to form a long common channel, more than 15 mm in length is termed as anomalous pancreaticobiliary union. A classification was proposed by the Japanese Study group in 2015. Type A – Stenotic segment of distal CBD joins the common channel with upstream CBD dilatation. Type B – Nonstenotic distal CBD joins the common channel. No localized dilatation of common channel seen. Type C– A narrow distal CBD joins the dilated common channel. Type D – Complex maljunction seen with other anomalies such as annular pancreas, divisum, etc. Other classifications for anomalies pancreaticobiliary union has been proposed by Komi et al. This classification system has been discussed in detail in chapter on choledochal cysts.

Relevance of APBDYU 1. Association with choledochal cyst – Anomalous pancreaticobiliary union has been seen in association with Todani type 1a, 1c and 4a cysts

2. Increased risk of Biliary strictures with cholangitis – affecting the distal duct or hilar duct 3. Biliary stones due to stasis in case stenotic variety leading to stagnation 4. Increased risk of pancreatitis 5. Increased risk of biliary tract cancers like cholangiocarcinoma or Ca gallbladder carcinoma

Pancreatic anatomy The pancreas is a retroperitoneal organ with both endocrine and exocrine functions. It secretes hormones like (insulin, glucagon and somatostatin), and also secretes pancreatic juice, involved in digestion. It can be divided into four main parts: Head, neck, body, Tail Head This is the thickest part of the pancreas and lies to the right of the superior mesenteric vessels. It is attached to the C loop of the duodenum. The uncinate process is a posterior extension of the head and lies behind the SMV. Neck This is thinnest part of the pancreas and is located anterior to the superior mesenteric vessels. The portal vein formation occurs behind the pancreatic neck by the union of the SMV and Splenic vein. Body This is the main part of the pancreas and lies to left of the mesenteric vessels. The peritoneum and omental bursa cover the anterior and posterior surface of pancreas, respectively. Tail The layers of the splenorenal ligament enclose the pancreatic tail in the splenic hilum. The pancreatic ductal system secretes the pancreatic juice. In most patients the pancreatic duct drains into the second part of duodenum at ampulla.

Relations Important posterior relations are the kidneys, aorta IVC and portosplenic mesenteric confluence. Anterior relations include lesser sac, lesser omentum, transverse mesocolon and infracolic compartment. Superiorly it is related the origin of coeliac trunk, common hepatic and splenic artery (Fig. 9.2.87).

FIG. 9.2.87 Relations of pancreas. Diagrammatic representation of important relations of pancreas.

Arterial supply The inferior and superior pancreaticoduodenal arteries provide arterial supply to the head. The neck, body and tail are supplied by the dorsal pancreatic artery, greater pancreatic artery (arteria pancreatica magna) and transverse pancreatic artery which are branches of the splenic artery (Fig. 9.2.88).

FIG. 9.2.88 Arterial and venous supply of pancreas. Illustration showing arterial and venous supply of the pancreas. The venous return of the distal pancreas is via multiple small veins that drain into splenic hilum. The drainage from head is via the pancreaticoduodenal veins into the PV and through the inferior pancreaticoduodenal vein into the SMV (Fig. 9.2.88).

Nodal drainage The lymphatic vessels of the pancreas follow the arterial supply. Drainage occurs into the pancreaticosplenal nodes and the pyloric

nodes, which drain into the superior mesenteric and coeliac lymph nodes (Fig. 9.2.89).

FIG. 9.2.89 Lymphatic drainage of pancreas. Diagrammatic representation of nodal drainage of the pancreas.

Radiology USG • For USG of pancreas patient should be fasting to reduce interference from overlying bowel gas, which may otherwise make visualization difficult. • In young patients, the pancreas is generally less fatty and therefore usually hypoechoic, fatty replacement of pancreas

occurs with age and can result in echogenicity (Fig. 9.2.90). • Endoscopic US (EUS), provides excellent information regarding pancreatic masses particularly in cystic lesions.

FIG. 9.2.90 Normal Pancreas on USG. Grey scale USG showing normal pancreatic head and body (arrows). CT On nonenhanced CT, the normal pancreas has a lobulated contour and slightly higher attenuation than the adjacent paraspinal muscles. Fairly homogenous enhancement is seen in the pancreatic parenchymal phase (late arterial), with HU up to 100–150. There may be slight attenuation differences between the pancreatic head and tail (0.73 = 99% likely to be cirrhotic (Fig. 9.3.5)

FIG. 9.3.5 Caudate lobe hypertrophy in cirrhosis. Unenhanced and enhanced CT showing enlarged caudate lobe with CL/RL ratio of >0.73. Normal hepatic volume In an adult patient of average weight (60 kg), the estimated liver volumes can range from 1024–1302 cm3 (Fig. 9.3.6).

FIG. 9.3.6 Normal liver volume. CT volumetry of an average adult male showing normal volumes of liver, right and left lobes.

Hepatic artery USG and Doppler provide important information regarding patency of artery in postoperative/transplant setting. Normal hepatic artery waveform is pulsatile and of low resistance. The normal resistive index measures 0.7. High or low resistivity index (RI) indicated pathology. The measurements of the hepatic arteries bare importance in transplant imaging. The diameter and length of the arteries are best measured on CT angiogram images. Arteries smaller in calibre than 2 mm may be difficult to anatomize. Replaced RHA is often longer in length than standard arteries. The normal diameters of the hepatic arteries are mentioned in Table 9.3.2 (Figs. 9.3.7–9.3.9). TABLE 9.3.2 Diameters of Hepatic Arteries Common hepatic artery Hepatic artery proper Left hepatic artery Right hepatic artery

0.50 ± 0.04 cm 0.45 ± 0.03 cm 0.30 ± 0.03 cm 0.36 ± 0.04 cm

FIG. 9.3.7 Normal CT angiogram. CT angiogram showing normal length and width of common hepatic artery.

FIG. 9.3.8 Normal CT angiogram. CT angiogram showing normal diameter of the left hepatic and middle hepatic artery.

FIG. 9.3.9 Normal CT angiogram. CT angiogram showing long normal calibre replaced right hepatic artery.

Portal vein The portal venous system is valveless and hence its diameter is influenced by respiratory variations. The portal venous diameter is greatest during inspiration and hence all measurement should be made in this phase (Table 9.3.3). The diameter of portal vein has importance in diagnosing portal hypertension and USG is often used for this purpose. USG also provides other important parameters like flow velocity and volume flow which are relevant in the setting of portal hypertension. The normal portal venous velocity measures 15–18 cm/sec.(Fig. 9.3.10) TABLE 9.3.3 Normal Measurements Diameter Length

11–13 mm 7–8 cm

FIG. 9.3.10 Normal portal vein on USG. USG and colour Doppler showing normal portal vein measuring 11 mm in diameter with hepatopetal flow on Doppler. Contrast-enhanced CT in venous phase is best to depict portal venous anatomy, variants and pathologies. It is the modality of choice in surgical planning (Figs. 9.3.11 and 9.3.12). Unlike USG, CT, however, does not provide functional information.

FIG. 9.3.11 Normal measurements of portal vein on CT. Contrast-enhanced coronal reconstructed images showing normal dimensions of main and right portal vein.

FIG. 9.3.12 Normal measurements of portal vein on CT. Contrast-enhanced CT portal venous phase, reconstructed images showing normal main, right and left portal veins.

Gallbladder The gallbladder wall thickness is the most important measurement as most GB pathologies affect the wall. The measurement can

accurately be done on any modality (Table 9.3.4) (Figs. 9.3.13 and 9.3.14). TABLE 9.3.4 Normal Measurements Capacity Length Diameter Wall thickness

50 mL 7–10 cm 3–4 cm 3 mm

FIG. 9.3.13 Normal ultrasound appearance of gallbladder. Grey scale USG showing normally distended gallbladder with wall thickness of 2 mm.

FIG. 9.3.14 Normal gallbladder on CT. Contrast-enhanced CT showing normal distension of gallbladder with normal wall thickness.

Cystic duct

This is best measured on MRCP. The cystic duct usually measures 2–4 cm in length. The normal diameter of the cystic duct is variable, ranging from 1 to 5 mm (Fig. 9.3.15).

FIG. 9.3.15 Normal cystic duct on MRCP. Thick slab images showing normal diameter of cystic duct. Length of the duct maybe variable. The corrugated appearance is normal. Cystic duct hypertrophy is seen when the diameter of cystic duct is more than 5 mm.

Intrahepatic biliary radicals The diameter of intrahepatic radicals is best evaluated at MRCP images. A diameter more than 3 mm or >40% larger than the diameter of adjacent intrahepatic portal venous radicals suggests dilatation (Figs. 9.3.16 and 9.3.17).

FIG. 9.3.16 Normal calibre biliary radicals. MRCP images showing normal calibre intrahepatic biliary radicals.

FIG. 9.3.17 Dilated intrahepatic biliary radicals. MRCP images in a patient with distal common bile duct (CBD) cholangiocarcinoma showing dilated intrahepatic biliary radicals and extrahepatic biliary tree.

CBD

Accurate measurement of CBD is of paramount importance in diagnosing biliary pathologies and in radiological evaluation of obstructive jaundice. Measurement can be done accurately on USG, CT and MRI, although the duct is best evaluated on MRCP. USG CBD is measured at the porta hepatis, in the most distal aspect of head of pancreas and midway between these points. To measure at a longitudinal view of the duct is taken. The duct is anterior and parallel to the portal vein at this level. The inner to inner diameter should be measured and the duct should measure not more than 6 to 7 mm at this level. This actually is the measure of the common hepatic duct (CHD) (Fig. 9.3.18). The duct is also measured in the head of pancreas and midway between the two, where the duct maybe slightly larger in calibre.

FIG. 9.3.18 Normal USG measurement of the CBD section to measure the calibre of the extrahepatic tree anterior to the portal vein. This is actually a measure of the CHD. On CT and MRI the bile duct wall is included in the measurement and hence diameter may increase by 1–2 mm. The diameter is best measured on coronal images. Measurements The upper limit of CBD on ultra sound (US) is 6–8 mm (lumen) and that of CHD is 6 mm.

On CT /MRI scan it is more common to accept a value of 8–10 mm for BD (Fig. 9.3.19).

FIG. 9.3.19 CBD on MRCP. MRCP images showing normal calibre CBD. Variation due to age: The diameter of the CBD increases with age. 1mm may be added to the upper limit of normal CBD for each decade of life after 60 years. Variation due to cholecystectomy: CBD diameter may increase 1–2 mm postcholecystectomy surgery but some patients may have a more profound dilatation of CBD (Fig. 9.3.20). Normal CBD measurements are given in Table 9.3.5.

FIG. 9.3.20 Postcholecystectomy prominence of CBD. MRCP images in a healthy asymptomatic patient showing dilated extrahepatic tree (arrows). TABLE 9.3.5 Normal Measurements CBD Length External diameter Internal diameter

6–8 cm 9 mm (range 5–13 mm) 8 mm (range 4–12.5 mm)

Pancreas Bulky pancreas is often the sole manifestation of pancreatic pathologies. The pancreatic thickness is the most important size parameter and is best done on CT/MRI. Visibility of entire pancreas may be challenging on USG as it is a retroperitoneal organ and confounding factors such as gases and bowel obscure the organ. Obesity is yet another detrimental factor. Thickness of pancreas varies with age. The thickness slowly increases from childhood to adulthood and is maximum between ages of 21 and 40 (Table 9.3.6). The thickness of gland then reduces with age. The head is the thickest part of the pancreas, followed by body and tail.

TABLE 9.3.6 Pancreatic Thickness Measurements Age Head Ultrasound (Mean ± SD, cm) 1 cm), irregular ampullary margin, extrahepatic biliary dilatation, pancreatic duct dilatation. • Difficult to differentiate from ampullary carcinoma

A 43-year-old, incidentally dete asymptomatic female: Axial CEC homogeneously enhancing lobulated ampulla ( arrow) projecting into the case of ampullary ade Duodenal gastrointestinal stromal tumor (GIST)

• Variable appearance, from small homogeneous mass to large necrotic mass; endophytic or exophytic to the bowel lumen

A 51-year-old-female with complain CECT image showing homogeneously mass projecting into the duodenal lu ampulla ( arrow) in a case of d

Diagnosis Imaging Features Ampullary/pancreatic • Arterial enhancing NET lesion

Images

A 50-year-old male presenting wit jaundice and weight loss: Coronal C hypervascular lesion involving the arrowhead) resulting in upstream d MPD with hepatic metastases ( arrow ampullary NET IPMN

• Dilated MPD with bulging of the papilla into duodenal lumen • Cystic lesions communicating with the pancreatic duct

A 75-year-old male asymptomatic p image showing multicystic lesion in pancreas having communication wit of branch-duct IPMN in the unci

Diagnosis Benign papillary stenosis

Imaging Features

Images

• CBD dilatation with normal (1.5 mm and hepatic artery to portal vein diameter ratio >0.45) with subcapsular hepatic arterial flow on Doppler. Gallbladder ghost triad and decreased gallbladder contraction index for age (Fig. 9.6.12C). Colour Doppler (Fig. 9.6.13): Hepatic arterial flow extending to the hepatic surface – subcapsular telangiectasia. Gold standard test: Hepatobiliary iminodiacetic acid (HIDA) scan (Fig. 9.6.14): Shows relatively good hepatic uptake with no evidence of excretion into the bowel at 24 h. 10. Rudimentary liver. 11. Ductal plate malformation: Multifocal cystic dilatation of segmental intrahepatic bile ducts as a result of ductal plate malformation. Dilatation depends on the level of the biliary tree that is affected (Fig. 9.6.15). • Biliary hamartoma: Disorganized clusters of dilated cystic ductal plate remnants that have failed to involute (Fig. 9.6.16). • Congenital hepatic fibrosis: Variable degree of periportal fibrosis with irregularly shaped proliferating bile ducts (Fig. 9.6.17). Manifests as fibropolycystic

disease. Biliary hamartomas, Caroli’s disease, polycystic liver disease and choledochal cysts often coexists. • Polycystic liver disease: Failure of union of intrahepatic biliary canaliculi and ductules with extrahepatic bile ducts, results in the formation of cysts within the liver. It is usually associated with cysts in the kidney and pancreas (Fig. 9.6.18). • Caroli’s disease (the simple type): Incomplete ductal plate remodelling resulting in persistent abnormal ductal plate remnants involving the large bile ducts. • Caroli’s syndrome (the periportal type of Caroli’s disease): Both the ductal plates and central intrahepatic bile ducts of the smaller peripheral bile ducts are affected, with the former leading to the development of fibrosis. Radiologically (Fig. 9.6.19): • Dilated IHBR with intraductal bridging. • Small portal venous branches partially or completely surrounded by dilated bile ducts. • Intraluminal portal vein sign – dilated ducts surrounding the portal vein. • Intraductal calculi.

FIG. 9.6.7 Riedel’s lobe of the liver.

FIG. 9.6.8 Sliver of the liver.

FIG. 9.6.9 Papillary process of the caudate lobe as indicated by the white arrow.

FIG. 9.6.10 Accessory hepatic lobe as indicated by the white arrow.

FIG. 9.6.11 Diaphragmatic slips.

FIG. 9.6.12 (A and B) USD findings of triangular cord sign. (C) Gallbladder ghost triad.

FIG. 9.6.13 Colour Doppler of hepatic arterial flow extending to the hepatic surface – subcapsular telangiectasia.

FIG. 9.6.14 Hepatobiliary iminodiacetic acid (HIDA) scan.

FIG. 9.6.15 Ductal plate malformation.

FIG. 9.6.16 MRI of the liver demonstrates multiple tiny T2 hyperintense cystic lesions consistent with biliary hamartoma.

FIG. 9.6.17 Pathologically proven case of congenital hepatic fibrosis with presence of Caroli’s disease.

FIG. 9.6.18 Multiple cysts of varying sizes and shapes in both lobes of the liver.

FIG. 9.6.19 ‘Central dot’ sign: Enhancing dots within the dilated intrahepatic bile ducts, representing portal radicles on CT. US: Dilated IHBR with intraductal bridging that appears as echogenic septa traversing the dilated bile duct lumen.

Gallbladder and extrahepatic biliary apparatus

Gallbladder and cystic duct develop from pars cystica of hepatic bud. Extrahepatic duct system of biliary apparatus (Fig. 9.6.20) At first, the extrahepatic biliary apparatus is occluded with epithelial cells, but it later recanalizes by vacuolation resulting from degeneration of cells. The narrow portion of hepatic bud between pars cystica and duodenal part of foregut forms the CBD. The undivided part of pars hepatica distal to the origin of pars cystica forms the CHD. The right and left branches of pars hepatica become right and left hepatic ducts.

FIG. 9.6.20 Extrahepatic Duct System of Biliary Apparatus. The bile duct at first opens on the ventral aspect of developing duodenum. Due to the differential growth of duodenal wall, and rotation of duodenal loop, it opens on the dorsomedial aspect of duodenum along with ventral pancreatic bud. Bile pigment begins to form during weeks 13 to 16 and enters the duodenum resulting in the green colouration of meconium.

Anomalies of the gallbladder I. Anomalies of shape: • Phrygian cap (Fig. 9.6.21): Fundus may be folded on itself to form a cap-like structure. • Hartmann’s pouch (Fig. 9.6.22): The wall of infundibulum may project downward as a pouch, which

may be adherent to the cystic duct or even to the bile duct and hence prone to calculi obstruction. • Diverticula in gallbladder: May arise from any part of the organ. • Multiseptated (Fig. 9.6.23) and bilobed gallbladder/boomerang gallbladder (Fig. 9.6.24). II. Anomalies of position: • Transverse position, retrohepatic, left-sided and subhepatic gallbladder. • Sessile gallbladder: The gallbladder may directly open into the bile duct instead of the cystic duct. • Floating/wandering gallbladder: The gallbladder will be lined by peritoneum on all sides. It may be attached to the liver by a fold of peritoneum or it may be completely free (risk of torsion is high), occasionally can herniate via the foramen of Winslow into the lesser sac. • Ectopic gallbladder: Can be found in the pelvis, epigastric area, also reported in the lung. • Intrahepatic gallbladder (Fig. 9.6.25): It may be embedded in the substance of liver, surrounded by hepatic parenchyma on all sides. III. Anomalies of number: • Duplication (Figs. 9.6.26 and 9.6.27): The lumen may be partially or completely divided by a septum (septate gallbladder), which may or may not extend into the cystic duct. The gallbladder may be completely or partially duplicated. • Agenesis of gallbladder (AGB): Failure of division of the caudal division of the primitive hepatic diverticulum or failure of vacuolization after the solid phase of embryonic development. Associated with other malformations in several systems in 40%–65%. • AGB without cystic duct remnant. • AGB with cystic remnant.

FIG. 9.6.21 Phrygian cap.

FIG. 9.6.22 Hartmann’s pouch.

FIG. 9.6.23 Multiseptated gallbladder.

FIG. 9.6.24 Bilobed gallbladder.

FIG. 9.6.25 Intrahepatic gallbladder.

FIG. 9.6.26 Duplication of gallbladder.

FIG. 9.6.27 (A to F) Septated gallbladder; duplication of the fundus; duplication of the body with single cystic duct; duplication of the entire gallbladder with two cystic ducts that unite into a single CBD giving a ‘Y shape’; complete/ductular duplication – the two cystic ducts enter separately into the biliary tree, giving an ‘H shape’; bilateral gallbladder.

Anomalies of the extrahepatic bile duct system

I. Abnormal length: There is considerable variation in the level at which various ducts join each other, with the result that occasionally some of them may become abnormally long or short (Fig. 9.6.28). II. Abnormal mode of termination (Fig. 9.6.29): • Cystic duct may join left side of CHD, passing either in front of it or behind it, to reach its left side. • Cystic duct may end in the right hepatic duct. • Cystic duct may pass downward, anterior to the duodenum, before joining the CHD. • Bile duct may open into the pyloric, or even the cardiac end of the stomach. • Biliary atresia (Fig. 9.6.30): Parts of the duct system, and sometimes the whole of it, may be absent. III. Duplication: Partial duplication of bile duct, complete duplication of bile duct, complete duplication of CBD + CHD + right and left hepatic ducts. IV. Accessory ducts arising from the right lobe may terminate in the right hepatic duct, the cystic duct, the bile duct, or even directly into the gallbladder. V. Choledochal cysts: Cystic dilatation of the biliary tree (Fig. 9.6.31). Anomalous formation of the pancreaticobiliary ductal junction results in a large common draining channel for the pancreatic and bile ducts. The pancreatic juices cause bile duct wall destruction and cholangitis, which together with distal stenosis due to scarring result in the formation of a choledochal cyst (Fig. 9.6.32). • Type I: Seen in utero and most common. Dilatation of the extrahepatic biliary duct. • IA: Cystic • IB: Saccular • IC: Fusiform • Type II: Diverticulum of the CBD (∼2% incidence). • Type III: Choledochocele involving the intraduodenal portion of the CBD – again of cystic, saccular and fusiform types (∼5% incidence). • Type IV: Intra- and extrahepatic duct dilatation (∼10% incidence). • IVa: Intra- and extrahepatic cysts • IVb: Multiple extrahepatic cysts • Type V: Caroli’s disease (rare).

FIG. 9.6.28 (A) Normal. (B) Right and left hepatic ducts join within liver parenchyma. (C) Long hepatic ducts. (D) Extra-long cystic duct.

FIG. 9.6.29 (E) Normal. (F and G) Joins left side of CHD, passing either in front of it or behind it. (H) Ends in the right hepatic duct.

FIG. 9.6.30 (A) Complete agenesis. (B) Gallbladder and cystic duct absent. (C) Cystic duct absent. (D) Hepatic duct absent. (E) Bile duct absent. (F) Terminal part of bile duct is absent.

FIG. 9.6.31 Choledochal cysts.

FIG. 9.6.32 Conventional cholangiography images demonstrating the types as depicted above.

Pancreas Functionally, the pancreas is both an exocrine and endocrine gland with difference in microscopic structure of the two components. Its exocrine function begins after birth but the endocrine function begins from the early embryonic period. By the seventh week of gestation, α-cells start secreting glucagon and by tenth week, insulin production by β-cells begins. The developmental primordium of the two structural and functional components is common. The pancreas develops from two endodermal buds; the dorsal and ventral pancreatic buds. The dorsal and ventral pancreatic buds arise from the dorsal and ventral walls of the terminal part of foregut (future second part of duodenum), caudal to hepatic bud, before rotation of midgut. • Dorsal pancreatic bud: • Appears during the fourth week and is larger in size when compared to ventral bud (Fig. 9.6.33A).

• It is cephalic to the ventral bud. • It grows between the two layers of dorsal mesentery of duodenum. • Ventral pancreatic bud: • It arises in close relation to hepatic bud, in the inferior angle between the duodenum and the hepatic bud. • It appears later and is smaller than the dorsal bud. • It grows between the two layers of ventral mesentery of duodenum. • Change in the position of pancreatic buds: • Right before the rotation of duodenal loop, the ventral pancreatic bud is on ventral aspect and the dorsal pancreatic bud is on dorsal aspect of duodenum. • With the rotation of duodenal loop to the right, the ventral pancreatic bud along with primitive bile duct comes to the right, and the dorsal bud to the left of the duodenum (Fig. 9.6.33B). • Due to the differential growth of wall of gut, the attachment of ventral pancreatic bud along with primitive bile duct shifts to the left moving closer to the dorsal pancreatic bud (Fig. 9.6.33C). • Fusion of buds: • Pancreatic tissue formed from ventral and dorsal pancreatic buds fuse to form one mass in the seventh week of gestation (Fig. 9.6.33E). • Derivatives of pancreatic buds: • Ventral pancreatic bud forms lower part of head and uncinate process of pancreas. • Dorsal pancreatic bud forms upper part of head, neck, body and tail of pancreas. • Pancreatic parenchyma: • The parenchyma develops from branching of endodermal pancreatic buds into the surrounding mesoderm. • The parenchyma of pancreas consists of exocrine and endocrine secreting units: The exocrine part of pancreas consisting of acinar secreting units, develops from proliferation and reorganization of cells at the terminations (ductules) of duct system and the endocrine part, that is, islets of Langerhans, develops from separation of groups of cells from the terminations of duct system. • Pancreatic ductal system:

• Initially, the ducts of dorsal and ventral pancreatic buds are separate and they open separately into the duodenum (Fig. 9.6.34A). • Opening of dorsal pancreatic duct is 20 mm proximal to the opening of ventral pancreatic duct. • Ventral pancreatic duct and CBD have a common opening in the duodenum. • The ducts of dorsal and ventral pancreatic buds anastomose establishing a cross-communication between the two. • The main pancreatic duct/duct of Wirsung is formed in its distal part, by the duct of dorsal bud, in its middle part by the oblique cross-communication between the ducts of two buds and in its proximal part by the duct of ventral bud. The main pancreatic duct, therefore, opens into the duodenum at the major duodenal papilla, along with the bile duct (Fig. 9.6.34B). • The accessory pancreatic duct of Santorini is formed by the proximal part of dorsal pancreatic duct (between the anastomosis and the duodenum). It remains narrow and opens into the minor duodenal papilla 20 mm proximal to the major duodenal papilla (Fig. 9.6.34C). • Repeated branching of the major and minor pancreatic ducts forms the interlobular and intralobular ducts and ductules. • Retroperitoneal location of entire pancreas except tail: • Though initially both buds were suspended in the respective mesogastria, due to their migration they occupy a position posterior to the peritoneum except the tail of pancreas which lies in the lienorenal ligament.

FIG. 9.6.33 (A) Smaller caudally located ventral bud seen arising in close relationship with the hepatic bud. (B) Rotation of duodenal loop to the right, the ventral pancreatic bud along with primitive bile duct comes to the right, and the dorsal bud to the left of the duodenum. (C) Ventral pancreatic bud along with primitive bile duct shifts to the left, closer to the dorsal pancreatic bud. (D) Fusion of the ducts. (E) Fusion of the pancreatic parenchyma.

FIG. 9.6.34 (A) Duct of the ventral pancreatic bud along with primitive bile duct have a common opening into the duodenum and lie caudal to the duct of the dorsal pancreatic bud. (B) Anastomosis of the dorsal and ventral pancreatic ducts forming an S-shaped main pancreatic duct. (C) Narrowing of the proximal part of the dorsal pancreatic duct, forming the accessory pancreatic duct (duct of Santorini).

Anomalies of the pancreas • Annular pancreas (Fig. 9.6.35): It is of two types; extramural and intramural. In the extramural type, the ventral pancreatic duct encircles the duodenum to join the main pancreatic duct, hence can result in obstruction. In the intramural type, the pancreatic tissue is intermingled with muscle fibres in the duodenal wall, and small ducts drain directly into the duodenum, commonly presents with ulcerations. Incomplete and complete types:

• Complete annular pancreas (Fig. 9.6.36): Pancreatic parenchyma or annular duct is seen to completely surround the second part of duodenum. • Incomplete annular pancreas (Fig. 9.6.37): Annulus does not surround the duodenum completely, giving a ‘crocodile jaw’ appearance. • Partial agenesis (Fig. 9.6.38): Agenesis of the dorsal pancreas is more common than the ventral pancreas. • Inversion of pancreatic ducts: Embryonic arrangement of the ducts persists and the greater part of the pancreas is drained through the minor duodenal papilla. • Meandering main pancreatic duct: Comprises of reverse ZZ type and loop type of pancreatic ducts. • Pancreatic divisum: Commonest anomaly. It is the failure of fusion of parts of pancreas derived from dorsal and ventral pancreatic buds with each other resulting in separate drainage systems for the head, uncinate process via the duct of Wirsung through the major papilla and the body, tail of pancreas via the duct of Santorini through the minor papilla. • Three types: Type 1: Commonest type is the one with no communication between the ducts. Type 2: Where the minor papilla drains the pancreas and major papilla drains the bile duct due to the absence of the ventral duct. This occurs in 20% of cases. Type 3: Accounts to ∼5% of the cases and is due to irregular filamentous anastomosis of the dorsal and ventral ducts. • Accessory pancreatic tissue (Fig. 9.6.39): It may be found in stomach, duodenum, jejunum, Meckel’s diverticulum, gallbladder and spleen. • Anomalous pancreaticobiliary union (APBU): Results from the uneven proliferation of the bile duct epithelium during foetal life. Presents as a confluence of the CBD and the pancreatic duct is outside the duodenal wall, with a common channel measuring more than 15 mm. Can result in choledochal cysts, pancreatitis and future neoplasms. • Pancreatic cysts: As a result of sequestration of primitive pancreatic ducts.

FIG. 9.6.35 Annular pancreas.

FIG. 9.6.36 Encerclage of the pancreatic tissue around the second part of duodenum (D) as indicated by the asterisk, indicative of complete annular pancreas. Note made of the CBD (C) as it enters the second part of the duodenum.

FIG. 9.6.37 Crocodile jaw appearance.

FIG. 9.6.38 Visualization of the head and uncinate process with thinning of body and absence of tail of pancreas.

FIG. 9.6.39 Smooth filling defect in gastric antrum. Central umbilication is present within lesion – suggestive of ectopic pancreas.

Spleen Spleen develops from mesoderm in the dorsal mesogastrium, close to the developing stomach that develops as a collection of mesenchymal cells to form small lobular masses of splenic tissue (spleniculi). These lobules later fuse to form single mass of spleen (Fig. 9.6.40).

FIG. 9.6.40 Single mass of spleen.

As the mesenchymal cells proliferate, the splenic mass projects in the left layer of the dorsal mesogastrium (Fig. 9.6.41).

FIG. 9.6.41 Splenic mass projects in the left layer of the dorsal mesogastrium. Because of the splenic projection, the dorsal mesogastrium is divided into an anterior part extending from the stomach to the spleen, the gastrosplenic ligament, and a posterior part that extends from the spleen to the posterior abdominal wall, the lienorenal ligament.

FIG. 9.6.XVII No evidence of communication between the two ducts. Minor papilla drains the body and tail of the pancreas and minor papilla drains the bile duct, head and uncinate process of the pancreas. The posterior layer of the dorsal mesogastrium fuses with the posterior abdominal wall. As a result of this fusion and change in

orientation of the stomach, the posterior part of dorsal mesogastrium between the spleen and the posterior abdominal wall now shifts its position. It extends between the spleen and the left kidney forming the lienorenal ligament (Fig. 9.6.42).

FIG. 9.6.42 Posterior abdominal wall extends between the spleen and the left kidney forming the lienorenal ligament. As a result of this fusion and change in orientation of stomach, the spleen comes to lie on the left side and takes part in forming left boundary of the lesser sac of peritoneum (Fig. 9.6.43).

FIG. 9.6.43 Spleen comes to lie on the left side and takes part in forming left boundary of the lesser sac of peritoneum. Capsule, septa and connective tissue framework including reticular fibres develop from mesoderm. The mesenchymal cells differentiate into lymphoblasts and other blood forming cells.

Anomalies of the spleen • Accessory spleen (Fig. 9.6.44): Commonest anomaly following splenic lobulations. It may be seen at the hila, at the gastrosplenic ligament, in the lienorenal ligament, along the splenic artery and within the pancreas. Clinical significance: Torsion of the accessory spleen should be assessed for. • Lobulated spleen (Fig. 9.6.45A), clefts (Fig. 9.6.45B) and notches on the spleen. Clinical significance: Splenic cleft should be differentiated from splenic lacerations. • Splenic agenesis: Absence of spleen should be ascertained only after ruling out wandering spleen/splenunculus elsewhere. • Polysplenia (Fig. 9.6.46): Left isomerism with multiple tiny spleens. • Situs inversus (Fig. 9.6.47), often presents with various variants/anomalies of the right sided spleen. • Ectopic or wandering spleen (Fig. 9.6.48): Commonly noted in the lower abdominal cavity/pelvis, secondary to laxity/abnormality in the suspensory ligaments and can be identified radiologically following the vascular source/enhancement characteristics of the spleen. Clinical significance: Prone to torsion.

FIG. 9.6.44 Accessory spleen as indicated by the white arrow; and as located at the hila.

FIG. 9.6.45 (A) Splenic lobulations. (B) Splenic clefts.

FIG. 9.6.46 Polysplenia.

FIG. 9.6.47 Situs inversus.

FIG. 9.6.48 Enlarged spleen noted in the pelvis as indicated by the asterisk. Absence of spleen in the left hypochondrium as indicated on the coronal and sagittal images.

9.7: Hepatobiliary system: Congenital anomalies Subramaniyan Ramanathan, Vineetha Raghu, Tahiya Salem Alyafei, Mahmoud Al Heidous

Introduction Congenital hepatobiliary anomalies include a variety of conditions often presenting with neonatal jaundice early in life or portal hypertension later in life, and some of them can be asymptomatic and incidentally discovered in adults. They may be due to several hereditary or developmental disorders. Physiological jaundice in the neonatal period typically occurs at 3–7 days, and bilirubin levels are 0.45. Overall, triangular cord sign shows the highest diagnostic accuracy with a reported sensitivity of 74% and specificity of 97%. The combination of gallbladder abnormalities and triangular cord sign can be used to increase the sensitivity to 95% (Fig. 9.7.1).

FIG. 9.7.1 Biliary atresia in a 45-day-old male. A. Ultrasound shows positive triangular cord sign measuring 6 mm (arrow). B. Ultrasound shows small gallbladder, 1.6 cm in length with irregular lumen (arrow). C. Ultrasound shows enlarged hepatic artery measuring 2.4 mm (arrow). D. HIDA scan shows no bowel excretion on 24-hours delayed film. Hepatobiliary scintigraphy (Hepatobiliary iminodiacetic acid or HIDA, mebrofenin, diisopropyl-iminodiacetic acid or the DISIDA scan), endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiography are further investigations which aid in the diagnosis. The HIDA scan reveals liver uptake with biliary nonexcretion of the radioisotope into the bowel at 24 hours, and has a sensitivity approaching 100%. However, it has a lesser specificity of 75%–80%. Severe hepatocellular dysfunction may also lead to nonexcretion of tracer into the gut and may confound the diagnosis. 99mtechnetium

Magnetic resonance cholangiopancreatography (MRCP) can be used to demonstrate the intrahepatic ducts and CBD in equivocal cases, thereby ruling out biliary atresia. However, it is a technically difficult examination to perform in neonates due to the need for sedation, cost and availability issues. Although both false positives and false negatives have been reported, limited available studies show good diagnostic accuracy with one recent study reporting approximate sensitivity of 97% and specificity of 95% for the MRI triangular cord sign. If the diagnosis could not be reached on imaging, liver biopsy can be useful in a certain subset of patients. Last resort for definitive diagnosis is intraoperative cholangiogram and it remains the gold standard. Portoenterostomy (Kasai procedure) is the surgical treatment of choice; however, it is unlikely to be of value if performed after the child is 3 months old. Later in the course of the disease, hepatic transplantation is the treatment of choice.

Alagille syndrome (alagille–watson syndrome) Alagille syndrome is a rare hereditary condition characterized by chronic cholestasis and has an autosomal dominant transmission with variable

penetration. However, about 50% of the cases are sporadic, occurring due to de novo mutations involving the JAG1 or NOTCH2 gene. It is an important cause of familial neonatal cholestasis with an incidence of 1 per 100,000 live births. In contrast to biliary atresia which predominantly involves the extrahepatic biliary tree, there is hypoplasia/paucity of the interlobular biliary ducts (PIBD). It may also present with abnormal facies, ocular abnormalities, hepatosplenomegaly, vertebral anomalies, peripheral pulmonary stenosis and cardiac malformations. Approximately 15% of these patients go on to develop cirrhosis and liver failure. Intracranial haemorrhage and moyamoya-like condition resulting from associated vascular anomalies may account for a significant percentage of mortality and morbidity. Differential diagnoses include biliary atresia, neonatal hepatitis and progressive familial intrahepatic cholestasis (Byler’s disease). Other disorders causing bile duct paucity include alpha-1-antitrypsin deficiency, cystic fibrosis and Zellweger syndrome amongst others. Imaging features depend on disease severity and include hepatomegaly, periportal fibrosis/cirrhosis, and splenomegaly, or sometimes, a normal liver. This condition needs to be differentiated from biliary atresia, as Kasai procedure is not useful and can also be detrimental in Alagille syndrome. Small gallbladder on US and nonvisualization of CBD on MRCP are reported in both BA and Alagille and cannot be used to differentiate them. However, triangular cord sign and hepatic artery enlargement are absent in Alagille syndrome and features of portal hypertension are less frequent. Nuclear scintigraphy (HIDA scan) findings are similar to biliary atresia with no bowel excretion of the isotope. Liver biopsy and histopathology are confirmatory for diagnosis. The only available management is orthotopic liver transplantation, failing which these patients do not survive beyond the third decade.

Fibropolycystic liver disease This is a spectrum of diseases of the liver and biliary system resulting from aberrations in the embryologic development of the ductal plates. Ductal plates are cylindrical layers of cells developing in the first to eighth week of gestation, surrounding a portal venous branch and eventually involuting partially (beginning at the twelfth week) to form the biliary ducts. Disturbances in this process of involution lead to ductal plate malformations. They encompass five important conditions, namely: 1. Choledochal cysts – extrahepatic bile duct 2. Caroli’s disease – large intrahepatic biliary ducts 3. Autosomal dominant polycystic liver disease – medium-sized intrahepatic biliary ducts 4. Congenital hepatic fibrosis – small interlobular biliary ducts 5. Biliary hamartoma – small interlobular biliary ducts The cysts in polycystic disease and biliary hamartoma do not communicate with the biliary radicles (as depicted on MRCP) indicating that they have lost communication with the biliary tree; whereas those in

choledochal cysts, and Caroli’s disease do have a communication. The importance of these conditions is that, although they have varied clinical presentations, they all develop from ductal plate malformations in varying stages of development, and can coexist with each other as well as with other renal abnormalities. Cystic biliary atresia is a rare variant of biliary atresia characterized by cysts affecting the obliterated biliary tract. It is usually suspected in an infant presenting with cholestatic jaundice, with US demonstrating a cyst at the porta hepatis. It is an important differential of the more common choledochal cyst. It is important to differentiate these two conditions because they have differing management protocols. The presence of the triangular cord sign, associated gallbladder abnormalities, lack of intracystic calculi or sludge, absence of intrahepatic biliary dilatation and relatively smaller size of the cyst support the diagnosis of cystic biliary atresia over choledochal cyst.

Choledochal cysts Choledochal cysts are characterized by varying degree and morphology of extra- and, sometimes, intrahepatic biliary dilatation. The incidence of these cysts follows a 4:1 female: male ratio with approximate incidence of 1–2:100,000–150,000 live births and more prevalent in Asian population. The possible aetiopathogenesis is an abnormal proximal insertion of the pancreatic duct into the CBD leading to a long common channel, reflux of pancreatic enzymes into the biliary tree, cholangitis, biliary obstruction and dilatation. The common channel measuring >1.5 cm long is described as the abnormal pancreaticobiliary junction (APBJ) and is reported in 96% of cases of choledochal cysts. Another theory is sphincter of Oddi dysfunction due to paucity of ganglion cells, leading to pancreatic reflux. Todani et al. have classified these cysts into five types based on their morphology (Table 9.7.2). A type VI cyst has also been described which refers to isolated dilatation of the cystic duct.

TABLE 9.7.2 Summary of Classification and Salient Features of Choledochal Cysts Type Frequency Morphology I

80%–90%

II

3%

III

5%

IV

10%

V

Rare

Dilatation of common bile duct with normal calibre of the duct proximally and distally IA: Cystic IB: Saccular IC: Fusiform Focal, saccular, true diverticulum of the supraduodenal common bile duct Choledochocele: Focal cystic dilatation of the intramural segment of common bile duct into duodenal lumen Multiple communicating intra- and extrahepatic duct cysts (IVA) or extrahepatic cysts alone (IVB) Multiple intrahepatic cysts communicating with the intrahepatic biliary tree

Abnormal Pancreaticobiliary Management Junction (APBJ) Complete surgical excision

Present Absent Present Absent

Surgical excision

Absent

Endoscopic sphincterotomy, excision or both

Present

Total excision of the dilated bile duct, including the pancreaticobiliary maljunction

Absent

Symptomatic management, surgical resection for monolobar disease, orthotopic liver transplantation for diffuse disease

Clinical features are variable; they may present with cholestatic jaundice or recurrent cholangitis. A classic triad of abdominal pain, right upper quadrant mass and jaundice has been described, more commonly in

children. These cysts vary greatly in size, and some of these can be massive, containing 5–10 L of bile. Later in life, the common presentations are abdominal pain, jaundice, fever, recurrent cholangitis and pancreatitis. Rarely, the cyst may rupture and present as biliary peritonitis. About 20% of cases present in adulthood. Complications include hepatic abscess, secondary biliary cirrhosis, portal hypertension, portal vein thrombosis, cystolithiasis, cholelithiasis and cholangiocarcinoma. Other cancers such as bile duct sarcoma, pancreatic, gallbladder and hepatocellular malignancies have also been reported. Malignant transformation is more common with type I, IV and V cysts and reported in 10%–30% of patients, the commonest type being cholangiocarcinoma US is the preferred initial investigation and usually reveals a cystic or fusiform dilatation of the CBD, intrahepatic cysts or a cyst at the porta hepatis with the gallbladder visualized separately. Typically, there is isolated extrahepatic dilatation alone or disproportionate dilatation of the CBD compared with the intrahepatic biliary radicles; this helps to differentiate extrahepatic choledochal cysts from obstructive biliopathy. In addition, the ducts proximal and distal to the cysts are of normal calibre. Complications of choledochal cysts are also reliably demonstrated on US. However, it is difficult with US alone to determine the extent and distribution of cysts. Also, US cannot optimally evaluate the pancreatic duct and pancreaticobiliary junction. CT may sometimes be useful when US is difficult in an obese patient or due to excessive bowel gas, and reveal cystic attenuation lesion separate from the gallbladder. However, it is not recommended in the paediatric age due to radiation risk. The biliary communication of these cysts is best demonstrated by MRCP, percutaneous transhepatic cholangiography (PTC) and ERCP. MRI with MRCP is noninvasive and is the preferred diagnostic tool as it can demonstrate the entire biliary tree along with pancreatic duct and APBJ. However, it may be technically challenging in children who are unable to hold their breath and often needs sedation. Intrahepatic cysts are seen as saccular dilated segmental biliary ductules communicating with the central biliary tree, and strictures as well are adequately depicted on the reformatted maximum intensity projection MRCP images. The length and location of the choledochal cyst need to be reported to aid in complete surgical resection. MRCP can be performed with liver-specific contrast agents which are excreted into the biliary tree on delayed images; this helps in confirming the biliary communication of these cystic lesions, thereby differentiating from polycystic liver disease and cystic biliary atresia (Figs. 9.7.2–9.7.5).

FIG. 9.7.2 Type I choledochal cysts. A. Axial T2weighted MRI shows focal cystic dilatation of proximal CBD (asterisk) suggesting type IA choledochal cyst. B. Coronal MRCP shows focal saccular dilatation along lateral aspect of CBD (asterisk) compressing the gallbladder (arrow) representing type IB choledochal cyst. C. Coronal MRCP shows fusiform saccular dilatation of CBD (long arrow) with no intrahepatic dilatation (short arrow) and distended gallbladder (asterisk) representing type IC choledochal cyst.

FIG. 9.7.3 Type III choledochal cyst. Focal cystic dilatation of the intramural segment of common bile duct into duodenal lumen (long arrow) representing choledochocele. Normal main pancreatic duct (short arrow).

FIG. 9.7.4 Type IVA choledochal cyst. A. Ultrasound shows cystic dilatations of intrahepatic (arrow) and extrahepatic (asterisk) biliary ducts. B. Axial T2 fat sat image shows diffuse cystic dilatation of intrahepatic ducts (arrows). C. Coronal MRCP shows diffuse cystic dilatation of CBD (asterisk) with cystic dilatation of intrahepatic ducts (arrow).

FIG. 9.7.5 Type IVB choledochal cyst. Coronal MRCP shows cystic dilatation of extrahepatic right and left ducts and proximal CBD (long arrow) with normal intrahepatic ducts (short arrow). GB – gallbladder. Sometimes, a HIDA scan may be performed and demonstrates variable findings depending on the extent of biliary obstruction. No intestinal drainage is seen in case of complete obstruction. Often, the dilated duct may be visualized on the scan with pooling of the isotope within. Treatment is usually surgical (for types I, II and IV) and encompasses excision of the cyst with a biliodigestive anastomosis (Roux-en-Y hepaticojejunostomy). For the anatomically different type III cysts, transduodenal cyst excision, or more recently, endoscopic sphincterotomy and cyst unroofing are the treatments of choice.

Caroli’s disease Caroli’s disease is characterized by nonobstructive dilatations of the intrahepatic bile ducts which may be segmental, monolobar, or diffusely involve both the right and left hepatic ducts. It corresponds to type V choledochal cyst. Two types have been described: Type I – Nonhereditary with segmental involvement and no associated anomalies Type 2 – Hereditary with diffuse involvement and associated renal malformations It is a rare autosomal recessive condition (1 in 1,000,000 live births), and common associations include choledochal cysts, medullary sponge kidneys, tubular ectasia, autosomal dominant and recessive polycystic kidney disease and hepatic fibrosis. Caroli’s disease and congenital hepatic fibrosis are thought to be arising from a similar embryologic insult – Caroli’s arising from involvement of the larger intrahepatic ducts, and congenital hepatic fibrosis arising from involvement of small interlobular bile ducts. The combination of these two conditions is termed Caroli’s syndrome, which refers to involvement of the larger as well as smaller intrahepatic biliary ducts. It is associated with biliary ductal calculi, recurrent cholangitis, strictures and hepatic abscesses. Hepatic fibrosis and portal hypertension may ensue following repeated hepatocellular insult. Malignancy is a known complication with increased risk of cholangiocarcinoma reported in 7% of patients with Caroli’s syndrome. US shows intrahepatic saccular or fusiform cysts with a central dot sign representing intraluminal portal venous radicle with surrounding ectatic bile duct. Some of these may demonstrate central enhancing fibrovascular bundles. CT can show similar features but is best avoided due to radiation exposure. MRCP is the imaging modality of choice and helps in establishing the diagnosis by demonstrating a normal extrahepatic biliary tree, with cystic dilatation of the intrahepatic bile ducts. Associated intraductal calculi, inflammatory changes (cholangitis) or, rarely, malignant changes may also be seen. Migration of the calculi to the CBD may occur, leading to diffuse biliary dilatation with clinical jaundice. The incidence of extrahepatic biliary dilatation in Caroli’s disease is about 26%–53%. MRCP with liver-specific contrast can show the biliary communication of cystic lesions, thereby differentiating from other cystic liver diseases (Fig. 9.7.6).

FIG. 9.7.6 Caroli’s disease. A. Axial T2-weighted MRI shows multiple cystic dilatation of intrahepatic biliary ducts with central dot sign (short arrow). B. Axial T2-weighted MRI shows multiple cystic dilatation of intrahepatic biliary ducts with some of them showing intraductal calculi (long arrow). Differentials include intrahepatic biliary strictures, primary sclerosing cholangitis, recurrent pyogenic cholangitis, hepaticolithiasis and abscesses or masses in the liver causing focal or segmental biliary dilatation. In primary sclerosing cholangitis, there is a more elongated appearance of the biliary radicles compared with the cystic or saccular dilatation in Caroli’s disease, associated intrahepatic biliary strictures, lobulated liver contour and pseudotumoral enlargement of the caudate lobe. In recurrent pyogenic cholangitis, there is characteristic left lobe atrophy, intra- and extrahepatic biliary dilatation, interspersed biliary calculi and pruning of the peripheral radicles. The treatment encompasses symptomatic management, surgical resection for monolobar disease, biliodigestive anastomosis for diffuse bilobar disease and orthotopic liver transplantation for advanced diffuse liver disease.

Polycystic liver disease This is a hereditary disease characterized by multiple intrahepatic and peribiliary cysts lined by biliary epithelium, and may be autosomal recessive (infantile type) or, more commonly, autosomal dominant (adult type). An isolated (nonhereditary) variant of polycystic liver disease has also been described. Associated polycystic kidney disease may be present in the hereditary variants of the disease. There is a variable prevalence of the incidence, size and number of cysts in these patients with 58%–75% of females and 42%–62% of afflicted males showing cysts. Children usually present with initial symptoms of renal disease. Other symptoms are related to an enlarged liver, and sometimes mass effect on adjacent organs and bile ducts. Complications include cyst rupture, haemorrhage and infections; progression to portal hypertension and cirrhosis is rare. Cholestatic jaundice may occur due to mass effect on the biliary tree. US may reveal cystic changes in the liver and kidneys, hepatomegaly, bilateral nephromegaly and increased echogenicity of the kidneys. These

cysts range in size from less than a millimetre to several centimetres and do not communicate with the biliary tree. Some of these cysts may demonstrate internal echoes or calcification due to recent or prior haemorrhage. Mass effect may be seen on the biliary tree with segmental biliary dilatation. CT or MRI also reveals well circumscribed nonenhancing cysts. The signal intensity of these cysts varies depending on the presence of haemorrhage (Fig. 9.7.7).

FIG. 9.7.7 Polycystic liver disease. A. Coronal T2weighted MRI shows multiple small simple hepatic cysts (arrow) with associated bilateral autosomal dominant polycystic kidney disease (asterisks). B. Axial T2-weighted MRI of upper part of liver shows multiple simple hepatic cysts (arrow). For the diagnosis of autosomal dominant polycystic liver disease, there must be >20 cysts in the liver replacing over 50% of the liver parenchyma, or >4 cysts in cases of associated ADPKD. Sometimes, this condition may be confused with Caroli’s disease and may be differentiated using liverspecific MR contrast agents. Treatment is often targeted towards renal disease with symptomatic therapy for liver involvement.

Congenital hepatic fibrosis Congenital hepatic fibrosis is an autosomal recessive disorder characterized by progressive periportal fibrosis of the liver parenchyma, usually with associated biliary duct ectasia. There is an association with autosomal recessive polycystic kidney disease. The periportal fibrosis causes irregularly shaped, dilated biliary ductules within the liver which are too small to be seen unless there is associated Caroli’s disease. The clinical symptoms are commonly related to portal hypertension (splenomegaly, gastrointestinal bleeding) or to associated renal abnormalities. Further in the course of the disease, features of true cirrhosis of the liver or cholangitis may develop occasionally. An enlarged hyperechoic liver, enlarged tortuous hepatic artery at the hilum, features of portal hypertension (including splenomegaly and varices) and renal cysts can be seen on US.

Volume redistribution with right lobe atrophy and left and caudate lobe hypertrophy is a feature seen in both advanced congenital hepatic fibrosis and viral or alcoholic cirrhosis. However, the differentiating feature is sparing of or enlargement of the medial segments of the left lobe in congenital hepatic fibrosis, while cirrhosis from other causes has atrophic medial segments. The liver may depict focal lesions such as large regenerative nodules and associated biliary hamartoma. Of note, the enlarged tortuous hepatic artery branches at the hilum may be mistaken for a portal cavernoma on a single venous phase contrast CT study, and are well depicted in the arterial phase. MRI may show periportal high T2 signal intensity due to periportal fibrosis and proliferating small biliary ductules. MRI can also demonstrate the associated renal malformations seen in two-thirds of the patients, which helps in the diagnosis. In clinical practice, imaging diagnosis is often difficult and liver biopsy is indicated (Fig. 9.7.8).

FIG. 9.7.8 5-year-old male presented with portal hypertension and diagnosed as congenital hepatic fibrosis. A. Axial trufi MRI of liver shows right lobe atrophy (R) with hypertrophy of medial (M) and lateral (L) segments of left lobe. B. Axial T2-weighted MRI of liver shows atrophic right lobe (R) and hypertrophic medial segment of left lobe

(M) with nodular surface in keeping with cirrhosis. C. Axial post contrast MRI of liver shows atrophic right lobe (R) and hypertrophic medial segment of left lobe (M) with nodular surface (arrows) in keeping with cirrhosis. As previously discussed, Caroli’s disease may be associated with this condition and this spectrum is termed Caroli’s syndrome. Management is directed towards treating the complications from portal hypertension and cirrhosis, with liver transplantation in selected patients.

Biliary hamartoma These are benign nonneoplastic malformations of the biliary tree composed of dilated bile duct-like structures surrounded by a fibrous stroma. They are not uncommon, having an incidence of 1%–5%. They are small, measuring less than 10–15 mm in size and demonstrate a rounded or irregular outline. They preferentially involve the subcapsular regions of the liver. When multiple and diffusely involving the liver, they are termed the von Meyenburg complex. They are mostly cystic; however, they may rarely be solid or mixed lesions. On US, they appear as uniformly sized anechoic cysts, sometimes as hyperechoic or hypoechoic lesions with associated comet tail artifacts due to their size being lesser than the resolution of US. They are hypodense on CT, T1 hypo, T2 hyperintense on MRI (approaching the intensity of cerebrospinal fluid) with absent diffusion restriction and no, or only thin peripheral postcontrast enhancement. Rarely, an enhancing mural nodule may be seen due to fibrocollagenous stroma. They do not communicate with the biliary tree (Fig. 9.7.9).

FIG. 9.7.9 Biliary hamartoma. A. Axial T2weighted MRI shows numerous tiny T2 hyperintense foci in both lobes of liver with no definite biliary communication (arrow). B. Coronal reformatted MIP images show numerous tiny T2 hyperintense foci in both lobes of liver with no definite biliary

communication. C. Coronal post contrast MRI shows no enhancement of cystic lesions (arrow). They are typically an incidental finding, and their primary importance is that they may be mistaken for other cystic lesions like Caroli’s disease, autosomal dominant polycystic disease, microabscesses or sinister conditions such as metastases. Metastases are more heterogeneous and demonstrate varying sizes and signal intensity. The cysts in autosomal dominant polycystic disease are more variable in signal and larger in size. Microabscesses show typical clinical features and diffusion restriction on MRI. Caroli’s disease will have the characteristic central dot sign and biliary communication can be demonstrated.

Conclusion Congenital hepatobiliary anomalies have a wide spectrum of clinical and imaging findings. Children can be asymptomatic in conditions such as biliary hamartoma, present with neonatal jaundice as in biliary atresia or with portal hypertension and cirrhosis in Caroli’s syndrome. US is the first imaging performed to look for the presence or absence of CBD, biliary dilatation, cystic changes and status of gallbladder. MRCP is often indicated to demonstrate the extent of the disease and further characterization of cystic diseases. Hepatobiliary scintigraphy is useful in the evaluation of neonatal cholestasis. It is pertinent to be familiar with the clinical and imaging features of each of these conditions to offer the best possible diagnosis and thereby guiding appropriate management.

9.8: Paediatric hepatobiliary lesions 9 .8. 1

DIFFUSE PARENCHYMAL DISEASES OF THE LIVER Ishan Kumar, Ashish Verma

Introduction The hepatic parenchyma is the site for multiple essential, interrelated, and complex metabolic activities to assimilate nutrients, detoxify the body, and synthesize vital molecules such as enzymes, hormones, cofactors and essential components of the coagulation pathway. The chemical reactions involved in each of these activities pose a threat to the hepatocytes, which may be damaged leading to the initiation of reparative processes. Further, the liver, being a highly vascular organ with multiple metabolic activities, is liable to be involved in many systemic vascular and metabolic disorders. On one hand, such changes cause healing of the tissue injury, but on the other hand, lead to diffuse parenchymal changes, which may result in suboptimal functioning of the organ. Such a condition is labelled as ‘diffuse liver disease’ and includes (a) diseases caused due to storage of certain chemical products of such chemical reactions labelled as ‘storage disorders’, (b) diseases caused due to reduction of blood flow to the organ, (c) parenchymal injury due to stasis of bile at various levels in the pathway due to varied causes, and (d) involvement of liver in systemic or organ-based inflammatory disorders. The mainstay of diagnosis of diffuse liver diseases is the detection of alterations in the biochemical parameters in blood indicative of liver function, which however is nonspecific to various aetiologies. The diffuse liver diseases in children are quite different from those in the adult population and constitute mainly of congenital or inherited metabolic and vascular diseases as opposed to diseases of acquired aetiologies in the latter population. The gross and microscopic pathological changes are accordingly different in the paediatric population and may be utilized to add specificity to the biochemical indicators as far as aetiological diagnosis is concerned. The invasive and potentially hazardous sampling mandated for histological evaluation of liver parenchyma has been replaced by an array of imaging modalities in recent times. The present chapter presents a review of the currently available imaging modalities (viz. cross-sectional imaging modalities such as ultrasonography, computed tomography [CT] and magnetic resonance [MR] imaging) for evaluation of diffuse liver diseases along with the pertinent imaging features and guidelines for their rational use in various indications. Also a short review of certain key technical and technological details is included.

Clinical manifestations Jaundice and hepatomegaly are the most common clinical manifestations of liver disease. Anorexia is a nonspecific sign, often present in acute or chronic liver disease. Jaundice is a sign of increased bilirubin content in the blood, that can exist in four forms: (i) unconjugated bilirubin bound to albumin, (ii) unbound unconjugated bilirubin, (iii) conjugated bilirubin and (iv) δ fraction. Direct fraction includes both conjugated bilirubin and δ bilirubin. Conjugated hyperbilirubinemia is due to decreased excretion by liver or biliary tract obstruction. Pruritus, spider angioma on face and neck, ascites, portal hypertension, botchy palmer erythema, subcutaneous xanthoma, gastrointestinal (GI) variceal bleed, encephalopathy,

renal dysfunction and pulmonary involvement are manifestations of advanced cirrhosis.

Biochemical tests Evaluation of total serum bilirubin and its fractional analysis into indirect (unconjugated) and direct (conjugated and δ fraction) bilirubin helps to distinguish between elevation caused by haemolysis and that due to hepatic dysfunction or biliary obstruction. Elevations in alkaline phosphatase (ALP), 5′ nucleotidase, and γ-glutamyl transpeptidase (GGT) levels are an indicator of biliary obstruction. However, it should be noted that normal growing children have significant elevations of serum ALP activity. AST (aspartate aminotransferase) and ALT (alanine aminotransferase) are significantly raised in acute hepatitis. ALT rise disproportionate to AST rise is seen in viral hepatitis. A predominant rise in AST is seen in echovirus infection, various metabolic diseases or alcohol-induced hepatitis. These aminotransferases are also elevated in NAFLD/NASH. ALT/AST rise is less marked in chronic liver disease. PT-INR, serum albumin levels can evaluate the hepatic synthesis function. Hypoalbuminemia suggests a bad prognosis. γ-Globulin is elevated in autoimmune hepatitis (AIH). Alpha-fetoprotein is raised in hereditary tyrosinemia or hepatic neoplasms.

Liver biopsy Indications of liver biopsy in the paediatric age group include neonatal cholestasis, metabolic liver disease, NAFLD, congenital hepatic fibrosis, abnormal biochemical liver tests of unknown aetiology, intestinal failure associated liver disease, acute liver failure and liver tumours. Although biopsy of children and infants is considered a safe procedure, due to incidences of shock, the North American Society for Pediatric Gastroenterology and Nutrition (NASPGHAN) has recommended liver biopsy in children not to be necessarily performed as outpatient procedures. Sonography-guided percutaneous liver biopsy has been reported to be safer, more efficient, more comfortable and only marginally more expensive than blind biopsy. The use of coaxial technique, determination of the number of passes and use of track embolization were at the discretion of the interventional radiologists. In cases of uncorrected PT-INR elevation, transjugular liver biopsy can be performed.

Imaging techniques Ultrasound (US) is a valuable tool in the diagnosis and management of diffuse liver diseases. It provides useful information about the size, surface, parenchymal architecture, biliary channels and blood flow of the liver. US examination of the liver is performed in the supine position with a convex (5–7.5 MHz) probe. High-frequency (7.5–12 MHz) linear transducers can be used in young infants because of their small size. US examination can be completed with the colour Doppler technique and US elastography, if needed. CT protocol typically requires image acquisition during the multiple phases with a slice thickness of 5 mm or less and a pitch ranging from 1 to 1.5. Contrast injected is 2 mL/kg through manual or mechanical injection. The arterial phase begins at 10–15 seconds and the portal phase is at 20–40 seconds after contrast injection. Equilibrium phase is obtained at 3 minutes, when needed. MRI protocol to evaluate paediatric liver chiefly includes free-breathing sequences, due to the challenge offered by an inadequate breath-hold in these patients. Due to the same reason, motion insensitive single-shot HASTE sequences or motion insensitive T1weighted spoiled GRE single-shot sequences are also widely utilized in paediatric MR examinations. In slightly older children with a relatively uniform breathing pattern, external trigger signals from a breathing belt, or navigator techniques may be used to overcome motion artefacts from breathing. T1- and T2-weighted turbo spin-echo (TSE) sequences and T2-weighted single-shot sequences in axial and coronal planes are initially acquired to evaluate the anatomy and screen for pathologies. This is followed by a gradient echo (GRE) images to examine vascular structures. Multiecho images with T1-weighting can be acquired to evaluate the fat content of lesions. Contrast-enhanced MRI with intravenous injection of gadolinium (Gd)-based contrast agent is performed as routine in

cases with suspected portal hypertension or in any associated suspected neoplastic lesion. This is usually clubbed with MRA for vascular mapping. Arterial phase and portal phase should be acquired 10–15 seconds and 20–30 seconds, respectively after the start of contrast agent injection. GRE T1-weighted sequence should be repeated continuously four or five times to include achieve all phases of liver perfusion. Finally, steady-state imaging should be performed in the equilibrium phase (3 minutes) using T1-weighted and T1weighted fat-suppressed imaging sequences. MRI contrast media should be administered with caution after evaluation of eGFR, and is safer than the iodinated contrast media needed for CT scan examination, and is hence preferred.

Hepatomegaly Liver size measurement is commonly obtained in one of the two ways (a) an anterior to the posterior measurement of the liver in the midclavicular line, (b) a dome-to-tip longitudinal measurement of the liver in the midclavicular line. Table 9.8.1.1 provides suggested upper limit values of liver and spleen length for various paediatric age groups. Despite advances in 3D US, volume measurements of liver size have not been incorporated in the routine clinical practice because it is time-consuming, requires considerable skill and technically difficult fusion of multiple 3D sweeps. TABLE 9.8.1.1 Suggested Upper Limit Values of Liver and Spleen Length for Various Paediatric Age Groups

1–3 months

Suggested Upper Limit in Longitudinal Liver Length (cm) in Midclavicular Line (Dome to Tip) 9

Suggested Upper Limit in Spleen Size (cm) 7

4–6 months

9.5

7.5

7–9 months

10

8

1–3 years

10.5

8.5

3–5

11.5

9.5

5–7

12.5

10.5

7–9

13

10.5

9–11

13.5

11

11–13

14

11.5

13–15

14

12

15–17

14.5

12

Age (month/years)

Nonalcoholic fatty liver disease Nonalcoholic fatty liver disease (NAFLD) is referred to as triglyceride accumulation in hepatocytes and encompasses a broad range of clinicopathological entities ranging from simple steatosis, steatohepatitis to cirrhosis. Its worldwide reported prevalence is approximately 2.6%–10% in the general paediatric population and as high as 38% of obese children under the age of 19 years. In India, the reported prevalence is as high as up to 22% in the general paediatric population and up to 45% in obese and overweight children. Hepatic steatosis currently is the most common cause of chronic liver disease in paediatric patients. Table 9.8.1.2 highlights the causes of hepatic steatosis in paediatric age group.

TABLE 9.8.1.2 Causes of Nonalcoholic Fatty Liver Disease Obesity

Glycogen storage disease

Wilson’s disease

Peroxisomal disorders

Alpha 1 antitrypsin deficiency Drugs – steroids, amiodarone, methotrexate, chemotherapy (lasparaginase), vitamin E, valproate, tamoxifen, antiretrovirals

Mauriac syndrome Hypobetalipoproteinaemia/abetalipoproteinaemia/hyperlipoproteinemi Lipodystrophies Schwachman syndrome Mitochondrial hepatopathy Metabolic liver disease Reye syndrome

Cystic fibrosis Severe malnutrition Coeliac disease Total parenteral nutrition Nephrotic syndrome The pattern of injury is similar to alcoholic liver disease. Nonalcoholic steatohepatitis (NASH) constitutes a subset of NAFLD, ranging from simple steatosis to inflammation and fibrosis. NASH in children has two distinct histological subtypes. Type 1 NASH resembles adult subtype with macrovesicular steatosis, lobular inflammation, and ballooning degeneration and perisinusoidal fibrosis. Type 2 NASH shows steatosis with portal fibrosis and is present in younger children with increased severity of obesity. ALT can be normal in 20% of the patient with NAFLD and liver biopsy is the gold standard for diagnosis as well as a semiquantitative assessment of disease severity. In clinical practice, the diagnosis and monitoring of NAFLD largely rely on ultrasonography. Grade I fatty liver refers to diffusely hyperechoic parenchyma with a wellvisualized diaphragm (Fig 9.8.1). Bright liver with loss of periportal echogenicity and indistinctly visualized vessels is referred to as grade II and blurring of the diaphragm is classified as grade III fatty liver. Limitations of the US are lack of objective quantification and diminished sensitivity in cases where biopsy-proven steatosis ratio is less than 30%. Moreover, hepatic fibrosis and inflammation in cases of NASH are sonographically indistinguishable from simple steatosis. Contrast-enhanced US can diagnose the presence of fibrosis in NAFLD, which is evident from the decreased accumulation of microbubbles in the liver parenchyma.

FIG. 9.8.1.1 Fatty liver. Axial CECT image of a 14-year-old child showing significantly reduced attenuation of liver parenchyma compared to splenic parenchyma, indicative of hepatic steatosis. The distinction between hepatic steatosis and fibrosis is important clinically, as fibrosis can progress to cirrhosis if left untreated. US elastography has emerged as a promising technique to screen the children with NAFLD to look for ongoing steatohepatitis/fibrosis. Transient elastography is the most popular elastography technique which has shown excellent accuracy in the adult population with chronic hepatitis. However, its accuracy in NAFLD is significantly lower and the data of effectiveness in the paediatric population is limited. Acoustic radiation force impulse imaging (ARFI) has been shown to have a good correlation with AST/ALT ratios in obese children with NAFLD. An ARFI elastography value of >1.19 m/s predicts NASH-related hepatic changes in these patients while a value >1.75 m/s is suggestive of cirrhosis. Another study on shear-wave elastography has shown a high correlation in paediatric NAFLD patients with biopsy-proven hepatic fibrosis. A value of >5.1 kPa strongly predicts the presence of fibrosis whereas a value of >6.7 kPa is suggestive of stage ≥F2 fibrosis (Brunt scoring system). CT is a common modality utilized for assessment of hepatic pathologies, however is seldom used for assessment of NAFLD because of the risk of ionizing radiation. On noncontrast CT, liver attenuation 0.65 calculated by comparing the transverse length of caudate and right lobe at the portal bifurcation, is a sign of cirrhosis. CT/MRI-based segmental volumetric analysis can reflect the morphological changes more effectively. Parenchymal changes Liver parenchyma in children appears as isoechoic to hypoechoic compared to the renal cortex in the US. The neonatal liver may reveal a bright echotexture. Hyperechoic parenchyma is seen in the fatty liver or liver fibrosis. Cirrhosis is seen as coarse and heterogeneous parenchyma. The liver surface in normal children appears as a hyperechoic, straight and regular line. The liver surface with diffuse irregularity or nodular surface is present in cirrhosis. CT and MRI in frank cirrhosis can reveal heterogeneous parenchyma along with the irregular surface. Diagnosis of early cirrhosis and fibrosis cannot be reliably made by the US where parenchyma may appear within normal limits. Similarly, CT and conventional MR sequences are also insensitive in early cirrhosis although early fibrosis can be seen as T1 hypointense/T2 hyperintense areas on MR and may show subtle

enhancement. These T2 hyperintensities can be present as perilobular bands, perivascular cuffing, bands surrounding regenerative nodules, patchy fibrotic areas, or diffuse reticulation (honeycomb pattern). The role of US elastography and MR elastography is increasing in paediatric liver diseases for the detection of fibrosis and early cirrhosis and has been discussed in the previous section. Portal hypertension and other vascular changes US examination should be complimented with Doppler of the portal vein and hepatic veins if US features are suspicious of cirrhotic or fibrotic changes. The diameter of the portal vein increases with age. The mean diameter of the portal vein is 3.5 mm in children 12-year-old children. Portal vein diameter is increased in portal hypertension; however, no reliable age-dependent cut-off values exist for the PV diameter in the diagnosis of portal hypertension in paediatric patients. Peak portal vein velocity in the paediatric age group is usually above 20 cm/s in a nonfasting child (15 cm/s in term neonate) along with some respiratory undulation. Peak portal vein velocity 65 HU (15–130) with low attenuation of hepatic vessels relative to liver parenchyma on noncontrast CT is suggestive of iron overload, however can also be seen in WD, glycogen storage disorder, long-term amiodarone administration. MRI is the primary radiological modality used for diagnosis of iron distribution, quantification and monitoring of treatment response in liver iron overload (Fig 9.8.1.6). Various MRI techniques have been devised for iron overload estimation.

FIG. 9.8.1.6 Iron deposition in liver. (A) Axial T2-weighted MR image in a patient of beta thalassemia with multiple transfusions showing hypointense liver parenchyma. (B) Quantitative iron estimation using liver: muscle signal intensity ratio method. Three ROIs are drawn in liver parenchyma and one on each paraspinal muscles and the obtained values are entered in free online calculator provided by the University of Renne which calculates liver iron concentration. 1. Liver-to-muscle signal intensity ratio This technique compares the signal intensity of liver parenchyma with the signal intensity of paraspinal muscles, which are assumed to be unaffected by iron content. GRE sequences are obtained with TR of 120 ms, flip angle 200, and varying TE of 2, 4, 9, 14 and 20 ms. Three ROIs of 1–2 cm are drawn in liver parenchyma and one on each paraspinal muscles.

Liver iron concentration can then be obtained using a free online calculator provided by the University of Renne. 2. T2 and R2 relaxometry and T2* and R2* relaxometry Images are obtained with TR 2500 ms, flip angle 900 and variable TE of 6, 9, 12, 15, 18 ms. The images can be used to draw automated ROI covering the right lobe of the liver (excluding vessels) in the largest area and a T2 map of the same images can be generated. The technique quantifies the T2 shortening due to proton exchange between bulk water and exchangeable protons in ferritin. T2* takes into account the contributions of the T2 (1/R2) effects and the microscopic inhomogeneities introduced in (B0) by the hemosiderin clusters. For T2* measurement single breath-hold multiecho GRE sequences with TR of 25 ms, flip angle of 20 degrees, TEs every 0.25 ms from 0.8 to 4.8 ms are obtained. R2 * (1/T2*) values can be generated with ROI drawn from a single midhepatic section by drawing an ROI following the boundaries of the liver and excluding hilar vessels. Liver iron concentration can be obtained using a formula: [Fe] = 0.202 + 0.0254 R2*. 3. Quantitative susceptibility mapping This technique detects the enhancement in the local magnetic field caused due to ferritin or hemosiderin using a 3D breath-hold multiecho GRE sequence with the use of chemical shift–encoded water/fat separation, T2*/R2* mapping, and B0 field mapping. A quantitative susceptibility map of the parenchyma is generated. A local relative susceptibility value (ΔB0) is obtained drawing ROI which is expressed in parts per million (ppm), related to local iron deposition. With the ongoing research, stress is being placed upon the multiparametric quantitative MR imaging protocol which includes MR elastography (for fibrosis), multiecho chemical shift–encoded GRE to measure proton-density fat fraction (for steatosis quantification) and R2* relaxometry (for iron overload estimation). Hepatic iron overload has been shown to predispose to the development of HCC in the younger age group. The detection of HCC in the setting of iron overload is less difficult on T2-weighted sequences because the presence of iron behaves like a nonspecific contrast medium, such as superparamagnetic iron oxide (SPIO). However, care should be taken while evaluating these lesions, which may appear like hepatic cyst or haemangioma. Any nodule detected in these patients should be evaluated and characterized by the use of intravenous gadolinium contrast.

Inherited and metabolic liver diseases The liver processes various metabolic processes of the body and hence it can be affected by multiple inherited metabolic disorders. The affection of the liver in these disorders may be in the form of hepatomegaly, cholestasis, acute liver failure or hepatic encephalopathy. Wilson’s disease WD is an autosomal recessive disorder of copper metabolism, first described in 1912 by Samuel Kinnier Wilson. The primary defect is a genetic abnormality located at chromosome 13 and q14.3, coding for copper-transporting P-type ATPase. An average diet contains 3–5 mg copper, 40% of which is absorbed in the upper GI tract and which is almost completely excreted in bile. The genetic defect leads to abnormality in this excretory function that leads to copper accumulation in the liver and other organs and tissues including brain and cornea. Liver disease in WD can range from asymptomatic transaminasemia, acute or chronic hepatitis, fulminant hepatic failure, and cirrhosis. WD can be misdiagnosed as AIH because both can result in similar autoantibodies. Imaging findings of liver manifestations can be categorized into four groups: (i) morphological changes, (ii) parenchymal changes, (iii) perihepatic changes, (iii) other findings. 1. Morphological changes occur because of cirrhosis with hepatic volume redistribution and irregular contour. However, unlike other causes of cirrhosis, there is normal caudate to the right lobe ratio. WD should be considered in children with cirrhosis without caudate lobe hypertrophy.

2. Parenchymal changes consist of the heterogeneous scarred liver with periportal cuffing. US identifies parenchymal involvement better than CT and MRI in the early period of the disease. In the US, there is increased hepatic echogenicity because of microvesicular steatosis and fibrosis. Advanced liver changes can be manifested in the US as (a) liver heterogeneity, (b) heterogeneity with multiple hypoechoic nodules and (c) heterogeneity with multiple hypoechoic and hyperechoic nodules. The patients with hypoechoic nodules respond better to penicillamine therapy and thus the US might help to identify the patients with a good prognosis. On CT, copper deposition in the liver may present with increased attenuation of the hepatic parenchyma, however, associated hepatic steatosis can decrease the overall attenuation which is within normal limits in most of the patients. Contrast-enhanced CT can show hypodense as well as hyperdense nodules and surface irregularity. The disappearance of hyperdense nodules has been documented after penicillamine therapy. Various MRI features of liver disease in WD has been described in the literature that includes (a) T1 hyperintense/T2 hypointense nodules (2 mm to 1 cm), (b) T1 hypointense nodules, (c) multiple hyperintense septae leading to ‘honeycomb pattern’, (d) highintensity septa, (e) absence of parenchymal changes on MR. 31P MR spectroscopy of the liver in WD can show elevated phosphomonoester (PME) resonance and reduced phosphodiester (PDE) resonance, which have been shown to normalize after penicillamine and vitamin K therapy. 1. A perihepatic subcapsular fat layer has been identified on the US as a perihepatic hypoechoic zone and on CT as perihepatic hypodense zone, showing attenuation similar to subcutaneous fat. 2. Other findings in WD include cholelithiasis, splenomegaly and features of portal hypertension. Gaucher disease Gaucher disease (GD) results from a deficiency of lysosomal enzyme β-glucocerebrosidase leading to the accumulation of ‘Gaucher cells’ in various organs. Imaging can help in the detection and characterization of liver infiltration, hepatomegaly, fibrosis, cirrhosis, iron deposition and HCC, all of which are associated with GD. On imaging, hepatosplenomegaly is the hallmark of GD (Fig 9.8.1.7). Recent literature recommends the utilization of CT or MRI over the US for volumetric assessment of liver and spleen sizes in GD with the expression of liver volume as multiples of normal volume (MN). Weight-based formula is used for calculation of liver and spleen volumes: normal liver volume (mL) = 25 × weight (in kg) ; and normal spleen volume (mL) = 2 × weight (in kg). A target liver volume of 1–1.5 MN and a spleen volume of 2–8 is aimed by the therapeutic regimens. On MRI, low ADC of liver and spleen indicates greater infiltration and worse prognosis, with ADC values correlating with chitotriosidase levels. Fibrosis can be detected and quantified using US shear-wave elastography, MR elastography, and nonimaging–based transient elastography. Studies have indicated the presence of liver iron deposition in GD due to associated hyperferritinemia, which can be quantified using R2* relaxometry.

FIG. 9.8.1.7 Gaucher disease. (A) US image showing echogenic homogeneous lesion (arrows). (B) CECT axial image showing hypodense lesions (arrows) in right lobe of liver along with hepatomegaly. These lesions represent ‘Gaucheroma’.

Hepatic nodules can be identified on imaging on GD. Most commonly these nodules represent a focal accumulation of Gaucher cells and are known as ‘Gaucheroma’. These lesions are hyperechoic on the US, hypoattenuating on CT, T1 hypointense/T2 heterogeneous nodules on MRI. These lesions do not merit biopsy; however, care should be taken to identify the lesions suspicious for HCC, that is large, irregular, hypoechoic, hypervascular lesions, which mandate further evaluation by multiphasic contrast CT or MRI. Besides the liver, evaluation of abdominal imaging should attempt to detect changes in spleen and visualized bones. GD in the spleen can manifest with splenomegaly, fibrosis, nodules, subcapsular infarcts and splenic necrosis. Osseous features of GD are osteopenia, osteonecrosis, pathological vertebral fractures and Erlenmeyer flask deformity. Glycogen storage diseases (GSD) These are a group of disorders caused by defects in metabolism or storage of glycogen which broadly present with hepatic, myopathic, cardiac or other manifestations. GSD type I (Von Girke disease) presents with hepatic involvement. The US in these patients shows hyperechoic liver parenchyma because of fatty replacement and glycogen deposition. CT shows variable attenuation because hepatic attenuation is increased by glycogen and decreased by steatosis. There is a well-known association with GSD and hepatic tumours such as adenoma, focal nodular hyperplasia and HCC (rare). Adenomas are the most common tumours in GSD which show variable echogenicity. These lesions may contain fat, haemorrhage, or rarely dystrophic calcifications. A fat component can be detected using chemical shift MRI. These lesions should be monitored serially and malignancy should be suspected in case of rapid growth. α1-Antitrypsin deficiency α1-Antitrypsin deficiency is a rare autosomal recessive disorder that can cause chronic severe paediatric liver disease. In infants, this disorder can have a presentation similar to biliary atresia or idiopathic neonatal hepatitis. Moreover, scintigraphy cannot distinguish between biliary atresia, because similar to atresia, it can show uptake by hepatocytes and absence of biliary excretion due to paucity of lobular biliary ducts. The US in the neonatal period can help distinguish between the two, as it shows normal gallbladder and hepatic parenchyma. Older children may show imaging evidence of hepatic fibrosis or cirrhosis. MR elastography in this disorder is accurate for identifying fibrosis with a cut-off value of >3 kPa predictive of fibrosis.

Liver disease with systemic diseases Various systemic illnesses can present with liver disease. The table summarizes the hepatic manifestations of various systemic liver diseases.

TABLE 9.8.1.7 Radiological Manifestations of Hepatobiliary Involvement of Systemic Diseases Systemic Illness Hepatobiliary Manifestation Imaging Findings Inflammatory Sclerosing cholangitis Dilatation and beading and bowel disease irregularity of the intra- and extrahepatic bile ducts (MRCP) Autoimmune hepatitis Nonspecific (normal, hepatomegaly, cirrhosis, periportal oedema) Hepatic steatosis Described Total parenteral Hepatic steatosis Described nutrition Cholestasis Gall bladder and intrahepatic biliary sludge, cholelithiasis Cystic fibrosis Focal biliary cirrhosis Periportal echogenicity (US) Periportal hyperintensity Steatosis/NASH/Cirrhosis/Portal Described hypertension Biliary manifestations Cholelithiasis, sludge in GB and IHBD Celiac disease Celiac hepatitis May vary from normal to coarsened echotexture on US Cirrhosis Infiltration by celiac associated lymphoma Cardiac disease Congestive hepatopathy (Fig Reticular enhancement pattern 9.8.8) on CECT with dilated IVC and/or hepatic veins Langerhans cell Sclerosing cholangitis Bilobar intrahepatic biliary histiocytosis (Fig radical dilatation 9.8.9) Acute/chronic liver disease Hepatomegaly Periportal hypodensity Hypodense nodules

Conclusion Paediatric diffuse liver diseases though forming a small subset of overall morbidity in children pose a formidable challenge for diagnosis as most cases present at a relatively early age. Imaging in these cases aims to make an aetiological diagnosis and rule out any associated complications, as the initial diagnosis is usually established by the biochemical analysis of liver function. Screening sonography usually forms the initial screening modality with MRI being the next stop problem-solving modality. CT scan has taken a back seat in current practice due to radiation exposure and the need to inject iodinated contrast media, both of which can be obviated by MRI. The former modality however remains essential in case an interventional procedure to treat portal hypertension is contemplated or percutaneous sampling from areas difficult to access by sonography is to be done. With the availability of an array of imaging modalities, it remains essential for an imaging expert to be clear as far as the choice of modality and order of its usage during the course on management is involved so that the most optimum imaging protocol can be offered to the patient.

FIG. 9.8.1.8 Congestive hepatopathy. CECT image of a patient with congestive heart failure showing heterogeneous and reticular enhancement of liver parenchyma (black arrows) and hepatomegaly. Note is made of bilateral pleural effusion (PE).

FIG. 9.8.1.9 Langerhans cell histiocytosis. (A) Axial CECT image in a patient of Langerhans cell histiocytosis showing bilobar dilated and intrahepatic biliary radicals showing thickened walls (black arrows). (B) CT of thorax of same patient showing cystic lesions in bilateral lungs (white arrows). 9 .8. 2

PEDIATRIC BENIGN HEPATIC MASSES (INCLUDING INFECTIONS) Kushaljit Singh Sodhi, Anmol Bhatia, Akshay Kumar Saxena

Introduction Liver neoplasms constitute around 2% of all neoplasms seen in the pediatric population, and around 6% of the total abdominal neoplasms. Only one-third of the liver tumours in children are benign, while two-thirds are malignant. Benign hepatic tumours in children include lesions which are specific to children like mesenchymal hamartomas and vascular tumours, and the lesions that are also seen in adult population, such as adenoma, focal nodular hyperplasia (FNH) and nodular regenerative hyperplasia (NRH). Further, benign hepatic lesions affecting children include a wide variety of infections of bacterial, fungal and parasitic origin. In the present chapter, we will be discussing about the benign hepatic tumours and hepatic infections commonly seen in the pediatric population.

Benign hepatic tumours in children Hemangioma Overview A wide variation has been reported in the use of terminology for the hepatic vascular malformations in literature. According to the standard nomenclature adopted by the International Society for the Study of Vascular Anomalies (ISSVA), liver vascular tumours in children are termed as liver hemangioma. Liver hemangiomas in children are classified as infantile and congenital. Infantile hemangiomas usually begin to grow after birth, continue to grow during the first year of life and enter an involuting phase between 1 and 7 years. These tumours are positive for glucose transporter-1 protein (Glut-1), a protein that facilitates the transport of glucose across erythrocyte cell membranes. On the other hand, congenital hemangiomas are fully developed at birth and are characterized by Glut-1 negativity. These are further subdivided into a rapidly involuting group and a noninvoluting group, with some overlap between these groups. Etiology and presentation Hemangioma is a model of the angiogenesis concept proposed by Folkman et al and its development is related to a combination of upregulation of factors that promote angiogenesis and downregulation of its inhibitors. Most of these tumours are diagnosed in the first year of life, with these being slightly more common in females. Most commonly, these present as an asymptomatic mass in abdomen; however, associated life-threatening presenting complications have also been reported. These include high-output cardiac failure as a result of large arteriovenous shunts or Kasabach–Merritt syndrome of coagulopathy, severe hypothyroidism and acute hemoperitoneum due to tumour rupture. Imaging Lesions can be focal, multifocal or diffuse. Multifocal lesions are usually small and homogenous in appearance, while larger lesions may show areas of hemorrhage, calcification, fibrosis and necrosis. The liver is grossly enlarged in diffuse disease, which may cause mass effect on surrounding organs and vessels. Multifocal lesions frequently are associated with multiple cutaneous infantile hemangiomas with a Glut-1 positive marker. Biopsy of these masses should be avoided as there is a risk of bleeding, and the diagnosis is made based on typical imaging features and involution at follow-up. Ultrasound. Well-defined hypoechoic or hyperechoic lesion, which may show heterogenous echotexture because of central hemorrhage/necrosis. A variety of flow patterns may be seen on colour Doppler due to the presence of shunts which may be portosystemic, or arteriovenous shunts. The hepatic arteries and veins usually enlarged, with large feeding arteries and draining veins seen surrounding as well as within the lesions. CT. The lesions are usually hypoattenuating to the liver parenchyma with speckled calcifications seen in up to 50% of cases. The enhancement pattern is similar to that of hemangioma in adults and shows intense peripheral nodular enhancement on arterial phase with progressive centripetal filling on venous and delayed phases. Small lesions usually show intense and uniform enhancement (Fig. 9.8.2.1).

FIG. 9.8.2.1 Axial CECT arterial phase image (A) showing a lesion with intense enhancement along the periphery with centripetal fill-in and enhancement of the entire lesion on delayed phase image (B) suggestive of hemangioma. MRI. The lesions show hypointense signal on T1-weighted images (T1WI) and hyperintense signal on T2-weighted images (T2WI). The tumour shows internal vascular flow voids and centripetal enhancement (Fig. 9.8.2.2). Heterogeneous signal may be seen due to presence of hemorrhage, thrombosis and necrosis. Calcifications may be seen in about 16% of cases.

FIG. 9.8.2.2 Congenital hemangioma in a 7-day-old baby. The lesion is hyperintense on T2WI (A). Dynamic imaging shows avid arterial peripheral enhancement (B) with gradual centripetal filling on portal venous (C), delayed (D) and five minutes scan (E) images. (Source: Courtesy of Dr. Govind Chavhan, The Hospital for Sick Children, Toronto, Canada.) Treatment and prognosis Treatment depends on the imaging appearance of the lesions and presence of complications. Patients with focal or multifocal lesions can be treated with corticosteroids. Cardiac failure is managed symptomatically. Focal nodular hyperplasia

Overview FNH is a rare benign epithelial liver tumour in children, with approximately only 7% of reported cases of FNH seen in pediatric patients, in whom the peak age at presentation is 2 to 5 years. FNH accounts for 2% of all primary pediatric hepatic tumours in children. The lesion has a complex appearance on histopathology showing nodules of well-differentiated hepatocytes which are subdivided by fibrous septa, and these septae coalesce to form a characteristic vascular stellate scar centrally. Etiology and clinical presentation The etiology of FNH is not certain, but some investigators believe that FNH may be a result of a hyperplastic response to some underlying vascular pathology, as represented by the central scar, possibly related to vascular thrombosis, followed by recanalization, and reperfusion. FNH is usually detected incidentally. Large lesions can present with an abdominal mass, as cited in approximately 20% of patients. Patients also may present with pain in abdomen. No AFP elevation is seen. Imaging USG. Seen as a homogeneous, well-circumscribed mass that may show variable echogenicity (Fig. 9.8.2.3A). The central scar appears hyperechoic. Calcification is rare. Doppler study reveals an increased flow in the central scar in a spoke-wheel pattern (Fig. 9.8.2.3B).

FIG. 9.8.2.3 Gray scale ultrasound image in an 8-year-old boy showing a heterogenous lesion in the liver, which on colour Doppler showing central as well as peripheral areas of vascularity. This was subsequently characterized as FNH on MRI ( Fig. 9.8.2.4). CT. FNH is typically well-circumscribed homogenous isodense lesion with a hypoattenuating scar. It typically shows early, uniform enhancement, and becomes isodense to the liver in the portal and delayed phases. The scar shows enhancement on delayed images. MRI. FNH shows isointense to slightly hypointense signal to the liver on T1WI and isointense to slightly hyperintense signal on T2WI. The central scar appears hypointense on T1 and hyperintense on T2WI (Fig. 9.8.2.4A and B). Dynamic imaging shows uniform enhancement of the lesion, which is hyperintense to the liver on arterial phase and shows isointense to slightly hyperintense signal on portal venous phase (Fig. 9.8.2.4C). Enhancement of the central scar is seen on delayed phase images (Fig. 9.8.2.4D). Varying degrees of diffusion restriction is seen in the lesions (Fig. 9.8.2.4E and F).

FIG. 9.8.2.4 MRI images showing a lesion in the left lobe of liver, which is isointense on T2WI (A) and T1WI (B) with a central T2 hyperintense (arrow in A) and T1 hypointense (arrow in B) scar. Dynamic images (C and D) showing homogenously enhancing lesion with nonenhancing scar in arterial phase (arrow in C) which is enhancing on delayed phase (D). Diffusion restriction is seen in the lesion on DWI (E) and ADC (F) images. Treatment FNH has no malignant potential. Serial hepatic ultrasounds are recommended for asymptomatic patients. Recommendations for symptomatic patients include discontinuation of oral contraceptives, surgical resection, ablative therapy or embolization. Mesenchymal hamartoma Overview Mesenchymal hamartoma is the second most common benign liver mass in children after vascular tumours, with most occurring in children less than 5 years of age. It affects boys slightly more often than girls. Histologically, they are composed of disordered, primitive, fluid-filled mesenchyme, hepatic parenchyma, and bile ducts, in addition to stromal cysts of variable size without a capsule. Etiology and clinical presentation It is postulated that a mesenchymal hamartoma arises from primitive mesenchymal tissues through a developmental aberration of excessive and uncoordinated proliferation during embryogenesis. Mesenchymal hamartoma generally is considered a congenital lesion related to a developmental anomaly.

The most common clinical presentation is painless abdominal distention. It has known to be diagnosed antenatally and an association with hydrops has been reported. Serum AFP levels are normal. Imaging USG. On ultrasound and CT, mesenchymal hamartomas typically are multicystic, heterogeneous masses with septa of variable thickness (Fig. 9.8.2.5). When the cysts are tiny, the lesion is hyperechoic and simulates a solid lesion. Internal echoes may be seen due to presence of gelatinous material or hemorrhage. Colour Doppler vascularity within the solid portions and septae only.

FIG. 9.8.2.5 Ultrasound image in a 1-year-old boy showing a multiseptated lesion which was seen arising from the liver with internal echoes suggestive of mesenchymal hamartoma. CT. Mesenchymal hamartomas are seen as complex cystic masses. Their septations and solid components show enhancement (Fig. 9.8.2.6).

FIG. 9.8.2.6 Axial (A) and coronal (B) CECT images in a 1-year-old boy showing a large multiseptated cystic lesion in the right lobe of liver suggestive of mesenchymal hamartoma. MRI. Multicystic lesion is seen which is hypointense on T1WI and hyperintense on T2WI. The signal intensity usually follows water intensity, but may vary, depending on the amount of protein within the cyst fluid, and the presence or absence of hemorrhage within the cyst (Fig. 9.8.2.7A and B). Septa and solid portions of the lesion usually show hypointense signal on T1- and T2-weighted images, with enhancement of septa and solid components seen (Fig. 9.8.2.7C).

FIG. 9.8.2.7 MR images of liver in a 2-year-old boy with mesenchymal hamartoma. T2WI (A) and T1WI (B) images are showing a multiseptated cystic lesion in right lobe of liver with T1 hyperintense signal in one of the cysts suggestive of proteinaceous contents. Postcontrast T1WI (C) image is showing enhancement of the septae. Treatment The natural history of mesenchymal hamartoma is that it enlarges during the first several months of life and later on stabilizes. Spontaneous partial regression has also been reported. Surgical resection is the treatment of choice for mesenchymal hamartoma. Observation of mesenchymal hamartoma is not recommended due to rare reports of malignant transformation to undifferentiated embryonal sarcoma. Hepatic adenoma Overview Hepatic adenoma, also referred to as hepatocellular adenoma is a relatively uncommon, benign hepatic neoplasm which is generally hormone induced. They are rare in the pediatric age group and tend to occur more commonly in younger females with history of oral contraceptive use. Hepatic adenomas are usually solitary, well circumscribed, pseudo encapsulated tumours. The term hepatic adenosis is reserved for multiple adenomas (>10) in patients lacking other possible risk factors for adenoma. The devastating complications like tumoural hemorrhage and malignant transformation make it imperative to differentiate them from other benign focal liver lesions. Etiology and presentation Although the precise etiological factors cannot be pin pointed, pediatric cases are frequently attributed to the use of steroids and adolescents who use oral contraceptives. Hepatic adenomas are also associated with glycogen storage disorders (type I and III), familial diabetes mellitus, galactosemia and metabolic syndrome. Association of adenomas with congenital or acquired disorders of hepatic vasculature, like absence of portal vein or obliteration and other hypervascular liver tumours, such as FNH and hemangioma, has recently been discovered. Most of the patients are asymptomatic and the lesions are incidentally detected on imaging. The occurrence of intratumoural hemorrhage, discovered in approximately 10% of patients, is quite worrisome, as it may result in abdominal pain. Rarely there could be intraperitoneal hemorrhage resulting in hypovolemic shock. Liver function tests are essentially normal, and AFP is not elevated. Malignant transformation to hepatocellular carcinoma is a far rarer complication, more so reported with multifocal adenomas in patients of Glycogen storage disorders.

Imaging The histology and imaging pattern in hepatic adenoma are closely knit. They are solitary in around 70%–80% of cases and present as a well-circumscribed, unencapsulated tumours. They are composed of benign proliferating hepatocytes with high amount of glycogen and fat content but lack the normal lobular anatomy. Pseudocapsule is formed by the compression of adjacent hepatic parenchyma to the tumour periphery and is seen in 25%– 30% of cases. Hypervascularity is seen due to extensive sinusoids and feeding arteries, whereas the poor connective tissue support leads to increased propensity to hemorrhage. Tumour heterogeneity on imaging is attributed to areas of necrosis, hemorrhage, fat, calcification and myxoid stroma. USG. Lesions may be hyperechoic owing to the high fat content or internal hemorrhage; but in glycogen storage disorders or in cases with diffuse fatty infiltration, the lesion may appear relatively hypoechoic (Fig. 9.8.2.8) to the liver parenchyma. Colour Doppler demonstrates peritumoural or intratumoural vessels which typically show a continuous flat or a triphasic waveform. These Doppler findings are absent in FNH which has a predominant central arterial flow pattern.

FIG. 9.8.2.8 Ultrasound image of liver in a 2-year-old boy with glycogen storage disorder showing a well-defined hypoechoic lesion suggestive of adenoma. CT. The attenuation on CT depends on composition of tumour as well as that of liver and the phase of contrast. On noncontrast scans, lesions are usually hypoattenuating due to intratumoural fat; although hyperattenuating areas because of recent hemorrhage, is seen in approximately 15%–43% of cases. Smaller lesions (4 cm and tumours with subcapsular and exophytic component. Inflammatory pseudotumour Overview Inflammatory pseudotumour, also known as plasma cell granuloma or postinflammatory tumour, is a benign and rare entity involving nearly every site in the body, most commonly the lungs and orbits. Inflammatory pseudotumour of the liver is quite rare in children and

seen more commonly in young adults with a male predominance. They are single or multifocal, circumscribed masses which are histologically characterized by benign connective tissue proliferation associated with plasma cells and mononuclear leukocytes infiltration. Solitary masses which are also called the type I lesions, tend to occur centrally involving the porta hepatis or bile duct leading to portal hypertension, portal phlebitis and obstructive jaundice. Multiple nodules which are also called the type II lesions, tend to involve both lobes without the involvement of porta hepatis and mimic the appearance of hepatic metastasis. Etiology and presentation The exact cause of hepatic inflammatory pseudotumour is unknown; however, the role of infectious and autoimmune causes have been implicated, including prior Epstein–Barr virus infection. The most common presentation is abdominal pain, followed by fever and anorexia. Biliary obstruction and portal hypertension may also be seen. Laboratory biochemical investigations may show elevated liver enzymes reflecting biliary obstruction, elevated inflammatory markers like erythrocyte sedimentation rate and C-reactive protein, as well as leukocytosis. Serum AFP is not elevated. Imaging The imaging findings of pseudotumour are very nonspecific and variable, depending on the amount of fibrous tissue and cellular infiltration. They can be solitary or multifocal, wellcircumscribed hepatic masses. USG. The lesion is usually a solid, heterogenous, hypoechoic mass. CT. On unenhanced CT, the lesions appear hypodense to the liver parenchyma and show heterogenous enhancement on postcontrast imaging (Fig. 9.8.2.11). Larger lesions may show a lower density core because of coagulation necrosis. Lesions with more fibrous content may reveal delayed enhancement. Sometimes features suggestive of biliary obstruction or pyelophlebitis may be seen.

FIG. 9.8.2.11 Axial CECT images (A and B) in a child with inflammatory pseudotumour showing an ill-defined heterogenous lesion in the left lobe of liver. Minimal periphepatic fluid and pericardial effusion is seen. The lesion was biopsied and reported as inflammatory pseudotumour. MRI. They usually show hypointense signal on T1WI and hyperintense signal on T2WI with heterogenous enhancement on postcontrast imaging. Treatment

The major diagnostic dilemma lies in distinguishing inflammatory pseudotumour from malignant hepatic tumour on imaging alone. Some clinicians resort to tumour resection due to strong preoperative probability of malignancy. However, in cases with established histopathological diagnosis of pseudotumour, conservative management approach can be adopted. Nodular regenerative hyperplasia Overview NRH is characterized by multiple monoacinar regenerating nodules surrounded by atrophic liver in the absence of hepatic fibrosis. This condition can occur in any age group with no gender predilection; however, it is quite rare in children. The nodules consist of focal proliferation of normal looking hepatocytes, some of which may demonstrate increased intracellular glycogen or lipid. Etiology and presentation The detailed etiopathogenesis of NRH remains unclear till date, but obliterative vasculopathy is the suspected etiology. It is hypothesized that disturbed regional blood flow leads to acinar atrophy with subsequent compensatory hyperplasia in the regions with preserved flow. This can be associated with myriad of underlying conditions like myelo/lympho proliferative disorders, autoimmune diseases, collagen vascular diseases, Budd–Chiari syndrome and patients on immunosuppressive or chemotherapeutic agents. The lesions may be incidentally detected on imaging or may lead to portal hypertension in some patients without underlying cirrhosis. Malignant transformation to hepatocellular carcinoma is a far rarer complication. Imaging NRH is an underdiagnosed entity with variable radiological appearance ranging from multiple small nodules, to nodules coalescing to form larger mass or to a grossly normal liver. Given the nonspecific imaging findings, sometimes differentiation from hepatic adenoma, FNH and liver metastasis may be difficult. Radiological or clinical evidence of portal hypertension in a noncirrhotic liver should steer one to think along lines of NRH. USG. Diffuse, tiny nodules may be inapparent on ultrasound manifesting as a grossly normal liver or a heterogenous liver echotexture with no focal lesion. When delineated, the nodules are mostly well defined, homogenous and hypoechoic; however, hyperechoic nodules have also been reported. Sometimes they may be hyperechoic, with reduced central echogenicity reflecting prior hemorrhage. CT. On unenhanced CT the nodules are typically hypodense to the surrounding parenchyma, but isodense lesions are also reported. On postcontrast imaging, the lesions usually do not enhance and appear hypodense, helping in differentiation from other hepatic tumours. Occasionally they may demonstrate diffuse enhancement or a peripheral rim-like enhancement. MRI. The lesions are mildly hyperintense on T1WI with a variable signal on T2W (Fig. 9.8.2.12). A T1 hyperintense to hypointense and T2 hyperintense rim can be seen. They may demonstrate signal drop out on opposed phase or fat-suppressed imaging owing to intratumoural fat. On postgadolinium contrast enhanced scan, the enhancement pattern is variable (Fig. 9.8.2.12). Most lesions become isointense to the surrounding liver in portal venous phase.

FIG. 9.8.2.12 MRI images showing regenerative nodules in a child in the background of chronic liver disease. Axial T2W (A) and T1W (B) images showing multiple T2 hypointense and T1 hyperintense lesions in both lobes of liver which are predominantly hypointense to the surrounding liver on postcontrast image (C). No evidence of diffusion restriction seen on DWI (D) and ADC (E) images. Treatment No specific treatment is needed for NRH except for discontinuation of associated drugs and treatment of underlying disease in the appropriate clinical setting. In the case of bleed or rupture, especially in larger mass, surgical resection may be warranted. Treatment of portal hypertension using portocaval shunts may be needed and carries a better prognosis than portal hypertension in cirrhotics.

Hepatic infections in children Viral hepatitis Overview Globally, viral hepatitis remains the most common cause of liver infection in children. The clinical symptoms may include fever, pain abdomen and jaundice in acute infections which in a few may progress to fulminant hepatic failure. Others may manifest chronic active infection (>6 months) or subclinical infection which may lead to cirrhosis or HCC in later period of life. Etiology

The most common causative agents include the five hepatotropic viruses; Hepatitis A, B, C, D and E viruses. Other viruses implicated in children include the mumps, measles, coxsackie, Epstein–Barr virus, cytomegalovirus and herpes simplex virus. The mode of transmission in children is usually faeco-oral route in hepatitis A and E and parenteral or perinatal transmission in Hepatitis B and C. Imaging Clinical findings and serological tests form the cornerstone for diagnosis in viral hepatitis Imaging plays a less important role and reveals either nonspecific findings or a completely normal liver. Ultrasound. Acute viral hepatitis on ultrasound may show hepatomegaly with diffusely decreased parenchymal echogenicity. There may be relative increase in periportal echogenicity, also called as periportal cuffing, giving rise to a ‘starry sky appearance’. Gall bladder may also show circumferential wall thickening with luminal compromise. In chronic hepatitis, liver may show coarsened echotexture with raised parenchymal echogenicity as in early stages of cirrhosis. Sometimes splenomegaly, ascites and periportal lymphadenopathy may also be seen. CT. Findings on CT are comparable to that of ultrasound. Hepatomegaly, heterogenous enhancement, periportal and gall bladder wall edema are some of the common findings. In patients with fulminant hepatic failure, parenchymal necrosis as well as regenerating nodules can be seen. On noncontrast CT, necrosis usually appears as hypodense areas whereas regenerating nodules are usually hyperattenuating relative to the liver parenchyma. On postcontrast scan, the two may show either identical enhancement or the regenerating nodules may show diminished enhancement relative to the adjacent liver parenchyma. MRI. MRI will also show nonspecific findings such as hepatomegaly and periportal hyperintensities on T2WI. Regenerating nodules will appear T1 hyperintense with low signal intensity on T2WI compared to the adjacent liver parenchyma. Treatment. Treatment in viral hepatitis depends on the disease severity and the causative agent. The options range from symptomatic treatment to antiviral agents to liver transplant in fulminant hepatitis. Pyogenic abscess Overview Pyogenic liver abscess refers to bacterial infection causing focal area of pus accumulation with inflammatory changes in the adjacent liver parenchyma. Although the incidence has reduced in developed countries, it is still common in developing nations. Immunocompromised states, underlying intraabdominal infection, inflammatory bowel disease or chronic malnutrition is the predisposing factor in the pediatric age group. Presenting complaints are usually fever and right hypochondrial pain. The mortality rate is around 6% to 14%. Etiology More often than not, the infection is polymicrobial. However, Escherichia coli, Klebsiella pneumonia, Staphylococci and streptococci are some of the common isolated organisms. The route of bacterial spread to the liver may be via portal vein, bile duct, hepatic artery, or contiguous spread from adjacent structures or by direct penetrating trauma to liver. Lesions are more often solitary and tend to involve the right lobe more frequently. Multiple lesions are usually encountered in cases associated with cholangitis, trauma or bacteremia. Imaging

Depending upon the stage and degree of disease severity, hepatic abscess can have a spectrum of imaging appearance. The lesions may be solitary or multiple, unilocular or multilocular, with irregular and thickened walls to well-defined margins. USG. The common sonographic findings include anechoic to hypoechoic mass, with internal echogenic debris and septations, fluid–fluid interfaces and hypoechoic rim of edema (Fig. 9.8.2.13). Occasionally, presence of anaerobic infection may give rise to echogenic air foci with posterior reverberation artifacts. Acoustic through transmission and absence of central flow on Doppler can help to exclude a solid neoplasm. Regions of early suppuration or evolving abscesses may appear solid with altered echogenicity, usually hypoechoic.

FIG. 9.8.2.13 Ultrasound image of liver in child with pyogenic abscess showing an ill-defined hypoechoic to hyperechoic lesion. CT. The typical CT findings include a hypoattenuating lesion with enhancing abscess walls and peripheral hypodense rim of edema (Fig. 9.8.2.14). Sometimes, fluid–fluid or air–fluid levels may be appreciated. A characteristic finding, known as ‘double target sign’ may be demonstrated on contrast-enhanced CT wherein the central hypoattenuating abscess cavity is surrounded by inner rim of a high density and outer rim of a lower density. Another characteristic feature of pyogenic abscesses is ‘cluster sign’ which as the name suggests is fusion of smaller abscesses to form a large abscess. Sometimes, a wedge-shaped, segmental area of arterial enhancement may be seen around the abscess which is attributed to obstruction of the local portal venules and compensatory increase in arterial flow. In the setting of chronic granulomatous disease, infection usually heals with formation of calcified granulomas.

FIG. 9.8.2.14 Axial CECT images of liver in a child with pyogenic abscesses showing two well-defined hypodense lesions with irregular shaggy walls and surrounding edema. MRI. On MRI, the central abscess cavity is hypointense to isointense on T1WI, hyperintense on T2WI with enhancing walls and surrounding T2 hyperintense rim of edema. The dynamic contrast enhancement findings on MRI are quite similar to postcontrast CT findings. High signal intensity on DWI and low signal intensity on ADC are usually seen. Treatment Pyogenic abscesses are usually treated using a combination of appropriate antibiotic therapy with percutaneous catheter drainage and aspiration. Small lesions (25 Hounsfield units) 3. Presence of imaging features of blood or blood degradation products on MRI 4. Heterogeneous fluid showing echogenic debris on ultrasonography 5. Visible rupture/defect in hepatic capsule Tumour rupture is generally identified on imaging; however, it can also be recognized after laparotomy/laparoscopy or paracentesis. While laparotomy/laparoscopy or peritoneal

fluid aspiration is not required, if it is performed, peritoneal fluid will reveal presence of tumour cells. Although tumour rupture can be determined at pathology, it is not possible to ascertain the timing of this rupture. Thus it cannot be designated as a PRETEXT factor until upfront surgery is carried out (before starting chemotherapy). Rupture recognized at resection after chemotherapy would be regarded a POSTTEXT factor. The following factors are essential while evaluating tumour rupture: 1. Biopsy – Haemorrhage in relation to biopsy of the tumour is not regarded as tumour rupture for the purpose of PRETEXT classification. 2. Surgical rupture – Surgical rupture is not regarded as tumour rupture for the purpose of PRETEXT classification. 3. Ascites – Nonhaemorrhagic simple ascites is frequently seen with hepatoblastoma and hepatocellular carcinoma and is not regarded as tumour rupture. 4. Subcapsular fluid – Fluid collections that are present beneath the capsule of liver (even if haemorrhagic) are not regarded as tumour rupture. Caudate (C) Involvement of the caudate lobe (Couinaud segment 1) has importance for surgical planning. In the case of involvement of the caudate lobe, the tumour is classified as at least PRETEXT II by convention. As the caudate lobe can be surgically resected with either a right or a left hepatectomy, it is still essential to determine the true extent of the tumour. Although resection of the caudate lobe is safer with modern surgical techniques, complications may be encountered and can be significant. Therefore, caudate involvement remains a distinct annotation factor, even though it is not used to risk-stratify patients. It is essential to know the boundaries of the caudate lobe to determine its involvement by the tumour. For the purpose of PRETEXT staging, the caudate is defined as the part of the liver that extends along the posterior surface of the liver between the portal vein and intrahepatic inferior vena cava. The borders of the caudate lobe are as follows: • The right margin is a line drawn along the right lateral border of the inferior vena cava, perpendicular to the inferior vena cava. • The left margin is the ligamentum venosum. • The anterior margin is formed by the porta hepatis and ligamentum teres. • The superior margin is the dome of the liver. • The inferior margin is formed where the liver passes between the main portal vein and the inferior vena cava. Lymph node metastases (N) Lymph node metastases are very rare with hepatoblastoma but are much more common in hepatocellular carcinoma. Lymph node metastases can be difficult to diagnose. Biopsy may be required for the diagnosis if imaging is equivocal or in children in whom a decision to transplant requires certainty regarding lymph node status. For PRETEXT staging, nodal metastases are regarded to be present if one of the following criteria is fulfilled: 1. Lymph node with a short-axis diameter of more than 1 cm or a portocaval lymph node with short-axis diameter more than 1.5 cm, or 2. Spherical shape of lymph node with loss of fatty hilum. Distant metastases (M) The commonest site of distant metastases from hepatoblastoma and hepatocellular carcinoma is lungs. Pulmonary metastases are present in 17% of children with hepatoblastoma at diagnosis. To be labelled as M positive, there must be at least one noncalcified pulmonary nodule greater than or equal to 5 mm in diameter; or two or more noncalcified pulmonary nodules, each greater than or equal to 3 mm in diameter. Children with characteristic imaging findings of pulmonary metastatic disease do not need biopsy; however, biopsy is required in those with equivocal findings as presence of metastatic disease significantly changes therapy. Hepatoblastoma is commoner in premature infants, especially in those with a very low birth weight and accompanying chronic lung disease of prematurity is often present. Also,

as general anaesthesia is often required while imaging in infants, atelectasis might be seen. It is hard to evaluate the lungs completely due to both these factors. Visualization of the lungs can be improved by: 1. Performing chest CT before abdominal CT in children who are sedated or are under general anaesthesia. 2. Positive pressure should be used for better lung inflation if the child is intubated. 3. Lung bases in children with persistent atelectasis can be better assessed with imaging in the prone position. Other than lung metastases, brain and bone metastases can also be seen with hepatoblastomas but are rare. Imaging beyond CT chest for metastatic evaluation should be performed only if the child is symptomatic or there is an unexplainable rise in serum AFP levels. Children with hepatoblastomas may have fractures at the time of diagnosis and some have paraneoplastic syndromes causing abnormal bone metabolism and bone scans. The PRETEXT groups (I–IV) and all the annotation factors should be reassessed each time the child is imaged. After diagnosis these are referred to as POST-TEXT (POSTTreatment EXTent of disease) factors. POSTTEXT factors do not apply after surgical resection of tumour. Fibrolamellar carcinoma FLC is a variant of HCC that is seen in young adults or adolescents in the absence of an underlying hepatic disease. Majority of the patients are less than 35 years of age and FLC may occur in children as young as 10 years. No sex predilection is noted. Patients mostly present with abdominal pain or a mass and nonspecific abdominal symptoms, uncommon presenting features include gynecomastia, jaundice and venous compression or thrombosis. Serum AFP levels are usually not elevated. Imaging features Abdominal radiograph may show hepatomegaly or stellate calcifications. On ultrasonography, the lesion appears as a circumscribed, isoechoic to hyperechoic mass with heterogeneous echotexture. A central scar, if present, appears hyperechoic and may show calcifications. CT demonstrates a mass with well-defined lobulated margins, which is hypodense relative to adjacent liver parenchyma, usually with a central scar with or without calcifications. After intravenous contrast administration, the tumour appears hyperdense relative to adjacent liver parenchyma in the arterial phase with variable attenuation in the portal venous phase. The central scar is hypodense relative to the rest of the tumour (Fig. 9.8.3.12A and B).

FIG. 9.8.3.12 Axial (A) and coronal (B) CECT images of the abdomen reveal presence of a large, lobulated mass lesion in right lobe of liver showing peripheral enhancement with central hypodense scar suggestive of fibrolamellar carcinoma which was subsequently proven on histopathology. On MR imaging, FLC appears hypointense to isointense on T1W images and slightly hyperintense to isointense on T2W images. The fibrous central scar and septa appear

hypointense on T1W and T2W images and the scar typically does not show enhancement. Scintigraphic studies may be useful in evaluation of FLC due to the relative lack of Kupffer cells, resulting in a photopenic defect at technetium 99m labelled sulphur colloid scanning. The differentials for FLC in younger patients include FNH, hepatocellular adenoma, HCC and metastases. FNH shows avid postcontrast enhancement (Fig. 9.8.3.13A–C) and may also contain a central scar, which is myxoid and appears hyperintense on T2W images and demonstrates delayed postcontrast enhancement. Table 9.8.3.3 enlists the differences between FNH and FLC. Hepatocellular adenoma does not show a central scar and appears heterogeneous on imaging due to intratumoural fat and haemorrhage. Conventional HCC is more likely to demonstrate regions of haemorrhage and necrosis along with underlying liver disease. Metastases are multifocal in comparison with FLC.

FIG. 9.8.3.13 Axial NCCT and CECT images of the abdomen in a 7year-old child show presence of an isodense mass lesion in the right lobe of liver on NCCT (A) which shows intense enhancement on postcontrast scan (B) with a hypodense central scar as evident on delayed scan (arrow in C) suggestive of focal nodular hyperplasia. TABLE 9.8.3.3 Differences Between Focal Nodular Hyperplasia and Fibrolamellar Carcinoma Focal Nodular Hyperplasia Fibrolamellar Carcinoma Homogeneous Heterogeneous with central stellate calcification Central scar Present but 2 cm, T2 hyperintense, rarely shows hypointense, calcification calcification common Uptake of hepatocyte A pronounced persistent Absence of enhancement specific agents (HSA) hyperintensity with HSA SPIO Pronounced uptake No uptake (superparamagnetic iron oxide) Invasion of adjacent Absent Present organs Lymphadenopathy Absent Present Metastases Absent Present Homogeneity

Treatment

Treatment is primarily surgical but may include orthotopic liver transplantation, systemic chemotherapy or hepatic intraarterial chemoembolization, according to the extent of disease. Favourable factors include a young age, lack of vascular invasion or thrombosis, lack of metastatic lymphadenopathy and negative surgical margins.

Epithelial origin (biliary) Cholangiocarcinoma Cholangiocarcinoma is an adenocarcinoma that arises from the epithelial cells of the intrahepatic and extrahepatic bile ducts. Cholangiocarcinoma is very rare in children and if present it is associated with underlying diseases. These conditions include HIV infection, biliary atresia, postradiotherapy, choledochal cysts (Fig. 9.8.3.14A and B), primary sclerosing cholangitis and inflammatory bowel disease. Cholangiocarcinomas can be intrahepatic or extrahepatic.

FIG. 9.8.3.14 In a known case of Caroli disease, USG image (A) reveals noncommunicating cystic areas in the liver parenchyma with one of them showing presence of nondependent echogenic soft tissue along its walls. Axial CECT abdomen image (B) reveals presence of enhancing soft tissue along the walls of one of the cystic lesions in segment IV of left lobe of liver (arrow in B) suggestive of development of cholangiocarcinoma, which was proven on histopathology. Note is made of hyperdense sludge and calculi within the dilated cystic areas, central dot sign is also seen within some of the cysts. Imaging features The mass forming intrahepatic cholangiocarcinoma is the commonest type of intrahepatic cholangiocarcinoma. On ultrasonography, it appears as a lesion of intermediate signal intensity with a peripheral hypoechoic halo of compressed liver parenchyma around it. On CT, it appears as an irregular hypodense mass and shows mild peripheral enhancement with focal dilatation of intrahepatic ducts around the tumour, capsular retraction can also be seen. The lesion appears hypointense on T1W images and hyperintense on T2W images, it shows peripheral rim enhancement with gradual progressive enhancement on delayed postcontrast scans.

Tumours of mesenchymal origin Undifferentiated (embryonal) sarcoma UES of the liver is an aggressive tumour of mesenchymal origin. It has been referred to as malignant mesenchymoma, mesenchymal sarcoma, embryonal sarcoma or primary sarcoma of the liver previously. It is usually seen in children between the age of 6 and 10 years with a slight male predilection. Patients present with an abdominal mass or

abdominal pain. The serum AFP level is normal. Metastases involving the lungs, pleura and peritoneum can be seen. Invasion of the inferior vena cava is rare. Imaging features UES shows a solid, cystic and mucoid composition. A characteristic imaging feature of UES is a predominantly solid appearance at ultrasonography; however, it appears cystic on CT and MR imaging due to the high water content of the prominent myxoid stroma. At ultrasonography, the tumour appears as a solid lesion and is isoechoic to hyperechoic relative to normal liver with small anechoic spaces. CT demonstrates predominantly water attenuation (88% of tumour volume) with foci of soft tissue, usually at the periphery or forming septa of variable thickness. A dense, enhancing peripheral rim may be observed, which corresponds to the pseudocapsule. Acute haemorrhage if present, may be seen as central hyperdense foci and calcification is uncommon. Occasionally, fluid-debris levels may be noted. Peripheral enhancement is seen predominantly on postcontrast delayed images. On MR imaging, UES shows fluid signal intensity on T1W and T2W images. A hypointense rim on T1W and T2W images reflects the fibrous pseudocapsule. Haemorrhage appears as focal areas of T1 hyperintensity and T2 hypointensity. Fluid levels may be seen and internal debris and septa are demonstrated on T2W images. Heterogeneous enhancement of the peripheral and solid portions of the mass is seen on postcontrast scans. MR imaging is superior to CT for determination of resectability and assessment for involvement of venous structures, the biliary tree and lymph nodes. The differential diagnostic consideration for UES is mesenchymal hamartoma; however, UES is rare under the age of 5 years while mesenchymal hamartoma is mostly diagnosed by age 2 years. Tissue sampling is required to make a definitive diagnosis. UES can be mistaken for a cyst, particularly hydatid cyst in endemic areas due to its cystic appearance on CT and MRI. Ultrasound can be useful to demonstrate the solid nature of the mass and delayed contrast-enhanced CT and MR imaging can also help demonstrate enhancement of the solid areas. Other cystic lesions in the differential diagnosis include abscess, cystic degeneration in hepatoblastoma or HCC and cystic metastasis. Patients with abscess would present with fever. Hepatoblastoma occurs in a younger age group, is associated with elevated serum AFP levels and cystic change is not commonly seen in hepatoblastoma. HCC affects the same age group but appears solid at CT and MR imaging, is associated with underlying liver disease and with raised serum AFP levels. Important facts about UES sarcoma are enlisted in Box 9.8.3.3. BOX 9.8.3.3 Impo r ta n t Fa c ts : U n dif f e r e n tia te d E mbr yo n a l Sa r co ma • Malignant liver neoplasm of mesenchymal origin with undifferentiated cells • Well-circumscribed liver mass in 6–10-year-old children • Usually large >10 cm in size • Lesion appears cystic on CT/MRI but solid on USG due to the presence of myxoid components • Septae and mural nodules can be seen • Peripheral enhancement seen on delayed scans Treatment The mainstay of treatment is complete surgical resection, but the use of multimodality treatment has shown an improved survival. Most of the unresectable tumours become amenable to resection after the use of neoadjuvant chemotherapy. Some of the unresectable tumours can be resistant to chemotherapy; however, total hepatic resection and living related donor liver transplantation can be performed in such patients. Epitheliod hemangioendothelioma Epithelioid hemangioendothelioma (EHE) is an uncommon soft-tissue tumour of vascular origin that may be found in the liver. Hepatic EHE is a tumour of intermediate malignant

potential, between that of benign IHE and the highly aggressive angiosarcoma. It is mostly seen in young to middle-aged adults, but a few number of cases have been reported in the paediatric population. A female predilection has been noted with a female-to-male ratio of 3:2. Presenting features include right upper quadrant pain, hepatomegaly and weight loss. Imaging features Multiple nodules, predominantly peripheral, can be seen in the early stage of multifocal form of disease. Confluent masses may form as the nodules merge as they enlarge, this gives rise to the diffuse pattern seen in the advanced stages of the disease. Individual masses exhibit a target-like appearance, that corresponds to the zonal architecture observed pathologically. Flattening or retraction of the adjacent hepatic capsule as a result of fibrosis is an unusual and characteristic finding of EHE that may be detected at crosssectional imaging. On ultrasonography, EHE may appear as individual nodules, confluent nodules or diffusely heterogeneous echotexture of the liver. The nodules are mostly hypoechoic, but may appear hyperechoic with or without a hypoechoic rim or isocheoic with a hypoechoic halo. On noncontrast CT, the peripheral nodules appear hypodense as compared to the normal hepatic parenchyma. Calcifications can be seen in 20% of cases. Unaffected portions of the liver may undergo compensatory hypertrophy. On contrast-enhanced CT, peripheral rim enhancement is seen and the central, relatively hypocellular portion does not enhance. On multiphasic CT peripheral and progressive centripetal enhancement is seen in larger lesions with incomplete fill-in on delayed phase images. Central enhancement with centrifugal progression at dynamic imaging can be seen in smaller lesions. As some areas of the lesions may become isodense to the hepatic parenchyma on contrast-enhanced scans noncontrast CT may be better for delineating the extent of disease. Capsular retraction can be seen on CT. The nodules show variable appearance on MRI, but a target-like appearance of concentric zones is frequently seen. The lesions appear hypointense to the hepatic parenchyma on T1W images and may show a more hypointense central portion, which likely correlates with areas of central haemorrhage, necrosis or calcification. On T2W images, lesions appear heterogeneously hyperintense with presence of a more hyperintense central portion. T1- or T2-weighted images may show a dark halo. Peripheral postcontrast enhancement is seen, although very large lesions may show more heterogeneous enhancement. The tumour, adjacent lymph nodes and extrahepatic sites of disease show moderate to intense uptake on Fluorine 18 (18F) fluorodeoxyglucose positron emission tomography (PET); hence, PET/CT can prove to be superior to CT or MR imaging for staging. As EHE usually presents as multiple nodules, the main differential diagnostic consideration is metastatic disease and angiosarcoma which is a multifocal vascular tumour are the differential diagnostic considerations for EHE which generally presents as multiple nodules. Angiosarcoma is an uncommon tumour associated with a rapidly progressive course, whereas EHE has a prolonged clinical course associated with mild symptoms. Treatment Surgical resection is the mainstay of treatment, as the tumour does not respond to chemotherapy. As EHE involves both lobes of liver diffusely, surgical resection is not an option for many patients. Living related donor liver transplantation may be considered for such patients, but outcomes are variable. Angiosarcoma Angiosarcoma is a rare malignant tumour of vascular origin which can arise anywhere in the body, including the liver. Elderly males are usually affected although the tumour may also occur in young girls and has been reported in children with a previous diagnosis of IHE. Toxins such as the contrast agent thorium dioxide (Thorotrast) and vinyl chloride have been implicated in the development of angiosarcoma in adults, but not in the paediatric population. Patients usually present with hepatomegaly and nonspecific symptoms including abdominal pain, anorexia, fatigue and weight loss. Anaemia, thrombocytopenia and consumptive coagulopathy may be present. Spontaneous tumour rupture with

hemoperitoneum occurs in 15%–27% of patients. Massive haemorrhage may be a complication of percutaneous biopsy and planning for surgical backup is important. Metastatic disease is common and most frequently affects the lung and spleen. Imaging features Multiple nodules, a big mass or both or a diffusely heterogeneous echotexture of the whole liver may be seen on ultrasonography. The amount of haemorrhage or necrotic change present within the nodules determines their echogenicity. On noncontrast CT, the nodules appear hypodense to normal hepatic parenchyma but may show hyperdense foci due to the presence of acute haemorrhage. Lesions are hypodense compared to the hepatic parenchyma on arterial and venous phase images with foci of early heterogeneous, infrequently central enhancement or ring enhancement, which is less in attenuation than the contrast-filled aorta. On delayed images, there is persistent enhancement but complete centripetal fill-in is not noted, likely due to the presence of central fibrosis or necrosis. 18F fluorodeoxyglucose PET CT may show intense uptake in the liver tumours and can be helpful in localizing extrahepatic disease. MR imaging reveals lesions of low signal intensity relative to normal liver on T1W images which may demonstrate hyperintense foci due to intratumoural haemorrhage. The lesions appear heterogeneously hyperintense to normal liver on T2W images and may contain dark septa or fluid levels consistent with haemorrhage. Infrequently, angiosarcoma may present as a diffusely heterogeneous signal intensity of the hepatic parenchyma without a focal mass. Dynamic MR imaging after intravenous administration of gadolinium shows markedly heterogeneous enhancement, which is progressive on delayed phase images with lack of central filling. The most important differential diagnostic consideration is metastases, the other one being IHE, the latter is a much more common multifocal vascular tumour. Angiosarcoma has been reported in patients with a previous diagnosis of the more common entity, IHE. Due to the risk of bleeding after biopsy, the diagnosis and management of IHE is based on the imaging findings and the patient is followed up closely. Failure to respond to treatment or presentation after the age of 1 year should prompt histologic confirmation of the diagnosis. Treatment Angiosarcoma is associated with a poor prognosis and the patients deteriorate rapidly leading to death within 6 months to a year from diagnosis irrespective of treatment. Surgical resection offers the best hope of survival. Acute tumour rupture can be treated with transcatheter arterial embolization, and transcatheter arterial chemoembolization may represent an alternative treatment modality for patients with dominant masses. Embryonal rhabdomyosarcoma Rhabdomyosarcoma is a very aggressive tumour which can occur anywhere in the body and is the commonest soft tissue sarcoma in children. It rarely arises in the biliary tree. Biliary rhabdomyosarcoma occurs almost exclusively in children and represents 1% of liver tumours in the paediatric population. The tumour is mostly diagnosed under the age of 5 years. The child presents with jaundice most commonly along with abdominal distention, fever, hepatomegaly or nausea and vomiting. Elevated levels of conjugated bilirubin and alkaline phosphatase are seen on blood examination and serum AFP is normal. Metastatic disease is present at diagnosis in as many as 30% of cases. Imaging features The lesion can be seen as a mass within the biliary ducts causing ductal dilatation and indicating its biliary origin. The common bile duct is a frequent site of involvement and a mass can be seen at or near the porta hepatis (Fig. 9.8.3.15A–C). Intrahepatic masses can also occur. Large lesions can show areas of fluid attenuation representing necrosis. Invasion into the adjacent organs and regional lymphadenopathy should be assessed.

FIG. 9.8.3.15 USG images (A–C) in a 3-year-old child reveals a markedly dilated common bile duct showing presence of a heterogeneously hypoechoic lesion within suggestive of embryonal rhabdomyosarcoma; bilobar intrahepatic biliary radical dilatation is seen. On ultrasonography, the lesion is seen as a heterogeneoulsy hypoechoic mass or as multiple hypoechoic nodules separated by septa. Portal venous thrombosis can be seen. Doppler evaluation reveals tumour arteries showing low resistance spectral waveforms. On CT, a hypodense to hyperdense mass is seen which may have prominent fluidattenuation components. The enhancement pattern is variable, ranging from intense heterogeneous globular enhancement to none. MR imaging shows a mass which is hypointense on T1W images and hyperintense on T2W images in the common bile duct or in biliary radicals or a heterogeneous intrahepatic mass with large fluid-intensity areas. MR cholangiopancreatography reveals a partially cystic lesion in the common bile duct and a mass adjacent to the duct that causes mural irregularity. The tumour can be mistaken for a choledochal cyst, if it is predominantly cystic and located at the porta hepatis. If the lesion is intrahepatic and intraductal growth is not evident, the differential diagnosis includes other hepatic neoplastic lesions that are found in the same age group. IHE is mostly seen in children less than 1 year of age and shows marked peripheral nodular enhancement with centripetal fill-in. MHL is mostly cystic. Hepatoblastoma and intrahepatic rhabdomyosarcoma can have similar appearance on imaging, but raised serum AFP levels are seen with hepatoblastoma and not with rhabdomyosarcoma. Treatment Multimodality therapy with surgery, radiation and chemotherapy have led to significantly improved outcomes in patients with local disease. Internal or external biliary drainage is important, as many chemotherapy agents depend on hepatobiliary excretion.

Metastatic disease Hepatic metastases from neuroblastoma and Wilms tumours are more common than primary hepatic tumours. Other tumours that can metastasize to the liver include rhabdomyosarcoma and lymphoma. Clinically patients present with hepatomegaly, jaundice, abdominal pain/mass and abnormal liver function tests. Imaging features

Sonography reveals multiple well-defined, hypoechoic focal lesions involving both lobes of the liver. On CT, metastases appear as multiple focal hypodense or hyperdense masses of varying sizes seen involving the liver diffusely (Fig. 9.8.3.16A and B). Hypovascular liver metastases arise from lung, gastrointestinal tract and pancreatic tumours, whereas hypervascular metastases originate from endocrine, renal and sarcomatous tumours.

FIG. 9.8.3.16 Axial (A) and coronal (B) CECT abdomen images show few hypodense focal lesions in the liver suggestive of metastases from a large neuroblastoma seen in left side of abdomen. On MRI the lesions are multiple and well circumscribed, they appear hypointense on T1W images and hyperintense on T2W images. Most lesions are hypovascular on arterial and portal venous scans. Neurobastoma metastases show peripheral enhancement on arterial phase scans with central progression of enhancement and peripheral washout on portal venous phase scans. It may be difficult to differentiate these lesions from multifocal IHEs. Presence of additional features such as primary tumour, bony lesions, MIBG avidity of lesions and elevated levels of urinary catecholamines help in diagnosis of neuroblastoma metastases. Diffuse replacement of hepatic parenchyma is usually due to neuroblastoma with a diffuse heterogeneous appearance of liver on MRI. The differential diagnosis includes hepatic fibrosis, cirrhosis, diffusely infiltrating HCC or hepatoblastoma.

Hepatic lymphoma Hepatic involvement by lymphoma is usually secondary. Non-Hodgkin lymphoma arising from liver is rare and is seen in immunocompromised children and can be a part of the spectrum of posttransplant lymphoproliferative disorder. Imaging features On imaging, primary Hodgkin lymphoma may be seen as solitary or multiple lesions. Secondary lymphomas are seen as multiple lesions, which may appear similar to metastases. They appear hypoechoic on ultrasonography. On CT the lesions appear isodense to hypodense relative to surrounding liver parenchyma and do not show substantial enhancement after administration of contrast (Fig. 9.8.3.17). Diffusely hypodense liver parenchyma may be seen with infiltrative type of Hodgkin lymphoma (Fig. 9.8.3.18). On MRI, it appears hypointense on T1W images and hyperintense on T2W images with minimal contrast enhancement.

FIG. 9.8.3.17 Axial CECT image of the abdomen reveals multiple hypodense lesions scattered in both lobes of liver and in the spleen along with retroperitoneal lymphadenopathy suggestive of secondary lymphoma.

FIG. 9.8.3.18 Axial CECT image of the abdomen reveals an enlarged liver with diffusely heterogeneous attenuation of the liver parenchyma indicating infiltrative pattern of lymphoma, note made of hypodense lesions in spleen and retroperitoneal lymphadenopathy.

Conclusion Primary liver tumours are infrequent in children. Ultrasonography is the initial imaging modality of choice and can be followed by CT or MRI for further characterization and evaluation of the lesion. CT has faster scan times obviating the need for sedation for long periods and CT chest is the gold standard for evaluation of pulmonary metastases in children with malignant liver tumours. MRI has the advantage of excellent soft tissue characterization and is not associated with risk of radiation exposure. The diagnosis of a hepatic mass should be made with a stepwise approach considering the age of the patient, serum AFP levels, clinical history and imaging findings. Recognition of distinctive imaging patterns in association with clinical data is vital for precise diagnosis and proper patient management. 9 .8. 4

VASCULAR ANOMALIES OF PEDIATRIC LIVER Deeksha Bhalla, Manisha Jana, Devasenathipathy Kandasamy

Embryology Paired vitelline veins are seen around the duodenum, which form anastomosis, around 4th to 5th week of gestation. These pass through the primitive liver where they are broken up into sinusoids and eventually drain into the sinus venosus. There is obliteration of the caudal part of the right and cranial part of the left vitelline vein. Right vitelline vein enlarges. The vitelline veins form the hepatic veins (HV), terminal part of inferior vena cava (IVC) and the portal vein (PV). The paired umbilical veins run on either side of the liver, and bring oxygenated blood to the foetus. The right umbilical vein and cranial part of the left umbilical vein involute on coming in contact with sinusoids. The ductus venosus carries blood coming from the placenta via the left umbilical vein to the IVC. At birth, the ductus venosus and umbilical vein start to involute. Their remnants are the ligamentum venosum and ligamentum teres, respectively.

Imaging technique The liver has a unique pattern of blood supply, in that 75% of the inflow is deoxygenated blood via the PV; while only 25% of the inflow is oxygenated blood via the hepatic artery. This lends itself to excellent depiction of both vascular anatomy as well as related pathology via multiphase (MP) imaging in two phases, namely the arterial and the portal venous phase. Ultrasonography (US) is the initial investigation for all patients, which is complemented by the use of computed tomography (CT) for depiction of vascular anatomy and enhancement. While the Image Gently campaign advocates the use of single phase CT in the vast majority of indications for pediatric liver imaging, due to concerns of radiation in this population, vascular anomalies constitute the niche where MP imaging is merited. Thus, vascular malformations such as hepatic artery aneurysms or arterioportal shunts (AP shunt); and vascular tumours such as infantile hepatic hemangioma (IHH) will need MPCT for evaluation, with timed contrast bolus delivery and acquisition. Single phase CT on the other hand, will suffice for the multitude of portal venous anomalies including aberrant course, absence or obstruction. The indications for magnetic resonance imaging (MRI) are niche, due to another important concern in children, the need for sedation. The most wellknown indication for MRI is the evaluation of venous patency as well as character of nodules in hepatic vein outflow tract obstruction (HVOTO).

Classification The entities may be classified into anatomic variants and anomalies of each vascular system (hepatic artery, PV, hepatic vein) and tumours. The classification is detailed in Table 9.8.4.1.

TABLE 9.8.4.1 Spectrum of Vascular Anomalies in the Pediatric Liver Hepatic artery i) Variants ii) Anomalies

Replaced right/left hepatic artery Accessory right/left hepatic artery Aneurysm (Fibrodysplasia, PAN, SLE) Pseudoaneurysm

Portal vein i) Variants ii) Anomalies a) Formation b) Course c) Acquired

Portal vein trifurcation ‘Z’ type branching Rudimentary portal vein Portal vein duplication Preduodenal portal vein Thrombosis Cavernous transformation Varix

Hepatic vein i) Variants ii) Anomalies Multi-vessel i) Shunts ii) Tumour invasion

Accessory hepatic veins HVOTO: Budd–Chiari–syndrome, veno-occlusive disease

Arterioportal shunt Arteriovenous shunt Portosystemic shunt: Congenital (Abernethy malformation), acquired

Neoplasms i) Benign

Congenital hepatic hemangioma Infantile hepatic hemangioma

PAN, polyarteritis nodosa; SLE, systemic lupus erythematosus; HVOTO, hepatic venous outflow tract obstruction.

Specific entities Hepatic artery Aneurysm/pseudoaneurysm True aneurysms of the hepatic artery are rare, seen in an estimated 0.002% population. These are often associated with systemic vasculitis such as polyarteritis nodosa (PAN), lupus erythematosus and fibrodysplasia. They are classified according to location as intrahepatic or extrahepatic, and according to number as solitary or multiple. Imaging Solitary extrahepatic is the most common form, followed by both intrahepatic and extrahepatic. Multiple aneurysms are seen in association with PAN. These are usually asymptomatic, discovered as incidental findings in studies done for other purposes. Pseudoaneurysms (PAs) on the other hand, usually present in an acute setting with gastrointestinal (GI) haemorrhage or abdominal pain. These are usually posttraumatic, either iatrogenic or accidental. Imaging US with doppler shows the classic ‘yin yang’ color flow pattern, and CT angiography will reveal the origin from the respective artery. PAs are usually extrahepatic, and more commonly involve the right hepatic artery (Fig. 9.8.4.1). The key features are summarized in Table 9.8.4.2.

FIG. 9.8.4.1 Hepatic artery pseudoaneurysm (PA) secondary to blunt trauma abdomen. A. Axial enhanced CT image shows a collection in the segment V/VIII of the liver, with a focal contrast-filled outpouching along its medial aspect (arrow). B. Coronal reformat depicts the collection along with irregular linear lacerations along its periphery and the PA. C. There is breach of liver capsule and extension of hematoma into the perihepatic space (arrow). TABLE 9.8.4.2 Diagnostic Features of Hepatic Artery Aneurysm and Pseudoaneurysm Aneurysm

Pseudoaneurysm

Origin

Systemic infection, vasculitides

Posttrauma, inflammatory

Presentation

Asymptomatic

GI bleed, pain

Extrahepatic

Extrahepatic

Location

Both intra and extrahepatic Number Appearance

Solitary, multiple in PAN

Solitary

Smooth arterial dilatation

‘Yin Yang’ color flow r CT: Focal outpouching Surrounding hematoma Irregular artery

Portal vein

Rudimentary portal vein The PV may undergo embryonic thrombosis in any segment; or may show a complete failure to develop, known as ‘agenesis’. This is accompanied by atrophy or agenesis of the respective lobe or segment, which has characteristic imaging findings. Complete absence of PV leads to a portosystemic shunt known as the ‘Abernethy malformation’, which is discussed later in this chapter. Imaging When it affects the right hepatic lobe it causes compensatory hypertrophy of left hepatic lobe and atrophy of the right hepatic vein. A retrohepatic gallbladder is seen. When the left hepatic lobe is affected, the duodenum and gallbladder are seen placed superiorly, and medial migration of the distal body of the stomach is seen. The respective rudimentary segments of PV may also be identified. Preduodenal portal vein This is a congenital anomaly that results from failure of the ventral limb of vitelline vein to regress. This results in the PV placed anterior to the second part of duodenum, with resultant compression of the duodenal lumen. In ~50% cases, it is associated with high intestinal obstruction. However, the causal relationship of preduodenal PV to obstruction is under doubt, as many children have associated anomalies including duodenal stenosis, atresia or Ladd bands. An association with heterotaxy syndromes and biliary atresia has also been reported. Imaging On upper GI contrast studies, it may be seen as a smooth extrinsic impression on the second part of duodenum. However, it is mostly discovered incidentally on surgery for duodenal atresia or malrotation (Fig. 9.8.4.2).

FIG. 9.8.4.2 Incidentally detected preduodenal portal vein (PV) in a patient with hyperbilirubinemia. A. Axial CT image shows the anomalous course of the PV (arrow), which is seen coursing anterior to the duodenum and the gallbladder. The gallbladder shows mural thickening (solid arrow). B. Coronal MIP image depicts the course of PV anterior to the second part of duodenum. C. The patient also had associated anomalies in the form of polysplenia (white arrow). Intrahepatic biliary radical dilatation (black arrow) and hepatic subcapsular collection (*) were noted. Portal vein thrombosis and cavernous transformation PV thrombosis may be seen in neonates due to a variety of predisposing factors unique to them such as omphalitis, umbilical vein catheterization, dehydration or sepsis. Outside of the neonatal age group, it may be seen due to portal hypertension (PH), prothrombotic states (such as protein C or S deficiency). Another potential cause is the involvement of PV by malignancies such as hepatoblastoma or hepatocellular carcinoma (HCC). Extrahepatic portal venous obstruction (EHPVO) is the thrombosis of extrahepatic PV, which may or may not involve the intrahepatic segment. Children may also present with hyperbilirubinemia secondary to ischemic or compressive bile duct strictures, known as ‘portal biliopathy’. The liver parenchyma is normal and prognosis is usually good if variceal bleeding is controlled. Mesocaval (Rex) shunts serve to relieve the PH, these are placed from the mesenteric vein to the left PV and bypass the obstructed segment. Imaging US is the imaging modality of choice in acute thrombosis, it depicts the extent, partial or complete and also the associated findings of proximal dilatation and collateral channels (Fig. 9.8.4.3).

FIG. 9.8.4.3 Portal vein thrombosis in a 3-year male child. A. US through the superior segments of the right lobe shows multiple hypoechoic liver abscesses in segment VII (arrow). B. There is echogenic intraluminal content in the main portal vein (arrow). C. Axial enhanced CT shows the clustered liver abscess in segment VII (arrow). D. There is thrombosis of the main portal vein as well as its branches (black arrow). Associated chest wall abscess is also seen (solid arrow). Chronic thrombosis leads to the formation of multiple collateral channels at the porta replacing the main PV referred to as ‘portal cavernoma’ (Fig. 9.8.4.4). Cavernoma formation is seen to develop as early as 6–20 days after the thrombotic event. This results in PH, due to ineffective drainage of the splanchnic circulation by collaterals. The patient presents with splenomegaly, ascites and often massive variceal bleeding.

FIG. 9.8.4.4 Fifteen-year female with extrahepatic portal venous obstruction (EHPVO). A. Axial enhanced CT image shows absent min portal vein (MPV) and multiple collaterals. Few of these are portoportal in pericholecystic location (white arrow), while the majority are portosystemic (gray arrow). B. Coronal reformatted image better depicts the multiple tortuous collateral replacing portal vein (arrow). Massive splenomegaly is seen. C. Maximum intensity projection (MIP) shows the portosystemic collaterals, from the intact splenic vein (arrow) and the left gastric vein. Two types of collateral circulation are seen. Portosystemic, via the left gastric and splenic veins (secondary to the PH) and portoportal, from the pericholecystic veins to the intrahepatic portal vein (Fig. 9.8.4.5). Portal biliopathy leads to dilatation of the common duct, with central intrahepatic biliary radical dilatation as the disease progresses.

FIG. 9.8.4.5 EHPVO in a 12-year male child. A. Axial CT image reveals a single large collateral seen at the hepatic hilum (arrow). Few smaller collaterals are seen adjacent to it. B. In a cranial section, multiple azygous collaterals are also seen (arrow). C. Coronal MIP image shows the Normal intrahepatic portal vein (arrow), the collaterals at porta, as well as left gastric collaterals draining into systemic circulation (solid arrow). Portal vein varix PV varix refers to dilatation of the PV which may be seen due to both congenital factors such as weakness of vessel wall, failure of involution of vitelline vein or may even be acquired. It may be seen in intrahepatic or extrahepatic locations, and cause compression of adjacent structures such as duodenum or bile duct. It may rarely undergo spontaneous rupture with extensive haemorrhage. Hepatic veins Budd–chiari syndrome The obstruction of hepatic venous outflow at any level from the HV to the cavoatrial junction is referred to as Budd–Chiari syndrome (BCS). This may be primary, due to hepatic venous thrombosis, or inferior vena caval webs or stenosis. Secondary forms are seen due to extrinsic compression of the HV or IVC by tumuors such as hepatoblastoma; or IVC compression due to an enlarged caudate lobe. This may develop at any age and presentation also varies. In the acute form, there is extensive centrilobular congestion, followed by necrosis and patient presents with acute liver failure. The subacute form develops slowly, over a period of 10–12 weeks, and thus allows for

decompressive collaterals to develop. The chronic form develops even more slowly, and there is postsinusoidal PH with ascites, upper GI bleed and nodular liver. The caudate lobe is characteristically spared, as it has separate venous drainage to the IVC. Imaging Doppler US is the investigation of choice for evaluation of the HVs and their ostia. Absent, turbulent or reversed flow may be seen. The PV shows hepatofugal flow, with velocity 3 mm is considered suggestive of BCS. Hepatic veno-venous comma-shaped collaterals may be seen. The pattern of parenchymal enhancement on CT or MRI is characteristic according to the disease stage (Fig. 9.8.4.6). The patterns are detailed in Table 9.8.4.3.

FIG. 9.8.4.6 Budd–Chiari syndrome in a 4-year-old male child. A. Axial fat-saturated T2 image shows loss of the IVC flow void. There is peripheral T2 hyperintensity in the liver parenchyma. Caudate hypertrophy is also noted. B. Coronal TRUFISP image shows only the right hepatic vein is patent (black arrow). There is a veno-venous collateral (white arrow). C. The comma-shaped venovenous collateral (arrow) is better seen in axial TRUFISP image. D. Post-gadolinium (venous phase) scan shows the caudate lobe hyperenhancement, as well as the peripheral heterogeneous enhancement, suggesting subacute disease.

TABLE 9.8.4.3 Liver Parenchymal Changes in Budd–Chiari Syndrome Modality MRI Parenchyma Nodules

Acute

Subacute

Periphery (oedema):

Periphery (collaterals):

Dark T1 WI

Dark T1WI

Bright T2 WI

Bright T2WI

Decreased enhancement

Heterogenous enhancement

Chronic Fibrosis, no differential enhancement

Regenerative: Hyperintense on T1 WI Hypointense on T2WI Arterial phase enhancement, no washout CT Parenchyma Nodules

Arterial phase:

Heterogenous enhancement

Caudate lobe enhancement (fan-shaped pattern)

Regenerative

Venous phase:

Hyperattenuating on arterial phase, no washout

Heterogenous enhancement Regenerative Hyperattenuating on arterial phase, no washout

Centre hypodense (Flip flop enhancement) Veno-occlusive disease (VOD) Also referred to as sinusoidal obstruction syndrome, results from congestion at the level of the sinusoids that causes centrilobular haemorrhagic necrosis; and eventually fibrosis. The consumption of pyrrolizidine and nonpyrrolizidine alkaloids has been implicated in the causation, along with several chemotherapeutic agents and haematopoietic stem cell transplant. Imaging Imaging features are mostly nonspecific. US may show attenuated HV flow and increased phasicity of PV flow, with eventual reversal to hepatofugal direction. CT and MRI show gall bladder wall oedema. MR with hepatobiliary contrast agents shows a reticular pattern of hypointensity on the hepatobiliary phase. The most important diagnostic clue however is, appropriate clinical setting and high index of suspicion.

Shunts Arterioportal shunts These are the most common intrahepatic shunts, and represent a pathway of communication between a hepatic arterial branch and portal venous branch. Similar to hepatic artery PAs, they commonly arise secondary to blunt, penetrating or iatrogenic trauma. Congenital lesions may also rarely be seen, and cause PH. These mostly present with symptoms by the first year. Imaging The characteristic is early opacification of the PV in the hepatic arterial phase on a multiphase CT or MRI. There is often accompanying hyperenhancement in a wedge-shaped area around the lesion. US dilatation of the hepatic artery and PV at the fistula site PV shows ‘arterialized’, pulsatile flow, with flow reversal to hepatofugal direction (Fig. 9.8.4.7). Embolization of the feeding artery with or without surgery must be performed early to prevent development of PH.

FIG. 9.8.4.7 Congenital arterioportal shunt (APS) in a 7year-old male child. A. Transverse section through the superior segments of the right hepatic lobe shows a large anechoic structure in segment VIII, which is in continuity with the portal venous branch (arrow). B. On colour Doppler, turbulent bidirectional flow is seen in the portal vein as well as the lesion, confirming its vascular nature. C. There is pulsatile, bidirectional flow on spectral doppler suggesting an APS. Arteriovenous fistula/arteriovenous malformation Similar to APS, Arteriovenous Fistula (AVF) represents abnormal direct communication between a hepatic arterial branch and a hepatic venous tributary. These are often seen in tumours such as focal nodular hyperplasia (FNH), hemangioma and HCC. Arteriovenous Malformations (AVMs) on the other hand, represent shunting of blood through a dysplastic capillary network, known as the ‘nidus’. Imaging As in APS, early opacification of a hepatic vein in the arterial phase is seen on imaging. IVC and HV show high pressure, arterialized flow on Doppler US. Hepatic AVMs on angiography are characterized by an ill-demarcated lesion without parenchymal blush, showing contrast pooling in vascular spaces and early venous opacification (Fig. 9.8.4.8).

FIG. 9.8.4.8 Hepatic arteriovenous malformation. A. On digital subtraction angiography (DSA), a nidus of dysplastic vessels is seen in the right hypochondrium (arrow). This was previously drawing feeders from the left gastric artery, which was embolized. Coil mass seen in situ (solid arrow). B. The nidus is now seen drawing feeders from the common hepatic artery (arrow). Early draining veins are also seen (solid arrow). C. The nidus was embolized using liquid embolic agent, N-butyl cyanoacrylate (NBCA). D. Complete embolization was achieved in this setting. Portosystemic shunts Portosystemic shunts represent connections between the portal venous system and a systemic vein without going through the liver. These can be congenital (CPS), or acquired. Acquired shunts develop in the setting of cirrhosis and PH. They involve well-recognized pathways such as gastrosplenic, gastrorenal, splenorenal and paraumbilical shunts. We will limit our discussion to CPS, which may be intrahepatic (IPSS) (Fig. 9.8.4.9) or extrahepatic (EPSS) (Figs 9.8.4.10 and 9.8.4.11). Their differences are highlighted in Table 9.8.4.4.

FIG. 9.8.4.9 Congenital porto-systemic shunt (CPS) in a 19-day-old male child. A. Longitudinal section through the right lobe shows a tubular anechoic structure. B. On transverse scan, the structure is seen draining into the intrahepatic inferior vena cava C. Superiorly, it is seen to join the dilated portal vein. There is unidirectional flow into the IVC on Color doppler. D. Enhanced CT images show the dilated vascular channel connecting right PV and IVC (arrow). E. Coronal reformatted image better depicts the connecting channel. This is type I intrahepatic portosystemic shunt.

FIG. 9.8.4.10 Abernethy malformation in a 5-year-old male. A. Axial TRUFISP sequence shows common trunk, that is the portal vein (arrow) at hepatic hilum draining into the IVC through a shunt vessel (solid arrow). B. On the axial HASTE sequence, flow voids are seen in the PV, IVC and the shunt vessel. C. Post-gadolinium sequence shows similar findings. No intrahepatic portal venous radicles are seen. This is suggestive of an end-to-end shunt (Type Ib).

FIG. 9.8.4.11 Abernethy malformation in an 11-year male child. A. The common trunk formed by union of splenic and superior mesenteric vein is seen, with distal varix (arrow). B. The side-to-side shunt between portal vein and IVC has been ligated (black arrow). Intrahepatic branches of the PV are seen (white arrow). C. Commashaped intrahepatic portosystemic collaterals are also seen (arrow). This was a type II malformation.

TABLE 9.8.4.4 Differentiation Between Types of Portosystemic Shunts Extrahepatic (Abernethy Malformation) Origin

Types

Vitelline veins fail to form anastomosis with the hepatic sinusoids or umbilical veins

Persistent communication between the vitelline veins and sinus venosus without sinusoid formation

I - Complete absence of portal vein, splanchnic blood is diverted into the IVC

I - Single large tube between RPV and IVC (most common type)

Ia - Splenic vein and SMV separately join IVC Ib - Common trunk joins IVC II - Portal vein present, side-to-side extrahepatic shunt Modality of choice Imaging features

Intrahepatic

II - ≥1 communication in one liver segment III - PS shunt through a varix IV - >1 communication, in >1 segment V - Patent ductus venosus

CT/MRI

US

Absent PV, shunt vessel on cross-sectional imaging

Doppler

US: Only two structures, i.e. enlarged hepatic artery and bile duct seen at porta

Pulsatile (tri/biphasic) flow in PV Shunt ratio = blood flow in shunt/flow in PV

The natural history and prognosis of the shunts varies. While intrahepatic shunts are expected to undergo spontaneous closure by the age of 2 years, children may be kept on follow up if asymptomatic. The decision to treat in any shunt depends on the shunt ratio and consequently, the risk of hepatic encephalopathy. Shunt closure may be achieved surgically, or by embolization. For patients with complete absence of PV, liver transplant remains the only option. Hereditary haemorrhagic telangiectasia (osler–weber–rendu syndrome) Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by the formation of telangiectasias in multiple organs, along with AVMs. This is due to a defect in a protein binding transforming growth factor (TGF), leading to abnormal vascular remodelling. The lesions can involve a multitude of organs, including lungs, liver, spleen, spine, skin and mucous membranes. The most common presentation is epistaxis due to nasal mucosa telangiectasias and hemoptysis due to pulmonary AVMs. Liver involvement usually occurs 20–22 years after the initial telangiectasia, and thus is uncommon in children. It is seen in ∼75%

adults, and presents with high output cardiac failure resulting from hyperdynamic circulation. Arterioportal, portosystemic and arteriovenous shunting are seen which also lead to PH, hepatic encephalopathy and biliary ischemia. Imaging The most common imaging findings is telangiectasias. On CT, these are small (usually 1 cm, and show persistent hyperenhancement beyond the arterial phase. A multitude of shunts may be recognized in both arterial (arterioportal, arteriovenous) and portal venous (portosystemic shunt) phases. There is enlargement of the hepatic arteries and veins due to the hyperdynamic circulation (Fig. 9.8.4.12).

FIG. 9.8.4.12 Hereditary hemorrhagic telangiectasia (HHT). A. Axial section of the thorax reveals a pulmonary nodule with an enlarged artery leading to it. B. A dilated draining vein is also seen, suggestive of pulmonary arteriovenous malformation. C. The segment II of liver shows ill-defined hypodensity (arrow) D. Similar lesion is also seen in segment III (arrow). These are transient attenuation defects. E. An enlarged hepatic artery is also seen, secondary to hyperdynamic circulation (arrow). An approach to the diagnosis of hepatic shunts is summarized in Fig. 9.8.4.13.

FIG. 9.8.4.13 Proposed algorithm for diagnosis of hepatic vascular shunts. RI, resistive index; CT, computed tomography; MR, magnetic resonance; DSA, digital subtraction angiography.

Vascular tumours Hepatic hemangiomas These are benign vascular neoplasms with endothelial cell proliferation. They are of two types, congenital and infantile. Congenital hepatic hemangiomas (CHH) are fully formed at birth, while IHH typically arise in the newborn period and reach maximum size till the age of 6–12 months. They may be unifocal, multifocal or diffuse. Children often present with high output cardiac failure, due to the extensive AV shunting through dilated vascular channels in the lesion. The differences between CHH and IHH are highlighted in Table 9.8.4.5.

TABLE 9.8.4.5 Differentiation Features Between Types of Hepatic Hemangiomas

Clinical course

Congenital Hepatic Hemangioma Fully formed at birth. Follows one of three courses

Infantile Hepatic Hemangioma Formation starts in newborn period, full size at 6–12 m, involute over 3–9 years

a. Rapidly involuting (RICH): complete involution by 2 years b. Partially involuting (PICH) c. Noninvoluting (NICH) GLUT-1 Lymphatic markers Response to propranolol Number of lesions Appearance AV shunts

Negative Negative

Positive Positive

Absent

Present

Usually solitary

multifocal, diffuse >solitary

Large, heterogeneous lesion with hemorrhage, necrosis, fibrosis Frequent

Small uniform lesion Rare

Imaging Solitary lesions are large, and display heterogenous echogenicity on US due to areas of haemorrhage, calcification and fibrosis. Multifocal lesions are smaller and uniformly hypoechoic or hyperechoic. In the presence of AV shunting, there is pulsatile flow in the draining veins on doppler US, and decreased resistive index (RI) of the feeding artery. With involution, the RI gradually increases and venous flow returns to normal. On MR, lesions are hyperintense on T2-weighted images, and may show T1 hyperintensity due to intralesional haemorrhage. The enhancement patterns on CT/MRI are similar, with peripheral arterial phase enhancement and progressive centripetal filling (Fig. 9.8.4.14). Central necrotic areas are seen in larger lesions. There is tapering of abdominal aorta below the level of celiac axis origin.

FIG. 9.8.4.14 Infantile hepatic hemangioma CT (MPCT) in a 7-month male child. A. Arterial phase image shows a hypodense lesion in segment VII with peripheral nodular arterial enhancement. B. There is progressive centripetal filling in the venous phase. C. There is near-complete filling seen in delayed phase with few nonenhancing areas. D. The volume-rendered image shows abrupt change in calibre of abdominal aorta below the origin of the celiac axis (white arrow). The celiac trunk and hepatic artery are hypertrophic (gray arrow). 9 .8.5

DISEASES OF GALLBLADDER IN CHILDREN Ramesh Chander, Navjot Singh

Introduction Pediatric gallbladder disease encompasses a wide spectrum-like cholelithiasis, choledocholithiasis, polyp, pseudolithiasis, acute cholecystitis (AC), hydrops and adenomyomatosis. Gallbladder diseases are more common in the adult population but now their prevalence in the pediatric age group is increasing as well. The main contributing factors to the rise of gallbladder diseases in the pediatric population are childhood obesity, screening and the use of advanced imaging modalities. In this chapter, the common gallbladder pathologies in detail along with the role of various noninvasive radiological imaging modalities like ultrasound, X-ray, CT, MRI and nuclear medicine are described.

Pathologies Cholelithiasis and choledocholithiasis In the recent years, the diagnosis of cholelithiasis and choledocholithiasis is increased in children, may be due to improved imaging modalities like ultrasonography. Pathogenesis Gall stones are of two types: cholesterol stones (pure/mixed) and pigment stones (brown or black) (Flowchart 9.8.5.1). Cholesterol gall stones are formed due to the supersaturation of bile with cholesterol in patients with biliary stasis. These are more common in adults and young females. Pigmented gall stones are more common in the pediatric population. In children with hemolytic disorder and children who are on total parenteral nutrition, there is supersaturation of bile with calcium bilirubinate resulting in the formation of black-pigmented stones. Brown pigment stones are seen in patients with infection and biliary stasis but these are more common in common bile duct (CBD) than in the gallbladder.

FLOW CHART 9.8.5.1 Types and Causes of Gall Stones in Children. Suchy FJ and Feldman AG. Diseases of the Gallbladder. Kliegman RM, Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM and Behrman RE. Nelson textbook of Pediatrics. ed 21. Elsevier: Philadelphia, 2020:8455– 8461. Diagnosis USG is the imaging modality of choice and provides the most accurate diagnosis. Gallbladder stones (Fig. 9.8.5.1) on ultrasound appear as a single or multiple stones, are usually mobile and produce posterior acoustic shadowing. The specificity and sensitivity of ultrasound in detecting gallstones is more than 95% but for detecting stones in CBD, that is choledocholithiasis (Fig. 9.8.5.2A and 9.8.5.2B), it is 50%–75%. Radiopaque gall stones can be detected

by plain X-ray and 20%–50% of gall stones in children are radiopaque. The best method of treatment and investigation of choledocholithiasis appears to be is laparoscopic cholecystectomy with intraoperative cholangiogram followed by endoscopic retrograde cholangiopancreatography (ERCP).

FIG. 9.8.5.1 Cholelithiasis: Ultrasound image of the gallbladder shows a small gallstone (black block arrow). (Source: Courtesy of Dr Alka Karnik Mumbai.)

FIG. 9.8.5.2 A. Choledocholithiasis: Ultrasound image shows dilated common bile duct (CBD) with sludge (black arrow) and a calculus (white arrow) in distal part of CBD. Note, sludge (black block arrow) is also seen in gallbladder lumen. B. Choledocholithiasis: Ultrasound image shows a calculus (white arrow) in distal part of CBD in head region of pancreas. (Source: Courtesy of Dr Alka Karnik Mumbai.)

Ceftriaxone-associated biliary pseudolithiasis Ceftriaxone is a third generation cephalosporin and is a well-liked drug by pediatricians due to its broad-spectrum antimicrobial properties. Cerebrospinal fluid penetration of ceftriaxone is good. The most common complications of ceftriaxone therapy are biliary sludge or biliary lithiasis. The term ‘Pseuodolithiasis’ is used for ceftriaxone-induced biliary lithiasis as this condition is reversible after discontinuation of therapy. Risk factors are renal failure, high dose (>2g or >200 mg/kg/day), prolonged treatment and gallbladder stasis. Most of these cases are asymptomatic and detected on USG (Fig. 9.8.5.3). Rarely, the patient complains of symptoms like abdominal pain, nausea and vomiting. Therefore, cessation of drug is required in symptomatic patients.

FIG. 9.8.5.3 Pseudolithiasis: Ultrasound images show hyperechogenic sludge (block white arrows) within the gallbladder lumen consistent with pseudolithiasis. (Source: Courtesy of Dr Alka Karnik Mumbai.) Acute cholecystitis AC is defined as inflammation of the gallbladder. It can be a calculus or acalculus type. Acute calculus cholecystitis can be due to obstruction of the neck of the gallbladder or cystic duct by gall stones resulting in biliary stasis and bacterial overgrowth. Acute acalculus cholecystitis is most commonly in the pediatric population in which no calculus/stone is seen in gallbladder lumen or cystic duct but only gallbladder sludge is noted. Causes of acute acalculus cholecystitis in the pediatric population are: • Parasitic infections obstructing the CBD (e.g. Ascaris lumbricoides infection) • Congenital anomalies of gallbladder like multiseptate gallbladder, diaphragm of the gallbladder, choledochal cyst, etc. • Due to gallbladder stasis like in children admitted in pediatric intensive care unit (PICU), patients on total parenteral nutrition, opiate abuse (causes spasm/dyskinesia of sphincter of Oddi) These all conditions interfere with emptying of the gallbladder. Diagnosis

Ultrasonographic features of AC include the following: • Gallbladder calculi in acute calculus cholecystitis and gallbladder sludge in acute acalculus cholecystitis. • The thickened anterior wall of the gallbladder (> 3 mm). • Positive Murphy sign (patient experiences pain on ultrasonographic probe pressure in the right upper quadrant). • Pericholecystic fluid in severe cases (indicates actual or impending perforation). • Gallbladder wall oedema appears as a hypoechoic halo in the gallbladder wall. • Overdistended gallbladder (GB volume >70 mL) • On colour Doppler, increased vascularity is noted in the gallbladder wall. Nuclear medicine If gallbladder ultrasound is negative and AC is suspected, hepatobiliary iminodiacetic acid (HIDA) scan is indicated. It is a scan used to dynamically access the gallbladder. After injecting, Technicium-99–labelled mebroformin is taken up by bile producing hepatocytes and subsequently, it is excreted into the biliary system. Imaging is done at 60 minutes and 4 hours after radioisotope administration. In normal cases, the gallbladder will be visualized at 60 minutes as it fills with radioactive bile. AC is excluded if the gallbladder is visualized at 60 minutes and this also shows that cystic duct is patent. In case of AC or obstruction of the gallbladder neck and cystic duct with stone, the gallbladder is not visualized at 4 hours postradioisotope injection. In cases of nonvisualization of the gallbladder, morphine analogues can be given to increase the tone of sphincter of Oddi, increase in CBD pressure which helps in gallbladder filling with a radioisotope. Nonvisualization of gallbladder 30 minutes postmorphine analogue infusion suggests AC in clinical settings. Computed tomography Cmputed tomography (CT) scan findings in AC are: • Calculus within gallbladder lumen or in cystic duct or both. • Focal or diffuse gallbladder wall thickening in a noncontracted gallbladder (wall thickness >3 mm). • Presence of pericholecystic fluid and no ascites. • Increase in dimensions of the gallbladder, transverse diameter >5 cm. • Increased bile attenuation value due to biliary sludge and sloughing of the mucosa. • Pericholecystic fat stranding. MRI/MRCP On MRI scans, pathological findings seen are similar to the CT scan findings. Magnetic resonance cholangiopancreatography (MRCP) shows calculi as a filling defect in the GB, cystic duct and CBD. Complications It includes empyema, gangrenous cholecystitis, gallbladder perforation and emphysematous cholecystitis. Hydrops of gallbladder (HGB) or mucocele of gallbladder

In children, acute gallbladder hydrops is a rare entity, presents as a palpable abdominal mass in right upper quadrant and patient may appear jaundiced. Colicky abdominal pain is noted in almost every patient that is confined to the right upper quadrant of the abdomen. The gallbladder is overdistended, filled with mucoid or clear watery fluid with a volume of more than 1500 mL. It is defined as distention of gallbladder with dimensions of more than 10 × 4 cm and anteroposterior diameter of >5 cm. Causes of acute HGB in pediatric population are: • Impacted stone in the gallbladder neck and cystic duct causing an obstruction • Kawasaki disease (mucocutaneous lymph node syndrome) • Familial mediterranean fever • Streptococcal infection (Scarlet fever) • Mesenteric adenitis • Typhoid • Leptospirosis • Viral hepatitis Diagnosis USG is the modality of choice to make the most accurate and specific diagnosis. USG findings are overdistended gallbladder of size >5 cm in AP dimension and stone impacted in the gallbladder neck/cystic duct. If the diagnosis is unclear, CT scan is helpful. Gallbladder polyp Gallbladder polyps are rarely reported in the pediatric population and are mainly seen in adults. These are the small masses that are seen protruding into the gallbladder lumen from wall of the gallbladder. As reported, these polyps are more common in obese boys. Polypoidal lesions of gallbladder are categorized into two groups: 1. Tumorous: are adenomas, adenomyoma and early gallbladder carcinoma. 2. Nontumorous: are inflammatory and cholesterol. In children, the majority of gallbladder polyps are cholesterol type. The next common forms are hyperplastic and adenomatous polyps. There are three diseases linked with secondary gallbladder polyps in children: 1. Metachromatic leukodystrophy: It is a rare hereditary lysosomal storage disease characterized by the accumulation of sulfatides in the nervous system and other tissues due to the deficiency of an enzyme called arylsulfatase A. Findings seen due to gallbladder involvement are multiple polypoidal masses along the wall of the gallbladder and thickened echogenic gallbladder wall. 2. Peutz–Jeghers syndrome: Gallbladder polyps associated with Peutz– Jeghers syndrome are hamartomatous type, can reach up to 7 cm size. They can be single or multiple. On colour Doppler, vascularity is noted within the polyp. 3. Pancreatobiliary malunion and CBD fusiform dilatation. Diagnosis

USG is 90% sensitive and specific imaging modality for diagnosis. Gallbladder polyps on USG (Fig. 9.8.5.4) appear as an echogenic lesion attached to the wall of the gallbladder and protruding into the lumen. There is no posterior acoustic shadowing as seen with the gallbladder stones and are immobile, that is no change in their position with change in the patient’s posture.

FIG. 9.8.5.4 Axial abdominal ultrasound scan of the gallbladder shows an echogenic polypoid (white arrow) lesion arising from fundal wall of gallbladder. Adenomyomatosis of gallbladder Adenomyomatosis of the gallbladder is a rare condition in the pediatric population. It is a benign and degenerative condition that is characterized by focal, diffuse or segmental proliferation of mucosal epithelium and its invagination into the thickened muscularis layer of the gallbladder. Due to the invagination of the mucosal layer into the hypertrophied muscular layer of the gallbladder, a diverticulum is formed known as Rokitansky–Aschoff sinuses. Most of the patients are asymptomatic and detected incidentally on USG. Segmental or ‘hourglass’ configuration of the gallbladder is due to the congenital transverse septum in the body of gallbladder. Usually, it is asymptomatic but a thorough investigation is required if the patient presents with nocturnal pain (red flag). Diagnosis Ultrasound: Findings on ultrasound (Fig. 9.8.5.5) are:-

1. Rokitansky–Aschoff sinuses: appear as either anechoic (if filled with bile) or echogenic (if filled with gall stone or biliary sludge). 2. Thickened gallbladder wall. 3. Comet tail artifact/ring down artifact: due to reverberation between the sinuses. 4. Polypoidal or papillary projections (at least 10 mm in length) within the sinuses.

FIG. 9.8.5.5 Ultrasound image shows normal wall thickness of infundibulum (block black arrow); central portion with wall thickening and luminal narrowing (black arrow) along with mild concentric wall thickening of fundal region (white arrow) consistent with adenomyomatosis of the gallbladder. (Source: Courtesy of Dr Alka Karnik Mumbai.) MRI T2W sequence is superior to other MR sequences to detect Rokitansky– Aschoff sinuses. On postcontrast images, the diffuse subtype shows early mucosal enhancement and delayed serosal enhancement. The localized subtype of adenomyomatosis shows homogenous enhancement. Gallbladder carcinoma The most common age bracket affecting the cancer of gallbladder is after 40 years. Gallbladder carcinoma is very rare in pediatric age group with only few case reports published in literature. The most common cause for gallbladder malignancy is gallbladder stones. However, it is also associated with chronic infection with Helicobacter bilis and Salmonella typhi. Owing to very rare prevalence and fatality of sickness, any gallbladder mass ought to be evaluated for the possibility of malignancy and treated in an exceedingly multimodality protocol.

Conclusion Ultrasound is most commonly used in the pediatric age group as it is costeffective, widespread available and lacks ionizing radiations. Minimal

preparation for a US examination is needed, as most patients require 4–6 hours of fasting to ensure adequate distention of the gallbladder. CT and MRCP, both may require sedation depending upon the age of pediatric patient. The role of nuclear medicine in pediatric population is to diagnose AC and it provides physiological information more than anatomical information like patency of the biliary system. 9 .8.6

LIVER TRANSPLANTATION IN CHILDREN S. Murthy Chennapragada

Learning objectives • To understand the indications and the types of paediatric liver transplants including the surgical aspects of transplantation. • To learn about the role of imaging in pretransplant workup and posttransplant assessment. • To identify the hepatic arterial, hepatic venous and portal venous complications after transplantations. • To describe the imaging features and appropriate interventional techniques used to detect and treat these complications.

Introduction Liver transplantation is the definitive treatment for end-stage liver disease in children. Since Dr Starzl performed the first paediatric liver transplantation in a child with biliary atresia in 1963, there have been remarkable advances in organ preservation techniques, surgical techniques, immunosuppression, intensive care management and surveillance protocols leading to improved survival rates. It still, however, remains one of the most complex and challenging areas in paediatric practice. As per the 2013 Organ procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Data Report the 1-year and 5-year survival rates for paediatric deceased donor liver transplant were of the order of 87% and 82%, respectively. The survival rates vary considerably depending on factors such as underlying disease; for instance, children transplanted for metabolic and cholestatic disease have better survival rates compared to those with acute hepatic failure. Other factors that influence the outcomes of liver transplantation in children include age at transplantation, type of graft used, cold ischaemic time, surgical technique, and expertise and experience of the transplant team including the intensive care/medical teams. Indications for liver transplantation in children The major indication for paediatric liver transplantation remains liver failure secondary to biliary atresia. Other indications include cholestatic liver failure, cirrhotic and non-cirrhotic metabolic liver disease, fulminant hepatic failure and primary hepatic malignancy (Table 9.8.6.1).

TABLE 9.8.6.1 Indications for Liver Transplantation Cholestatic Disorders Biliary atresia Progressive familial intrahepatic cholestasis Alagille disease (intrahepatic biliary hypoplasia) Sclerosing cholangitis (primary and secondary) Congenital hepatic fibrosis Caroli disease Langerhans cell histiocytosis Metabolic disorders with cirrhosis Aloha 1 antitrypsin deficiency Cystic fibrosis Wilson’s disease Tyrosinemia Galactosemia Neonatal haemochromatosis Gestational alloimmune liver disease Glycogenosis type IV Niemann Picks disease

Metabolic Disorders Without Cirrhosis Urea cycle disorders Criggler Najjar syndrome Hyperoxaluria Gaucher’s disease Familial hypercholesterolemia Glycogenosis type IA Protein C deficiency Organic acidemia Wolman’s disease Acute Liver failure Hepatitis Neonatal hepatitis Hepatitis B, C, non-ABC Autoimmune hepatitis Primary liver tumours Hepatoblastoma Hepatocellular carcinoma Haemangioendothelioma Others Budd Chiari syndrome Cryptogenic cirrhosis

Sepsis with uncontrolled infection, extrahepatic spread of malignancy, endstage organ failure and irreversible neurological injury are contraindications for undertaking transplantation.

Types of liver transplantation Deceased Donor Liver Transplantation also known as cadaveric organ grafting is a common type of liver transplantation in adults. Often the whole graft from the donor is transplanted into the recipient after native hepatectomy. The most significant limitation is availability of donor organs. In particular age and size-matched donors may not be readily available for paediatric patients, and thus many children die while on the waiting list for transplant. Living Donor Liver Transplantation (LDLT) usually is undertaken when there is an urgent need for transplantation and graft availability is limited. It accounts for about 10% of adult liver transplants but this can be much higher, especially in regions where organ availability is very limited. For instance, in North America, Europe and Australia majority are deceased donors while in Japan and South Korea the vast majority are living donors. The benefit of LDLT is the reduced incidence of preservation injury to the graft. Usually, a left lateral hepatectomy is performed, although right hemi hepatectomy can be done for larger recipients. Graft to recipient weight ratio of 1:100 is used as a guide to determine the size. Whole liver transplantation: This often depends on the availability of an age-matched and weight-matched graft in children. The surgical anastomoses

undertaken are: a) hepatic arterial: usually an end-to-end anastomosis between the donor common hepatic artery (or sometimes using a Carrel patch); b) end-to-end anastomosis between the donor and recipient portal vein (sometimes using an interposed vein graft in case of portal vein thrombosis); c) hepatic venous anastomosis: either by a supra- and intrahepatic IVC anastomoses, or by using a piggyback technique (where a graft with donor IVC and hepatic veins is anastomosed with the preserved recipient IVC); d) biliary anastomosis: often an end-to-end anastomosis between the donor and recipient bile ducts (or a choledocho enterostomy in case of a preexisting bile duct disease or presence of a Roux en Y loop). Split liver grafts: Rudolf Pichlmayr performed the first split liver transplant in 1988. When a split liver graft technique is used, the graft is divided into a right and a left lateral graft (Fig. 9.8.6.1) which are then transplanted into two recipients. The obvious advantage of this technique is that the number of beneficiaries from each donor liver can be doubled. Typically, an extended right split (segments I, V–VIII) is transplanted into an adult recipient and a left lateral split (segments II and II) into the child recipients. Sometimes the latter can be the entire left lobe, or for very small recipients a monosegmental graft or a hyper reduced graft. Volumetric analysis aids in determining the size of the graft particularly in the child recipient.

FIG. 9.8.6.1 (A) Schematic drawing demonstrates Couinaud’s segments of the liver and left lateral lobe segments used for split liver grafts. (B) Split liver transplantation: Schematic representation of the donor organ divided into a larger right lobe graft (usually used for the adult recipient) and the smaller left lobe graft (typically used for the paediatric recipient). The typical surgical technique used and anastomoses created are as follows (Fig. 9.8.6.2). The liver is usually divided along a plane that runs 1 cm to the right of the middle hepatic vein. Hepatic veins are anastomosed using piggyback technique. The donor left hepatic artery is anastomosed end to end with the recipient HA. This often may require microsurgical anastomoses and reconstruction with microvascular techniques. The PV is anastomosed end-toend, either to the recipient’s PV trunk or by using an interposed vein graft. Biliary anastomosis is achieved by hepaticojejunostomy. Often the left hepatic

duct that remains with the left lateral split is anastomosed to the Roux en Y loop (which may be preexisting in cases of BA that have undergone prior Kasai procedure).

FIG. 9.8.6.2 Split liver graft: vascular and biliary enteric anastomoses. IVC: inferior vena cava; LHV: Left hepatic vein; LPV: left portal vein; PV: main portal vein; HA: Hepatic artery. Auxiliary Partial Orthotopic Liver Transplantation (APOLT) is a technique where a partial liver graft is implanted in a recipient with acute liver failure, leaving behind also a part of the native liver (Fig. 9.8.6.3). The graft liver enables native liver regeneration at the same time as decreasing the need of prolonged immunosuppression. This technique can be used in children as well as adults although children and young adults seem to have better outcomes. In a child or a small adult, typically native left hepatectomy is performed and a left lobe or left lateral segment graft is used to augment it.

FIG. 9.8.6.3 APOLT: partial liver graft is implanted in a recipient alongside part of the native liver. (A) Schematic diagram showing the graft and native liver with anastomoses. (B) Intraoperative picture showing the graft and native liver in situ. (C and D) Axial and coronal CT images demonstrate the graft and native liver in situ with respective vascular anastomoses. (Source: (B) Courtesy of Dr G Thomas).

Pretransplant imaging Evaluation of donor liver for suitability for transplantation and safe harvesting organ is important, particularly for LDLT. Assessment of the donor organ includes parenchymal evaluation, estimation of the size/volume, vascular and biliary anatomy. Criteria used for split-liver procurement include donor age 40 kg, suitable vascular anatomy for reconstruction in the recipient, LFTs 80%) although in the early phase biliary dilatation may not be evident. MRCP has higher sensitivity and specificity for biliary strictures. It provides a good anatomical delineation of the ducts and their anastomoses and can aid in planning percutaneous interventions (Fig. 9.8.6.11B). However, in the paediatric population, the need for additional anaesthesia and sedation may limit its utilization. In the workup for biliary strictures often a liver biopsy is undertaken to evaluate for other causes for cholestasis.

FIG. 9.8.6.11 A US image demonstrates dilated peripheral intrahepatic bile ducts in a 3-year-old postliver transplant presenting with recurrent cholangitis and progressive jaundice. B MRCP provides a better overview of the status of the bile ducts and the biliary enteric anastomosis. Biliary obstruction (Fig. 9.8.6.12) from strictures is treated primarily by percutaneous transhepatic cholangiography and biliary balloon dilatation (cholangioplasty). This is usually performed under general anaesthesia. Access to the intrahepatic bile ducts is obtained under ultrasound guidance and cholangiograms obtained under fluoroscopic control. After identifying the site of the stricture a catheter and guidewire combination is used to traverse the stricture and over the wire the stricture is dilated with a balloon to an appropriate diameter. A drain catheter is then left traversing across the stricture. There is considerable variability in protocols used for duration of this catheter’s dwell in time. The authors group prefer to leave the drain in for at least 6 weeks. A pullback cholangiogram is performed after this period to assess the result of bilioplasty before removal of the drain.

FIG. 9.8.6.12 Percutaneous transhepatic cholangiograms showing a tight biliary enteric anastomotic stricture (A), treated with balloon dilatation cholangioplasty (B). Post dilatation there is good improvement on the calibre of the anastomosis (C). PTC with cholangioplasty has high technical success rates (80%–90%). Unfortunately, clinical success rates vary, particularly depending on the cause and nature of the structures. Short segment pure anastomotic strictures tend to respond best to cholangioplasty while diffuse multifocal strictures respond poorly with high rates of recurrence. These also show higher rates of progressive parenchymal fibrosis and eventual graft dysfunction needing retransplantation. Surgical revision of anastomosis may be needed for recalcitrant anastomotic strictures. Parenchymal Acute Rejection results from inflammation of allograft elicited by antigenic disparity between donor and recipient, which affects primarily the interlobular bile ducts and vascular endothelia. It commonly occurs within the first 3–6 months after transplantation. Presentation is nonspecific with altered liver enzymes. Imaging findings are non-specific. Diagnosis I made on the basis of liver biopsy. 75% of cases respond well to early corticosteroid regime. Neoplastic Posttransplant immunosuppression renders children with liver transplant at higher risk of cancer. In particular, the incidence of Posttransplant Lymphoproliferative disease is higher in children compared to adults. PTLD is associated with Epstein Barr virus and may present as lymph nodal enlargement. Mesenteric and periportal lymph nodes are commonly involved although extra abdominal involvement including bone marrow involvement is not uncommon. US imaging often helps in detection of the enlarged lymph nodes; however, a CT is usually performed to assess these nodes better. FDG

PET imaging is used to assess for metabolic activity of the enlarged lymph nodes and aid in monitoring response to medical treatment.

Summary Paediatric liver transplantation is the definitive treatment for end-stage liver disease in children. Advances in surgical techniques, imaging technology, surveillance protocols and immunosuppression regimes have resulted in improved survival rates. Split liver graft technique has improved organ availability particularly for paediatric recipients. Understanding of the unique anatomical features of split and reduced grafts is important for graft assessment. Imaging, in particular, helps in early detection of postoperative complications and aids timely and appropriate interventions thus reducing graft dysfunction and graft loss. Fig. 9.8.6.13 provides a schematic flowsheet for imaging and intervention algorithm for assessment post paediatric liver transplantation.

FIG. 9.8.6.13 Flowchart for imaging and intervention algorithm in the assessment of paediatric liver transplant. Acknowledgement The author would like to acknowledge Dr G Thomas for providing the illustrations to redraw for Fig. 9.8.6.1 and 9.8.6.3, and Dr S Murthy Chennapragada for providing the illustration to redraw for Fig. 9.8.6.2.

9.9: Imaging in portal hypertension and cirrhosis with emphasis on LI-RADS Shrinivas B. Desai, Ritu K. Kashikar, Aman Snehil, Ajay Jhaveri

Introduction Cirrhosis is a late stage of irreversible scarring of the liver causing abnormality in liver structure and function. Multiple conditions and factors can cause repeated liver damage and scarring ultimately leading to cirrhosis. The most feared complication of liver cirrhosis is the development of hepatocellular carcinoma (HCC). Portal hypertension (PHT) is seen with a variety of conditions but cirrhosis happens to the most important cause. Imaging plays a vital role in noninvasive diagnosis and treatment planning of both cirrhosis and PHT. Liver imaging reporting and data system (LI-RADS) is a standardized reporting system assigning an observation risk of representing HCC. This chapter focuses on discussing aetiologies and imaging of PHT with a lucid review of L1RADS 2018 version.

Portal hypertension The portal blood circulation is a unique circulatory circuit as it connects two capillary beds between the liver parenchyma at one end and the gastrointestinal tract and splenic parenchyma at the other end. The portal system ramifies in the liver and ultimately ends in the hepatic sinusoids from where the blood ultimately drains into the inferior vena cava (IVC). The portal vein (PV) originates from the capillary beds in the stomach, intestine and the spleen. The main PV is formed behind the neck of the pancreas by the confluence of the superior mesenteric vein (SMV) and splenic vein. It continues to the porta hepatis where it bifurcates into the left and right branches as it carries nutrient rich but oxygen poor blood to the liver (Fig. 9.9.1). The PV makes up for 75%– 80% of the liver’s blood supply while the hepatic artery which arises from the celiac trunk makes up for the remaining 25%.

FIG. 9.9.1 Diaphragmatic representation of portal circulation. A pathological increase in the portal venous pressure is referred to as PHT. PHT is most often a sequel of chronic parenchymal liver disease and leads to major life-threatening complications due to bleeding from the collateral circulation (most commonly oesophageal varices). Direct measurement of portal pressure (PP) is invasive and often not feasible in most patients and thus imaging plays an important role in the diagnosis of PHT and its complications.

Definition The normal portal venous pressure ranges between 5 and 10 mmHg, which is the equivalent of 7–14 cm H2O. The normal hepatic venous pressure gradient (HVPG) is the pressure gradient between the PV and the IVC, is typically 1–5 mmHg. Presence of PHT is indicated by a wedged hepatic venous pressure of more than 5 mmHg. Other definitions include a splenic pressure of more than 15 mmHg or an intraoperative PP of greater than 30 cm H2O. The complications of PHT are seen when HVPG is greater than 10 mmHg and hence this value defines clinically significant PHT. Variceal bleeding is seen with a pressure greater than 12 mmHg.

Aetiopathogenesis and classification of portal hypertension In ideal conditions, the portal circuit is a high flow, low resistance circuit as it has to allow substantial flow rates of 700–1000 mL/min to the hepatic parenchyma from the gastrointestinal tract. Anatomical changes in the organization of the hepatic lobule can result in rise in the portal

resistance. These can occur in the form of collagen deposition in the space of Disse, fibrotic scars formed due to regenerative nodule (RN) formation, loss of normal elasticity of the endothelium and distal venous thrombosis. Changes in splanchnic haemodynamics due to factors that increase splanchnic blood flow and increase in intrahepatic vascular resistance due to transformation of stellate cells into myofibroblasts also contribute to the increase in PP gradient. In Western countries, alcoholic cirrhosis and viral cirrhosis are the leading causes of PHT and oesophageal varices. The viral causes form majority of cases leading to cirrhosis and PHT in the Far East and Middle Eastern countries while Schistosomiasis remains an important cause in the African countries. Worldwide, nonalcoholic steatohepatitis (NASH) and hepatitis C are the emerging causes of chronic liver disease (CLD) and PHT. PHT can be classified as cirrhotic and noncirrhotic depending on whether it is associated with cirrhosis or not. This distinction is important as noncirrhotic causes like PV thrombosis are at high risk of development of bleeding but tend to have a better chance of surviving a variceal bleed than a patient with decompensated alcoholic cirrhosis due to preserved hepatic synthetic functions in the former. PHT can also be classified on the basis of the location of the pathology into prehepatic, hepatic and posthepatic causes. Hepatic causes can further be divided into presinusoidal, sinusoidal and postsinusoidal. The causes of portal hypertension have been denoted in Table 9.9.1.

TABLE 9.9.1 Causes of Noncirrhotic Portal Hypertension Extrahepatic Presinusoidal PHT Hepatic Schistosomiasis Cirrhosis Budd–Chiari syndrome Congenital hepatic fibrosis Noncirrhotic Right heart alcoholic liver disease failure Noncirrhotic portal fibrosis Infiltrative disorders Constrictive pericarditis • Amyloidosis Nodular regenerative Suprahepatic • Systemic hyperplasia IVC thrombosis mastocytosis Primary biliary cirrhosis or Pulmonary • Malignancy primary sclerosing cholangitis hypertension • Myeloproliferative Tricuspid valve disorder regurgitation Intrahepatic postsinusoidal PHT Extrahepatic presinusoidal Veno-occlusive PHT disease Portal vein thrombosis Peliosis hepatis SMV thrombosis Hypervitaminosis A Splenic vein thrombosis Intrahepatic Presinusoidal PHT

Sinusoidal PHT

Imaging in portal hypertension The direct measurement of the PP by measuring the HVPG is invasive, expensive not readily available in all patients. Thus, imaging plays an important role in the diagnosis of PHT. Various modalities are used for the imaging diagnosis of PHT. Ultrasonography (USG) and Doppler evaluation have the advantage of being inexpensive, readily available and bedside modality (Table 9.9.2).

TABLE 9.9.2 Portal Hypertension • Presence of PHT is indicated by a wedged hepatic venous pressure of more than 5 mmHg. • Imaging is the only noninvasive means of measurement. • Anatomical changes in hepatic lobules lead to fibrosis in space of Disse and lead to PHT. • In Western countries, alcoholic cirrhosis and viral cirrhosis are the leading causes of PHT and oesophageal varices. • NASH and hepatitis C are the important causes of CLD and PHT worldwide. • Distinction between cirrhotic and noncirrhotic causes important, prognosis better in the later.

Ultrasonography and doppler The role of ultrasound and Doppler in imaging of PHT is to: • establish the diagnosis. • suggest the cause. • evaluate risk of complications. • provide prognostic information. Grey scale imaging Grey scale imaging is useful in evaluating the splenoportal anatomy. The evaluation should begin with the liver morphology. Signs of cirrhosis like nodularity of the liver surface with relative atrophy of the right lobe and prominence of the left lobe and caudate should be looked for. Hepatic echotexture appears coarse and more echogenic (Table 9.9.3). TABLE 9.9.3 Grey Scale USG in Portal Hypertension • PV diameters of greater than 13 or 15 mm have a sensitivity for diagnosing PHT of only 40% and 12.5%, respectively. • Increase in PV diameter less than 20% with deep inspiration has been reported to indicate PHT with a sensitivity of 80% and specificity of 100%. • Hepatic vein straightness, uniformity of hepatic vein wall echogenicity and length of visualized segment. • Splenomegaly. • Subclinical ascites. 1. Portal vein diameter

Increase in portal venous diameter is a sign of PHT (Fig. 9.9.2). Portal venous diameter of more than 13 or 15 mm has low sensitivity for diagnosing PHT of only 40%–12.5%, respectively. Absolute measurement of the portal diameter as a sign of PHT is also fallacious as in presence of collateral circulation or hepatofugal flow; there may actually be a decrease in the PV diameter. Therefore, a more accurate sign is respiratory variation of PV diameter. An increase in PV diameter of less than 20% with deep inspiration has been reported to indicate PHT with a sensitivity of 80% and specificity of 100%.

FIG. 9.9.2 PV diameter. (A) Grey scale USG showing normal diameter of PV. (B) Dilated porta vein suggesting PHT. 2. Hepatic vein morphology

This has been reported to be an accurate indicator of cirrhosis. Hepatic vein straightness, uniformity of vein wall echogenicity and visualization of at least 1 cm segment of the hepatic vein are the parameters used for evaluation. a. Hepatic vein straightness is classified into three categories (straight, slightly wavy and very wavy) has high sensitivity and specificity. b. Uniformity of hepatic vein wall echogenicity also has a high sensitivity and specificity. c. Length of visualized segment: The vein to be evaluated must be a peripheral tributary in the segment V or VI with a minimal width of 3 mm and a length of 3 cm. 3. Splenic size Splenomegaly is defined as bipolar splenic diameter of greater than 12 cm or largest splenic cross-sectional area passing through the hilum of greater than 45 cm2, and occurs secondary to PHT (Fig. 9.9.3). A total of 65%–80% patients with cirrhosis have splenomegaly on ultrasound. Patients with cirrhosis due to viral hepatitis and primary biliary cirrhosis show splenomegaly more frequently than those with alcoholic cirrhosis.

FIG. 9.9.3 Splenomegaly in a case of cirrhosis. Grey scale USG showing splenic size of 14.5 cm s/o splenomegaly. 4. Subclinical ascites

This is an accurate sign of PHT. USG is extremely sensitive with respect to detecting subclinical ascites. Perihepatic space is the most usual site of visualization of minimal ascites. Doppler assessment of portal hypertension (Table 9.9.4) A. Portal vein a. Direction of flow: Normally, the PV flow is toward the liver (hepatopetal) and varies with respiration and heart rate (Fig. 9.9.4). As PHT increases, flow may become biphasic or bidirectional with absent end diastolic flow. Worsening the degree of PH causes reversal of flow, which may even be monophasic and hepatofugal. Reversal of PV flow direction, that is, hepatofugal flow is 100% specific for the diagnosis of PHT and the prevalence of this sign is approximately 8% in patients with cirrhosis (Figs. 9.9.5– 9.9.7). b. Portal vein velocity: The portal flow velocity, in normal patients, ranges between 13 and 23 cm/s but in patients with PHT, the mean PV velocity may vary depending on the presence and location of spontaneous shunts (Fig. 9.9.8). The PV velocity usually decreases initially as PP increases in cirrhosis as a consequence of the increased hepatic resistance. Cut-off of 15 cm/s has a sensitivity and specificity of 88% and 96%, respectively, to diagnose PHT. The velocity tends to increase in the presence of a patent paraumbilical vein and decrease in the presence of lienorenal collaterals. PV velocity is usually measured at the hilum and care must be taken to ensure the Doppler angle is less than 60 degrees to ensure accurate measurements. c. Portal vein volume flow: PV blood volume flow per minute can be calculated by measuring both the velocity and crosssectional area of the PV at the site of measurement. Normal value is 825 ± 200 mL/min. The flow volume increases in initial stages when PV is dilated. Subsequently, in advanced cases the flow volume decreases (Fig. 9.9.9). d. Portal congestion index: The ‘congestion index’ takes into account PV dilatation and decreased flow velocity, both of which are physiological changes associated with PHT and is calculated as the ratio of PV cross-sectional area (cm2) to mean PV flow velocity (cm/s).

TABLE 9.9.4 Doppler in Portal Hypertension Doppler Findings in PHT • Reversal of PV flow direction, that is, hepatofugal flow is 100% specific for the diagnosis of PHT and the prevalence of this sign is approximately 8% in patients of cirrhosis • PV velocity of 15 cm/s has a sensitivity and specificity of 88% and 96%, respectively, to diagnose PHT • PV congestion index above 0.1 suggests the diagnosis of PHT with a 95% sensitivity and specificity • Portal venous thrombosis • RI > 0.78 in the intrahepatic branches of the hepatic artery has a sensitivity of 50% and a specificity of 100% for the detection of PHT • Monophasic HVW has a sensitivity and specificity of 74% and 95%, respectively, in the diagnosis of severe PHT • Dilatation of the splanchnic veins – the SMV and the splenic vein – more than 11 mm • Hundred per cent specific sign for PHT on colour Doppler is the presence of collaterals

FIG. 9.9.4 Hepatopetal flow in PV colour Doppler image showing normal hepatopetal flow in PV with respiratory phasicity.

FIG. 9.9.5 Hepatofugal flow in PV. Doppler image showing hepatofugal flow in the PV (arrows) suggesting PHT.

FIG. 9.9.6 Sluggish hepatopetal flow. Case of cirrhosis with PHT showing sluggish hepatopetal flow in PV with the absence of respiratory phasicity.

FIG. 9.9.7 Reversal of flow at the portosplenic confluence. Case of PHT showing reversal of flow in the portosplenic confluence.

FIG. 9.9.8 Normal portal venous velocity. Colour Doppler image showing normal portal venous velocities (18 cm/s) with respiratory phasicity.

FIG. 9.9.9 Portal vein flow volumes. Case of PHT with sluggish flow with low flow volumes (442 cm/s). In normal subjects, this ratio is approximately 0.07 and a value above 0.1 suggests the diagnosis of PHT with a 95% sensitivity and specificity.

e. Portal thrombosis: Acute thrombosis usually appears as hypoechogenic content filling the vessel lumen with mild increase in the luminal diameter with absent flow on colour Doppler. Chronic thrombosis is associated with echogenic luminal contents and reduction in luminal diameter. There may be recanalization through collaterals in the later stage which leads to cavernoma formation (Fig. 9.9.10).

FIG. 9.9.10 Portal venous thrombus. C/O liver cirrhosis showing echogenic thrombus in the lumen of the main PV suggesting thrombosis (arrow). B. Hepatic artery The normal spectral waveform of the hepatic artery is a low resistance flow pattern with forward flow in diastole and a resistivity index in the range of 0.5–0.7. In PHT, the resistivity index of the hepatic artery increases with high resistance flow pattern due to increased peripheral vascular resistance. Resistance index (RI) > 0.78 in the intrahepatic branches of the hepatic artery has been reported to have a sensitivity of 50% and a specificity of 100% for the detection of PHT (Fig. 9.9.11).

FIG. 9.9.11 Hepatic artery waveform. Hepatic artery waveform in patient with PHT showing elevated resistance index (0.87) and pulsatility index (1.78). Pulsatility index (PI) > 1.05 suggests severe PHT with a sensitivity of 86% and specificity of 88% (Fig. 9.9.11). C. Hepatic veins Patency of hepatic veins should be evaluated to rule out Budd–Chiari syndrome as a cause of PHT. The normal hepatic venous waveform (HVW) reflects right atrial activity and this results in a triphasic waveform with one positive and two negative waves. In PHT, this waveform becomes monophasic or biphasic. A monophasic HVW has a sensitivity and specificity of 74% and 95%, respectively, in the diagnosis of severe PHT (Fig. 9.9.12).

FIG. 9.9.12 HVW. Monophasic waveform in hepatic vein in a patient with PHT. D. Splanchnic veins Dilatation of the splanchnic veins – the SMV and the splenic vein – more than 11 mm are suggestive of PHT with a sensitivity and specificity of 72% and 100%, respectively. A reduction in the respiratory variation of the splenic vein and SMV to less than 40% had a sensitivity and specificity of 79.7% and 100%, respectively, for the diagnosis of PHT (Fig. 9.9.13).

FIG. 9.9.13 Splanchnic venous waveform. (A) Dilated splenic vein with splenic hilar collaterals in PHT (arrow). (B) Loss of respiratory phasicity. E. Splanchnic arteries The splenic artery reveals an increase in the resistivity index and an RI of >0.63 and a PI of >1 have a sensitivity and specificity of 84.6% and 70.4% for the diagnosis of PHT. F. Portosystemic collateral channels (Table 9.9.5)

Presence of portosystemic collaterals like patent paraumbilical vein, dilated left gastric and short gastric veins are 100% specific sign for PHT (Figs. 9.9.14–9.9.16). Recanalization of the paraumbilical vein, known as the Cruveilhier–Baumgarten syndrome is observed in 43% of patients with PHT, and this is the easiest collateral to assess during the US examination. TABLE 9.9.5 Portosystemic Collaterals

FIG. 9.9.14 Collaterals. Colour Doppler image showing short gastric collaterals (arrows).

FIG. 9.9.15 Collaterals. (A) Grey scale image and (B) Doppler showing lienorenal collaterals in the interface between the spleen and the kidney.

FIG. 9.9.16 Collaterals. Recanalized paraumbilical vein in a patient with advanced PHT. Various portosystemic collaterals that occur in PHT have been discussed in details in subsection on CT findings in PHT. No Doppler parameter is considered reliable enough to measure PP with sufficient accuracy for use in clinical practice. Oesophageal varices are often present in patients with portosystemic collaterals. Appearance or increase in number of collaterals along with splenomegaly has a high association with variceal formation and growth. Role of usg in aetiologic diagnosis of portal hypertension USG helps in diagnosis of prehepatic causes like portal stenosis or thrombosis by demonstrating the patency and morphology of the splenoportal system. Arteriovenous fistulae and tumours causing vascular thrombosis as aetiology can be readily detected. USG helps in diagnosis of features of cirrhosis and thus helps differentiate noncirrhotic causes of PHT. USG allows diagnosis of fatty liver disease, which is an emerging cause of cirrhosis. Among the posthepatic causes, USG aids in establishing the diagnosis of Budd–Chiari syndrome by demonstrating the patency and morphology of the IVC and hepatic veins.

CT scan Owing to the inability of CT to detect flow direction, portal flow rates or pressure gradients, CT is not the primary modality in diagnosis of PHT.

Similar to USG dilatation of portosystemic system is a feature of PHT (Fig. 9.9.17). Changes in cirrhosis if present can be seen in the form of surface nodularity, nodules and fibrous septae. CT plays an important role in diagnosis of portal venous thrombosis and evaluating its extent. An acute thrombus is seen as a hypodense filling defect in the vessel causing distension of the venous lumen. Surrounding fat stranding can be seen. A chronic thrombus appears as an eccentric filling defect usually along the wall and is often associated with decrease in vessel diameter. Calcification may be seen in chronic thrombi.

FIG. 9.9.17 CT in PHT. Contrast-enhanced CT in venous phase in a patient with cirrhosis showing dilated tortuous portosplenic system (arrows) with collaterals (red arrows). Multidetector computed tomography (MDCT) is a useful tool to evaluate portosystemic collateral circulation and recognize complications of PHT. 3D angiography can help understand portal venous and complex variceal anatomy and plan treatment. The various portosystemic collaterals are discussed below. They can be classified into those draining into superior vena cava (SVC) and those draining into the IVC. • Collaterals draining into SVC: 1. Coronary veins or left gastric veins: They are the most frequently depicted collaterals in PHT and are seen in the lesser sac. CT usually shows the cephalic portion of collateral near the gastro-oesophageal (GE) junction (Fig. 9.9.18). One coronary vein (left gastric vein) of over 5–6 mm in diameter on USG with an abnormal hepatofugal flow is an indicator of PHT. 2. Oesophageal varices: They are the most clinically important collaterals. These represent venous dilatations in the submucosa of the oesophagus. They communicate with

the anterior branch of the left gastric vein and drain into the azygos or hemiazygos system. These are better identified on cross-sectional modalities, endoscopy and endoscopic ultrasound. On CT, they appear as tubular enhancing structures. CT plays an important role in detection and grading of oesophageal varices (Fig. 9.9.19). 3. Paraoesophageal varices: These are located outside the oesophageal wall; they supply the posterior branch of the left gastric veins. They are seen in 22%–38% of CT scans as dilated collateral vessels surrounding the oesophagus and the descending thoracic aorta (Fig. 9.9.20). 4. Gastric varices: These along with oesophageal collaterals are the most important collaterals and they often coexist together. Staging of collaterals by Sarin on endoscopy also highlights the coexistence of these collateral channels. Gastric varices are supplied by short gastric or posterior gastric veins and appear as a network of tortuous blood vessels located at the level of the gastric fundus and splenic hilum. They usually drain into the oesophageal or paraoesophageal veins but can also drain into left renal vein via a gastrorenal shunt (Fig. 9.9.21). • Collaterals draining into IVC: 1. Splenic varices and gastrorenal shunts: They are tortuous blood vessels at the hilar region of the spleen and superior pole of the left kidney and represent collaterals found between the splenic vein or short gastric veins and the left renal vein (Fig. 9.9.22). It should be noted that the tortuous splenic vein frequently seen at the hilum of the enlarged spleen should not be called perisplenic varices. 2. Splenorenal and splenocaval shunts: Sometimes large splenorenal shunts are seen appearing as large vein draining into a dilated left renal vein. Splenocaval shunts comprise of large veins extending from the spleen coursing toward the pelvis draining into the internal iliac or gonadal vein and subsequently into IVC (Fig. 9.9.23). 3. Paraumbilical varices: In PHT with the development of hepatofugal flow, this vein can get recanalized. It runs from the left branch of the PV connecting to the periumbilical collaterals, eventually draining into the inferior epigastric veins and, less commonly, into the superior epigastric veins. Clinically, this produces the appearance of ‘caput medusae’. On CT, they appear as tubular structures more than 2–3 mm in diameter and usually anastomose with the superior epigastric or internal thoracic veins (Fig. 9.9.24). 4. Gallbladder varices: They have been reported in 12% of the patients with PHT and are more commonly seen in patients with extrahepatic PHT. They are supplied by a branch of the right PV, and they drain into the SMV or into the intrahepatic PV. 5. Rectal varices: These can be visualized by transrectal scanning by an endocavitary probe and are not usually seen

on transabdominal scans. They represent the anastomosis between the superior rectal veins with ultimately drain into portal circulation with the middle and inferior rectal veins that drain into the internal iliac vein (Fig. 9.9.25). 6. Retroperitoneal-paravertebral varices: These are also known as veins of Retzius and connect mesenteric with lumbar veins, which are tributaries of portal and systemic circulation, respectively. 7. Omental and mesenteric varices: They are numerous small collaterals found across greater omentum. Due to the small size, they may be confused with omental metastasis (Fig. 9.9.26). Mesenteric collateral vessels usually appear as dilated and tortuous branches of the SMV within the mesenteric fat (Fig. 9.9.27).

FIG. 9.9.18 Portosystemic collaterals. Contrastenhanced CT showing dilated coronary veins near the GE junction (arrows).

FIG. 9.9.19 Portosystemic collaterals. Contrast enhanced CT in a patient with cirrhosis with HCC and tumour thrombus showing submucosal venous dilatation in the oesophagus suggestive of varices (arrows).

FIG. 9.9.20 Portosystemic collaterals. Paraoesophageal collaterals in a patient with PHT (arrows).

FIG. 9.9.21 Portosystemic collaterals. Contrastenhanced CT in venous phase showing gastric varices (arrows).

FIG. 9.9.22 Portosystemic collaterals. Contrastenhanced CT in venous phase showing splenic varices (arrows).

FIG. 9.9.23 Portosplenic collaterals. (A to C) Contrast-enhanced CT images in splenorenal collaterals showing multiple collaterals in between the spleen and the kidney (arrows). The left renal vein is dilated ( yellow arrow in A).

FIG. 9.9.24 Portosystemic collaterals. Contrastenhanced CT showing recanalized left paraumbilical vein (arrows). Note the vein connects the left PV (yellow arrow) with periumbilical collaterals.

FIG. 9.9.25 Portosystemic collaterals. Case of PHT with melaena showing extensive rectal varices.

FIG. 9.9.26 Case of liver cirrhosis with PHT showing multiple omental varices (arrows).

FIG. 9.9.27 Portosystemic collaterals and directions of flow in PHT.

Role of MRI and newer techniques Magnetic resonance imaging (MRI) is a noninvasive modality used in the evaluation of PHT without the use of ionising radiation. It provides evaluation of parenchymal abnormalities, collaterals and characterization of tumours (Fig. 9.9.28). Spin echo sequences allow characterization of liver masses and liver parenchyma. Loss of flow void allows for detection of thrombosis. Time-of-flight (TOF) angiography is useful in assessing the portal venous system and allows for successful detection of PV thrombosis. The disadvantages of TOF are motion artefacts caused by breathing, long acquisition times and incomplete coverage of the portal venous system.

FIG. 9.9.28 Contrast-enhanced MRI. Venous phase images in a case of cirrhosis with PHT showing large lienorenal collaterals (arrows).

Novel imaging techniques include phase contrast, T1 mapping and magnetic resonance elastography (MRE). The advantage of phase contrast over TOF imaging is that phase contrast imaging acquires information regarding the flow direction in addition to the information regarding the flow velocity. On-phase contrast images signal within vessel is hyperintense when flow is cranial and hypointense when flow is caudal. Look-Locker imaging technique using gradient echo (GRE) MRI sequences with inversion recovery pulse is used to quantify fibrosis by measuring precontrast T1 relaxation times.

Role of interventional radiology Interventions in PHT can be aimed at diagnosis or more commonly at management of complications of PHT. HVPG measurement, which is the gold standard for the diagnosis of PHT, can be achieved through cannulation of the PV. Transjugular hepatic biopsy is another diagnostic invasive technique that also allows indirect measurement of PP. 1. Transjugular intrahepatic portosystemic shunt (TIPSS) is the most commonly used intervention to treat PHT. Polytetrafluoroethylene (PTFE)-covered stents are deployed through the hepatic parenchyma, bridging the hepatic vein and PV. TIPSS reduces the portosystemic pressure gradient by functioning as a side-to-side portocaval shunt, reduces recurrence of variceal bleeding and is indicated for treatment of refractory ascites. Disadvantages include deterioration of hepatic function caused by diversion of portal venous blood flow and shunt dysfunction. TIPSS is contraindicated in patients with congestive heart failure, severe pulmonary hypertension, severe tricuspid regurgitation and hepatic failure. 2. Balloon-occluded retrograde transvenous obliteration (BRTO) of varices: This procedure is used for the management of gastric varices. In this technique, a catheter is advanced from the femoral vein into the outlet of the gastrorenal, usually in the region of the left renal vein. The shunt is then occluded with a balloon and sclerosant is injected retrograde to occlude the gastric varices. 3. Coil-assisted retrograde transvenous obliteration (CARTO): Modified version of the original BRTO procedure and involves placement of coils instead of sclerosant.

Imaging in cirrhosis (Table 9.9.6) Introduction and definition

Histological development of RNs surrounded by fibrous septae in response to chronic liver injury, progressing PHT and end-stage liver disease is termed as cirrhosis. Although initially considered an end-stage phenomenon in CLD, recent evidence suggests that the histological fibrosis can be reversible in early stages with the initiation of specific therapies, for example, in viral cirrhosis with the initiation of antiviral therapy. The one-year mortality rate in cirrhosis varies widely from 1% to 57% depending on the occurrence of complications. Cirrhosis can have a wide variety of causes ranging from congenital to acquired and infectious to noninfectious. It is also a major aetiologic risk factor for the development of HCC. Imaging plays an important role in aetiologic diagnosis of this diverse entity as well as in the diagnosis and management of its complication and surveillance for oncological transformation.

TABLE 9.9.6 Aetiology of Cirrhosis INFECTIVE • Hepatitis B • Hepatitis C BILIARY PATHOLOGY • Primary Biliary Cirrhosis • Secondary Biliary Cirrhosis(due to prolonged obstruction to biliary drainage) TOXIC • Alcohol • Methotrexate AUTOIMMUNE • Autoimmune Hepatitis • Primary Sclerosing Cholangitis METABOLIC • Wilson’s disease • Hemochromatosis • alpha-1 Antitrypsin Deficiency • Glycogen Storage Disorder type IV • Non-Alcoholic Fatty Liver Disease VASCULAR • Cardiac cirrhosis due to right heart failure • Veno Occlusive Disease CRYPTOGENIC/ IDIOPATHIC

Aetiopathogenesis and epidemiology Liver cirrhosis represents the outcome of hepatic fibrosis resulting from a variety of CLDs. The aetiology of cirrhosis varies with geography. Alcoholic liver disease, hepatitis C infection and nonalcoholic fatty liver disease (NAFLD) are the major causes in the Western countries. Chronic hepatitis B infection is the major cause in the Asia-Pacific region. Other causes include inherited conditions like haemochromatosis and Wilson’s disease and autoimmune phenomena like primary biliary cirrhosis, primary sclerosis cholangitis, and autoimmune hepatitis. NAFLD has become a leading emerging cause of cirrhosis in Western countries, with

a prevalence of as high as 30% in the general population in the United States. The various causes are listed in the following table. Pathogenesis The pathogenetic mechanisms in cirrhosis are initiated by any event which leads to hepatocyte damage. The various cells involved in the process of fibrosis are hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells. Through a complex interplay of cytokines namely platelet derived growth factor, transforming growth factor beta, tumour necrosis factor alpha, various proinflammatory interleukins and interferons, the space of Disse is filled by collagen fibrotic bands that ultimately reflect as progressive fibrosis resulting in cirrhosis. This process tends to distort the normal hepatic lobular architecture and results in the formation of islands of hepatocytes separated by bands of fibrosis that present as nodules (Fig. 9.9.29).

FIG. 9.9.29 Pathogenesis of cirrhosis. The natural history of cirrhosis suggests a stepwise carcinogenesis in the nodules. RNs are formed by localized proliferation of hepatocytes and their surrounding stroma. It gradually increases in size and cellularity and with changes of nuclear atypia is transformed into a dysplastic nodule (DN). Simultaneous molecular changes may result in the development of an HCC focus, which then enlarges to clinically detectable size. Pathogenesis of HCC has been discussed in chapter 9.11 on focal liver lesions (Fig. 9.9.30).

FIG. 9.9.30 Stepwise carcinogenesis of nodules. Nodules in cirrhosis: An overview (Table 9.9.7) Histologically, liver cirrhosis is associated with distortion of normal hepatic architecture with fibrotic bands and a spectrum of hepatic nodules. These nodules represent localized proliferation of hepatocytes and their surrounding stroma in response to hepatocyte damage. Most of the nodules are benign RNs but they may progress along a well-defined carcinogenetic pathway to DNs and HCC. TABLE 9.9.7 Cirrhosis-Related Nodules Regenerative lesions • Cirrhosis-associated • Monoacinar • Multiacinar Dysplastic or neoplastic lesions • Hepatocellular adenoma • Dysplastic focus (0.65 suggestive of hypertrophy The liver surface has been most commonly used as the indicator for the diagnosis of cirrhosis Aetiology of cirrhosis can be evaluated Doppler may detect associated PHT Ultrasound elastography is a noninvasive technique used to measure tissue stiffness Cirrhotic liver are usually small in size and appear shrunken. Hepatomegaly is, however, not an uncommon finding in early cirrhosis. The liver reveals coarse echotexture (Fig. 9.9.31).

FIG. 9.9.31 Cirrhosis of liver. (A) Grey scale USG images showing coarse echotexture with (B) surface nodularity (arrow). The liver surface has been most commonly used as the indicator for the diagnosis of cirrhosis. Surface nodularity represents presence of RNs in the hepatic parenchyma. The sign is considered positive when a straight and regular echogenic line of the liver surface appears as a dotted or irregular line or there is presence of areas of different echogenicity within the hepatic parenchyma. Both the lobes of the liver should be assessed and preferably with a high frequency transducer (Fig. 9.9.32).

FIG. 9.9.32 Liver cirrhosis. Coarse heterogeneous echotexture seen with linear transducer. Paucity of peripheral hepatic vessels accentuated echogenic wall of the PV and regenerating nodules with displacement of surrounding vessels are other signs. There is right lobar atrophy with relative hypertrophy of the caudate lobe. A ratio of transverse diameter of caudate lobe to transverse diameter of right lobe of greater than 0.65 is defined as caudate lobe hypertrophy. This has a high sensitivity, specificity and diagnostic accuracy of 84%, 100% and 94%, respectively (Fig. 9.9.33).

FIG. 9.9.33 Caudate lobe hypertrophy. Splenomegaly and ascites are other grey scale signs which point to the concomitant presence of PHT in the background of cirrhosis. Additional note should be made of the hepatic parenchymal echogenicity and an

increase in the echogenicity implies presence of hepatic steatosis, which can be an aetiological factor. Biliary causes must be ruled out by evaluating for dilatation of the biliary radicles. Presence of ascites and splenomegaly are ancillary signs, which signify the presence of PHT in cirrhosis. Doppler findings Doppler findings help in diagnosis of cirrhosis in suspected cases of CLD by establishing the presence of PHT which is taken as corroborative evidence for the existence of cirrhosis. These parameters which look at PV diameter, flow velocity, direction of flow and respiratory variation in diameter have been discussed in detail before in the section under PHT. Doppler USG also allows detection of various portosystemic collaterals which increase the diagnostic accuracy as well as allow for the monitoring and detection of complications. Doppler can also show neovascularity in tumours. Elastography Ultrasound elastography is a noninvasive technique used to measure tissue stiffness. It is based on the principle that the velocity of sound waves will increase as the Young’s modulus or tissue stiffness increases. Hepatic fibrosis in the case of cirrhosis increases the stiffness of liver parenchyma and thus the shear wave velocity increases as compared to normal parenchyma. Ultrasound elastography has been widely accepted as a reliable noninvasive tool to quantify and monitor the hepatic fibrosis. Four types of US elastography are in use (Table 9.9.9). These include transient elastography, acoustic radiation force impulse imaging (ARFI), supersonic shear wave imaging and real-time elastography.. Transient elastography is performed with Fibroscan. The assembly constitutes a vibrator mounted on an ultrasound probe. Vibrations are generated by the vibrator which leads to shear wave propagating through the liver. The shear wave velocity is a measure of the liver stiffness. The velocity is expressed in kilopascals (kPa). Transient elastography has been commonly used for evaluation of fibrosis in patients with CLD, an NAFLD. Limitations include poor reliability in obese patients, those with ascites and patients with narrow intercostal spaces.. ARFI is directly integrated on a US machine. The shear wave is generated by the acoustic pulse produced by the ultrasound probe. The shear wave velocity is measured in m/s. The velocity increases in proportion to increasing fibrosis. Studies have shown better results compared to Transient elastography (TE) in patients with confounding factors such as obesity (Fig. 9.9.34).

TABLE 9.9.9 Types of Elastography • Transient elastography • ARFI • Supersonic shear wave imaging • Real-time elastography

FIG. 9.9.34 ARFI in liver cirrhosis. ARFI scan showing liver stiffness of 23–24 kPa suggestive of cirrhosis. Shear wave elastography is a distinct type in which multiple wave beams are emitted at increasing depth. This allows evaluation of velocity over a wide range of frequency at the same time. Multiple studies have used cut-offs ranging from 6.65 to 8.9 kPa for TE and 1.3 to 2.58 m/s for ARFI and report sensitivity of 68%–98% and a specificity of 52%–93% for the diagnosis of cirrhosis. Although data supporting accuracy of elastography is encouraging, the major challenge to overcome is the standardization of technique and the low reproducibility of measurements derived from operator-dependent performance.

Role of CT and MRI CT evaluation in cirrhosis Ideal protocol for CT evaluation includes a triphasic scan with late arterial, portovenous and delayed phase images. Cirrhotic livers reveal irregular lobulated surface and altered coarse architecture (Fig. 9.9.35). The fibrotic changes appear as bridging bands or focal confluent fibrosis. Bridging bands appears as hypoattenuating bands of variable thickness, which reveal delayed enhancement. Confluent fibrosis appears as a wedge-shaped peripheral hypoattenuating area with delayed enhancement. Overlying capsular retraction and associated volume loss are also seen.

FIG. 9.9.35 CT appearance in cirrhosis of liver. (A) Unenhanced and (B and C) contrast-enhanced CT showing atrophy of liver with coarse architectures, surface nodularity and caudate lobe hypertrophy (arrows). Features of PHT are seen in the form of splenomegaly with ascites and collaterals (yellow arrows). Morphologic changes of the liver vary with the stage of cirrhosis. More than 60% of patients with early cirrhosis have hepatomegaly. With time, the liver size decreases. Additional early detectable morphologic changes of the liver include widening of the porta hepatis, enlargement of the interlobar fissure and expansion of pericholecystic space. Features of late cirrhosis include hypertrophy of caudate lobe or left lateral segments with atrophy of medial or posterior segments (Figs. 9.9.36–9.9.38). Additionally, enlarged pericholecystic space also called expanded gallbladder fossa sign and sharp indentation in the posterior surface called right posterior hepatic notch sign are seen (Figs. 9.9.39 and 9.9.40).

FIG. 9.9.36 CT in cirrhosis. Unenhanced and contrast-enhanced CT showing cirrhotic liver with gross hypertrophy of caudate lobe (arrows).

FIG. 9.9.37 CT in cirrhosis. (A) Unenhanced and (B) enhanced CT in a patient with cirrhosis showing widened porta hepatis and fissures (arrows).

FIG. 9.9.38 CT features of late cirrhosis. Unenhanced CT in a case of advanced cirrhosis showing enlarged left lateral segments and caudate lobe (arrows).

FIG. 9.9.39 CT in advanced cirrhosis. Contrastenhanced CT in venous phase showing expansion of gallbladder fossa (arrows). Note the gallbladder wall oedema (blue arrow) which is common in cirrhosis.

FIG. 9.9.40 CT in advanced cirrhosis. Unenhanced and contrast-enhanced CT in venous phase showing notching along the surface of right posterior segments (arrows). Right posterior hepatic notch sign is frequently seen in patients with viral-induced cirrhosis. Marked caudate lobe enlargement is typically associated with alcoholic cirrhosis. Hepatic steatosis, if present, leads to generalized decrease in parenchymal attenuation while conditions like haemochromatosis and Wilson’s disease lead to generalized increase in hepatic parenchymal attenuation on the plain scan. The splenic parenchyma attenuation is taken as a reference standard. Other features like collateral vessels and ascites may be seen. Diffuse gallbladder thickening and submucosal thickening of small bowel loops occur due to haemodynamic changes and concomitant hypoproteinaemia. Gallbladder wall oedema in the setting of cirrhosis is common and should not be misinterpreted as cholecystitis. Oedematous wall thickening of the colon particularly the caecum and ascending colon are commonly seen. Mesenteric oedema in the form of increase in

mesenteric attenuation is also a common feature in cirrhosis (Figs. 9.9.41 and 9.9.42).

FIG. 9.9.41 Oedematous colonic wall thickening in cirrhosis. Contrast-enhanced CT coronal images showing oedematous wall thickening involving the colon, termed cirrhosis-related colopathy.

FIG. 9.9.42 Mesenteric thickening in cirrhosis. Contrast-enhanced CT showing stranding in the mesenteric fat with fluid in the mesenteric sleeves, a finding common in patients with cirrhosis (arrows). CT evaluation of liver nodules An RN is a well-defined area of liver parenchyma that has enlarged in response to necrosis and altered circulation. These can be classified into micronodular (3 mm). Hepatitis C and alcohol are the common causes of macronodular cirrhosis. Most cases of

cirrhosis present a mixed picture. These nodules are usually isodense on plain scan. Siderotic nodules appear hyperdense on plain scan. RNs do not enhance in the arterial phase and are isodense to the remaining parenchyma on the venous phase, making them indistinguishable from the hepatic background. These nodules are usually less than 2 cm in diameter (Fig. 9.9.43).

FIG. 9.9.43 Regenerating nodules. Contrastenhanced CT in venous phase showing innumerable tiny hypodense nodules in both lobes (arrows). A DN is defined as a nodular region of dysplastic hepatocytes without histologic features of malignancy. DNs can be further characterized as low grade or high grade, according to the degree of dysplasia. DNs classically appear isodense on nonenhanced scan. Those that contain iron or metal chelates may appear hyperdense on nonenhanced CT (Table 9.9.10). Low-grade DNs have portal perfusion and hence are indistinguishable from regenerating nodules unless size >2 cm. They also appear isoattenuating to background on venous phase. High-grade DNs reveal variable arterial enhancement either in totality or in part of the nodules depending on the degree of dysplasia and neovascularity. This imaging appearance of malignant transformation in DNs is called nodule in nodule appearance and well identified on both CT and MRI (Fig. 9.9.44).

TABLE 9.9.10 CT Features of Cirrhosis • Morphological changes in the form of surface irregularity and altered coarse architecture • Fibrosis appears as hypodense bands separating nodules showing delayed enhancement • Hepatomegaly may be present in early cirrhosis followed by decrease in size • Associated fatty liver, haemochromatosis can be seen on nonenhanced scan • RNs appear as small hypo/isodense nodules with portal perfusion, low-grade DNs appear similar • High-grade DNs are precursors of HCC and may have variable arterial enhancement • Both RN and DN may appear hyperdense on plain scan • HCC classically show arterial phase hyperenhancement with portal venous washout and capsule appearance • Larger HCC may show mosaic attenuation, central necrosis • HCC have a propensity to invade the portal and to a lesser extent hepatic veins with resultant tumour thrombosis

FIG. 9.9.44 DN. (A and B) Unenhanced CT images showing a well-defined 1.3 cm hyperdense nodule in segment 8 in dome region. Lesion shows no arterial enhancement ( arrow in C) and is hypoattenuating to the background liver on delayed phase ( arrow in D). Angiogenesis and neovascularity which manifest as increasing arterial hyperenhancement are major changes in the process of transition from DN to HCC. The detection rate for DNs smaller than 2 cm has been reported, in pretransplant three-phase helical CT study, to be 39%. HCC is classified histologically as trabecular, pseudoglandular, compact and scirrhous, with the trabecular pattern being the most common. Imaging features vary with size. HCC may vary in morphology from a solitary large mass lesion to multicentric variety constituting a dominant lesion with satellite lesions to an infiltrative pattern (Figs. 9.9.45 and 9.9.46). Less frequent patterns include multifocal pattern with lesions less than 2 cm in both lobes.

FIG. 9.9.45 HCC in segment 2. (A and B) Contrastenhanced CT in late arterial phase in case of cirrhosis showing well-defined heterogeneously enhancing mass measuring 3.5 cm in segment 2 (arrows). (C and D) Venous phase images showing washout (arrows).

FIG. 9.9.46 Infiltrative HCC in cirrhosis. Contrastenhanced CT in late arterial phase shows ill-defined infiltrative lesion in the right lobe of the liver (arrows) A thrombus with neovascularity is seen in the right PV which is distended (red arrows). (E) Contrast-enhanced MRI showing the tumour (better appreciated compared to CT). (F) PET-CT showing increased uptake. On imaging, the cardinal feature is arterial hyperenhancement with washout on the delayed phases. There may be additional features of pseudocapsule appearance. HCC may spread and invade the PV with resultant neovascular tumour thrombus. Invasion into hepatic veins is seen to a lesser extent. Biliary invasion of HCC has also been described, but when seen should raise possibility of combined HCC – cholangiocarcinoma. The lungs, adrenals, lymph nodes and bones are common sites of metastasis from HCC. CT allows accurate staging of

HCC. It can detect number of lesions, vascular involvement and metastatic disease. Spontaneous rupture of HCC is an unusual complication identified in approximately 8% of the cases. Patients usually present with abdominal pain. On nonenhanced scan, hyperdense collection signifying blood can be seen in perihepatic space. Ruptured HCC may not show classic enhancement characteristics of arterial enhancement and washout. Due to state of haemodynamic shunning, there is arterial vasoconstriction and resultant hypoenhancement of the ruptured neoplasm as well as other tumours if present. The lesion may show internal haemorrhagic areas which appear on imaging as nonenhancing clefts. Protrusion beyond the liver margins with hypodense cleft of fluid between the ruptured neoplasm and the liver is called the enucleation sign. This has been discussed in chapter 9.11 on focal liver lesions. PET-CT is not commonly used in diagnosing HCC. Approximately 60% of HCCs are non-FDG avid. Moderately or poorly differentiated HCCs are often FDG avid. PET-CT can, however, be used to stage the disease and to diagnose metastasis particularly used in pretransplant workup. MRI evaluation in cirrhosis (Table 9.9.11) MRI evaluation in cirrhosis uses nonenhanced pulse sequences like T1, T2 and T2*. Diffusion-weighted images are also useful for nodule evaluation. Assessment of steatosis in liver or intrahepatic lesion can be accurately performed with chemical shift and gradient recalled images. TABLE 9.9.11 MRI in Cirrhosis • Modality of choice in nodule characterization • Aetiology of cirrhosis like fatty liver disease, iron overload can be better detected • RN appear hypointense and T2 and have variable signal on T1W1 images. They are portally perfused and isoenhancing to the surrounding parenchyma on hepatocyte phase • High-grade DN may show foci of T2 hyperintensity, nodule within nodule appearance seen on contrast study • HCCs appear hyperintense on T2W1 images and show arterial phase enhancement followed by portal venous washout and delayed capsule appearance • Hepatocyte specific agents improve detection rate of small HCCs 3 mm) in size in both lobes (arrows), with interspersed reticulation (yellow arrows). These nodules appear isointense to one another on delayed phase of dynamic study ( arrows in D) and do not show arterial enhancement (not shown).

FIG. 9.9.50 Siderotic nodules. (A and B) T1W1 inand opposed-phase images showing multiple tiny hypointense nodules in both lobes (arrows). DNs have variable MR signal. The imaging characteristics, particularly in low-grade lesions may overlap with those of regenerating nodules. Low-grade DNs appear hypointense on T2-weighted images, while highgrade lesions are hyperintense. The signal intensity on T1W1 images is variable ranging from hypo-, iso- or hyperintense (Fig. 9.9.51). Most DNs are portally perfused and do not show arterial enhancement. Foci of arterial enhancement in DN is suggestive of development of HCC. This is called the nodule in nodule appearance (Fig. 9.9.52).

FIG. 9.9.51 DN in cirrhosis. (A and B) T2W1 images showing a well-defined hypointense nodules (2.2 cm) protruding from the surface of segment 5. Nodule appears hyperintense on T1W1 images ( arrows in C).

FIG. 9.9.52 Nodule in nodule appearance. (A) T2W1 images showing a 3 cm hypointense nodule in 4/5. The lesion appears hyperintense T1W1 images ( arrows in B) with central hypointense area (red arrow). The small central nodule shows arterial enhancement with washout ( arrows in C, E and F). This suggests DN with central focus of malignancy. Small HCCs appears show variable signal on TIW1 images and are mildly hyperintense on T2. Large well-differentiated HCC also appear slightly iso- to hyperintense relative to liver on T2W1 images. However, intralesional heterogeneity is often seen in the form of areas of necrosis, haemorrhage and fat. Necrosis is seen as T2 hyperintense and TI hypointense areas, while haemorrhagic regions may show hyperintense signal on T1W1 images. Intralesional fat is readily diagnosed as an area of signal drop on opposed-phase images. On contrast study, HCCs typically show arterial enhancement and intratumoural neovascularity (Fig. 9.9.53). However, 10%–20% HCCs are hypovascular and appear hypointense relative to liver on arterial phase.

FIG. 9.9.53 HCC in cirrhotic liver. (A) T2W1 images showing a well-defined heterogeneously hyperintense lesion in segment 7. Lesion shows heterogeneous arterial enhancement ( arrows in B) and another smaller nodule is seen adjacent to it (red arrows). Delayed phase images show washout ( arrow in D). Typically, HCC shows portal venous or delayed washout, appearing hypointense relative to background liver. Capsule appearance on delayed phase is a characteristic feature of HCC. Hepatobiliary specific agents have a distinct advantage in diagnosing HCC < 2 cm in size. HCCs appear hypointense to liver on the hepatocyte phase due to their decreased uptake of gadolinium and hence detection rate of smaller lesion is better. Features seen with large HCC include mosaic attenuation and extracapsular spread with satellite nodules. Tendency for vascular invasion is also higher in large HCC. Tumours can invade lumen of portal and less commonly hepatic veins. The signal intensity and enhancement characteristics of the thrombus parallel that of the tumour, unlike a bland thrombus which appears hypointense. Diffusion restriction is also seen in tumour thrombi. Larger tumours, particularly in setting of cirrhosis also have a propensity to rupture. Infiltrative HCC is almost exclusively seen in the setting of cirrhosis and usually invades the lumen

of the PV (Fig. 9.9.54). These patients often have high AFP levels. The imaging features have been discussed earlier in the chapter.

FIG. 9.9.54 Infiltrative HCC in cirrhosis. (A) T2W1 images showing an ill-defined infiltrative hyperintense lesion in right lobe of liver ( arrow in A) showing diffusion restriction ( arrow in B). Contrastenhanced venous phase images show permeative nature of lesion composed of multiple tiny nodules with ill-defined margins ( yellow arrow in C). A large tumour thrombus is seen in the right PV ( red arrow in C). (D) Hepatocyte phase images show good tumour liver contrast. On contrast study using SPIO particles, moderately or poorly differentiated HCC appear hyperintense to background liver on T2 and T2* images. Pitfalls in dynamic contrast-enhanced MR include inability to characterize well-differentiated small HCC. These are portally perfused and may be difficult to distinguish from DNs. On the contrary, benign lesions like A–V shunting, active inflammation may show arterial phase enhancement and sometimes obscure underlying small HCC. In addition to HCC, other malignant tumours like intrahepatic cholangiocarcinomas and mixed cholangiocarcinoma HCC can be seen with higher prevalence in cirrhotic patients. The distinguishing imaging features of these tumours have been discussed in chapter 9.11 on focal liver lesions below in subsection on LI-RADS.

Newer techniques in cirrhosis MR elastography MRE was introduced for clinical practice in 2007 and is now widely available. Currently, MRE is the most accurate noninvasive imaging technique for detection and staging of liver fibrosis. MRE of the liver is performed in the MRI and does not require contrast administration. A passive driver is applied to the upper abdomen and chest over the right lobe. Low frequency mechanical waves are generated by an active driver, which is conducted to the passive driver. The passive driver produces shear waves, which are transmitted across the liver. The stiffer the liver with longer the wavelength of the propagating shear wave. A modified phase contrast pulse wave images these shear waves and data are displayed in the form of elastograms, which typically depict shear stiffness in units of kilopascals (kPa) and may be displayed in a grey scale or with a colour scale. Fibrosis can be scored from F1 to F4 Figs. 9.9.55 and 9.9.56).

FIG. 9.9.55 MRE. Normal MRE in a healthy patient with mean stiffness index 2.5.

FIG. 9.9.56 MRE in cirrhotic. MRE image in a patient with cirrhosis showing mean stiffness index 9–11 kPa. Advantages of MRE 1. Ability to depict tissue stiffness over the entire liver cross-section.

2. It also has a higher technical success rate than USG elastography and can be performed accurately in obese individuals. 3. It can also be performed in cases of concomitant ascites and colon interposition. 4. It provides flexibility in imaging protocol as it can be performed prior to or after contrast injection. 5. Being a quantitative technique, it is important that MRE has excellent intraobserver and interobserver reproducibility. This allows it to be used as an excellent monitoring technique. Limitations: 1. Currently the main limitation is that it may fail in patients with haemochromatosis or iron overload. 2. Liver stiffness due to other conditions like acute inflammation cannot be differentiated from fibrosis. 3. Postprandial measurements tend to be higher due to increased portal flow and can lead to overestimation of fibrosis. 4. Acute biliary obstruction and passive congestion of the liver can also give rise to increased liver stiffness and findings need to be interpreted with caution in these conditions. MR fat evaluation Hepatic fat estimation by MRI chemical shift methods or MRI spectroscopy have been proven to be highly accurate. These imaging techniques have significant role to play in the imaging of NAFLD, which is an emerging cause of CLD. Iron estimation MRI is the investigation of choice in estimating liver iron. This has been discussed in details in chapter 9.10 on diffuse liver diseases. Newer techniques Diffusion-weighted imaging is not very useful in detection of advanced cirrhosis and fibrosis. MR perfusion is being evaluated for detection of fibrosis. However, extensive postprocessing and lack of availability limits use. It has been proposed that spin–lattice relaxation time MRI can be used in fibrosis evaluation. The T1-p values in fibrotic livers are higher than healthy individuals, allowing differentiation. Results, however, need validation. Treatment of HCC has been discussed in chapter 9.11 on focal liver lesions and also in hepatic interventions. Liver imaging reporting and data system LI-RADS is a radiology-based system that categorizes liver observations in patients with an increased risk for HCC. The aim of this system is to allow standardization of terminologies and reporting of liver observations, in patients with increased risk. Evolution of LI-RADS

LI-RADS was first released in the year 2011 by ACR, following 3 years of deliberation. Major updates were released in 2013, 2014 and 2017. In 2018, American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its HCC clinical practice guidance. LIRADS is consistent with NCCN guidelines. Whom does LI-RADS apply to: LI-RADS applies to patients with cirrhosis or chronic hepatitis B viral infection or current or prior HCC including adult liver transplant candidates and recipients posttransplant. LI-RADS is not applicable to patients without the above-mentioned risk factors, patients 5%. CT The main advantages of CT for assessing steatosis are relatively fast acquisition, ease of performance, and quantitative results. Estimation of fatty liver is done on non-contrast enhanced images. The normal liver density is around 60 HU, which is approximately 10 HU higher than normal spleen. Fat accumulation in the liver manifests as proportionate decrease in density. Both the absolute and relative (to the spleen) values are used to characterize steatosis; a cut-off value of 40 HU has been suggested to predict fat content greater than 30% (Figs. 9.10.6 and 9.10.7)

FIG. 9.10.6 CT in fatty liver. Non enhanced CT showing mild decrease in normal liver attenuation (45–55 HU) suggesting mild fatty changes.

FIG. 9.10.7 CT in fatty liver. Non enhanced CT showing severe decrease in normal liver attenuation (13–18 HU) suggesting severe fatty changes. Liver attenuation index Attenuation difference between liver and spleen on unenhanced CT scan is a commonly used quantitative parameter to evaluate hepatic steatosis. This avoids errors in attenuation value measurement from different CT scanners and different reconstruction algorithms. Normal liver parenchymal attenuation on nonenhanced CT is slightly higher than the spleen. Liver attenuation progressively decreases as percentage steatosis increases (Table 9.10.7) (Fig. 9.10.8) TABLE 9.10.7 Fat Quantification on CT Principle: Fat has low attenuation a proportionate decrease in density is seen with increasing fat accumulation in liver Assessment of hepatic steatosis using CT is based on the measurement of attenuation value of liver parenchyma, expressed as Hounsfield units (HU) Attenuation difference between liver and spleen on unenhanced CT scan has been the most commonly used Cut-off value of attenuation difference to detect moderate to severe degree hepatic steatosis-9 Not accurate for detecting mild steatosis

FIG. 9.10.8 CT LAI. Nonenhanced CT images (A to C) showing ROI on each hepatic segment. At least 25 ROI s are drawn in liver. Similar size approximately 5 ROI are drawn in the spleen. The average attenuation is calculated for both and the difference is called the Liver attenuation index. Methods of liver fat quantification on CT have been discussed in details in chapter on liver transplant. Disadvantages Limited diagnostic accuracy for detecting mild degree hepatic steatosis is one of major drawback of CT. Disorders causing hyperdensity of liver such as iron, glycogen deposition can lead to errors in interpretation. The concomitant presence of iron and fat may not be accurately diagnosed on CT. Low CT density values may also be caused by oedema and inflammation. Likewise, the spleen is an imperfect reference standard as it can be affected by haemosiderosis and haemochromatosis in a small minority of patients. Dual-energy CT Dual-energy CT with its ability to perform material decomposition is more accurate in quantifying hepatic steatosis and allows staging of fibrosis. Imaging is done with two different energies (typically 80 kVp and 140 kVp). DECT has the potential to quantitate liver fat content independent of ROI (region of interest) placement. MRI Magnetic resonance imaging (MRI) is presently the most accurate imaging modality for the evaluation of hepatic steatosis. Several different methods have been developed and introduced in MRI for the evaluation of hepatic steatosis.

Chemical shift imaging (dual echo) In this technique typically, two gradient echoes are acquired, one employing a TE in which the water peak (4.7 ppm) and the dominant fat peak (1.3 ppm) are ‘out of phase’ and hence subtractive (SOP), and the other using a TE in which the two peaks are ‘in phase’ and therefore additive (SIP). Because two echoes are acquired, this is often called ‘dual-phase’ or ‘dual echo’ imaging. Fat Signal Percentage is calculated as [SIP – SOP]/[2 × SIP] ×100. The dynamic range of magnitude based chemical shift techniques has typically a 0%–50% signal fat-fraction (Fig. 9.10.9)

FIG. 9.10.9 Chemical shift imaging. T2W1 images (A and B) showing hepatomegaly with increase in parenchymal signal. T1 W1 in and opp phase images (C and D) showing signal drop on opp phase imaging. Multi-echo dixon sequences This technique uses both magnitude and phase information from three or more images acquired at different echo times appropriate for more accurate separation of water and fat signals as against only magnitude information in dual-echo. These methods provide estimates of fat fraction with a dynamic range of 0%–100%. Proton density Fat fraction (PDFF) is calculated as Sf/(Sw + Sf) where Sw = SI of the water component, Sf = SI of the fat component. PDFF specifically reflects the concentration of triglycerides in the hepatocytes as lipids within the other structures such as cell membranes and organelles are occult. Sensitivity up to 96% and specificity up to 100% for detecting any degree of steatosis have been reported. A fat-fraction threshold of 5.56% is commonly used to define steatosis; however, the optimal cut-off value still needs to be defined (Figs. 9.10.10 and 9.10.11).

FIG. 9.10.10 Calculation of hepatic fat fraction using MRI. TIWI in and opp phase images (A and B) showing mild signal drop on opp phase images. Fat fraction calculation using Dixon technology (C) shows 12% fat suggesting mild changes.

FIG. 9.10.11 Calculation of hepatic fat fraction using MRI. TIWI in and opp phase images (A and B) showing significant signal drop on opp phase images. Fat fraction calculation using Dixon technology (C) shows 28% fat suggesting severe changes. MRS

MRS can directly measure the chemical composition within tissue based on the frequency composition of the signal originated from the voxel of interest. Water proton peak appears as a single peak at 4.7 ppm, whereas fat peaks appear as multiple peaks around 1.3 ppm. PDFF can be calculated as the ratio of the sum of the signal intensities derived from the protons in fat divided by the sum of the signal intensities originated from the protons in both fat and water (Fig. 9.10.12).

FIG. 9.10.12 Magnetic resonance spectroscopy spectrum of hepatic fat. Water and fat peaks are displayed at different frequencies; water appears as a single peak at 4.7 ppm, whereas fat appears as four peaks, including the dominant methylene (CH 2) peak at 1.3 ppm (3), a methyl (CH 3) peat at 0.9 ppm (4), an α – olefinic and α – carboxyl peak at 2.1 ppm (2), and a diacyl peak at 2.75 ppm (1); the areas of these four fat peaks and the water peak can be measured by spectral tracing. PDFF can be calculated as (sum of fat peaks) ÷ (sum of fat peaks + water peak).

TABLE 9.10.8 Imaging Modalities in Assessment of Fatty Liver Disease Technique Advantages US Widely available, easy to perform, fast Inexpensive CT

Widely available, easy to perform, fast

Disadvantages Quantitative assessment is not possible. Mild steatosis may be missed. Confounding factors such as obesity, bowel gas may alter interpretation. Ct involves radiation exposure and a low sensitivity for detection of mild steatosis

Moderate cost Quantitative assessment MRI basic (in/out of phase)

Available on all scanners

MRI complex (PDFF)

Quantitative assessment

Contraindication to metallic implants, pacemakers

High accuracy and reproducibility

Limited by large body habitus (most scanners)

Increased sensitivity for mild steatosis

Measurement independent of scanning parameters

Patients with pacemaker, metallic implants may be contraindicated. It is mainly a qualitative assessment and expensive investigation when compared with US and CT

High cost, limited availability

MRS data are usually obtained from a single voxel manually placed in the liver parenchyma usually right posterior segment of the liver. Reported MRS sensitivities and specificities for detection of mild hepatic steatosis are 80.0%–91.0% and 80.2%–87.0%, respectively, outperforming CT and US. MRS can also provide excellent reproducibility of measurement. It is also unaffected by confounding factors like fibrosis, iron overload and glycogen.

Small sample volume usually less than 3 × 3 × 3 cm3 is a major limitation of MRS, particularly in patients with uneven fatty change. Despite these practical limitations, MRS is considered to be the gold standard MR method for hepatic fat quantification.

Patterns of fat deposition Diffuse deposition This is the most frequently encountered pattern and considering the homogenous involvement poses no diagnostic dilemma. Focal deposition and focal sparing Focal fat deposition and focal sparing in diffuse fatty liver are less common. These usually occur in specific locations like adjacent to falciform ligament or ligamentum venosum, in portal hepatis or gallbladder fossa. Imaging findings are suggestive of fatty pseudolesions rather than true masses. Occurrence in characteristic locations, absence of mass effect on vessels and structures, geographic configuration and contrast enhancement similar to or less than adjacent liver (Fig. 9.10.13).

FIG. 9.10.13 Focal fat. Unenhanced CT (A) showing geographic hypodense area in the left lobe of liver. Contrast-enhanced CT in late arterial (B), portal venous (C) and venous phase (D) showing persistent hypodense without mass effect with normal vessels coursing through the affected region. Perilesional steatosis Fat deposition around insulinoma metastasis can occur as a local effect of insulin on the liver parenchyma. On ultrasound, it appears as an echogenic rim shows signal drop on out of phase images. Eisenberg has reported perilesional steatosis around focal nodular hyperplasia. Multifocal deposition Sometimes multiple small foci and seen scattered throughout the liver. These may appear as small round nodules (Fig. 9.10.14). Opposed phased imaging is more useful than CT or US to establish diagnosis. These may, however, pose a diagnostic dilemma in patients with known malignancy.

FIG. 9.10.14 Multifocal fat deposition. Unenhanced CT images (A–C) showing patchy mass like hypodense areas in both lobes of liver (arrows). Enhanced CT in portal venous (D–F) and venous phase showing confluents relatively hypoenhancing areas with vessels coursing through them (arrows). Perivascular deposition Perivascular fatty infiltration is a recently described entity, mostly seen in alcoholic patients. This pattern is characterized by halos of fat that surround the hepatic veins, the portal veins, or both hepatic and portal veins (Fig. 9.10.15). Normal vessels coursing through the lesion without attenuation in calibre suggest the diagnosis.

FIG. 9.10.15 Perivascular fat. Contrastenhanced CT (A) showing hypodense areas of fat deposition in the perivenular location (arrows). Findings are confirmed on T1W1 in and opposed phase images (B and C) which show signal drop on opp phase (arrows). Subcapsular deposition Peritoneal dialysis with insulin in the dialysate in patients with renal failure and insulin-dependent diabetes. Exposure of subcapsular hepatocytes to a higher concentration of insulin results in fat deposition in the subcapsular regions. Intracellular lipid containing lesions (intratumoural or intralesional steatosis) Some hepatic lesions such as hepatic adenoma, hepatocellular carcinoma, regenerative nodules and focal nodular hyperplasia can show intracellular steatosis (Fig. 9.10.16). These areas show signal drop on opposed phase. However, postcontrast imaging characteristics of these lesions allow differentiation from areas of focal steatosis.

FIG. 9.10.16 Lipid containing lesions. Unenhanced CT (A) showing large hypodense mass in right lobe with areas of macroscopic fat along its inferior aspect (arrows). Postcontrast arterial phase images (B) showing neovascularity (arrows). Postcontrast venous phase images (C) showing heterogenous enhancement of the mass with relatively nonenhacing fatty areas (arrows). Perilesional or peritumoural fatty sparing Perilesional sparing has been reported in haemangioma and hepatocellular carcinomas. This may mainly represent decreased portal flow due to either compressed or atrophic hepatocyte cords in expanding metastases or arterioportal perfusion abnormalities in haemangiomas. Differential diagnosis The differential diagnosis of focal fat infiltration is discussed in Table 9.10.9. TABLE 9.10.9 D/D Focal Fat Infiltration • Hypovascular metastasis • Perfusion abnormalities • Periportal abnormalities Hypovascular metastases Accurate history and chemical shift imaging showing signal drop help in differentiation of focal fat from metastasis. Perfusion anomalies

These are visible only during the arterial and portal venous phases after contrast agent administration. The morphologic appearance of fat deposition and perfusion abnormalities is similar. Perfusion abnormalities however are visible only during the arterial and portal venous phases (Fig. 9.10.17). They are not seen as an attenuation difference on nonenhanced CT.

FIG. 9.10.17 Perfusion abnormalities. Contrast-enhanced late arterial phase images (A and B) showing wedge-shaped areas of hyperenhancement in the periphery of segment 8/4A (arrows). These areas are isodense to liver on venous phase (C) and were not seen on unenhanced scan (not shown). Periportal abnormalities Periportal oedema, inflammation, haemorrhage and lymphatic dilatation may mimic perivascular fat. With the exception of haemorrhage all other conditions affect periportal region symmetrically (Fig. 9.10.18). Patients with haemorrhages may show other signs of injury. Chemical shift imaging is helpful in cases with diagnostic challenges.

FIG. 9.10.18 Periportal oedema/cuffing. Contrast-enhanced CT in a patient with acute viral hepatitis showing hepatomegaly with symmetric hypodensity in the periportal regions (arrows). Complications NAFLD increases overall mortality by 57% mainly from liverrelated and cardiovascular causes, and increased risk of incident T2DM by approximately twofold. NASH increases the risk of HCC, even in people without cirrhosis (Table 9.10.10). TABLE 9.10.10 Complications of NAFLD

There is recently, increasing attention on NAFLD-related chronic kidney disease (CKD). There is also emerging evidence that NAFLD is linked to other diseases such as colorectal cancers, metabolic bone disease (vitamin D deficiency, osteoporosis), psoriasis and rare metabolic diseases (lipodystrophies, glycogen storage diseases). Disease progression NAFLD is a slowly progressive disease, both in adults and in children, but fibrosis rapidly progresses in 20% of cases. Liver disease is the third most common cause of death after CVD and cancer.

Treatment Perhaps the most important treatment option, lifestyle modification (including diet and exercise). Medications and supplements are also part of the treatment consideration when dealing with NAFLD (Table 9.10.11). TABLE 9.10.11 Treatment of NAFLD

Lifestyle management Lifestyle intervention with diet and exercise is still the mainstay in the management of patients with NAFLD. Diet

Patients with NAFLD should not consume heavy amounts of alcohol. Commonly individuals are recommended to restrict caloric intake by approximately 500–1000 kcal/day in conjunction with regular interactions with a dietician. Food with high glycaemic index (GI) and high saturated fatty acids (SFAs) should be avoided. Weight loss Several studies indicate weight loss of >5% is associated with improvements in steatosis and inflammation, and >10% weight loss may also reduce liver fibrosis. Pharmacological management Pioglitazone statins, Vitamin E (α-tocopherol) at daily dose of 800 IU/day have been used in pharmacological management. Long term benefits are, however, still questionable. Liver transplantation Patients with end-stage liver disease due to NAFLD are candidates for liver transplantation. TABLE 9.10.13 Imaging Pearls-Fatty Liver • NAFLD is the most common cause of fatty liver disease • 90% alcoholic patients have fatty liver • Can progress to steatohepatitis and eventually cirrhosis • MRI is the imaging modality of choice in detection and quantification • MR spectroscopy is the gold standard • CT-LAI is a good quick method for fat quantification, but less accurate in mild infiltration • Dietary modification is the mainstay for treatment

Alcoholic liver disease Alcoholic liver disease (ALD) represents damage to the liver due to alcohol overconsumption. American guidelines define significant alcohol consumption as be defined as >21 drinks per week in men and >14 drinks per week in women over a 2-year period prior to baseline liver histology. The European Association for the Study of the Liver (EASL) defines 30 g per day for men and 20 grams per day for women as significant hepatotoxicalcohol amounts. Pathogenesis of ALD

Generally, more than 95% of absorbed alcohol is metabolized by the liver, and small amount is directly excreted through the lungs, urine, and sweat. Chronic alcohol consumption leads to accumulation of reactive oxygen species and causes oxidative stress. lipopolysaccharides (LPS) and acetaldehyde cause liver inflammation. The spectrum of ALD

The spectrum of ALD includes alcoholic fatty liver, alcoholic hepatitis, steatohepatitis, liver fibrosis, cirrhosis and liver cancer. The only stage of alcoholic liver disease than is completely reversible through abstinence is hepatic fat accumulation. Thereafter, if corrective measures are not taken fibrosis and cirrhosis may develop, followed by eventual liver failure. Ballooning degeneration, spotty necrosis, polymorphonuclear infiltrate, and perivenular and perisinusoidal fibrosis in the space of Disse are hallmarks of alcoholic hepatitis. Heavy alcohol consumption is associated with fibrosis progression. Early diagnosis of ALD Clinical symptoms Early manifestations of ALD are fatty liver and mild hepatitis. Common symptoms include fatigue, loss of appetite, bloating, nausea, vomiting and obesity. Serological markers elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGTP).

The elevation in liver enzymes is nonspecific. Elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGTP) can be seen. Elevated triglycerides and bilirubin can be seen. A 2- to 7-fold increase in AST and ALT is seen in alcoholic hepatitis in contrast to other causes of fatty liver. Gamma-glutamyltranspeptidase (GGT) is another sensitive index to diagnose fatty liver in cases of excessive alcoholism. Detection of specific biomarkers Carbohydrate-deficient transferrin (CDT) is a highly specific biomarker for the detection of chronic alcohol abuse. It is a fundamental tool to define the severity of the disease and to differentiate AH from decompensated cirrhosis.

Imaging The imaging features of alcohol related fatty disease are similar to those described in previous section. Current therapies Complete abstinence from alcohol is the cornerstone in the treatment of alcoholic liver disease. Nutritional therapy It is recommended to supply nutritional support by providing high protein, low-fat diets, and balancing the levels of vitamin B, C, K and folic acid. The daily protein intake of ALD patients should be 1.5 g/kg of body weight. Alcohol withdrawal therapies Disulfiram is an irreversible alcohol dehydrogenase inhibitor that is often used to treat alcoholism. Others which are commonly used are Acamprosate, Baclofen, opioid antagonist naltrexone. Hormone related therapies Corticosteroids have been used to improve the nutritional status of AH patients. Antioxidants such as vitamin E and silymarin have been investigated and evaluated for the treatment of AH. Losartan is considered a treatment to prevent the development of hepatic fibrosis and progression and regression of fibrosis stage Prednisolone, is used to inhibit the inflammation of hepatocytes. Liver transplantation Liver transplantation is the main choice for patients with advanced stages of ALD.

Iron overload Iron overload syndromes encompass a wide range of hereditary and acquired conditions. The term ‘iron overload’ can be used to describe a condition resulting in increased total body iron stores, with or without organ dysfunction. Iron overload syndromes are broadly divided into two groups: Inherited or Primary iron overload and Secondary iron overload syndromes. Primary iron overload syndromes are now known to be caused by mutations in several iron regulatory genes (Tables 9.10.14 and 9.10.15). TABLE 9.10.14 Primary Iron Overload Syndromes • HFE related haemochromatosis (Type 1) • Non-HFE related haemochromatosis • Juvenile haemochromatosis (Type 2) • Transferrin receptor 2 haemochromatosis (Type 3) • Ferroportin diseases (Type 4) TABLE 9.10.15 Secondary Iron Overload Syndromes Iron-loading anaemias • Thalassemic syndromes (β Thalassaemia) • Sideroblastic Anaemias • Chronic Hemolytic Anaemia • Aplastic Anaemia • Pyruvate Kinase Deficiency Chronic liver disease • Hepatitis C infection • NAFLD • Alcoholic liver disease • Porphyria Cutanea Tarda Iatrogenic • Red Blood cell transfusion • Long-term hemodialysis Miscellaneous • Aceruloplasminaemia • African iron overload • Neonatal iron overload HFE-related haemochromatosis

HFE-related haemochromatosis (HH) is the most common inherited disorder of iron metabolism. A homozygous mutation in the hereditary haemochromatosis gene, HFE is responsible for hereditary haemochromatosis. In general, primary haemochromatosis is rare, particularly in Indian population. Iron storage disorders encountered in practice are usually due to secondary overload. Secondary iron overload Haematological disorders The four main haematological disorders causing iron overload are thalassaemias, congenital and acquired sideroblastic anaemia, congenital dyserythropoietic anaemias and acquired myelodysplastic syndrome Chronic liver disease Chronic viral hepatitis, most commonly Hepatitis C virus infection (HCV), may be associated with iron overload. Alcoholic liver disease is associated with iron deposition initially in the hepatocytes, but with advanced disease, iron accumulates in both hepatocytes and macrophages. Mild to moderate elevation of iron indices and hepatic iron concentration are frequently observed in patients with NASH. Porphyria cutanea tarda (PCT) This iron-dependent condition maybe is associated with mild to moderate iron overload in 60%–70% patients. Aceruloplasminaemia Aceruloplasminaemia is an autosomal recessive condition due to a mutation in the ceruloplasmin gene. Ceruloplasmin is required for mobilization of iron from liver. Deficiency of ceruloplasmin results in iron deposition in liver, pancreas, basal ganglia and other organs. Iron-mediated cellular injury Iron deposition in hepatocytes is an important catalyst for lipid peroxidation resulting in the formation of reactive oxygen species. This leads to damage to hepatic organelles and generation of stellate cells with Kupffer cell activation, eventually causing fibrosis (Table 9.10.16).

TABLE 9.10.16 Mechanism of Iron Induced Hepatic Damage

Clinical manifestations of iron overload (Table 9.10.17) Liver disease. The liver is the most frequently involved organ as it is the primary organ of iron storage. Hepatomegaly on palpation or elevated serum aminotransferases levels are seen in asymptomatic patients. Significant liver iron deposition is seen in 38%–97% patients, progression to fibrosis in 10%–25% and cirrhosis in 4%– 6% (Fig. 9.10.19). TABLE 9.10.17 Clinical Manifestations of Iron Overload

FIG. 9.10.19 Cirrhosis inpatient with iron overload. Known case of thalassemia with repeated blood transfusions showing significant decrease in hepatic signal on T2W1 images (A) with changes of frank cirrhosis with multiple siderotic nodules and portal hypertension with splenomegaly (arrows in B and C). Endocrine diseases – like diabetes are seen in >70% of patients with cirrhosis. Hypogonadism, Thyroid dysfunction can also be seen. Arthropathy develops in 25%–50% of patients. Accumulation of iron in the heart can result in cardiomyopathy (both restrictive and dilated), arrhythmias (sick sinus syndrome, atrial fibrillation) and heart failure. Hyperpigmentation may be one of the earliest signs of disease and has been reported in up to 90% of patients in one study. Iron overload and cancer risk Patients with hereditary haemochromatosis are at an increased risk of hepatocellular carcinoma (HCC). Some studies have shown an increased risk of extra-hepatic cancer including colorectal cancer,

breast cancer in women, oesophageal cancer, lung and malignant melanoma.

Serological tests for iron overload (Table 9.10.18) Serum ferritin Serum ferritin generally correlates with total body iron stores. Serum ferritin values of more than 1000 ng/mL suggest iron overload, although the correlation is nonlinear. TABLE 9.10.18 Serological Tests for Iron Overload SERUM MARKERS • Serum iron • Serum transferrin • Transferrin saturation • Serum ferritin TISSUE IRON CONCENTRATION/DISTRIBUTION • Liver iron concentration (LIC) by: • Liver biopsy • Quantitative MRI • Cardiac MRI • MRI of other tissues/organs Transferrin saturation In hereditary haemochromatosis, transferrin saturation is the most specific key screening marker. A Transferrin Saturation of ≥45% identifies 97.9%–100% of C282Y homozygotes. Unsaturated iron binding capacity (UIBC) The UIBC is the inverse of Transferrin Saturation may be used as a low-cost alternative screening test for detecting hereditary haemochromatosis. Genetic analysis Genotype testing can be done for determination of the common HFE gene mutations.

Imaging in iron overload

Ultrasonography US cannot estimate liver iron. Complications like liver fibrosis, cirrhosis or HCC can be however be diagnosed. Computed tomography Iron overload is seen as homogenous increase in hepatic attenuation to 72 HU or more (Fig. 9.10.20). CT has low sensitivity (63%) and high specificity (96%) for the diagnosis of iron overload. Sensitivity of CT is reduced in patients with coexistent conditions like steatosis which cause decrease in hepatic attenuation. Besides conditions like Wilson disease, glycogen storage, and long-term administration of amiodarone cause increase in liver density which decreases the specificity. Owing to radiation exposure it not an ideal modality for long term repeated follow up in young patients.

FIG. 9.10.20 CT in iron overload. Nonenhanced CT images (A–C) showing diffuse increase in hepatic density (100–104 Hu). Studies have shown role of dual energy CT in iron quantification. Reducing the kilovolt peak and kilo-electron volt (keV) values will show an increase in liver attenuation in the presence of iron overload and a decrease in the presence of steatosis. MRI Principle MR is the imaging modality of choice for qualitative and quantitative assessment of liver iron. Determination of severity, monitoring response to therapy can all be assessed with high sensitivity, specificity and positive and negative predictive values. superparamagnetic properties of the iron ions result in T1 and T2 and T2* shortening which leads to proportionate signal drop (Table 9.10.19). Baseline T2W1 images show diffuse hypointensity in affected organs relative to the paraspinal muscles (Fig. 9.10.21).

TABLE 9.10.19 MR Liver Iron Assessment

FIG. 9.10.21 MRI in haemochromatosis. T2W1 image (A–C) showing significant decrease in hepatic signal intensity relative to the paraspinal muscles. Dual echo Gradient in and out of phase MR imaging shows decreased signal intensity in the affected tissues on the in-phase images compared with the out-of-phase images (Fig. 9.10.22). This signal change is the opposite of that seen in fatty liver. The reason being that echo

time of the in-phase sequence is usually higher than that of the outof-phase sequence; therefore, the in-phase pulse sequence is more sensitive to iron deposits because of the increased T2* effect. Associated fat in liver may affect interpretation of results (Fig. 9.10.23).

FIG. 9.10.22 Dual echo in haemochromatosis. Known case of secondary haemochromatosis showing marked signal drop on in-phase images (B) compared to opp phase (A).

FIG. 9.10.23 Haemochromatosis with fatty changes. In this known case of haemochromatosis T1W1 opp phase images (C and D) show signal drop compared to in-phase due to concomitant presence of fat in liver.

Quantitative detection of iron overload Liver iron concentration (LIC) may be determined by MRI Susceptibility by the shortening of T2, which is measured by a proportional decrease in the iron concentration. There are two methods for the assessment of LIC by MRI: Signal intensity ratio (SIR) methods and relaxometry methods.

SIR method This technique is a semi quantitative estimation of liver to muscle signal intensity ratio. The signal of the normal liver should always be higher than the paraspinal muscles. Therefore, a liver hypointense to muscles suggests iron overload ratio (Fig. 9.10.24).

FIG. 9.10.24 Diagrammatic representation of signal intensity ratio method. GRE sequences are used due to their greater sensitivity to the paramagnetic effect of iron. It is necessary to use several of them, between three and six, in order to quantify all the levels of iron overload (Fig. 9.10.25). To generate LIC estimates, the values can be entered into a free web-based calculation tool from the University of Rennes, France.

FIG. 9.10.25 SIR method for estimation of liver iron. GRE images (only 2 shown) show significant decrease in hepatic signal intensity relative to the paraspinal muscles (ROI). Advantages. This is the simplest method for quantification of liver iron overload with high sensitivity (89%) and specificity (80%). 3.0 T is more sensitive to milder liver iron overload.

Limitations (19.5 mg/g dry weight) Severe iron overload more than 350 µmol/g dry weight is not detected accurately. Another limitation of SIR is that the technique does not correct for fat, despite the fact that it uses ‘in – phase’ echoes.

Relaxometry (T2 and R2/T2* and R2*) Relaxometry is the quantitative evaluation of the MRI signal loss. There are two approaches: the calculation of the T2 time constant, based on spin-echo sequences, and of the T2* time constants, based on gradient-echo sequences. R2/T2 relaxometry This is a commercially available and FDA-approved technique, based on five T2-weighted spin-echo (SE) acquisitions during freebreathing with increasing TEs for the calculation of R2. Advantages – Nonlinear correlation is seen between R2 measured liver iron content and biopsy iron content. Since images acquisition is done during free breathing it can be readily performed in children and patients with breath-holding issues. Limitations – More variable in higher iron overload when liver iron content is over 20 mg/g dry weight, making liver iron content calculation less precise. This technique requires long imaging time (∼ 20 minutes), with the definitive need for sedation in paediatric imaging, complex data processing with centralized data analysis, and a former calibration of instruments. T2* and R2* relaxometry It is based on quantification of relaxation time T2 or T2* by means of measuring signal decay at various echo times. R2* relaxometry is a reliable method providing a linear correlation with the LIC. This technique is very quick and acquired in a single breath-hold. On 1.5-T scanners, the quantification of the LIC is possible up to 20 mg/g dry weight with a first TE about 1 ms. Another major advantage of R2* relaxometry is the possibility of 3D acquisitions and parallel imaging, which allow to acquire a complete volumetric coverage of the liver. MR protocol – relaxometry Multi-echo gradient-echo (ME – GRE) sequences are used to determine the R2. The first echo time (TE) is the key parameter and should be chosen as short as possible, that is, 1 ms or less. This provides correct R2* evaluation (and consequently fat fraction) and to avoid a major LIC underestimation in case of high overload. An appropriate number of echoes (8–12 with 12 being recommended)

with short echo spacing (around 1 ms) should be used (Fig. 9.10.26). A low TR between 25 and 120 ms with a low flip angle without fat suppression is set. A single axial image through the liver and spleen is acquired in one breath-hold. Images must be obtained prior to gadolinium administration, which can alter results.

FIG. 9.10.26 Calculation of T2* and R2*. Multi echo gradient imaging for calculation of liver iron in a normal volunteer. Measurement of R2*? Freely available software is available in which the group from Rennes recently launched, MR Quantification. MRI vendors also

propose dedicated inbuilt tools. An advantage that results from this is the possibility of calculating the PDFF in addition to iron overload. How to obtain the liver iron concentration from the R2*? The conversion formula proposed from R2* calculated after subtraction of the background noise on 3T is LIC (μmol) = R2*/3.2 The cut-off value for pathological LIC and hence iron overload has been defined as 36 μmol Fe/g or 2 mg Fe/g of dry weight. The LIC should be calculated and reported; a simple R2* value of the liver does not help clinician. Advantages • linear correlation with biopsy – determined liver iron content, which makes R2* relaxometry a reliable technique for noninvasive liver iron overload quantification • increased sensitivity at 3T allows for more precise analysis and detection of mild iron overload • Cardiac iron assessment by MRI can be performed during the same examination as liver R2* – or T2* – mapping. Limitations It can be difficult to quantify severe iron overload beyond 150 μmol/g due to faster decay in signal The postprocessing algorithms may not be universally available. Methods of liver iron measurement (like R2*) should not be used interchangeably when monitoring response to therapy. Forms of iron deposition Classification of iron overload can also be done according to deposition patterns (Table 9.10.20a and Table 9.10.20b). TABLE 9.10.20a Classification of Iron Overload Depositional Pattern Reticuloepithelial Parenchymal (Fig. 9.10.27) Renal Mixed

Liver Spleen

Bone Pancreas Kidney Marrow Yes No No No Yes No

Yes Yes

Yes No

No Yes

No No Possible Possible

No Possible

Yes Possible

TABLE 9.10.20b Classification of Iron Overload Parenchymal Reticuloendothelial Renal Chronic anaemias caused by ineffective erythropoiesis + resultant multiple transfusions Anaemia with intravascular hemolysis + multiple transfusions

FIG. 9.10.27 Parenchymal deposition pattern. T2W1 images (A, B) showing low signal of liver and pancreas (arrow in B). Liver biopsy Liver biopsy is a quantitative, specific and sensitive method that provides a direct assessment of LIC. Liver biopsy was considered the gold standard for the diagnosis of hereditary haemochromatosis prior to the availability of genetic testing and continues to have a role in diagnosis and prognosis. In addition, it has been used in diagnosis of non-HFE-related haemochromatosis, as genetic testing in these conditions is not widely available (Table 9.10.21).

TABLE 9.10.21 Comparison Between Liver Biopsy and MRI Comparison of LIC Assessment by Liver Biopsy and MRI LIC by MRI Liver biopsy Invasive method Validated reference standard

Noninvasive technique Comparable accuracy to liver biopsy

Variability due to biopsy sample size and different iron deposition in the liver possible Inadequate standardization across laboratories Allows histological diagnosis

Impractical for longitudinal assessment/monitoring

Assessment of entire liver can be done. Additionally, organs such as heart can be assessed. Condition such as fibrosis can be quantified. Good tool for serial evaluations

Although inexperienced hands liver biopsy is safe, it carries a risk of complications of approx. 0.5%. Treatment of iron overload (Tables 9.10.22 and 9.10.23).

TABLE 9.10.22 Treatment of Iron Overload

TABLE 9.10.23 Pearls, Iron Overload Can be as a result of primary inherited haemochromatosis or secondary conditions leading to overload Liver is primarily affected organ Can progress to cirrhosis Diffuse hyperdensity on nonenhanced CT MRI imaging modality of choice for diagnosis and quantification T2* AND R2* relaxometry is the gold standard Treatment involves phlebotomies, Erythrocytoapheresis and chelation therapy Phlebotomies This technique involves removal of blood in an attempt to reduce ferritin levels. Erythrocytoapheresis

This technique involves selective removal of erythrocytes while other blood components like leukocytes, platelets, and plasma are returned. This allows greater withdrawal of iron and decrease hemodynamic events related to phlebotomies. Dietary changes Dietary restriction of iron-rich foods and restriction of alcohol intake have been recommended. Pharmacological measures Three chelating substances available for clinical use are: deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX). Orthotropic liver transplantation Orthotropic liver transplantation (OLT) is indicated in patients with haemochromatosis who develop decompensated cirrhosis and/or HCC.

Glycogen storage disorders This is a heterogeneous group of disorders characterized by abnormal glycogen metabolism caused by enzyme deficiencies. This form is also known as Primary Hepatic glycogenosis. Various subtypes of glycogen storage disease exist which involve different organs such as liver, muscles, myocardium hematopoietic system, and kidneys. Out of these hepatomegaly is seen in Types Ia (von Gierke), Ib, II (Pompe), III (Forbes), IV (Anderson), VI and IX. Potential for malignant transformation to HCC is seen in type 1 a and 1b and increased risk of cirrhosis is seen in types III and IV. An increased incidence of hepatic adenomas is seen in types Ia, Ib and III. The diagnosis of glycogen storage disease should be considered in all children in whom hepatomegaly in combination with hypoglycemia, growth retardation, and disproportional distribution of body fat is detected. Patients with GSD have a higher incidence of adenomas than in normal populations. 60% patients with type Ia glycogen storage disease have more than 10 hepatic adenomas. This condition is known as adenomatosis. Adenomas in GSD-I usually occur by the second or third decade of life and tend to be dominant in males with a male-to-female ratio of 2:1. Adenomas in GSD-1 tend to be small, multiple, and nonencapsulated. Increase in the size and number of adenomas increases the risk for associated haemorrhage. β-catenin-mutated HCA are common histological variant seen in patients with glycogen storage disorder. HCAs in GSD-I have greater potential to undergo malignant transformation, which was reported in about 10% of patients

Secondary hepatic glycogenosis is a rare disorder occurring due to factors affecting glycogen metabolism. high dose corticosteroid, azathioprine use, dumping syndrome, disorders of urea cycle and most commonly poorly controlled diabetes are related factors. Pathology Pathologically intracytoplasmic accumulations of glycogen and small amount of lipid are found. Liver biopsy shows glycogen deposition in hepatocytes, seen as diffusely swollen hepatocytes with pale cytoplasm and empty nuclei.

Imaging (Table 9.10.24) US Shows hepatomegaly with varying degree of fatty liver. Adenomas are common and can appear well circumscribed and may be hypoechoic, isoechoic, or hyperechoic in relation to the liver. Change in ultrasound characteristics of adenomas over serial scanning may suggest malignancy or haemorrhagic necrosis. Any interval change in appearance of lesion should be viewed with suspicion for developing malignancy and patient should be investigated further with contrast enhanced CT or MRI. TABLE 9.10.24 Pearls, Glycogen Storage Diseases Glycogen Storage Diseases The most common inherited disorder is GSD type 1 Depending on type they have propensity to develop adenomas, cirrhosis and HCC Increased density of liver due to glycogen, associated fat may alter attenuation T2 signal is decreased and T1 signal may be increased. Presence of fat may change signal Malignant transformation in adenoma should be considered if rapid change in size or enhancement characteristics CT Glycogen storage causes increase in liver density. Considering these patients also have fat deposition in the liver, which lowers hepatic density. The final liver parenchymal attenuation is an interplay between the amount of fat and glycogen deposited. In cases where glycogen storage is predominant, hepatic density presents as increased attenuation on CT images, while increased fat deposition leads to decreased attenuation.

Adenomas are hypervascular to the liver parenchyma on arterial phase imaging and nearly isoattenuating during the portal venous phase (Fig. 9.10.28). Haemorrhage if present appears as hyperdensity on nonenhanced scan. Imaging characteristics of adenoma are similar to those seen in normal livers and have been discussed in chapter on focal liver lesions. Adenomas usually show a stable size or slow growth on follow up imaging. Rapid growth, change in enhancement characteristics should suggest malignant degeneration.

FIG. 9.10.28 Hepatic adenomatosis in a patient with glycogen storage disease. Contrast-enhanced CT (A–D) showing multiple (>10) well defined arterial enhancing lesions diffusely distributed in both lobes consistent with adenomatosis. MRI On MR images, the T2 signal in the liver parenchyma is slightly decreased when glycogen storage is dominant. Due to shortening of T1 relaxation time T1 signal in the liver parenchyma increases. Presence of concomitant fat is diagnosed as signal drop on opposed phase images. Homogeneous or heterogeneous, the commonest variant of adenoma seen in GSD is the β-catenin-mutated. This variant shows variable T1 and T2 signal and appears as a homogeneous or heterogeneous hypervascular mass with persistent or nonpersistent enhancement during the delayed-phase images. hence it may be difficult to distinguish from malignant transformation. Treatment: In general, no specific treatment exists to cure glycogen storage diseases (GSDs). In some cases, diet therapy is helpful. This may reduce liver size, prevent hypoglycemia, allow for reduction in symptoms, and allow for growth and development.

Wilsons disease

Wilson’s disease, also called hepatolenticular degeneration, is an autosomal recessive inherited disorder of copper metabolism. Mutation in the copper transporting enzyme leads to excessive absorption of copper from the gastrointestinal tract, abnormal urinary excretion of copper and decreased levels of ceruloplasmin, which is the serum protein to which 95% of body copper is bound. Accumulation then occurs in other organs, including the basal ganglia, renal tubules, cornea, bones, joints and parathyroid glands. This excessive copper gets deposited in hepatocytes until all binding sites are used, after which unbound copper causes oxidative damage. Accumulation of unbound copper then occurs in other organs, like the basal ganglia, cornea, bones, joints, renal tubules and parathyroid glands. Clinical presentation Age of disease onset is variable, occurring as early as 5 years to as late as 40 years of age. The presentation may vary depending on type of mutation and degree of dysfunction of copper-transporting adenosine triphosphatase. Those with completely nonfunctioning enzyme usually present in childhood or early adolescence with signs and symptoms including fatigue, hepatosplenomegaly, variceal bleeding, ascites, and encephalopathy. Patients may also present with acute fulminant hepatic failure. Neurologic symptoms usually occur later, in early adulthood after cirrhosis is present. Symptoms in patients with subclinical hepatic involvement include asymmetric tremor, ataxia, speech disturbance, personality changes, and Parkinson-like symptoms including decreased movement and facial expression. Green to brown deposits in the cornea are known as Kayser–Fleischer rings, the presence of which is a diagnostic finding in 98% untreated cases. 1. Lab investigations 95% cases show low serum ceruloplasmin concentration (100 pg/day) can be useful in diagnosis and treatment monitoring. 3. Liver aspartate transaminase, although nonspecific, is also elevated early in the disease. Pathology Copper initially accumulates in the cytoplasm, followed by lysosomes. Morphologic abnormalities of the mitochondria are also seen. Liver biopsy specimens show fat droplets, nuclear glycogen deposits, and cellular necrosis. Eventually, fibrosis, loss of hepatic architecture, and cirrhotic changes are seen.

Imaging (Table 9.10.25) USG USG can show contour irregularity and nodules associated with Wilson’s disease. The macro nodules are predominantly hypoechoic. Some series report a unique feature of a normal caudate to right lobe ratio (15.5 cm at the midclavicular line. GB wall oedema, periportal hypodensity often seen but are nonspecific Heterogeneous enhancement of liver in arterial phases CT CT findings in hepatitis are usually nonspecific. On nonenhanced CT Hepatomegaly is seen with possible decrease in hepatic attenuation. Gallbladder wall thickening and hepatic periportal hypodensity are important CT findings in acute viral hepatitis, but are nonspecific. These findings have also been reported in patients with AIDS, trauma, neoplasm, liver transplants, liver transplant rejection and congestive heart failure. Heterogeneous enhancement of liver in arterial phases has been described in the icteric phase. Periportal/hepatoduodenal lymphadenopathy is commonly seen. If chronic hepatitis and cirrhosis develops multiple regenerative nodules may be seen, and the liver becomes smaller and nodular with time as fibrosis increases. These nodules give rise to the macronodular pattern of postnecrotic cirrhosis. MRI On MRI, acute hepatitis shows nonspecific findings such as hepatomegaly with heterogeneous signal intensity on T2-weighted sequences, and a heterogeneous pattern of enhancement on arterial-phase of dynamic study (Fig. 9.10.31). Hyperenhacement can persist into venous and delayed phases. Periportal oedema can be seen as high signal on T2W1 images. Gall bladder wall oedema is also well seen (Fig. 9.10.32).

FIG. 9.10.31 MR in Acute hepatitis. T2W1 axial images (A) showing hepatomegaly with heterogeneous hyperintensity. Postcontrast arterial phase (B) showing heterogeneous enhancement.

FIG. 9.10.32 MRI in acute hepatitis showing hepatomegaly with periportal cuffing (arrows in B). Gall bladder wall oedema is seen (arrows in C). Mild perihepatic fluid is seen (arrows in D). Note patient is a known case of pancreatitis with walled-off necrosis in body (blue arrow in B).

Gaucher’s disease This is an inherited metabolic disorder in which deficiency of lysosomal enzyme β-glucocerebrosidase causes accumulation of Gaucher cells within multiple organs, usually the liver, spleen, and bone marrow. Phenotypic presentation of Gaucher disease with three classically described types. • Chronic, non-neuronopathic form (type 1), manifesting with prominent involvement of the reticuloendothelial system with liver, spleen, and marrow involvement, • Acute neuronopathic (type 2) • Subacute–chronic neuronopathic (type 3) Type 1 Gaucher disease is most often diagnosed in childhood or early adulthood. Hepatic involvement and Imaging in Gaucher’s disease. Hepatosplenomegaly is a hallmark of Gaucher disease and uniformly present beginning in childhood. Liver disease is a major contributor to Gaucher disease-related mortality. There is increased risk for liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) in this condition, especially in previously splenectomized individuals, although this is rare. Other important clinical manifestations of Gaucher disease include hematologic abnormalities such as anaemia and hyperferritinemia. Imaging Hepatosplenomegaly is seen. Ultrasound shows multiple tiny hypoechoic lesions distributed diffusely which represent accumulations of Gaucher’s cells. On CT these focal accumulations of Gaucher cells are hypoattenuating and appear hypointense on T1-weighted imaging, and heterogeneous on T2-weighted imaging. In an appropriate clinical setting these do not warrant biopsy (Fig. 9.10.33).

FIG. 9.10.33 Gaucher’s cell infiltration. Contrast-enhanced CT (arterial (A), portal venous (B) and venous phase C–E) in a 10-year male with known Gaucher’s disease showing illdefined hypodense lesion in segment 6/7 of liver (blue arrow) representing infiltration with Gaucher’s cells. Vessels are seen coursing through the abnormality (orange arrow) with attenuation in calibre and resultant atrophy. Others similar non confluent patches are seen in

left lobe (yellow arrows). Gross splenomegaly is seen. Hyperferritinemia in patients with Gaucher’s manifests as increase in iron deposition and appears as increased attenuation on CT, signal drop-out on out-of-phase gradient T1-weighted MRI and low signal on T2*-weighted MRI. Liver stiffness may be only mildly elevated in Gaucher disease patients without cirrhosis, and can be quantified with elastography.

Nodular changes to nodular diseases Nodular diseases affecting the liver parenchyma primarily include those associated with cirrhosis and Budd Chiari syndrome and have been discussed in separate chapters. Other diseases that cause nodular infiltrative pattern include sarcoidosis, haematological malignancies like lymphoma, leukaemia and metastatic disease. Infective diffuse nodular processes are discussed in chapter on hepatic infections.

Sarcoidosis This is a multisystemic inflammatory disease characterized by the formation of noncaseating granulomas and accumulation of inflammatory cells. lungs and lymphoid system are the most commonly affected organs. Hepatic affection is seen in 50%–65%. Elevated alkaline phosphatase is seen in 15% patients with liver involvement. portal hypertension, cirrhosis and chronic cholestatic disease are rare but can be seen.

Imaging USG shows hepatomegaly with multiple tiny hypoechoic lesions distributed diffusely in both lobes. The most common hepatic abnormality seen is hepatomegaly. Associated splenomegaly or adenopathy near the hilum or coeliac regions can be seen. Only 5%–15% of patients with hepatic sarcoidosis show nodular lesions in the liver on CT and/or MRI ranging from 1 mm to several centimetres. Nodular mildly enhancing lesions ranging in size from 1 mm to several cm can be seen on CT or MRI in 5%–15% cases. These may coalesce into larger lesions. Usually, intact hepatic vasculature can be seen penetrating through these lesions. Such nodular lesions are hypodense on CT and generally lowsignal intensity on both T2-weighted and gadolinium-enhanced T1weighted images of MRI.

Sarcoid can involve the intra or extrahepatic biliary tree intrahepatic involvement is granulomatous and produces cholestatic and primary biliary cirrhosis like picture. enlarged portal nodes may produce cholestasis.

Lymphoma/leukaemia Liver involvement in Systemic haematological malignancies is usually in the form of enlargement. Sometimes tiny discrete hypoattenuating nodules maybe seen throughout the parenchyma. These may reveal enhancement in venous phase. Associated splenomegaly and lymphadenopathy maybe seen (Fig. 9.10.34).

FIG. 9.10.34 CT in leukaemic infiltration. Unenhanced and contrastenhanced CT shows hepatomegaly with coarse architecture secondary to infiltration. Associated marked splenomegaly is also seen.

Langerhans cell histiocytosis Liver involvement in children with multisystem LHC is known to be high with reported incidence values from 19% to 60%.

Liver involvement manifests as hepatomegaly with multiple hypodense nodules (Fig. 9.10.35). Biliary involvement can be seen resembling primary sclerosing cholangitis with irregular biliary dilatation. Presentation with anaemia, pancytopenia, associated pulmonary, osseous involvement aid in diagnosis (Fig. 9.10.36).

FIG. 9.10.35 Histiocytosis. Contrastenhanced CT (A–D) in a 2-year-old boy showing gross hepatosplenomegaly with multiple tiny nodules diffusely distributed in liver (arrows). Lung window image (E) shows ground glass attenuation in right lower lobe. Bone window (F) shows lyticlesion in left iliac bone (arrow).

FIG. 9.10.36 Histiocytosis. Contrastenhanced CT of the abdomen in a 10-year-old boy shows hepatomegaly with multiple hypodense nodules in both lobes. HRCT window shows multiple cysts (arrows). Lytic lesions are seen in skull bone, mandible and petrous bone (arrows). Other diffuse liver diseases like infiltrative metastasis have been discussed in chapter in focal liver lesions, while hepatic tuberculosis has been elaborated in chapter on infections.

Conclusion Imaging particularly MR with recent advances has changed the face of diagnosis of diffuse liver diseases. The emphasis has shifted from biopsy in most settings to applications of MRI in qualification and quantification of important disorders such as fact and iron deposition. Pattern recognition on imaging provides vital clues as to the diagnosis and can help guide further management.

Diffuse liver diseases-approach Diffuse liver disease – what should a radiologist report Liver size – enlarged, shrunken Contour – smooth, irregular Density – hyper/hypodense T1 signal – hyper/hypo/isointense T2 signal – hyper/hypo/isointense Nodules – present/absent Enhancement – homogenous/heterogenous Vascularity of nodules – hyper/hypovascular

Associated findings –splenomegaly, lymphadenopathy, biliary dilatation Findings on special sequences – chemical shift, multi-echo, MRS, R2 T2 etc. TABLE 9.10.27 Disorders Causing Low Hepatic Attenuation • Fatty liver • Steatohepatitis • Amyloidosis • Radiation-induced hepatitis TABLE 9.10.28 Disorders Causing High Hepatic Attenuation • Haemochromatosis • Glycogen storage disorders • Wilsons disease • Amiodarone toxicity TABLE 9.10.29 Homogenous Hepatomegaly • Hepatitis • Gaucher’s disease • Haematological malignancies • Metabolic disorders TABLE 9.10.30 Nodular Infiltrative Diseases • Cirrhosis • Budd Chiari syndrome • Sarcoidosis • Haematological malignancies • Infiltrative metastasis

TABLE 9.10.31 Disorders Causing Lobulated Hepatic Contour • Cirrhosis • Budd Chiari syndrome • Pseudo cirrhosis of liver TABLE 9.10.32 Hypervascular Diffuse Nodular Disorders • HCC • Diffuse hypervascular metastasis • Nodular regenerating hyperplasia TABLE 9.10.33 Hypovascular Diffuse Nodular Diseases • Multiple regenerative nodules • diffuse hypovascular metastasis • multiple myeloma • lymphoma, leukaemia • Sarcoidosis • Langerhans cell histiocytosis

9.11: Focal liver lesions Ritu K. Kashikar, Shrinivas B. Desai, Pooja Punjani Vyas, Nilesh Doctor, Vivek Shetty

Modalities in diagnosis of focal liver lesions Owing to advances in technology, focal liver lesions (FLLs) are increasingly encountered. Imaging particularly computed tomography (CT) and magnetic resonance imaging (MRI) play a vital role in diagnosis and characterization of FLL, thus avoiding unnecessary biopsies and interventions. Multiphase CT accurately diagnosis most liver lesions. Better soft tissue contrast and lack of ionizing radiation makes MRI a preferred modality in diagnosing FLLs. MRI with or without contrast for characterization of liver lesions regardless of preexisting liver disease has been assigned the highest rating as per American College of Radiology Appropriateness Criteria (Table 9.11.1).

TABLE 9.11.1 Classification of Focal Liver Lesions BENIGN Solid lesions of epithelial origin • FNH • HCA Solid lesions of nonepithelial origin • Cavernous haemangioma • AML • Solitary fibrous tumour Pitfalls • Focal fat • THID Cystic liver lesion Developmental cyst • Hepatic cyst • Polycystic liver disease • Biliary hamartoma • Caroli’s disease Infective cyst • Amoebic abscess • Pyogenic abscess • Hydatid cyst Miscellaneous • Pseudocyst • Haematoma • Biloma MALIGNANT Tmours of hepatocellular origin • HCC • Fibrolamellar carcinoma

• Cholangiocarcinoma Tumours of nonepithelial origin • Epithelioid haemangioendothelioma • Angiosarcoma • Primary hepatic lymphoma • PEComa Malignant cystic lesion • Biliary cystadenoma/carcinoma • Undifferentiated embryonal rhabdomyosarcoma • Cystic HCC • Cystic metastasis Hepatic metastasis • Hypervascular metastasis • Hypovascular metastasis • Cystic metastasis • Diffuse liver metastasis

Imaging protocol USG Ultrasound is often the initial modality for diagnosis and also the incidental detection of FLLs. Limitations to USG include the detection of small lesions less than 2 cm in size, particularly in patients who are cirrhotic or undergoing chemotherapy. Characterization of FLLs, involvement of crucial structures such as blood vessels, local staging and decisions such as operability are also not accurate with ultrasound alone and require confirmation with CT/MRI. The liver typically images in supine and left lateral positions. A curvilinear transducer with a frequency of 1.5 Hz is used. The subcostal diagonal, subcostal longitudinal or sagittal and transverse right intercostal lateral views are used. Right lobe of liver is imaged through an intercostal approach when the patient is taking deep inspiration. Subcostal view is used to image the three hepatic veins in one view. Transverse, longitudinal and oblique views of the liver are taken to image all the segments of liver. Colour and power Doppler have increased sensitivity for FLL detection, but sensitivity is still inferior to contrast-enhanced CT and MRI.

The introduction of microbubble contrast agents (CAs) and the development of contrast-specific techniques have opened new perspectives in ultrasound of the liver. The technique is based on a new class of intravascular microbubble agents which contain perfluoro gases instead of air. This when combined with scanning modes sensitive to harmonic responses of microbubbles enable tissue signal suppression.

CT The advent of the multislice technique and isotropic voxel have improved the spatial resolution of CT, allowing the recognition of small FLLs in difficult areas. Multislice CT has a sensitivity and specificity in the diagnosis of malignant FLLs of 63% and 64%, and 92 and 97%, respectively. Contrast media administration with dose based on the patient’s weight (approximately 600 mg iodine/kg of bodyweight), an iodine content of 350–400 mg/mL and a high injection rate of 4–5 mL/s are imperative to attain good contrast enhancement. Region of interest in the abdominal aorta and a threshold of 100 HU allows correct timing for threshold. A delay of approximately 18 s after the threshold provides the first arterial phase, allowing detection of hypervascular FLLs such as hepatocellular carcinoma (HCC). The late arterial phase is obtained approximately 10 s after the early arterial phase and shows progressive enhancement of hypervascular lesions, improving detection rate, while the optimal hepatic enhancement in the portal phase is reached approximately 50–60 s after the threshold. Portal venous thrombi are also best detected in this phase. The venous phase aids in the detection of washout, hepatic venous thrombosis. Delayed phase is often required in lesions such as cholangiocarcinoma and haemangioma, which show progressive enhancement (Table 9.11.2, Fig. 9.11.1). TABLE 9.11.2 CT Protocol Phase Plain Early arterial Late arterial Portal venous Venous Delayed

Timing 18 s 30 s 50–60 s 2 min 4–5 min

FIG. 9.11.1 Multiphase CT of liver showing plain, early arterial, late arterial, portal venous and hepatic venous phase. Note maximum enhancement of the liver parenchyma in the portal venous phase. Delayed phase images are required for tumours such as cholangiocarcinoma and large haemangiomas, which reveal delayed enhancement.

MRI As mentioned previously, MRI is the modality of choice in diagnosis of FLLs. Most FLLs appear hyperintense on T2W1 images with varying intensity depending upon the water content and flow dynamics. FLLs are typically hypointense on T1W1 images with the exception of fat containing, haemorrhagic lesions and those containing chelates of metals like regenerating/dysplastic nodules. In- and opposed-phase images help in detection of intralesional fat. Diffusion-weighted images are beneficial particularly in noncirrhotic population and best suited in detection of metastasis. Postcontrast images obtained with extracellular agents are parallel to those obtained with CT (Fig. 9.11.2). The pre- and postcontrast MRI protocol is mentioned in Table 9.11.3.

FIG. 9.11.2 Precontrast and postcontrast MRI protocol. The precontrast protocol includes T2W1, T1 in- and opposed-phase, diffusionweighted imaging (DWI), T2W1 fat suppressed (FS) and 3D T1 gradient-recalled echo (GRE) and 3D magnetic resonance cholangiopancreatography (MRCP), if needed. The postcontrast phase is parallel to that of CT. Note delayed phase showing excreted contrast in the biliary tree and gallbladder is obtained when using a hepatocyte-specific agent.

TABLE 9.11.3 MRI Protocol Precontrast images

T2-weighted single-shot fast spin-echo (SE) T1-weighted in- and opposed-phase GRE DWI T2-weighted FS fast SE 3D T1-weighted FS spoiled GRE T2-weighted MRCP (optional)

Postcontrast images

Dynamic 3D T1-weighted FS spoiled GRE (in hepatic arterial, portal venous and equilibrium phases) Delayed hepatocyte phase (if applicable)

MR contrast agents There are two main categories of CAs used in liver imaging – the extracellular and the hepatocyte-specific (Fig. 9.11.3). Extracellular agents are more widely used and provide information similar to contrast-enhanced CT study. The advantage of the other category of CAs, that is, hepatocyte-specific agents, is the ability to provide this extracellular information with added benefit of delayed phase information. Tumours of hepatocellular origin with functioning hepatocytes take up and biliary excretion with take up and retain these agents appearing isointense to background liver. Lesions without functioning hepatocytes fail to retain contrast and hence appear hypointense to background liver on delayed phase. This allows better detection and characterization of focal liver lesion particularly those lesser than 2 cm (Table 9.11.4).

FIG. 9.11.3 Grey scale USG showing hyperechoic haemangiomas in liver with posterior acoustic enhancement. TABLE 9.11.4 Imaging Pearls • Grey scale USG has limitations in diagnosis of FLLs, particularly small lesions in setting of cirrhosis. Contrastenhanced USG improves specificity. • Multislice CT has a high specificity and sensitivity in diagnosis of FLL. • MRI particularly with advent of hepatocyte-specific agents is the best modality in detection and diagnosis of FLL.

Benign focal liver lesions 1. Haemangioma Haemangioma is the most common benign hepatic tumour. The incidence in general population varies from 1% to 20%. Females have a higher preponderance with variable female to male ratios of 2:1 to 5:1. Imaging in particular MRI has high reliability in diagnosing classic haemangioma. The sensitivity and specificity of MRI is greater than 90% in diagnosis.

Aetiology The aetiology of haemangioma is unknown. Since haemangiomas are known to run in families, a genetic origin has been implicated, while other mesenchymal tumours are thought to be congenital.

Presentation

Most patients are asymptomatic and often the lesion is discovered as an incidental finding. Pain in the right upper abdomen is the most common complaint; others include loss of appetite, nausea, vomiting and abdominal discomfort. Symptoms are usually seen in large haemangiomas or those with complications. Liver function tests and tumour markers like AFP and CA19.9 are within normal limits.

Histology Blood-filled cavities of varying sizes lined by flat endothelial cells and supported by fibrous connective tissue are seen on histology. Three histological subtypes have been described: the capillary haemangioma, the cavernous haemangioma and the sclerosing haemangioma.

Imaging The imaging features of a haemangioma depend on its size; typical haemangiomas are mostly less than 3 cm in diameter.

USG Haemangiomas are hyperechogenic, homogeneous lesion presenting a posterior acoustic enhancement (Fig. 9.11.3). The hyperechogenicity of haemangiomas is related to the interfaces between vascular spaces, fibrous stroma and the slow blood flow. Typically, haemangiomas have slow flow and hence do not show vascularity on colour or power Doppler. The sensitivity and specificity of ultrasound in differentiating haemangioma from other malignant lesions are high, with values of approximately 94.1% and 80%, respectively, for lesions less than 3 cm in diameter. Unlike HCC, no flow is seen on colour Doppler. A peripheral echogenic rim around hypoechoic lesions can suggest haemangioma. On the contrary, perilesional hypoechoic rim called the target sign is seen in lesions such as metastasis (Table 9.11.5). TABLE 9.11.5 Hyperechoic Lesion on USG • Adenoma • HCC • Metastasis

Adenomas can be distinguished on the basis of the absence of posterior acoustic enhancement and characteristic pattern of peripheral vascularity seen in adenoma. Another differential diagnosis to be considered is focal nodular hyperplasia (FNH), which has the characteristic ‘spoke-wheel sign’.

Contrast-enhanced USG Contrast-enhanced ultrasound (CEUS) improves specificity for the diagnosis of haemangioma. The vascularity pattern with contrastenhanced USG is similar to that seen with CT. The typical hemangioma (HH) shows peripheral nodular enhancement in the arterial phase with complete (but sometimes incomplete) centripetal filling in the portal venous and late phases. This particular pattern of enhancement helps in differentiating haemangiomas from other lesions like adenomas, FNH, HCC or metastasis. This characteristic enhancement pattern has a sensitivity of 98% for histologically proven HH. One should be aware that an HH can rarely have a centrifugal enhancement. CT Computed tomographic (CT) findings consist of a hypoattenuating lesion on nonenhanced images. Haemangiomas show peripheral discontinuous nodular enhancement on arterial phase of dynamic contrast-enhanced CT. The density of the nodules is equivalent to that of the aorta. Centripetal filling with is seen on venous phase, which progresses to uniform enhancement. The enhancement persists on delayed phase (Fig. 9.11.4).

FIG. 9.11.4 CT in haemangioma. Contrastenhanced CT in arterial, portal venous and delayed phases showing two haemangiomas in the same patient in segments 6 and 3. Both show peripheral nodular discontinuous enhancement in arterial phase with density paralleling that of aorta ( arrows in A and D). Gradual centripetal filling-in is seen subsequently ( arrows in C, F and G). Note the larger haemangioma does not fill-in completely, a feature common in slightly larger haemangiomas. Washout of contrast on delayed phase is not seen in haemangioma and if seen, alternate diagnosis must be considered. This classical pattern of enhancement cannot be highlighted in very small lesions of less than 5 mm, which can be difficult to characterize. In patients with severe fatty infiltration of the liver, HH can appear hyperdense relative to the adjacent liver parenchyma on nonenhanced scan.

MR

Haemangiomas are hyperintense on T2-weighted images, which is identical to that of cerebrospinal fluid. T2 hyperintense signal is classically described as ‘light bulb bright’. Malignant lesions of the liver do not appear as bright on T2W1 images. They appear hypointense to adjacent liver on T1-weighted images. Long relaxation T2W1 images further improve accuracy in diagnosis of haemangiomas and help in differentiation from metastasis. Haemangiomas, unlike other liver lesions retain hyperintense signal on long relaxation T2W1 images. A threshold of 112 ms has 92% accuracy, 96% sensitivity and 87% specificity for differentiating haemangiomas from metastasis. On gadolinium administration, the enhancement pattern is similar to that seen with iodinated contrast on CT. Classic enhancement pattern in combination with characteristic T2 appearance are diagnostic for haemangioma (Fig. 9.11.5).

FIG. 9.11.5 (A) T2WI axial images showing a well-defined hyperintense (light bulb) lesion in segment 8 of the liver ( arrow in A). The lesion retains signal on long echo images ( arrow in B) suggestive of slow flow. (C and D) Postcontrast images showing peripheral nodular enhancement in arterial phase ( arrow in C) and subsequent centripetal filling ( arrow in D). Certain pitfalls exist in diagnosing haemangiomas using gadoxetate disodium. Due to the lack of hepatocytes, haemangiomas appear hypointense to the background liver on delayed hepatocyte phase and mimicking malignant process (Table 9.11.6).

TABLE 9.11.6 Imaging Pearls – Hemangioma 1. Imaging appearance of haemangiomas depends on size 2. Classic haemangioma is hyperechoic on USG and shows peripheral discontinuous nodular enhancement on both CT and MRI with centripetal filling-in 3. Long echo T2 images show persistent hyperintense signal and help in differentiating from other pathologies 4. Larger haemangiomas may show central T2 hyperintense scar corresponding to an area of necrosis which does not enhance on delayed phase 5. Haemangiomas do not show peripheral washout while the central portion fills in Lesions shown peripheral nodular arterial enhancement (Table 9.11.7): 1. Haemangiomas 2. ICC 3. Atypical HCC TABLE 9.11.7 Distinguishing Features Between Hemangioma vs Malignant Tumors with Peripheral Enhancement Haemangiomas No peripheral waashout on delayed Peripheral enhancement discontinuous, nodular and equal to aorta

Malignant Tumours With Peripheral Enhancement Peripheral washout sign on delayed phase Enhancement is more heterogeneous and disorderly and not equivalent to aorta

FDG-PET On fluorodeoxyglucose-positron emission tomography (FDGPET)/CT, most hepatic haemangiomas appear lowattenuation lesions with FDG avidity equal to background liver parenchyma and are easily determined to be benign. However, a small percentage of haemangiomas may be FDG-avid. If an FDG-avid hepatic lesion demonstrates the characteristic enhancement pattern, this is consistent with an FDG-avid haemangioma.

Technetium-99m pertechnetate-labelled red blood cell scintigraphy has high specificity in the diagnosis of haemangiomas. In this technique, there is decreased activity in haemangiomas on early images and increased activity on delayed blood pool images. Therefore, radionuclide scintigraphy has a sensitivity of 78% and an accuracy of 80% and may be a valuable tool when the diagnosis cannot be achieved with other imaging modalities. Atypical haemangiomas 1. Giant haemangiomas Large haemangiomas are often heterogeneous with internal clefts and septae. They are termed as giant haemangiomas when they exceed 4 cm in diameter. Discrepancies are there in definition with some authors defining giant haemangiomas as lesions greater than 6 cm or 12 cm in diameter. These may cause symptoms of abdominal pain and distension. These haemangiomas demonstrate changes such as haemorrhage, thrombosis, extensive hyalinization, liquefaction and fibrosis. The central cleft-like area may be due to cystic degeneration or liquefaction. Imaging. On USG, they reveal heterogeneous echotexture. They are hypoattenuating and heterogeneous on nonenhanced CT with central areas of low attenuation. After intravenous administration of contrast material, the typical early, peripheral and globular enhancement is observed. These may show irregular or ‘flameshaped’ discontinuous peripheral enhancement as opposed to typical nodular enhancement pattern seen in smaller haemangiomas. Although centripetal pattern of enhancement is seen during the venous and delayed phases, the fillingin incomplete. Central scars are defined in this subset of haemangiomas (Fig. 9.11.6).

FIG. 9.11.6 Giant haemangiomas. (A to D) Postcontrast images showing well-defined lesion with peripheral nodular arterial enhancement and centripetal filling ( arrow in A). There is, however, failure to completely fillin with no enhancement of the central scar ( arrow in C and D). This pattern is usually seen in giant haemangiomas. At MRI, T2-weighted images show a markedly hyperintense cleftlike area and some hypointense internal septa within a hyperintense mass. On delayed phase, incomplete filling and central scar are seen similar to CT (Fig. 9.11.7).

FIG. 9.11.7 Haemangioma with scar. (A to E) Precontrast MRI images showing a well-defined T2 hyperintense lesion with central necrosis in segment 6 ( arrows in B and C). Note diffusion restriction in the lesion without ADC drop ( arrows in D and E). (F to J) Postcontrast images showing centripetal enhancement pattern with filling of the lesion on delayed phase with the exception of the central scar ( arrows). Complications include intratumoural haemorrhage, inflammatory changes or consumptive coagulopathy (Kasabach– Merritt syndrome). These may warrant management such as arterial embolization or resection. 2. Rapidly filling (flash) haemangiomas

This pattern is seen 16% of all haemangiomas, and is seen more often in small haemangiomas (42% of haemangiomas) 30%) and a risk of malignant transformation (5%–10%). The highest predilection for malignant transformation of all HCAs is seen in β-catenin activated subtype. Pathology Gross features On gross appearance, adenomas are well-circumscribed often encapsulated lesions with size varying between 1 and 30 cm. Lesions may be solitary or multifocal. They typically arise in nonfibrotic liver, however, the inflammatory subtype has been reported in the background of cirrhosis The cut surface of HA may be tan-yellow or red-brown depending upon the presence of steatosis or peliosis/haemorrhage/old haemorrhage, respectively. Microscopy Sheets of benign-appearing hepatocytes with interspersed thinwalled, unpaired arteries are classically seen in HCA. Other variable features are steatosis, inflammatory cell infiltrate, sinusoidal dilatation, myxoid changes and presence of pigments such as bile pigment, lipofuscin or Dubin–Johnson-like pigment (Table 9.11.14). TABLE 9.11.14 Fat-Containing Liver Lesions – D/D Benign • Adenomas • Agiomyolipomas • Lipomas

Imaging in HCA

Malignant • HCC • Metastases from liposarcomas, teratomas, ovarian dermoids, Wilms tumors and certain renal cell carcinoma

Usg The typical small HCA is isoechoic in comparison to the surrounding liver parenchyma. Adenomas with high lipid content are hyperechoic on ultrasound. Intratumoural haemorrhage can also result in increased echogenicity and heterogeneity, or cystic areas. Calcifications are seen as hyperechoic foci with acoustic shadowing. Peripheral peritumoural vessels and intratumoural vessels with a flat continuous or triphasic form are seen on colour Doppler. FNH does not show this pattern of vascularity and hence this finding may be useful in distinguishing the two disease entities. On contrast-enhanced USG, arterial phase reveals centripetal or diffuse enhancement. Telangiectatic HCA with or without inflammation typically exhibit iso- or hyperenhancement in comparison to the surrounding liver parenchyma. Hypoenhancement is seen in portal venous phase with delayed washout in all subtypes. USG and contrast-enhanced USG features of histologic subtypes have been described. HNF-1α-inactivated HCAs are hyperechoic due to fat content and may be misdiagnosed as haemangiomas. The enhancement pattern is however that of arterial enhancement. With venous washout in contrast to haemangiomas which show portal venous hyperenhancement. On CEUS, telangiectatic HCA with or without inflammatory changes shows central multilocular vessel supply similar to FNH. These lesions might show centrifugal hyperenhancement during the early arterial phase which may persist on portal venous phase. Nevertheless, most adenomas are not specifically diagnosed at US and are usually further evaluated with CT or MRI. CT Multiphase CT is a good diagnostic modality in diagnosis of HCA. Fat or haemorrhage can easily be identified on unenhanced images. CT evidence of fat within the adenoma is seen in only about 10% of cases. Lesions show strong arterial enhancement and subcapsular feeding vessels. Enhancement is more heterogeneous in larger tumours and those with internal haemorrhage. The enhancement usually does not persist in adenomas because of arteriovenous shunting (Fig. 9.11.15).

FIG. 9.11.15 Hepatic adenoma CT. (A) CT abdomen in plain, (B to D) arterial, venous and parenchymal phases showing well-defined arterial enhancing lesion in segments 2 and 3 ( arrow in A) with delayed washout. Note: There is marked fatty infiltration of the background liver, hence the lesion appears hyperdense on plain and delayed phases. MR MRI is the modality of choice in diagnosis of adenomas and distinguishing various subtypes. Although the lesions can reveal varying signal on T1W1 images, recent reports have suggested that most adenomas are bright on T1-weighted images, 77% of cases in a study by Paulson et al. Other studies have, however, lesser incidence of T1 hyperintensity varying from 35% to 59%. Heterogeneous signal on TW1 images may be due to areas of increased signal intensity resulting from fat (36%–77% of cases in different series) and haemorrhage (52%–93%). Forty-seven to seventy-four per cent of HCAs are predominantly hyperintense relative to liver on T2weighted images (Fig. 9.11.16). Majority of lesions are, however, heterogeneous owing to areas of haemorrhage and necrosis. Contrast-enhanced dynamic MR study shows early enhancement with peripheral subcapsular vessels.

FIG. 9.11.16 Hepatic adenoma. (A) T2WI images showing large well-defined hyperintense lesion with central heterogeneity. (B) The lesion is mildly hyperintense on T1WI images. (C and D) In- and opposed-phase images revealed signal drop in opposed-phase suggestive of intralesion fat (arrows). (E) The lesion reveals heterogeneous enhancement in arterial phase with peripheral subcapsular vessels (arrows). (G) On delayed phase, the lesion is hypo- to isointense to the background liver. No obvious pseudocapsule is seen. MR appearances can vary depending on the histological subtype (Table 9.11.15).

TABLE 9.11.15 MRI Features of Adenoma Subtypes Adenoma MRI Features Subtype Inflammatory 1. Hyperintense on T2 2. Focal fat +/– 3. Hypervascular mass with persistent enhancement during dynamic evaluation and may show a variable uptake in the hepatobiliary phase specially at the periphery 4. Atoll sign – peripheral hyperintensity may be seen on T2 HNF alphamutated

β-Cateninmutated HCAs

1. Significant intralesional fat is characteristic 2. Less hypervascular than inflammatory 3. Hypointense on delayed phase with heterogeneity 1. Heterogeneously hyperintense and hypointense on precontrast T2 and T1W1 images, respectively 2. Homogeneous or heterogeneous hypervascular mass with persistent or nonpersistent enhancement during the delayed phase

Characterization of HCA subtypes with MRI 1. Inflammatory On plain MRI, inflammatory HCA is often hyperintense on T2W images and hypointense on T1W sequence corresponding to areas of sinusoidal dilatation and inflammatory infiltrates. Foci of fat appear as areas of signal drop on opposed-phase images. They are hypervascular masses with persistent enhancement on dynamic study. Variable update of contrast especially at the periphery may be seen on hepatobiliary phase. Marked T2 hyperintense signal with persistent delayed enhancement has high sensitivity and specificity of 85% and 87%, respectively, for the diagnosis of inflammatory subtype. Peripheral hyperintensity on T2W1 images reflects the abnormal ductal reaction with altered biliary excretion and has been described as ‘atoll sign’ (Fig. 9.11.17).

FIG. 9.11.17 Adenoma with atoll sign. T2WI axial image showing an inflammatory adenoma with atoll sign. Note: Isointensity of the centre of lesion on T2WI images (red arrow) with hyperintense signal band in the periphery resembling an atoll (blue arrow). 2. Hnf alpha-mutated HNF-1α-mutated HCA has areas of fat deposition and shows significant signal drops on out-phased in comparison with inphased sequences. Significant signal drop on T1 out-phase imaging has sensitivity, specificity, positive predictive and negative predictive values of 85%, 100%, 10% and 94%, respectively. On T2W images, the lesion tends to appear as iso- or hypointense nodule without significant restriction on DWI (Fig. 9.11.18). Complicated adenomas or adenomas containing different tissues may however show restriction. ADC maps may appear nonspecific, with values between 0.9 and 1.3.

FIG. 9.11.18 HNF alpha-mutated adenoma. (A and B) T2W1 images showing an ill-defined mixed signal intensity lesion in segment 7 (arrows). (C and D) TIW1 in- and opposedphase images showing signal drop in the lesion suggesting intralesional fat (arrows). The lesion shows mild diffuse enhancement with washout on delayed phase (arrows). On dynamic evaluation using hepatocyte specific agents, HNF1α-mutated HCA appears hypervascular with variable degrees, and tends to be hypointense on portal venous and hepatobiliary phase with homogeneous appearance. 3. β-catenin-mutated HCAs

β-catenin-mutated HCAs are heterogeneously hyperintense and hypointense on T2W1 and T1W1 images and appear as homogeneous or heterogeneous hypervascular lesions with persistent or nonpersistent enhancement during the delayed phase images. Malignant transformation leads to lesions mimicking HCCs without additional peculiar features. Unclassified HCAs Presence of haemorrhage is one the most important reasons justifying categorization into the unclassified group. No specific features have been defined for this subtype (Table 9.11.16). TABLE 9.11.16 Imaging Pearls – Hepatic Adenoma • HA is a less common benign neoplasm seen in association with OC pills and anabolic steroids • Three distinct types based on genetic and pathologic differences, which may show different features on MRI • Presence of haemorrhage and fat with slight hypointensity on delayed phase helps in differentiating from FNH. Distinguishing from HCC may be difficult. Epidemiological, setting of liver disease may help. Differential diagnosis of HCA Differential diagnosis includes lesions which show arterial phase hyperenhancement like HCC and FNH (Tables 9.11.17 and 9.11.18). In view of higher propensity for haemorrhage differential would also include other lesions/causes of nontraumatic haemorrhage (Table 9.11.19).

TABLE 9.11.17 Differentiating Features Between Adenoma and HCC Adenoma Does not usually occur in setting of cirrhosis Association with OC pills, anabolic steroid Arterial enhancement + Contain intralesional fat Characteristic peripheral vascularity May or may not washout No associated vascular thrombus

HCC Clinical setting of cirrhosis No association with OC pills Arterial enhancement + Intralesional fat seen in up to 40% Classic neovascularity Portal venous/delayed washout Associated with malignant thrombus

TABLE 9.11.18 Differentiaitng Features Between Adenoma and FNH Adenoma FNH Association with OC pills Nonstrong evidence of association with OC pills Intralesional fat, Intralesional fat, haemorrhage not haemorrhage common common Central scar not common Central scar common and when present is usually due to haemorrhage Scar usually represents Scar shows delayed enhancement area of necrosis and does not enhance on delayed phase Adenomas reveal FNH also shows intense arterial moderate arterial enhancement enhancement Adenomas usually appear FNH typically fade to isointensity to slightly hypointense on the background liver with the delayed phase using exception of the central scar on hepatobiliary specific CAs delayed phase using hepatobiliary specific CAs

TABLE 9.11.19 D/D Nontraumatic Haemorrhagic Liver Lesions HCC

This is often seen in large peripheral HCCs that bulge exophytically into the abdominal cavity without overlying normal liver parenchyma. Adenoma Haemorrhage seen in lesions >5 cm in size. FNH Haemorrhagic FNH is rare and may manifest as isolated subcapsular or intraparenchymal haemorrhage. Diagnosis is usually not achievable preoperatively. Haemangioma Rare, seen in giant haemangiomas. Metastasis Metastasis from tumours like lung, pancreas, stomach, kidney, breast, prostate, testicle, gallbladder, skin (melanoma) and nasopharynx, and from choriocarcinoma can rupture leading to haemoperitoneum. HELLP haemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). This catastrophic obstetric condition progresses rapidly with complications such as disseminated intravascular coagulation, hepatic necrosis and haemorrhagic infarction. Subcapsular haematoma and hepatic rupture with intraperitoneal bleeding can occur as a consequence of the haemorrhage. Management The risk factors for malignant transformation in HCA are male sex (6–10 times more common), size more than 5 cm, androgen use and β-catenin subtype. HCCs arising from an HCA are typically well differentiated with a normal serum alpha-fetoprotein (AFP) level and have good prognosis. 1. All males with HCAs should undergo resection irrespective of size. 2. Females with HCA 20% increase in diameter), resection is advised as the risk of rupture with haemorrhage is high. 4. In women with a lesion >5 cm or symptomatic HCAs, surgical resection is appropriate. Discontinuing hormonal treatment and observing for regression in size for 6 months is also an option.

5. In patients with multiple HCAs, only those >5 cm in size need to be resected. 6. RFA is an option for those with growing residual tumours if the size is 3–4 cm. 7. Bleeding from a ruptured HCA can be initially managed with transarterial embolization of the feeding vessel. This may even cause the tumour to regress.

Angiomyolipoma Angiomyolipoma (AML) is a benign tumour composed of smooth muscle, fat and thick-walled blood vessels. It rarely occurs in the liver. Most lesions occur sporadically and about 6%– 10% occur in the setting of tuberous sclerosis. AMLs in the setting of tuberous sclerosis are multiple, associated with bilateral renal AMLs and are seen in 13% of patients with the disorder. Hepatic AML (HAML) is more likely to occur in women. HAML is often misdiagnosed as HCC with a frequency of more than 50% due to significant overlap of the imaging features. Histology and gross appearance AMLs are defined with smooth muscle cell (SMC) positivity for the immunohistochemical stain HMB-45. Perivascular epithelioid cell (PEC) is a term proposed to describe the SMCs found in HAML, which are always positive for HMB-45, and has been postulated as the underlying neoplastic mesenchymal cell. HAML can range in size from 0.1 cm to greater than 36 cm. They are usually solitary, although multiple lesions have been reported particularly in patients with tuberous sclerosis. HAMLs are well circumscribed but not encapsulated. The cut surface is soft, yellow to tan or grey in colour, and may show areas of haemorrhage and necrosis. The surrounding liver parenchyma is not cirrhotic or fibrotic. HAMLs are classified on the basis of the line of differentiation and the predominant tissue component. The most common type of HAML is the mixed lipomatous type, where the tumour is composed of at least 70% adipose tissue. The myomatous type has as much as 10% adipose tissue; there are also lipomatous and angiomatous types composed predominately of adipose and vascular structures, respectively. Each of these types has a heterogeneous mix of the three types of cells, the most important being the SMCs. Line of differentiation and predominant tissue component are the basis for classification of HAML. The mixed lipomatous type is the most common type with adipose tissue comprising 70% of tumour. Approximately 10% adipose tissue is seen in myomatous

type. Lipomatous and angiomatous subtypes are seen composed predominantly of adipose and vascular tissues, respectively. All the subtypes comprise an amalgamation of the three cell types, most importantly SMCs. Preoperative diagnosis is based on the identification of the following three components: 1. Hypervascular on imaging 2. Fatty component on CT, MRI and US 3. Positive actin and HMB-45 stains on biopsy specimen

Imaging US On USG, a well-defined predominantly hyperechoic mass is seen owing to the presence of intralesional fat. Increased vascularity within the lesions may also contribute of hyperechogenicity. Lesions with larger percentage of smooth muscle component may show hypoechoic appearance with heterogeneity. Intralesional aneurysms may be seen. Colour Doppler sonography shows punctiform or filiform vascular distribution pattern if the tumour has predominance of angiomatous tissue. Homogenous hyperenhancement in the arterial phase and prolonged enhancement in the portal venous phase have been described as classical enhancement pattern by Li et al. CT On unenhanced CT, these lesions appear as well-defined hypoattenuating lesions due to the presence of intralesional fat. The density of the fat component is less than 20 HU (Fig. 9.11.19). Typical heterogeneous enhancement is seen. Those with predominant angiomatous or myxomatous component may not show significant intralesional fat and impose a diagnostic challenge. Contrast-enhanced dynamic CT shows enhancement in arterial phase which persists in the portal phase, and, occasionally, delayed washout depending on the component of the tumour tissue. Early draining hepatic veins and intratumoural vessels can be the helpful features for distinguishing AML from HCC, with high specificity but low sensitivity. These lesions typically do not show a peripheral capsule or pseudocapsule.

FIG. 9.11.19 Angiomyolipoma of liver. Plain CT abdomen showing a large fat density lesion in right lobe with thin intralesional septae (arrows). Another small lesion is seen in segment 3 biopsy confirmed HAML. MR Signal intensity on T1-weighted sequences depends on the amount and distribution of fat. Lesions with predominant fat component are hyperintense on T1W1 images, while rest of components contribute to heterogeneity. Suppression of signal can be seen in fat saturated sequences. On T2-weighted sequences, HAMLs are homogeneously or heterogeneously hyperintense. Tubular or curvilinear structures with high signal intensity on T2W TSE and low signal intensity on T1W1 images may be detected in mixed and angiomatous types, representing vessels with slow blood flow (Table 9.11.20).

TABLE 9.11.20 Imaging Pearls AML • Benign tumour composed of smooth muscle, fat and thickwalled blood vessels • 6% to 10% occur in patients with tuberous sclerosis • Usually been misdiagnosed as HCC with a frequency of more than 50% due to significant overlap of the imaging features • Lipomatous, myxomatous and angiomatous types • Fat component seen on imaging in 70% • Persistent enhancement several minutes after injection of extracellular CAs on MRI is a feature used to distinguish these from HCC With gadolinium, most HAMLs demonstrate hyperenhancement during the arterial phase and may be hyperintense, isointense or hypointense during the portal venous and delayed phases. Persistent enhancement several minutes after injection of extracellular CAs is a feature used to distinguish these from HCC (Table 9.11.21). In contrast, when evaluated using gadoxetic acid, AML shows hypointensity during the delayed phase, hence MRI using hepatobiliary specific agents may be confusing in distinguishing the two entities. TABLE 9.11.21 Angiomyolipoma D/D Angiomyolipoma Although 6% to 10% occur in patients with tuberous sclerosis Most reveal intralesional macroscopic fat Early draining veins have been reported Can show persistent enhancement several minutes after injection of extracellular CAs

HCC Occurs in the setting of chronic liver disease Fat may be seen Feature not seen at imaging Usually show hypointensity on delayed phase using extracellular agents

Management Variability in the imaging appearance of AML almost always necessitates biopsy for histological confirmation. Histologic diagnosis is based on the identification of the various components. Once the diagnosis is established, lesions 5 cm, an aggressive approach with

surgical resection is advised as the risk of malignant transformation is high.

Solitary fibrous tumour This is a rare benign hepatic neoplasm and is similar to tumours arising from the pleura and mediastinum. The tumour occurs in adults with female to male ratio of 2:1. The lesion is usually associated with good prognosis. Large size, cellular pleomorphism, atypia, high mitotic activity and central necrosis may however suggest malignant change. Presentation Patients present with abdominal pain, distension, fatigue weight loss or gastrointestinal obstruction. These are due to tumourrelated mass effect. Hypoglycemia has also been reported. Pathology Oval spindle cells separated by abundant thick bands of collagen are seen. Immunohistochemistry showing positivity of CD34 is important in distinguishing from other spindle cell tumours. Lack of reactivity for other markers such as S100, CD117 and CD31 further helps to confirm the diagnosis of solitary fibrous tumour. The presence of mitotic figures is associated with but not predictive of aggressive clinical behaviour.

Imaging These lesions are mildly hyperechoic on sonography. They appear as a heterogeneous mass with irregular central enhancement during the portal venous phase on contrast-enhanced CT. Solitary fibrous tumour is hypointense on T1-weighted sequences, variably hypointense or hyperintense on T2-weighted sequences and demonstrates heterogeneous enhancement, which may be avid and progressive. Treatment Solid fibrotic tumours are considered benign and are usually asymptomatic. Yet, in nearly half of the cases, patients also have an associated extrahepatic malignancy involving the gastrointestinal system, especially colonic cancer, and small foci of metastasis may be observed. Therefore, if there is uncertainty in imaging resection seems is justified.

Focal fat

It is common in the medial segment of the left lobe of the liver, adjacent to the falciform ligament, central tip of segment IV, along with the gallbladder and can be multifocal. Focal fat deposition in the liver may mimic a mass lesion. Common locations include segment IV of the liver, adjacent to the falciform ligament and central tip of segment IV, along with the gallbladder. Multifocality can be seen. Imaging On USG, focal fat appears as echogenic areas showing geographic pattern. Hepatic vasculature seen coursing through these areas. It is hypodense to liver on noncontrast-enhanced CT with difference in density persisting on contrast study (Fig. 9.11.20).

FIG. 9.11.20 Focal fatty infiltration. (A to C) CT abdomen obtained in plain, arterial and venous phases showing a hypodense area with geographic pattern involving left lobe of the liver ( arrow in A). Note: The hepatic vasculature is seen coursing through this area without displacement ( arrows in B and C). Focal fat areas are usually well-defined wedge-shaped. Iso- to hyperintense signal on in-phase images followed by homogeneous signal drop on opposed phase is highly diagnostic. The lesions may appear hypointense to liver on portal venous phase of dynamic study. Areas appear isointense to liver subsequently. Focal fat is discussed in detail in chapter 9.10 on diffuse liver diseases.

Transient hepatic attenuation difference

Transient hepatic attenuation difference (THAD) is an attenuation difference of the liver appearing during bolus-enhanced dynamic study not corresponding to mass. It may or may not be tumour related and can be classified into lobar, segmental, diffuse and polymorphous types depending on the morphology (Fig. 9.11.21).

FIG. 9.11.21 Vascular dynamics in THAD. THAD appears as an area of increased enhancement in hepatic arterial phase that returns to isoenhancement on portal venous phase. Presence of THAD should prompt investigation of aetiology, as it may be encountered in a battery of benign and malignant conditions that alter vascular dynamics (Fig. 9.11.22).

FIG. 9.11.22A Lobar THAD in a patient with left portal vein thrombosis. CT abdomen obtained in (A) arterial, (B) late arterial and (C and D) parenchymal phases showing a wedgeshaped arterial enhancing area involving the left lobe with normal vasculature coursing through it ( arrows in A and B). This area then subsequently appears isodense to the background liver. Note: Thrombus in the left portal vein ( arrow in D).

FIG. 9.11.22B Polymorphous THAD in a patient with acute cholecystitis. (A and B) Patchy areas of hyperenhancement in segments 4b and 5 of the liver around the inflamed gallbladder in arterial phase becoming isodense to liver in venous phase.

Benign cystic liver lesions Cystic lesions of the liver can be classified as developmental, neoplastic, inflammatory or miscellaneous. USG and MRI outscore CT in characterization of cystic lesions. Hepatic cyst These are benign developmental lesions that do not communicate with the biliary tree. Seen more often in women and are

asymptomatic. Usually multiple but can sometimes be solitary. Histology True hepatic cysts contain serous fluid and are lined by a nearly imperceptible wall consisting of cuboidal epithelium, and a thin underlying rim of fibrous stroma. There is no communication with the biliary tree. Presentation Simple liver cysts are usually asymptomatic. Symptoms may arise in larger cysts. This occurs in 15%–16% of patients with HCs. Imaging USG On USG, these appear as well-defined anechoic lesions with posterior acoustic enhancement. No mural nodule or vascularity is seen (Fig. 9.11.23).

FIG. 9.11.23 Grey scale USG showing simple cyst in liver. Well-defined hypoechoic lesion with posterior acoustic enhancement. CT These are round or ovoid hypodense, well-defined lesions, with smooth thin imperceptible walls (Fig. 9.11.24). Cysts are of homogeneous density without enhancement of its wall or content. Lack of mural nodularity, wall calcification or fluid– debris levels. Septa are usually absent. CT has a sensitivity of greater than 90% for HC and gives more detailed information about gas contents and calcification within the cyst.

FIG. 9.11.24 Simple cyst. Unenhanced and enhanced CT images showing a well-defined hypodense cystic lesion with exophytic extension in segment 5 (arrows). Note the lesion has imperceptible walls with no enhancing septae. MRI Simple cysts appear homogeneously hypointense on T1-weighted images and reveal very high signal intensity on T2-weighted images. The signal is isointense to fluid on all pulse sequences. Hyperintense signal on heavily T2-weighted images, helps in differentiating them from solid lesions like metastasis (Fig. 9.11.25). No restricted diffusion or enhancement is seen.

FIG. 9.11.25 MRI showing simple cyst. (A and B) T2W1 and long echo T2W1 images showing well-defined hyperintense lesion in segment 2 (arrows), appearing hypointense on T1W1 images and showing thin peripheral wall enhancement ( arrow in D).

Septated/haemorrhagic simple cyst Simple cysts may sometimes contain up to two septae in contrast to complex cysts, which are multiseptated (Table 9.11.22). Haemorrhage has been reported in simple cysts and results in the development of a complex cystic lesion, which may be indistinguishable from a cystic tumour. These cysts may require treatment in the form of marsupialization.

TABLE 9.11.22 Imaging Features of Simple Versus Complex Cysts Simple • Thin, smooth walls • May contain up to two septae

Complex • Septated • Mural irregularity or nodularity • Debris • Calcification • Fluid levels

Polycystic liver disease This is a congenital disorder that can be seen in association with autosomal dominant polycystic kidney disease (ADPKD), although the two conditions may not always coexist. It is caused by the maldevelopment of ductal plate that affects small intrahepatic biliary radicals. It can be associated with other disorders of ductal plate such as Caroli’s disease. The liver is usually significantly enlarged with diffuse, multiple innumerable cysts of varying sizes. Adjacent organ compression can occur due to hepatomegaly related mass effect.

Histology There are two types of cysts: 1. Intrahepatic – they are lined by cuboidal biliary epithelium and contain serous fluid. 2. Peribiliary – arise from peribiliary gland and usually arise at puberty and may increase in size during adulthood.

Presentation Majority of patients are asymptomatic. Massive hepatomegaly, complications occur in a minority. Common complications include haemorrhage, rupture or super infection.

FIG. 9.11.26 Septated liver cyst. (A) CT abdomen arterial and (B and C) venous phases showing hypodense cystic lesion in segment 5 with thin internal septae without nodularity. Imaging Multiple coalescent cysts distributed throughout the liver. Cysts may sometimes give multilocular appearance. Like simple cysts, they follow density/signal intensity of CSF. The cystic wall is very thin and regular without enhancement (Fig. 9.11.27). Increased attenuation at nonenhanced CT or hyperintensity at T1W1 may suggest haemorrhage or infection. Calcifications in the cyst wall indicate prior haemorrhage or infection.

FIG. 9.11.27 (A to E) Nonenhanced CT images in a patient with autosomal dominant kidney disease show innumerable hypodense cysts of varying sizes in both lobes of liver (arrows). Few of the cysts are seen coalescing in one another (yellow arrow). Patient also with multiple cysts in both kidneys (blue arrows).

Ciliated hepatic foregut cyst Wheeler and Edmondson first used the term ciliated hepatic foregut cysts (CHFC) in the year 1984. It is an uncommon benign solitary cyst with histological similarity to bronchogenic and oesophageal duplication cyst, pathology. Origin from abnormal budding of the embryologic foregut has been suggested. The cysts are lined with pseudostratified, ciliated, mucin secreting columnar epithelium with smooth muscle in the cyst wall and an outer fibrous capsule. Gross appearance and demographics CHFC is found within or in close proximity to the medial left hepatic lobe (segment 4), with characteristic subcapsular location. It is typically unilocular with an average size of 3.6 cm (range of 1.1–13 cm). Most cases are diagnosed in the fifth or sixth decade, with a slight male predominance (1.1:1 ratio). Clinical presentation Most are asymptomatic and discovered incidentally. They can become infected or large enough to compress adjacent organs. Obstructive jaundice and portal hypertension due to mass effect on

the biliary tree and portal vein have been reported with large CHFC. Malignant transformation is another rare complication. Imaging CT The cyst fluid is often complicate and denser than simple fluid leading to difficulty in diagnosis on CT. Features may sometimes mimic a necrotic or hypovascular mass. MRI MRI better demonstrates their cystic nature and proteinaceous fluid content. They are well defined, T2 hyperintense, and mostly unilocular lesions. Variable protein concentration may cause T1 signal to range from hypointense to hyperintense. Rarely, they may be associated with a fluid–fluid level. Contrast-enhanced images easily confirm their cystic nature by demonstrating only thin wall enhancement. D/D CHFCs should be diagnosed on the basis of their classic subcapsular location in the medial segment of the left hepatic lobe. Important differentials include simple or complicated (infected or haemorrhagic) cysts and biliary cystadenomas. Classic subcapsular location in the medial segment of the left hepatic lobe aids in diagnosis (Table 9.11.23). TABLE 9.11.23 Imaging Pearls – Ciliated Foregut Cyst • Uncommon solitary benign hepatic cyst • Cyst lined by a pseudostratified, ciliated, mucin-secreting, columnar epithelium • Obstructive jaundice, portal hypertension, malignant transformation have been reported • Hypodense lesion on CT. May be hyperintense on T1W1 images depending on protein content • Their classic subcapsular location in the medial segment of the left hepatic lobe is characteristic Treatment Symptomatic or large lesions should be excised. However, owing to reports of malignant transformation there has been suggestion for excision/enucleation of lesions regardless of size.

Biliary hamartomas These are benign liver lesions that result from ductal plate malformations involving the small interlobular bile ducts. They are also known as von Meyenburg complexes, multiple bile duct hamartomas or biliary microhamartomas. They originate from embryonic bile ducts that fail to involute and are considered as the spectrum of ductal plate anomaly (fibropolycystic disease) where only the smallest bile ducts are involved. Usually seen as incidental findings at imaging, these lesions are of no clinical significance. Pathology They consist of focally disordered collections of bile ducts surrounded by abundant fibrous stroma that do not communicate with the biliary tree. They appear as few to numerous small (10 mm) may appear hypoechoic or anechoic and comet tail artefact may be seen. The comet tail is a reverberation artefact when reflective objects are interrogated. CT On CT, these appear as multiple hypoattenuating hepatic nodules with cystic density scattered throughout both the lobes of the liver. The sizes are variable and are typically less than 1 cm in diameter. Can be distinguished from simple hepatic cysts by their relatively irregular outlines and smaller sizes. Majority of these do not show postcontrast enhancement and few show peripheral or homogeneous enhancement. MRI Biliary hamartomas appear hypointense on T1-weighted images and strongly hyperintense on T2-weighted images. On heavily T2weighted images, the signal intensity increases further and against a background of dark liver parenchyma, this appearance is described as ‘starry sky appearance’. They have lobulated margins, thin septations and a characteristic thin rim of enhancement due to adjacent compressed liver parenchyma and inflammation. At MR cholangiography, they appear as multiple tiny cystic lesions that do not communicate with the biliary tree. (Fig. 9.11.28).

FIG. 9.11.28 MRI showing biliary hamartoma. Heavily T2WI images ( arrows in A to C) showing multiple tiny T2 hyperintense lesions in both lobes of liver not communicating with the biliary tree. Presence of a 1-mm to 2-mm ‘mural nodule’ may be seen within at least one lesion owing to adjoining septae increases diagnostic specificity of biliary duct hamartoma (BDH). Overall, these cyst wall features may help in the differentiation from simple cysts (Table 9.11.24). Lack of restricted diffusion helps distinguish them from microabscesses. TABLE 9.11.24 Differentiation Between Biliary Hamartomas and Simple Cyst

Lesions larger than 2 cm are referred to as giant BDH. Larger lesions >10 cm in size have been reported with complications such as haemorrhage and right upper quadrant pain. These may mimic other complex neoplastic cystic lesions such as biliary cystadenomas. Clue to diagnosis includes coexistence of other smaller hamartomas in the liver and lesser degrees of intralesional complexity when compared with cystadenoma.

Caroli’s disease

Caroli’s disease is an autosomal recessive congenital abnormality characterized by saccular dilatation of the intrahepatic bile ducts. It belongs to the spectrum of fibropolycystic liver disease with malformation of the ductal plate. Associations include fibrocystic anomalies of the kidneys such as medullary sponge kidney, ADPKD and autosomal recessive polycystic kidney disease (ARPKD). Two forms of Caroli’s disease are the pure simple form (type 1) and complex form (type 2) (Table 9.11.25). TABLE 9.11.25 Caroli’s Disease and Syndrome Pure or simple form (type 1), also called Caroli’s disease Complex form or periportal type (type 2) called Caroli’s syndrome

Where only the larger bile ducts are affected. Also called as Caroli’s syndrome, which is associated with other ductal plate abnormalities, such as hepatic fibrosis.

Clinical symptoms are usually seen in childhood and adolescence and depend on the form of Caroli’s disease. The commoner complex type presents with portal hypertension due to hepatic fibrosis. The rarer simple type presents with recurrent cholangitis, that is, attacks of pain in right hypochondrium, fever and rarely jaundice. The liver involvement can be diffuse, lobar or segmental. It usually presents in childhood and about 75% of affected patients are boys. This disease has a high risk of malignant transformation to cholangiocarcinoma and hence requires close follow-up by imaging studies. US On USG, the lesion appears as a cystic lesion, which communicates with the bile duct and is separate from the gallbladder. Associated extrahepatic ductal dilatation is seen in 50% of the cases. Intraluminal bulbar protrusions of the wall resulting in irregularity of the bile duct wall can be seen. Portal venous radicles partially or completely surrounded by dilated bile ducts can be seen. A specific sign for cystadenoma is the central dot sign. This sign signifies the presence of a central colour-filled portal venous radicals either in close proximity of or within a dilated biliary radical. CT On CT, Caroli’s disease appears as hypodense dilated cystic structures of varying sizes that communicate with the biliary tree with segmental or diffuse distribution. The ‘central dot’ sign is

seen, similar to USG and is seen as tiny dots of contrast enhancement within the dilated intrahepatic bile ducts, which represent the intraluminal portal vein radicals. Multiple intraluminal biliary calculi may be seen. MRI Dilated and cystic intrahepatic biliary radicles which are hypointense on T1-weighted images and hyperintense on T2weighted images are seen. Enhancement of the intraluminal portal vein radicals with MRI equivalent ‘central dot’ sign is seen on postcontrast T1-weighted images (Fig. 9.11.29).

FIG. 9.11.29 MRI in Caroli’s disease. (A to E) T2W1 axial and coronal images in case of Caroli’s disease showing cystic dilatation of intrahepatic biliary radicals (red arrows). Note extensive hepatolithiasis (white arrows). This patient also had medullary sponge disease of the kidneys ( blue arrow in E) showing ectatic tubules. MRCP shows saccular, dilated and nonobstructed intrahepatic bile ducts that communicate with the biliary tree. Cholangiography

Cholangiography allows direct imaging of the biliary tree and shows saccular, cystic or fusiform dilatations of radicals communicating with the biliary tree. Calculi may appear as filling defects. Complications These are the result of biliary stagnation leading to cholangitis, stone formation and liver abscess. In patients with Caroli’s syndrome, portal hypertension and haematemesis may be seen due to ruptured oesophageal varices. Biliary obstruction can lead to secondary biliary cirrhosis. Cholangiocarcinoma can occur as a complication with reported prevalence of 7% (Table 9.11.26). TABLE 9.11.26 Complications of Caroli’s Disease • Cholangitis • Stone formation • Liver abscess • Portal hypertension leading to oesophageal varices • Cholangiocarcinoma D/D These include primary sclerosing cholangitis and recurrent pyogenic cholangitis (RPC). Primary sclerosing cholangitis is characterized by multiple irregular strictures of the intra- and extrahepatic bile ducts, nonsaccular biliary dilatation, beading lobulated hepatic contours and caudate hypertrophy. Nonsaccular biliary radical dilatation is seen in RPC. In addition, patients with RPC show central dilatation with peripheral tapering and dilatation both proximal and distal to stones (Table 9.11.27).

TABLE 9.11.27 D/D Caroli’s Disease Primary Sclerosing Cholangitis Saccular Dilatation not dilatation saccular Intrahepatic Affects intraradicals and extrahepatic biliary trees with strictures, beading Central dot Caudate lobe sign enlargement Carolis

Liver fibrosis

Lobulated hepatic contours, may progress to cirrhosis

Recurrent Pyogenic Cholangitis Dilatation not saccular Both intra- and extrahepatic trees. Intrahepatic ducts usually show central dilatation with sudden tapering toward the periphery. Affects left lateral and right posterior segments more commonly Stones formation ++

Malignant liver lesions Classification of malignant liver lesions based on cell of origin has been discussed previously in Table 9.11.1. Malignant lesions can also be classified on the basis of vascularity (Table 9.11.28). TABLE 9.11.28 Classification of Malignant Hepatic Lesions According to Vascularity

HCC in cirrhosis HCC is one of the most common cancers worldwide, accounting for 85%–90% of all primary liver cancers. It is also the third leading cause of cancer-related mortality globally. The development of HCC

is related to chronic liver inflammation that leads to fibrosis and cirrhosis. Incidence and epidemiology The most common worldwide aetiological cause of HCC is hepatitis B infection, followed by hepatitis C. Alcohol is the third leading cause of HCC worldwide. Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the United States and has implicated in causation of HCC. In India, 80% of all HCCs occur in the setting of cirrhosis of which 60% of cases are hepatitis B carriers. The approximate number of cases per year in India is 22,000. The disease shows a bimodal peak, one at 40 to 55 years of age and other above 60 years. Aetiology wise hepatitis B is the most cause accounting for 70%– 80% of cases, while 15% of cases are related to hepatitis C and 5% to both hepatitis B and C. Approximately 8% of cases are alcohol related and no aetiology is known in 10%. Some geographical areas may be predisposed to iron overload and aflatoxin as an aetiological factor. The prevalence of NAFLD in India ranges from 9% to 32%. The incidence of NAFLD-induced cirrhosis and HCC is currently lower in India than in the West, but on an upward trend (Table 9.11.29). TABLE 9.11.29 HCC – Aetiology in India • 70%–80% – related to the hepatitis B virus • 15% – related to hepatitis C • 5% – both HBV and HCV • 8% alcohol • NAFLD • Iron overload and aflatoxin in some regions Epidemiology and clinical features The common age of presentation (median) is around 52 years. Disease is seen in children below 14 years of age and above 60 years in adults, peaking around 45 to 55 years. HCCs occurring in the age group below 14 years are usually in hepatitis B positive. Male to female ratio of 5:1 has been reported. Ninety per cent of patients are symptomatic at diagnosis. Duration of symptoms is usually ranges from 5 months to almost a year. Presenting symptoms may include weakness, anorexia, abdominal pain, weight loss or with ascites, jaundice and gastrointestinal bleeding. Ascites

is seen in about 60% of patients at presentation. Sometimes fever, leukocytosis and recurrent hypoglycemia occur as a paraneoplastic syndrome. Fifty per cent of patients are in hepatic decompensation at presentation. Haematemesis and melena occur in 25% of patients. Biochemistry The majority of patients are anaemic with a mean haemoglobin of 10.8 g/dL (5.1 to 15.2 g/dL). Serum bilirubin may be elevated. Albumin can be mildly or moderately depressed. About 55%, 39% and 33% patients have raised AST, ALT and SAP, respectively. Serum AFP has a sensitivity of 39%–65%, specificity of 76%–94% and a positive predictive value of 9%–50%. The normal value of AFP is around 10–20 ng/mL. The European Association for the Study of the Liver (EASL) has suggested AFP level greater than 400 ng/mL as diagnostic for HCC. Values as high as this are, however, seen in only 46% of patients and normal values are seen in approximately 20% of cases. Des carboxy gamma globulin (PIVKA – protein induced in vitamin K absence). Des-γ-carboxy prothrombin (DCP) is a prothrombin precursor produced in HCC. Due to the deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, γ-carboxylated glutamic acid (Gla) residues are incompletely carboxylated, leaving some Glu residues. These precursors with Glu residues are called DCPs.. DCP is a specific marker for HCC and elevated levels are found in 44%– 81% of cases. High level of DCP has been considered to be associated with large tumour and recurrence of HCC. Association between an elevated DCP level and worse tumour behaviour has been established. Hepatocarcinogenesis This occurs in preneoplastic and neoplastic phases (Flowcharts 9.11.1 and 9.11.2). 1. Preneoplastic phase: Years or decades before cirrhosis. Epigenetic mutations are seen without structural changes with phenotypically normal cells. 2. Neoplastic phase: Aberrant cells undergo chromosomal alterations and acquire atypical phenotypic features.

FLOWCHART 9.11.1 Preneoplastic phase HCC.

FLOWCHART 9.11.2 Neoplastic phase HCC. Pathologic changes during hepatocarcinogenesis Multistep carcinogenesis The process of carcinogenesis involves evolution of a cirrhotic nodule into HCC. This involves changes at cellular, vascular and molecular levels. A. Cellular changes. At the cellular level, the less differentiated subnodules expand within the well-differentiated parent nodules and eventually replace them. These subsequently grow into HCCs (Flowchart 9.11.3).

FLOWCHART 9.11.3 Cellular changes. B. Vascular changes. The vascular changes involve decrease in density of portal triads with increase in density of unpaired paired arteries as a nodule progresses toward HCC. An established HCC shows classic arterial hypervascularity compared to background liver (Flowchart 9.11.4).

FLOWCHART 9.11.4 Vascular changes.

C. Molecular changes. The expression of organic anionic transporting polypeptides (OATP) diminishes progressively as nodule progresses to HCC. Low OATP expression is seen in both early and progressed HCCs, highgrade dysplastic and some low-grade dysplastic nodules (Flowchart 9.11.5).

FLOWCHART 9.11.5 Molecular changes. Summary of multistep carcinogenesis This is expressed in diagrams below(Flowchart 9.11.6).

FLOWCHART 9.11.6 Hepatic nodules Nodules seen in cirrhotic nodule include cirrhosis-associated regenerative nodule, dysplastic nodule, early and progressed HCCs. Cirrhotic nodule Cirrhosis-associated regenerative nodules are multiple well-defined rounded regions of the cirrhotic parenchyma surrounded by scar tissue and typically measuring 1–15 mm in diameter. These contain phenotypically normal cells and are considered benign. They can however mutate to dysplastic nodules. Dysplastic nodule These are nodules usually 1–1.5 cm in size showing different microand macroscopic features when compared with background liver. Dysplastic nodules are classified as low grade or high grade, depending on the presence of cytologic and architectural atypia. Low-grade dysplastic nodules show neither cytologic atypia nor architectural alterations beyond those seen in

cirrhotic nodules. Unlike regenerating nodules, unpaired arteries are however seen. High-grade dysplastic nodules show features of cellular atypia and architectural alterations (Tables 9.11.30 and 9.11.31). TABLE 9.11.30 Low-Grade Dysplastic Nodules • Hepatocytes show no cytologic atypia • Neither expansile subnodules nor architectural alterations beyond those of cirrhotic nodules • They however contain unpaired arteries and clone-like populations (aggregates of cells with greater copper, iron or fat accumulation than background liver) TABLE 9.11.31 High-Grade Dysplastic Nodules • Cells show cellular atypia, although the atypia is insufficient to establish a diagnosis of HCC • Architectural alterations • Expansile subnodules • High risk of malignant transformation Early HCC These are usually 1–1.5 cm in diameter and rarely more than 2 cm in size. Early HCCs are slowly growing lesions that replace rather than destroy or displace adjacent portal tracts or central veins. On histology, small well-differentiated cells resembling highgrade dysplastic nodules are seen in early HCC The key histological feature that distinguishes them from dysplastic nodule is the presence of stromal invasion. Vascular invasion is however not present. These nodules progress to overt HCC, the rate of progression is however variable. Progressed HCC These show features of vascular invasion and have the ability to metastasize. Also known as small progressed HCC and small distinctly nodular HCCs are progressed HCCs smaller than 2 cm in size with nodular well-defined margins. They grow by compressing and expanding into the adjacent liver. These consist of moderately differentiated cells and show a tumour capsule and

internal fibrous septae. The remaining 20% consist of both welldifferentiated and moderately differentiated components. Large HCCs are defined as those greater than 2 cm in diameter. These have a higher histological grade, aggressive biology and a high propensity for vascular invasion and metastasis. A characteristic feature seen is mosaic architecture which is defined as presence of multiple tumoural nodules separated by septae and areas of haemorrhage and necrosis. Multifocal HCC Multifocal HCC is seen in one-third of cases and is defined by the presence of tumour nodules separated by nonneoplastic parenchyma. Synchronous development of multiple tumours or intrahepatic metastasis may be the reason for multifocality. The prognosis of patients with multifocal HCC due to intrahepatic metastasis tends to be worse than in those with multicentric development of independent tumours. Other pathological features (Table 9.11.32): TABLE 9.11.32 Pathological Features

CN

No

Venous Drainage No

DN

No

+/–

No

Early HCC

↑

+

No

Progressed HCC

↑↑

++

Yes

Neoangiogenesis

Tumour Capsule No

1. Neoangiogenesis. This is defined as the presence of unpaired (or nontriadal) arteries and sinusoidal capillarization. Unpaired arteries are isolated arteries unaccompanied by bile ducts or portal veins. These arteries increase in size and number as nodule progresses from high-grade dysplastic nodules, early HCCs and progressed HCCs. Sinusoidal capillarization means alterations in the sinusoidal endothelium that make the sinusoids resemble systemic capillaries. The portal tracts progressively decrease as nodules progress from regenerating to dysplastic early to progressed HCC. A. Low-grade dysplastic nodule – preserved vascular profile similar to that of background cirrhotic nodules.

B. High-grade dysplastic nodules and early HCC – low portal venous flow and arterial flow. C. Progressed HCC – elevated arterial flow with reduced or absent portal venous flow. 2. Venous drainage. Regenerating, dysplastic nodules and early HCC drain into hepatic veins. As the nodules grow into progressed HCC, drainage occurs into sinusoids for lesions without fibrous capsule and subsequently into portal veins for HCC with fibrous capsule. 3. Tumour capsule and fibrous septae. Presence of tumour capsule and fibrous septae is the characteristic of progressed HCC, seen in 70% lesions. Presence of capsule is a feature of advanced HCC. Capsulated HCCs have better prognosis than HCCs of similar size and grade without capsules or with disrupted capsules. This feature is however not seen in early HCCs and hence prognosis in capsulated HCCs is worse than early uncapsulated HCC. 4. Fat content. Intranodular steatosis increases with lesion grade. Approximately 40% early HCCs are steatotic. 5. Iron content. In cirrhotic livers without diffuse iron deposition, iron may accumulate preferentially in low-grade dysplastic nodules and some high-grade dysplastic nodules. With further dedifferentiation, hepatocytes become ‘resistant’ to iron accumulation and most highgrade dysplastic nodules, early HCCs and progressed HCCs are iron free. A solid iron free nodule in a diffusely iron overloaded liver is likely dysplastic or malignant. 6. Organic anionic transporting polypeptides. These are a family of proteins expressed in hepatocytes along with the basolateral (sinusoidal) membrane and involved in transport of bile salts. The degree of OATP8 expression correlates inversely with HCC tumour grade, such that expression levels tend to be lower in higher grade than in lower grade HCCs. Staging Various staging systems are used in prognostication of HCC. In HCC patients, however, there exists a lack of consensus on how to best classify patients.

1. Tnm staging. Pathologic TNM staging of HCCs, AJCC eighth edition. Primary tumour (pT): • TX: Primary tumour cannot be assessed • T0: No evidence of primary tumour • T1: Solitary tumour ≤2 cm or >2 cm without vascular invasion • T1a: Solitary tumour ≤2 cm (with or without vascular invasion) • T1b: Solitary tumour >2 cm without vascular invasion • T2: Solitary tumour >2 cm with vascular invasion or multiple tumours, none >5 cm • T3: Multiple tumours, at least one of which is >5 cm • T4: Tumour involves a major branch of the portal vein or hepatic vein or tumour directly invades adjacent organs other than the gallbladder or tumour perforates the visceral peritoneum Regional lymph nodes (pN) (Table 9.11.33): • NX: Regional lymph nodes cannot be assessed • N0: No regional lymph node metastasis • N1: Regional lymph node metastasis • Notes: Regional lymph nodes include hilar, hepatoduodenal ligament, inferior phrenic and caval lymph nodes TABLE 9.11.33 Stage Grouping Stage IA: Stage IB: Stage II: Stage IIIA: Stage IIIB: Stage IVA: Stage IVB:

T1a T1b T2 T3 T4 Any T Any T

N0 N0 N0 N0 N0 N1 Any N

Distant metastasis (pM): • M0: No distant metastasis • M1: Distant metastasis Prefixes: • y: Preoperative radiotherapy or chemotherapy

M0 M0 M0 M0 M0 M0 M1

• r: Recurrent tumour stage Limitation – liver function is not considered. 2. Okuda staging system. The Okuda staging system incorporates both cancer-related variables and liver function–related variables to determine prognosis: • Disease involving >50% of hepatic parenchyma • Ascites • Albumin ≤3 mg/dL • Bilirubin ≥3 mg/dL These are combined into stages: • Stage A: 0 criteria • Stage B: 1–2 criteria • Stage C: 3–4 criteria Higher stages were correlated with a poorer prognosis. This system, however, has limitations in stratifying patients with early or intermediate stage disease. 3. BCLC. Barcelona clinic liver cancer (BCLC) staging uses a set of criteria to guide the management of patients with HCC. The classification takes the following variables into account: • Performance status (PS) • Child–Pugh score • Radiologic tumour extent • Tumour size • Multiple tumours • Vascular invasion • Nodal spread and extrahepatic metastases The classification system sorts patients into one of four categories: • Stage 0 (very early stage) • Asymptomatic early tumours • PS 0 • Child–Pugh A • Solitary lesion measuring 2 cm or early multifocal disease characterized by up to three lesions measuring 2 • Child–Pugh C • It is not a radiological stage, only clinical • Symptomatic treatment only

• Equivalent to Okuda stage III The BCLC system is well suited to define subset of patients with early stage disease who can benefit from curative therapies. Lack of discrimination within the broad spectrum intermediate category is a limitation. 4. Radiological staging. This staging system uses multidetector row CT (MDCT) or MRI in determining the size, number of HCCs and nodules in the liver and other features that is presence of vascular invasion and metastasis. MDCT is sensitive for detection of primary tumour (sensitivity of 71%–87%), but the sensitivity for detecting additional lesions in multifocal HCC is lower, particularly those 20 mm (100% sensitivity) and 10–20 mm (84% sensitivity), but has low sensitivity for detection of smaller lesions. • MRI with hepatocyte-specific agents (gadoxetate): Addition of MRI with gadoxetate can lead to change in staging in 14%–28% of patients, affecting management in 13%–19% of patients. Detection of additional HCC on MR with gadoxetate following MDCT results in 28% decrease in the rate of HCC recurrence and 35% decrease in overall mortality. • Due to its inability to reliably visualize the entire liver, CEUS has a limited role in HCC staging. Most important application of CEUS in staging is to detect tumour in vein (sensitivity and specificity up to 100%). LI-RADS Liver Imaging Reporting And Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting and data collection of liver imaging. In 2018, American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its HCC clinical practice guidance. LI-RADS assigns a lesion as having probability of HCC. LI-RADS version 2018 – details will be discussed in chapter on LI-RADS (Chapter 9.9). Organ Procurement and Transplantation Network (OPTN) is the unified transplantation network in the United States and runs under the administration of United Network for Organ Sharing (UNOS). OPTN classification is the part of the imaging

policy of UNOS that consists of in order to determine the eligibility and priority for liver transplantation.

FLOWCHART 9.11.7 UNOS refers to LI-RADS for the definitions of OPTN classes 1 to 4, the LI-RADS v2014 included key modifications to achieve congruence between LR-5 and OPTN class 5. The most important class of the classification is the class 5 that includes untreated and treated definitive HCCs and has several subclasses, based on the appearance and the lesion size. The subclasses are (here only size noted): • 5A: Size: 10–19 mm • 5B: Size: 20–50 mm • 5X: Size: >50 mm or tumour in vein • 5T: For treated definite HCC Radiologic T-stage The radiologic T-staging system used by LI-RADS and UNOSOPTN was developed by the American Liver Tumor Study Group. It identifies four stages (Table 9.11.34).

TABLE 9.11.34 Radiologic T-Stage Stage Description 0 No HCC 1 2 3 4

One HCC 5 cm or 2 or 3 HCCs, at least one >3 cm 4a – four or more HCCs, regardless of size 4b – HCC + tumour in vein

The tumour stage is based on tumour size, number and macrovascular invasion. Extrahepatic disease (either lymph node or metastases) does not affect the T- stage. Imaging in HCC USG USG is important not only for surveillance but also characterization of HCC. Grey scale Nodular HCC lesions appear round or roundish in shape with welldefined margins. The massive HCC lesions are irregular. Smaller lesions 20 mm, typical US patterns such as the mosaic pattern, peripheral sonolucency (halo), lateral shadows are seen (Fig. 9.11.30). The ‘lateral shadow’, is a linear US feature observed at the edge of a tumour, represents the refraction that occurs when ultrasound passes through spherical tissue and the surrounding tissue at different speeds.

FIG. 9.11.30 HCC on grey scale USG. The ‘halo sign’ corresponds to the thin fibrous capsule of the HCC and is seen as a hypoechoic rim. Small HCCs are classified by Moribana into two groups – those with halo were classified as type 1, while those without halo were classified as type 2. Type 2 lesions were further classified into subgroups 2a, 2b and 2c. The type 2a lesions are homogeneously hyperechoic and have the lowest malignancy potential according to them. Type 2b lesions are hypoechoic with a smooth margin, while type 2c lesions are hypoechoic with an irregular or unclear margin. The highest malignancy potential was seen in type 2c lesions.

Colour doppler findings Blood flow is low in nodular lesions 2 cm, basket pattern of vascularity is seen which represents a fine network of arterial vessels that surrounds the tumour nodule (Fig. 9.11.31). In massive lesions, irregular vascular patterns in addition to basket patterns are seen. A–P shunts and tumour emboli can be seen in larger nodules.

FIG. 9.11.31 Colour Doppler USG showing neovascularity in HCC. Colour Doppler image showing linear neovascular channels in HCC ( arrow in A). Note the basket pattern of vascularity around the lesion ( arrow in B).

CEUS Hyperenhancement in arterial phase is seen on CEUS similar to contrast-enhanced CT and MRI (Fig. 9.11.32). Washout in HCC tends to be late and often begins later than 90 s after injection, whereas metastases or intrahepatic cholangiocarcinomas (ICCs) usually show arterial phase hypervascularity followed by show rapid washout. The washout pattern in HCC differs on CEUS. Washout in HCC is late and often begins later than 90 s after injection. This feature contrasts that of metastasis and ICC which washout rapidly. Hence it is advocated to observe HCCs for up to 5 min following contrast administration, to avoid missing the late washout.

FIG. 9.11.32 Contrast-enhanced USG in HCC. Contrast-enhanced USG in HCC showing hyperenhancement of lesion (arrows). Large HCC may show heterogeneous arterial phase enhancement pattern due to areas of fibrosis, necrosis or internal haemorrhage.

CEUS-LI RADS by american college of radiology The American College of Radiology (ACR) has also endorsed the use of CEUS in the diagnostic work-up of HCC. CEUS will be discussed in detail in chapter on LI-RADS (Chapter 9.9).

CT/MRI (extracellular contrast agents) imaging features of hepatocellular carcinoma Contrast-enhanced CT and MRI are the accepted modalities in staging of HCC. Multiphase CT and MRI should be obtained in staging HCC using standard protocol. In case hepatobiliary specific agents are used, hepatocyte phase should be obtained. 1. Arterial enhancement

Arterial hyperenhancement is seen in 80%–90% of HCCs. Those smaller than 1.5 cm are only seen in the arterial phase (Fig. 9.11.35). About 10% to 20% of HCCs with the lack of arterialization may be hypovascular to the surrounding parenchyma on the immediate contrast-enhanced images. Large HCCs reveal more heterogeneous in enhancement (Fig. 9.11.35). 2. Washout Washout is defined as hypointensity/density in relation to the surrounding liver on portal venous or delayed phase. This sign has high specificity in diagnosis of HCC of approximately 95%–96%. Lack out of washout in an arterially enhancing lesion, however, does not exclude malignancy (Fig. 9.11.33).

FIG. 9.11.33 CT abdominal showing a welldefined arterial enhancing lesion. Washout of contrast is seen in venous phase. (C) Delayed phase images showing a ‘capsule’ around the lesion (arrow). 3. Capsule Peripheral smooth rim of hyperenhancement in the portal venous or delayed phase unequivocally thicker or more conspicuous than the rims surrounding the background nodules is defined as capsule. When present, a capsule or pseudocapsule strongly suggests a diagnosis of HCC and is often seen in large HCCs (Fig. 9.11.35). This finding is more frequently observed in the Asian population with frequency of 24%–90% versus 12%–42% of cases in the nonAsian population. The distinction between the true tumour capsule and the pseudocapsule can only be made at pathology. Transarterial chemoembolization (TACE) is reportedly more effective in HCCs with a capsule than in unencapsulated HCCs. Extracapsular extension has been shown to be a negative prognostic factor seen pathologically in 43%–77% of HCC.

As per LI-RADS nodules, 2 cm or larger in size showing arterial enhancement and capsule can be diagnosed as definite HCC even in the absence of washout appearance, while nodules 10–19 mm showing arterial hyperenhancement require presence of both washout appearance and capsule to be diagnosed as definite HCC. Peripheral enhancement in the arterial phase is not classified as capsule and is termed as corona (Fig. 9.11.34).

FIG. 9.11.34 HCC in cirrhotic liver with peripheral corona enhancement. (A) T2W1 axial image showing mildly hyperintense lesion in segment 6. Lesion shows predominantly peripheral enhancement in arterial enhancement ( arrow in B), which persists on subsequent phase. Peripheral arterial enhancement should not be misconstrued as capsule appearance.

FIG. 9.11.35 Hypovascular HCC. T2W1 axial image shows a predominantly hypointense lesion, measuring 3.5 cm in segment 2 with exophytic extension (arrows). Lesion is slightly hyperintense to liver on T1W1 images ( arrow in B). (C) No arterial enhancement is seen, which was confirmed on subtraction images. Delayed phase shows peripheral pseudocapsule ( arrow in D). Retention of lipiodol following TACE in lesion confirms malignancy ( arrow in E). Pitfalls of capsule appearance: 1. Some small ICCs show peripheral enhancement in all phases, which may be misinterpreted as a ‘capsule’. It should, however, be noted that the peripheral enhancement in ICC tends to peak in the arterial phase and diminish in later phases, rather than progress. 2. Fibrous tissue surrounding cirrhotic nodules and dysplastic nodules may show delayed enhancement and falsely diagnosed as ‘capsule’, thus, radiologists should apply this feature only if the enhancing rim unequivocally is thicker or more conspicuous than the fibrous tissue surrounding background nodules. 4. Arterial phase hyperenhancement plus washout or capsule appearance (Fig. 9.11.33) This feature is diagnostic for HCC. In patients at risk for HCC, combination of these findings has nearly a 100% specificity in diagnosis of HCC (Table 9.11.35).

TABLE 9.11.35 Major Imaging Features of HCC • Arterial enhancement • Portal venous/delayed washout • Capsule appearance • Arterial phase hyperenhancement plus washout or capsule appearance Other features of HCC Vascular invasion The incidence of vascular invasion in setting of HCC ranges from 6.5% to 48%. This finding is more common in patients with tumours that are larger or of higher grade. Involvement of the portal venous system with tumour thrombus is more common than the hepatic veins (Fig. 9.11.36). The thrombus can propagate from affected hepatic veins into the inferior vena cava (IVC) and subsequently into the right atrium (Fig. 9.11.37). Specific imaging features of vascular invasion include direct extension of a parenchymal tumour mass into an adjacent vessel and the presence of arterial enhancing neovessels within an occluded vein. Distension of the main portal vein with thrombus with diameter more than 23 mm has sensitivity and specificity of 63% and 100%. Tumour thrombus, however, can be seen in the absence of parenchymal tumour..

FIG. 9.11.36 HCC with malignant portal vein thrombus. (A and B) T2WI coronal images showing a heterogeneously hyperintense mass in segment 7 (arrows). A hyperintense thrombus is visualized in the portal vein which is distended ( blue arrows in A and B). Neovascularity of the thrombus seen in arterial phase ( arrow in C) and there is restricted diffusion within the tumour and thrombus ( arrows in E).

FIG. 9.11.37 Malignant hepatic venous and IVC thrombus. (A to C) Venous phase CT images showing thrombus with neovascularity in the middle and left hepatic veins ( arrows in C) with extension of the thrombus seen into the IVC and right atrium ( arrows in A and B). Note: Ill-defined infiltrative tumour in the left lobe. Features of malignant thrombus a) Typically seen in contiguity with or in close proximity to the primary tumour and hence shows similar imaging features as the primary tumour. b) Expands the involved vessel. c) Demonstrate T2 hyperintense signal intensity and arterial enhancement with washout, as well as restricted diffusion. Patients with tumour thrombus are typically not candidates for surgical resection or transplant. Due to high risk of liver failure and death, patients with vascular invasion are not candidates for TACE. Radioembolization with yttrium-90 can be done with fewer complications (Table 9.11.36). TABLE 9.11.36 Differentiation Between Malignant and Benign Thrombus Malignant Thrombus • Shows contiguity with tumour • Signal intensity and enhancement characteristics similar to tumour • Presence of intrathrombus neovascularity • Diffusion restriction • Causes significant expansion of vessel

Benign Thrombus • Hypodense/hypointense • No enhancement or diffusion restriction • No neovascularity • No significant vascular distension

Increased T2 signal intensity HCCs typically demonstrate mild to moderate increased signal intensity on T2-weighted sequences (Fig. 9.11.38). However, the absence of high T2 signal intensity in a lesion should not exclude HCC especially when other suggestive features are present. Although T1 hyperintensity within a cirrhotic nodule is more typical of dysplastic nodules, it can also be seen in HCCs due to the presence of fat, copper, proteins, melanin, haemorrhage and glycogen within the lesion.

FIG. 9.11.38 T2 hyperintensity in HCC. (A) T2WI images showing a well-defined minimally hyperintense lesion in segment 7 ( arrow in A). The lesion reveals restricted diffusion ( arrow in B). There is enhancement of the lesion in arterial phase with washout and capsule appearance on venous phase ( arrows in C and D). Restricted diffusion Helpful in diagnosis especially when other MRI features of HCC are present (Fig. 9.11.38). Conversely, not all HCCs demonstrate restricted diffusion. Diffusion restriction in HCC in the setting of cirrhosis may be more difficult to identify than in the cirrhotic setting. Role of diffusion in evaluation of response to therapies such as TACE and embolization is controversial. Mosaic appearance Twenty-eight to sixty-three per cent of HCCs can exhibit a mosaic appearance. This pattern is seen as heterogeneity of signal on T2W1 and postcontrast T1W1 images and is more common in larger tumours. Tumoural nodularity interspersed with fibrous septae, necrosis, haemorrhage and fatty infiltration is responsible for this appearance (Fig. 9.11.39).

FIG. 9.11.39 HCC – mosaic appearance. Arterial phase CT showing heterogeneous mosaic pattern of enhancement in large right lobar HCC with extensive neovascularity. This pattern of enhancement is always suggestive of malignant neoplasm. Contrast-enhanced CT and MRI using extracellular agents is accurate in diagnosing most HCCs. There are, however, certain disadvantages in diagnosing small, hypovascular HCCs. These are mentioned in Table 9.11.37. TABLE 9.11.37 Limitations of CT/MR With Extracellular Agents • Only those HCC with neovascularity sufficient to manifest as arterial enhancement and with washout or capsule appearance on venous or delayed phase can be unequivocally diagnosed. • About 40% HCCs do not show arterial phase hyperenhancement and cannot be diagnosed as definite HCC. • About 40%–60% small HCC may not show washout or capsule despite arterial hyperenhancement and cannot be definitely diagnosed as HCC. Diagnosis and staging of HCC with hepatobiliary agents These agents allow assessment of both intratumoural neovascularity and hepatocyte function based on the signal of lesion relative to the liver in the hepatocyte phase. The most important cause of delayed phase hypointensity is decreased expression of OATP8 leading to inability to uptake hepatobiliary agents. This feature is seen in most HCCs, including many early HCCs, and some high-grade dysplastic nodules. Nodules with preserved or elevated OATP like most low-grade dysplastic nodules,

some high-grade dysplastic nodules and only a minority of HCCs expression uptake the agents and tend to be isointense or hyperintense. The most important benefit of imaging the hepatobiliary phase is that it helps to identify early HCCs (Fig. 9.11.40). Neovascularization may be incomplete in early HCC and hence these may not appear as arterially hyperenhancing lesions. The decrease in expression of OATP8, however, precedes neoarterialization during hepatocarcinogenesis, hence early HCCs can be readily diagnosed on hepatocyte phase as hypointense nodules to the background liver (Table 9.11.38).

FIG. 9.11.40 Detection of small HCC with hepatocyte-specific agents. Contrast-enhanced MR using hepatocyte-specific agents showing small (1.2 cm) arterial enhancing nodule in segment 5 of liver appearing hypointense to background liver on hepatocyte phase with capsule appearance ( arrow in B).

TABLE 9.11.38 Hepatocyte-Specific Agents – Importance in HCC • Allows assessment not only of tumour vascularity but also of hepatocellular function. • Delayed phase hypointensity is largely due to decreased expression of OATP8. • Most HCCs, including many early HCCs, and some high-grade dysplastic nodules are hypointense in the hepatobiliary phase due to underexpression of OATP. • The most important benefit of imaging the hepatobiliary phase is that it helps to identify early HCCs, as these have incomplete neoarterialization, and may only be visible in hepatobiliary phase. Uncommon features of hepatocellular carcinoma a) Diffuse infiltrative hepatocellular carcinoma These are uncommon infiltrating lesions with poorly defined margins and usually show mild to moderate T1 hypointensity and mild to moderate T2 hyperintensity which are often heterogeneous. On the arterial phase, diffuse infiltrative HCC may appear hypovascular or demonstrate ‘patchy or miliary enhancement’ (Fig. 9.11.41). They show homogeneous or heterogeneous reticular hypointensity to the background live on portal venous and delayed phases. Tumour thrombus in portal venous system frequently complicates this variant. Hence identification of tumour thrombus in portal vein should prompt search for this neoplasm, which may be hard owing to heterogeneous permeative appearance of the lesion in background cirrhotic liver. Diffuse or infiltrating HCCs are commonly associated with marked elevation in serum AFP levels.

FIG. 9.11.41 Diffuse infiltrative HCC. (A) T2WI axial images showing ill-defined minimally hyperintense lesion occupying almost the entire right lobe of the liver. The lesion shows markedly restricted diffusion ( arrow in B). (C) Postcontrast arterial phase images revealed minimal enhancement. There is patchy enhancement in the portal venous phase with multiple tiny nodules interspersed within ( arrow in B). (E) Delayed phase images reveal hypointensity within the area compared to the background liver. These findings suggestive an infiltrative pattern of HCC with permeative type of spread. Note: The hepatic veins are coursing through this region ( arrow in D). Such features can be seen in this particular variant of HCC. b) Fatty metamorphosis HCCs may sometimes contain fat. HCCs contain intracellular lipid more often than macroscopic fat, which results in loss of signal intensity on the opposed-phase GRE T1-weighted images. The

presence of fat within a lesion more than 2 cm in size in a cirrhotic liver favours a primary HCC (Fig. 9.11.42).

FIG. 9.11.42 Fat containing HCC. (A and B) T1W1 in- and opposed-phase images showing a well-defined fat containing nodule measuring 2.1 cm in segment 8. Note: (B) Signal suppression within the lesion on opposed-phase images, confirming intralesional fat. c) Icteric HCC Invasion of HCC into the biliary radical or involvement of adjacent radicals is atypical for HCC. Such findings when present should favour the diagnosis of ICC or a mixed HCC – cholangiocarcinoma. However, biliary involvement has been reported. d) Ruptured HCC Spontaneous rupture of HCC is known and is a potential lifethreatening condition. Rapid growth of lesion and erosion into adjacent vessel may contribute. Rupture occurs in 3%–26% of all patients with HCC, with mortality rates as high as 32%–66.7%. Prognosis is poor due to hypovolemic shock, background of liver and concomitant renal failure. Patients usually present with shock, severe abdominal pain and collapse. On ultrasound, the rupture site appears as a hyperechoic area located around the tumour. Haemoperitoneum is often seen with echoes in the ascitic fluid. MDCT is usually the modality of choice. Tumours located at the periphery of the liver with protruding contour. Hyperdense areas suggestive of blood products are seen within the interstitium of the tumour on nonenhanced scan. Arterial phase images show nonenhancing low attenuating lesion with focal discontinuity. Peripheral rim enhancement may be seen

in some cases. Separation of the tumour content from the peripheral enhancing rim and intraperitoneal rupture of tumour content into the perihepatic space is termed ‘enucleation sign’ (Fig. 9.11.43). Not only ruptured tumours but also nonruptured ones may be converted to a nonenhancing low attenuating pattern. This occurs because of loss of homeostatic function within the HCC itself during hypovolaemic shock, resulting in compensatory arterial vasoconstriction and ischemic changes within HCC.

FIG. 9.11.43 Ruptured HCC. A 45–year-old cirrhotic patient with acute pain and in shock. (A) Unenhanced CT showing large mixed density exophytic mass in right lobe with linear hypodense areas within the interstitium (arrows). Note: Mixed density subcapsular fluid around the lesion and the liver (blue arrow). (B) Arterial phase images show only mild enhancement. The linear areas of rupture are well appreciated on the portal venous and venous phase appearing as hypodensities within the exophytic component (arrows).

e) Multifocal HCC HCC is multifocal in one-third cases. This is defined as presence of tumour nodules unmistakably separated by intervening nonneoplastic parenchyma. Multifocality may be due to synchronous development of multiple, independent liver tumours (multicentric hepatocarcinogenesis) or intrahepatic metastases from a primary tumour (Fig. 9.11.44).

FIG. 9.11.44 Multifocal HCC. (A and B) T2W1 showing innumerable discreet lesions in both lobes of liver in a patient with hepatitis C cirrhosis.

D/D of HCC – cirrhotic liver 1. Haemangioma: Small flash filling haemangiomas may simulate HCC, as they demonstrate early homogeneous arterial phase enhancement. If an enhancing nodular area demonstrates washout, the diagnosis of HCC is more likely. This feature coupled with threshold growth further consolidates the diagnosis. Due to fibrosis or alterations in blood flow, cavernous haemangiomas in cirrhotic livers show progressive decrease in size and more atypical imaging characteristics, including loss of the peripheral nodular enhancement. They can also be associated with adjacent capsular retraction. These may be difficult to distinguish from HCC. Prior imaging showing lesion with enhancement pattern characteristic of haemangioma may aid in diagnosed. If diagnosis still unclear another imaging or close follow-up may be needed. 2. Transient hepatic intensity difference (THID): These are well-defined areas of enhancement only on the arterial

phase and not on other phases. THIDs are usually triangular or fan-shaped, peripherally located, have straight margins and may follow the segmental anatomy of the liver. They do not demonstrate signal abnormality on T1 and T2W1 images or washout appearance on venous and delayed phases. Other features include uptake of hepatocyte-specific agents like the background liver on hepatocyte phase and normal vessels are often seen coursing the lesions. These typically show a waxing waning course and are often not seen on follow-up scan. These may, however, be seen around a neoplastic process due to siphoning of arterial blood in the region and hence presence of THID should prompt detailed evaluation of the region to look for underlying tumour. 3. Confluent Fibrosis: Can appear mass-like and have hyperintense T2 signal intensity, although it typically is wedge-shaped, demonstrates delayed enhancement, and is commonly centrally located, in the anterior and medial segments of the liver. Hepatic fibrosis may be poorly marginated, mimicking infiltrating HCC. It characteristically demonstrates volume loss with focal capsular retraction of the adjacent liver surface, unlike HCC, which generally has mass effect and often expands the contour (Fig. 9.11.45). 4. Cholangiocarcinoma: Incidence of cholangiocarcinoma is higher in patients with cirrhosis. Distinguishing cholangiocarcinoma from HCC in the cirrhotic setting is of paramount important as treatment differs. HCC being a hypervascular lesion is amenable to treatment with transarterial chemoembolization while ICC tends to be less responsive. Imaging plays a vital role in distinguishing the two entities. Features favouring ICC include peripheral enhancement in arterial phase with centripetal filling-in on delayed phase. Peripheral washout sign if seen on delayed phase favours ICC. Distal biliary dilatation and lobar atrophy with vascular encasement rather than thrombosis are other ancillary features that may suggest ICC. 5. Mixed HCC – Cholangiocarcinoma

FIG. 9.11.45 Confluent hepatic fibrosis. Biopsy proven case of confluent hepatic fibrosis showing wedge-shaped T2 hyperintense lesion in segment 5 of liver ( arrow in A and B). (C) Postcontrast venous phase images, showing enhancement (arrow), which persists in (D) delayed phase. HCC-CC is defined when both histological types are found within the same hepatic tumour, therefore, it does not apply for synchronous separated HCC and cholangiocellular carcinoma. In the year 2010, WHO reclassified combined HCC(cHCC)-IHC into the classical type and those with stem cell features. Presence of unequivocal HCC and ICC components which have transition zones allows differentiation from collision tumours. cHCC-CC are tumours with aggressive behaviour and is associated with poorer prognosis compared to HCC and more favourable than CC in patients undergoing liver resection. The reported incidence of this tumour ranges between 0.4% and 4.7%. Imaging

Contrast-enhancement pattern resembles HCC pattern or pattern of cholangiocarcinoma. CT/MRI Lesions usually appear isodense to hypodense as compared to liver parenchyma on plain scan. They reveal intermediate to high signal intensity on T2W1 images. On administering contrast, enhancement patterns are varied, depending on the component of cholangiocarcinoma and HCC (Figs. 9.11.46 and 9.11.47).

FIG. 9.11.46 Mixed HCC–IHC. (A to C) T2W1 images showing an ill-defined hyperintense lesion in segments 8,7 and 4a of the liver with peripheral biliary dilatation ( arrow in B). A hyperintense thrombus is seen in right portal vein ( arrow in C). The mass and thrombus show enhancement on contrast study ( arrows in D and E). Lesion shows both biliary dilatation and a tumour thrombus and hence has mixed features.

FIG. 9.11.47 Mixed HCC – cholangiocarcinoma. (A and B) T2W1 images showing a large well-defined hyperintense lesion in left lobe and segment 8, causing bilobar biliary dilatation ( red arrows in B). Tumour is seen invading the lumen of the right, left and main portal veins ( blue arrows in B and D) with resultant tumour thrombus and is otherwise hypovascular. Classification system has been described on the basis of enhancement patterns as per Sanada et al. and Aoki et al. Sanada’s type I/Aoki’s type b: Early hyperenhancement followed by washout in the delayed phase: These resemble HCC on imaging and have HCC-predominance histopathologically. Sanada’s type II: Peripheral enhancement in both the early and delayed phases. May be due to central fibrotic or necrotic components along with a peripheral cHCC-CC component. Sanada’s type III/Aoki’s type A: Two distinctive enhancement patterns in the same tumour, one following the typical HCC pattern (early enhancement with delayed phase washout) and the second imitating CC (delayed enhancement on late imaging).

LI-RADS in HCC-CC The LI-RADS algorithm includes analysis of additional imaging features that can help categorization and may be applied cases with

ambiguous features. These are: • Rim or peripheral arterial phase hyperenhancement • Portal venous and delayed phase progressive central enhancement • Peripheral washout • Marked restricted diffusion • Retraction of liver surface • Biliary obstruction disproportionate to that expected based on size of mass The diagnosis of cHCC-CC should be strongly considered in the following circumstances (Table 9.11.39): 1. If the lesion demonstrates imaging features of both CC and HCC, regardless of marker levels. 2. If both AFP and CA19-9 are elevated, regardless of imaging appearance. 3. If the imaging appearance contradicts the tumour marker, for example, typical HCC enhancement pattern with elevated CA19-9 or conventional CC enhancement pattern with abnormal AFP. 4. Postbiopsy, the diagnosis is made on the basis of immunohistopathological features. TABLE 9.11.39 D/D HCC in Cirrhotic Liver • Haemangiomas • Transient hepatic intensity difference • Confluent fibrosis • Cholangiocarcinoma • Mixed HCC – cholangiocarcinoma

Treatment of HCC Selection of optimal treatment strategy for HCC requires consideration of multiple factors; the most relevant among them are the status of the underlying liver disease and the stage of the tumour. HCCs appearing in noncirrhotic livers are good candidates for a liver resection. Even major lobectomies are generally well tolerated. However, in most patients, the underlying liver disease precludes a safe resection. Liver transplantation, if feasible,

provides the best outcome in such patients as it treats the underlying liver disease as well as the tumour. If resection or transplantation are not feasible, several nonoperative techniques are available for control of the tumour like percutaneous ethanol injection (PEI), RFA, microwave ablation (MWA), TACE, stereotactic body radiotherapy (SBRT). The treatment modalities have been shown below. Treatment modalities: 1. Surgery A. Liver resection B. Liver transplantation 2. Local ablation and external radiation A. PEI B. Thermal ablation C. External radiation 3. Transarterial A. TACE B. Selective internal radiation therapy (SIRT) 4. Systemic A. First line B. Second line 5. Palliative 1. Surgery Resection in a cirrhotic liver is a balancing act between performing an oncologically adequate surgery and preserving adequate functioning liver tissue to avoid hepatic decompensation. Understanding of the segmental anatomy, along with improvements in anaesthesia and critical care have played a major role in reducing the mortality and morbidity associated with hepatectomy. Preoperative evaluation and proper patient selection play an important role in performing a safe resection. Patients with major noncompensated heart or respiratory failure or those with poor performance status are poor surgical candidates. Liver resection can be performed under careful management strategies in patients with moderate organ dysfunction. Comorbid illnesses can increase the risk of postoperative mortality and morbidity in patients undergoing liver resection. Assessment of Functional Hepatic Reserve

Accurate assessment of functional hepatic reserve is essential for preventing postoperative liver failure and mortality, especially in cirrhotics. Several preoperative assessment methods are available. Detailed discussion of the methods is out of the scope of this chapter. a. Child–Pugh score: It is the standard score to assess liver function and consists of five components: Ascites, hepatic encephalopathy, serum bilirubin, prothrombin time and serum albumin. According to the CP classification, major liver resection is possible in CP class A patients without cirrhosis, whereas limited resections for small tumours located near the liver surface are possible in CP class B patients and patients with cirrhosis. In CP class C patients, however, liver resection is not indicated, even if the resection volume is small. b. Portal hypertension: It is defined as a hepatic venous pressure gradient of 10 mmHg or higher. It can be practically diagnosed by the presence of oesophageal varices and/or a platelet count of less than 100,000/µL in association with splenomegaly. Bruix et al. have reported that liver resection for HCC in patients with portal hypertension resulted in a high incidence of postoperative liver decompensation of as much as 73%, with a poor 5-year survival rate of less than 50%. c. Indocyanine green (ICG) retention rate: In eastern countries, ICG clearance rate at 15 min is commonly used as an indicator of liver function. A set of criteria (Makuuchi’s criteria) consisting of ICG-15, ascites and bilirubin are widely used to decide surgical indications and to estimate tolerable resection volumes in cirrhotic patients. d. Preoperative simulation and volume estimation: Threedimensional virtual hepatectomy simulation software, which has recently been developed, enables accurate preoperative recognition of the anatomic relationships between tumours and vessels in the liver. Using this software, 3D simulation imaging can be constructed using digital data obtained by MDCT. This technique is useful for planning appropriate liver resection procedures. Accurate preoperative estimations of the volume to be resected and that to be preserved (future liver remnant) are also effective indicators to judge the extent of resection that can be safely performed. In a normal liver, a minimum of 20% of functional liver has to be preserved to prevent posthepatectomy liver failure. In a cirrhotic liver, a minimum of 40% of functioning parenchyma must be preserved.

Surgical techniques: In addition to the amount of liver parenchyma preserved, the intraoperative blood loss and duration of occlusion of hepatic inflow have a major impact on the development of postoperative liver failure. Several energy devices for liver transection and surgical techniques have been developed to reduce blood loss. Use of anatomic liver resections, hemihepatic vascular occlusion, intraoperative ultrasound and various devices for parenchymal division, liver resection can be performed safely even in a cirrhotic liver.

B) Liver transplantation Ideal candidate: LT is recommended as the first-line option for HCC within Milan criteria (single tumours ≤5 cm in diameter or no more than three tumours ≤3 cm in diameter) but unsuitable for resection. Contraindication: Tumour vascular invasion and extrahepatic metastases are an absolute contraindication. Liver transplantation is discussed in detail in later chapters. 2. Local ablation and external radiation 1. Percutaneous ethanol injection: This leads to coagulative necrosis of the lesion as a result of cellular dehydration, protein denaturation and chemical occlusion of small tumour vessels. PEI is a well-established technique for the treatment of nodular-type HCC that leads to complete necrosis in 90% of tumours 2 cm in size are incompletely ablated using this technique with recurrence rates as high as 49%. Ethanol injection is an option in cases where thermal ablation is not technically feasible, especially in tumours. 2. Thermal ablative procedures: These include RFA, MWA, laser ablation and cryoablation (freezing). Patients with BCLC 0 and A tumours are usually treated with RFA. Thermal ablation can be done in single tumours 2–3 cm in diameter as an alternative to surgery. Technical factors such as location, proximity of vessels, hepatic and extrahepatic factors influence ablation. Tumours 5 mm nodular area of arterial phase enhancement and/or washout on portal venous/delayed phase imaging (Fig. 9.11.50). Imaging is typically performed at 1 month, 3 months and then every 3–6 months following treatment.

FIG. 9.11.50 Residual tumour post-RFA. (A and B) Contrastenhanced arterial phase showing peripheral nodular arterial enhancement suggesting residual disease (arrows). Post-TACE follow-up Lipiodol causes staining of the treated tumour for months while DEB-TACE and TAE washout after few hours. After conventional TACE imaging with noncontrast CT is done within 24 hours to evaluate lipiodol distribution. Complete necrosis is associated with presence of lipiodol in entire tumour. Thin nonnodular rim enhancement around the treated lesion is seen following TACE. This rim is, however, less than 5 mm in width and shows persistent enhancement without washout. When these features are seen it usually does not indicate recurrence. Residual tumour appears as nodular, usually >5 mm, areas that demonstrate arterial enhancement and subsequent washout. Followup with imaging is at 1 month, 3 months and then every 3–6 months. MRI may be more sensitive in post-TACE follow-up since it is unaffected by lipiodol artefacts (Fig. 9.11.51).

FIG. 9.11.51 Post-TACE follow-up. (A) Unenhanced CT showing hyperdense areas of lipiodol deposition in segment 8 HCC (arrow). No arterial enhancement is seen within the lesion ( arrow in B) suggesting nonviable tumour. Imaging after TARE Enhancement post-TARE is different compared to RFA and TACE. It is common for patients to develop patchy arterial enhancement throughout the treatment zone, which is poorly predictive of residual disease prior to 3 months posttreatment. After 3 months, this patchy enhancement becomes less conspicuous and residual tumour shows arterial enhancement with washout. After 3 months posttreatment, as with other treatment methods, successfully treated areas will show a lack of arterial enhancement. Due to the above-mentioned reasons, follow-up post-TARE is preferred at 3 months (Fig. 9.11.52).

FIG. 9.11.52 Postradioembolization. Postcontrast arterial phase images in a patient who underwent TARE for segment 8 HCC with vascular thrombus shows ill-defined hypoenhancing area suggesting nonviable tissue. Hyperintense areas along superior aspect of lesion haemorrhagic necrosis (arrows) and were seen on precontrast images as well. HCC in noncirrhotic liver Although HCC typically arises in the setting of cirrhosis, around 20% develop in the noncirrhotic liver. Lack of regular surveillance in the noncirrhotic population leads to delay

in diagnosis of this lesion with advanced disease at presentation. Bimodal age distribution is seen with peaks during the second and seventh decades. Among these the FLC variant comprises 1%–9%. Aetiologies 1. Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: A strong association has been reported between fatty liver disease and HCC in noncirrhotic livers, and may be the result of metabolic syndrome. NAFLD, with or without NASH is the hepatic manifestation of metabolic syndrome and predisposes to HCC in noncirrhotic patients. 2. Viral hepatitis: 30% of HBV-related HCC occurs in noncirrhotic patients.. The incidence of HCC in noncirrhotic HCV patients is lower and ranges from 4.4%– 10.6%. HCC may develop even after eradication of the virus. 3. Genotoxic substances a. Alcohol: Alcohol should still be treated as a serious risk factor for the development of HCC. Alcohol can cause endotoxin production, oxidative stress and inflammation causing direct genotoxic effect in the development of HCC. b. Aflatoxin B1: Aflatoxin B1 (AFB1) is an extremely potent hepatocarcinogen that is a secondary metabolite produced by fungi, Aspergillus flavus and Aspergillus parasiticus. Like cirrhotic patients, noncirrhotic patients with chronic HBV are also at a higher risk for aflatoxin-mediated HCC. c. Iron overload: There are several case reports that have highlighted the role of excess iron as a potential carcinogen. d. Miscellaneous:. Various carcinogens have been implicated such as, azo dyes, nitrosamines, vinyl chloride, aromatic amines, pesticides, organic solvents and arsenic. e. Sex hormones: Several case reports have established a link between chronic anabolic androgen steroid abuse and noncirrhotic HCC in young professional bodybuilders. 4. Inherited diseases Hereditary haemochromatosis alpha-1 antitrypsin deficiency and acute hepatic porphyrias also been considered as a cause of noncirrhotic HCC. Other inherited diseases at risk include Wilsons disease, GSDs and Alagille syndrome. Budd–Chiari syndrome and nodular regenerative hyperplasia and HAs are also associated with small risk (Table 9.11.41). TABLE 9.11.41 Aetiologies of HCC in Noncirrhotic Liver • Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis • Chronic viral hepatitis B • Alcohol • Alpha 1 antitoxin • Iron overload • Chemical carcinogens and sex hormones • Hereditary haemochromatosis and alpha-1 antitrypsin deficiency • Acute intermittent porphyria • GSDs • Wilsons disease • Alagille’s syndrome • Adenomas Clinical features As mentioned previously, lack of surveillance, symptoms and preserved hepatic function in the noncirrhotic population account for delay in diagnosis. Average age of presentation is 69 years. Abdominal pain is the most common symptom. Other symptoms include fatigue, weight loss abdominal distension, jaundice and fever of unknown origin.

Presentation with paraneoplastic syndromes like hypercalcemia or hypoglycemia can be seen. Diagnosis 1. AFP in noncirrhotic HCC – elevation of AFP is less common compared to cirrhotic HCC (31%–67% vs 63%–84%). Levels >400 ng/mL are essentially diagnostic for noncirrhotic HCC. This implies that elevated AFP levels may suggest an HCC, but normal levels should never be used to exclude the diagnosis. 2. Des-γ-carboxy prothrombin – DCP has been reported to be more sensitive and specific than AFP for the diagnosis of HCC with a cut-off of >40 mAU/mL. Imaging HCC in noncirrhotic liver is usually solitary and larger in size compared to those in cirrhotic liver. USG The appearance of HCC on US is variable and nonspecific ranging from hypo- or hyperechoic lesions with or without heterogeneity or necrotic areas. Colour Doppler will show intratumoural vascularity similar to HCC seen in cirrhotic liver. CEUS shows a typical HCC vascular pattern. CT Unenhanced CT shows a large well-circumscribed encapsulated hypoattenuating lesion. Lesion may be heterogeneous on nonenhanced scan owing to intratumoural tumour fat, foci of haemorrhage and necrotic areas (Fig. 9.11.53). They classically show heterogeneous arterial hyperenhancement with venous washout. Mosaic attenuation with hypo- and hyperenhancing areas on a single phase is common (Fig. 9.11.54). Intratumoural neovascularity is seen in the form of small serpiginous vessels within the interstitium.

FIG. 9.11.53 Fat containing HCC. Noncontrast CT showing a welldefined hypodense lesion occupying the right lobe with eccentrically located area of fatty metamorphosis (blue arrow). Neovascularity identified within the lesion on arterial phase ( arrow in B). (D) Delayed phase images show washout compared to background liver with pseudocapsule (arrow).

FIG. 9.11.54 HCC in noncirrhotic patient. (B) Late arterial phase images showing a well-defined intensely enhancing mass in segments 4, 8 and 5 of the liver with central nonenhancing area (arrow). (E and F) Delayed phase images show washout of contrast from the lesion with a thick surrounding capsule (arrows). Note: Enhancement of the central scar-like area on the delayed phase (yellow arrow). This is an HCC in a noncirrhotic liver with scar-like tissue.

MRI MRI is superior to CT for the diagnosis of HCC. Tumour is usually hypointense on T1W1 sequences but signal varies depending on the degree of fibrosis, necrosis and fat. Most masses are hyperintense to liver on T2W1 images. Enhancement is usually heterogeneous in arterial and late arterial phases due to large areas of necrosis. Venous phase shows washout. Capsule may be seen on delayed phase. MRI is the best modality for diagnosis of intralesional fat, which can be seen in 10%–17%. Role of percutaneous biopsy Histological diagnosis via liver biopsy may only be necessary if imaging studies are inconclusive for being compatible with HCC. Patients who are not candidates for upfront resection should undergo biopsy to establish diagnosis for the purpose of systemic therapy. Management Surgical resection is the treatment of choice for HCC in noncirrhotic liver. Patients with extrahepatic spread of disease or significant disease in the liver in both lobes are often not candidates for surgery. Lobectomy with vascular reconstruction is required in most cases. These surgeries are feasible due to the preserved liver function and low perioperative mortality when compared to cirrhotic livers. Perioperative morbidity and mortality are low when compared to the cirrhotic liver, 29.5% and 2.7% Recurrence Tumour recurrence is the major cause of death in noncirrhotic livers with HCC since no effective postoperative adjuvant chemotherapy exists. Liver transplantation European Liver Transplant Registry recommends that Milan criteria should not be used to exclude patients with noncirrhotic HCC for liver transplantation. An international consensus conference report recommends LT in patients with nonresectable HCC or in patients who experience intrahepatic recurrence after surgical resection; provided these patients have no macrovascular invasion or extrahepatic spread. Systemic therapy Sorafenib has been used as first-line therapy for patients with advanced HCC. Recently two new systemic drugs have been approved by FDA for advanced HCC. These include regorafenib, a multikinase inhibitor and nivolumab, a PD-1 (programmed cell death protein 1) inhibitor, both of which have shown survival benefit. Local ablative therapies are not effectively used in the treatment of HCC in noncirrhotic liver (Table 9.11.42). TABLE 9.11.42 Imaging Pearls – HCC in Noncirrhotic Liver • 20% of HCCs have been known to develop in a noncirrhotic liver • Median age of these patients is 69 years • Classically show heterogeneous enhancement with classic arterial hyperenhancement and venous washout • Mosaic attenuation common • Surgical resection is the treatment of choice for HCC in noncirrhotic liver Fibrolamellar carcinoma This variant of HCC is seen in young patients without history of previous liver disease. Both males and females are equally affected with mean age of 23 years at presentation, range 10–35 years.

Presentation Patients may present with abdominal pain, palpable mass and rarely gynaecomastia or venous thrombosis. Elevation of serum AFP is usually not seen in this variant. However, mild elevation may occur in approximately 10% of patients. Areas of haemorrhage and necrosis are more common in conventional HCC, which usually occurs in background of a cirrhotic liver. Imaging US FLC are usually mixed in echogenicity. A hyperechoic central scar can be present and may show calcifications with posterior acoustic shadowing. CT FLC typically reveal heterogeneous arterial enhancement with extensive tumoural vessels. Similar to large HCC in noncirrhotic liver, these lesions also show mosaic pattern of enhancement. The central scar is generally hypoattenuating on both pre- and postcontrast CT; it is thick and irregular in appearance. Unlike FNH, the central scar does not show enhancement on delayed phase of dynamic study. Calcification is seen in mass usually in the scar and is best detected on CT. The central scar is seen in 20%–71% of patients and coarse calcifications within the central scar are seen in 35%–68% of patients. Portal vein thrombosis and biliary obstruction are rare findings in FLC (Fig. 9.11.55).

FIG. 9.11.55 Fibrolamellar carcinoma. (A) Plain CT abdomen showing a lobulated hypodense lesion with calcification in segments 4b, 5 and 6 of the liver (arrow). (B) Arterial phase images showing heterogeneous mosaic pattern of enhancing with intense neovascularity. An eccentrically located scar is visualized within the lesion ( arrows in D and E). (E) No enhancement of the scar is seen on the delayed phase. Nodal metastatic lesions are most commonly seen at the hepatic hilum and hepatoduodenal ligament occurring in up to 50%–60% of cases. Metastasis occur mostly to the lungs, peritoneum and adrenal gland in up to 20%–30% of cases (Table 9.11.43).

TABLE 9.11.43 Tumours Showing Central Calcification • Metastases (especially in colorectal tumours). • Fibrolamellar carcinoma (FLC) • Cholangiocarcinoma – uncommon • Haemangiomas – uncommon MR Fibrolamellar variant is slightly hyperintense on T2-weighted images. The central scar of FLC is often better seen on MRI and is low in signal on both T1- and T2-weighted images in contrast to FNH, which has a high T2 signal scar. Central scar shows minimal or no enhancement on delayed phase of dynamic contrast study. FLCs appear hypointense compared with surrounding normal liver in hepatobiliary phase of gadoxetic acidenhanced liver MRI imaging. Hence this CA has an important role in diagnosing cases with diagnostic dilemma. Unlike HCC or adenomas, FLC has no detectable intrinsic fat. The most important prognostic factor in FLC is tumour resectability. Median 5-year survival rate for patients with a surgically removable fibrolamellar HCC being nearly 76%. The differential diagnosis include large HCC, mixed HCC – cholangiocarcinoma due to similar pattern of neovascularity and mosaic attenuation and FNH due to the presence of central scar (Tables 9.11.44 and 9.11.45). TABLE 9.11.44 D/D of FLC D/D Fibrolamellar Variant of HCC • Large HCC • Mixed HCC – cholangiocarcinoma • FNH TABLE 9.11.45 D/D FNH and FLC Focal Nodular Hyperplasia Central scar hyperintense on T2W1 images Delayed enhancement of central scar

Fibrolamellar Carcinoma Scar hypointense on T2W1 No delayed enhancement of scar

Mosaic pattern of enhancement defined as areas of hypo- and hyperenhancement in the tumour on same phase is a specific sign of malignancy and is not seen in benign lesions (Table 9.11.46). TABLE 9.11.46 Lesions Showing Mosaic Pattern of Enhancement • Large HCC • Fibrolamellar carcinoma • Mixed HCC – cholangiocarcinoma Role of biopsy Biopsy is not needed in cases where imaging findings are diagnostic. In patients with doubtful diagnosis on imaging percutaneous biopsy may be indicated. Treatment FLC are good candidates for aggressive surgical treatment. Liver resection is the treatment of choice for FLC. Five-year recurrence-free survival is as low as 18 %.

however. Only FLC which is not amenable to resection but confined to the liver is considered a suitable indication for liver transplantation. The role of neoadjuvant or adjuvant chemotherapy is controversial (Table 9.11.47). TABLE 9.11.47 Imaging Pearls FLC • Variant of HCC seen in younger individuals • Present with large masses • Not associated with high AFP • Show central scar which does not enhance on delayed phase, scar calcification +/– • Mosaic pattern of enhancement • Nodal metastasis common • Surgery main stay for treatment Intrahepatic cholangiocarcinoma Cholangiocarcinoma is an adenocarcinoma that arises from the bile duct epithelium. It is the second most prevalent liver cancer after HCC. There are several risk factors in the development of ICC. These include biliary tract diseases (i.e. primary sclerosing cholangitis [PSC], choledochal cyst or hepatolithiasis), parasitic infestation of the biliary tract by Clonorchis sinensis or Opisthorchis viverrini, and chronic liver diseases (CLDs), such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or cirrhosis from other causes (Table 9.11.48). TABLE 9.11.48 Associations on Intrahepatic Cholangiocarcinoma • Primary sclerosing cholangitis • Choledochal cyst • Caroli’s disease • Clonorchiasis • Intrahepatic stone disease • Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection • Cirrhosis Histology Several histological classifications exist. According to WHO classification, most ICC are well-differentiated adenocarcinomas. However, other histologic variants also exist like adenosquamous and squamous carcinoma, signet-ring cell carcinoma, mucinous carcinoma, mucoepidermoid carcinoma, clear cell carcinoma, lymphoepithelioma-like carcinoma and sarcomatous ICC. Cholangiocarcinogenesis Premalignant bile duct lesions were proposed in the 2010 WHO classification and include biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB). BilIN is classified as grade 1, 2 and 3 depending on mild, moderate of severe dysplasia and are precursors of periductal infiltrating ICC. IPNB has been suggested as a precursor lesion in the dysplasia–carcinoma sequence and can progress to intraductal growing ICC. A. Classification according to site and histology Cholangiocarcinoma can also be classified according to the site of duct involvement (Table 9.11.49).

1. Perihilar large duct ICC, which involves the intrahepatic large bile ducts. 2. Peripheral small duct ICC, which involves the intrahepatic small bile ducts. TABLE 9.11.49 Classification According to Site of Duct Involvement Perihilar Large Duct Large to midsize tubular or papillary proliferations of the tall columnar epithelium. Produce more mucin than do peripheral small duct ICCs. Ill-defined or infiltrating tumour margins and increased necrosis. Perineural, vascular and lymphatic invasion and lymph node metastases are more frequently associated with perihilar large duct ICCs. These invade into the surrounding liver with spread along portal tracts, showing combined features of mass forming, periductal infiltrating or intraductal lesions.

Peripheral Small Duct Small tubular or trabecular proliferation of low columnar to cuboidal cells. Mucin hypersecretion is much rarer in peripheral small duct. Usually of the mass-forming type and tend to be smaller at the time of detection. Have more expansive tumour borders and are less likely to exhibit perineural or lymphatic invasion compared with the perihilar large duct type. Associated with preserved portal tracts. Advanced peripheral small duct ICC often appears as extensive fibrotic scarring in the tumour centre, with necrosis and intrahepatic metastasis.

B. Classification according to morphology The Japanese liver cancer study have classified cholangiocarcinoma into (Table 9.11.50): 1. mass-forming 2. periductal infiltrating 3. intraductal growth types. TABLE 9.11.50 Classification of Intrahepatic Cholangiocarcinoma Morphology Pathology Mass forming Most common accounting for 78% of cases. These tumours tend to be large. Multicentricity around the tumour is common. Periductal Second most common type variety. These tumours spread longitudinally infiltrating along biliary radicals causing luminal stenosis. These, constitute approximately 16% of ICCs. Intraductal Rarest type of ICC (approximately 6%) and presents as a papillary tumour within the dilated bile duct lumen. spread along the mucosa with multiplicity. Sometimes, this type of tumour produces a large amount of mucin, causing partial biliary obstruction. Classification is valuable for the interpretation of imaging features and the development of a differential diagnosis for predicting tumour dissemination and prognosis and planning the surgical approach. Clinical presentation The most frequent clinical presentation is related to symptoms typical of hepatic mass, including abdominal pain, malaise, night sweats and cachexia. These usually do not present with jaundice. Tumour markers The most commonly used markers are carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). Various cut-off values have been proposed for CA19-9, generally between 100 and 200 U/mL. The sensitivity and specificity of CA10-9 is lower in the setting of PSC. High CEA levels may also be observed in cholangiocarcinomas. The usual cut-off is 5 ng/mL. The combined use of CEA and CA19-9 may improve the diagnosis of cholangiocarcinoma.

Staging The most commonly used classification system to qualify advancement and resectability of ICC is the American Joint Committee on Cancer (AJCC) TNM staging system, currently in its seventh edition, consisting of four stages (Table 9.11.51). TABLE 9.11.51 TNM Staging of Intrahepatic Cholangiocarcinoma Definition T STAGE Tx No description of the tumour’s extent is possible because of incomplete information. T0 There is no evidence of a primary tumour. T1 There is a single tumour that has grown into deeper layers of the bile duct wall, but it is still only in the bile duct.The cancer has not grown into any blood vessels. T2a There is a single tumour that has grown through the wall of the bile duct and into a blood vessel. T2b There are two or more tumours, which may (or may not) have grown into blood vessels. T3 The cancer has grown into nearby structures such as the intestine, stomach, common bile duct, abdominal wall, diaphragm (the thin muscle that separates the chest from the abdomen) or lymph nodes around the portal vein. T4 The cancer is spreading through the liver by growing along the bile ducts. N STAGE Nx Nearby (regional) lymph nodes cannot be assessed. N0 The cancer has not spread to nearby lymph nodes. N1 The cancer has spread to nearby lymph nodes. M STAGE M0 The cancer has not spread to tissues or organs far away from the bile duct. M1 The cancer has spread to tissues or organs far away from the bile duct. Stage GROUPING Stage T1, N0, M0 I Stage T2, N0, M0 II Stage T3, N0, M0 III Stage T4, N0, M0/any T, N1, M0 IVa Stage Any T, any N, M1 IVb Imaging USG USG is often the first imaging modality employed in patients with obstructive jaundice or abdominal pain. It helps to exclude more common aetiologies for obstructive jaundice such as choledocholithiasis. Imaging appearance depends on the morphology of lesion. Mass forming intrahepatic cholangiocarcinoma. Mass-forming cholangiocarcinoma appears as a well-defined irregular mass with associated capsular retraction. Thirty-five per cent of all tumours show peripheral hypoechoic rim consisting of compressed liver parenchyma and tumour cells. Those greater than 3 cm are usually hyperechoic while those less than 3 cm are hypo- or isoechoic. Periductal infiltrating type. The infiltrating type cholangiocarcinoma appears as a small, mass-like lesion or diffuse bile duct thickening. Lesion may or may not cause obliteration of the bile duct lumen depending on tumour extent The primary role of ultrasound in this setting is to rule out benign causes of biliary obstruction.

Intraductal type. Four imaging patterns have been described with this subtype. Imaging patterns include: a. Diffuse and marked duct ectasia with a grossly visible papillary mass. An intraductal polypoid lesion is echogenic relative to the surrounding liver. This lesion is usually confined to the bile duct wall, so that the wall will appear intact at us. The presence of abundant anechoic mucin may, however, obscure visualization of an intraductal lesion. b. Diffuse and marked duct ectasia without a visible mass. c. An intraductal polypoid mass within localized ductal dilatation d. Intraductal cast-like lesions within a mildly dilated duct e. A focal stricture-like lesion with mild proximal ductal dilatation. Contrast-enhanced USG. Various enhancement patterns have been described. Regions with hypercellularity typically show hyperenhancement. Peripheral irregular rim-like hyperenhancement is seen in tumours with abundant carcinoma cells at the edge and marked fibrous stroma in the centre. Other enhancement patterns like homogeneous or heterogeneous hyperenhancement have been described. CT – mass forming ICC. On CT mass forming cholangiocarcinoma appears as a hypodense mass on nonenhanced scan with peripheral irregular arterial enhancement on arterial phase and gradual centripetal filling-in on subsequent phases. The peripheral portion of ICCs contains abundant viable tumour cells, hence the hyper enhancement, while coagulative necrosis and fibrous stoma constitute the central portion, hence shows delayed enhancement. The peripheral washout sign is frequently seen in ICC and represents washout of contrast from the periphery while the central stoma enhances on delayed phase (Fig. 9.11.56). Distal biliary dilatation may or may not be seen depending on location of the lesion.

FIG. 9.11.56 Intrahepatic cholangiocarcinoma. (A) Arterial phase image showing a well-defined lobulated lesion in segments 6 and 7 of liver showing irregular continuous peripheral enhancement. Gradual centripetal filling of the lesion is seen on subsequent phases. Note: Involvement of right portal vein and its posterior division by the mass with atrophy of segments 6 and 7 ( arrows in B and C). There is in addition, dilatation of biliary radicles with crowding in segment 7 ( blue arrow in D). A small satellite nodule is also visualized suggestive of metastasis ( yellow arrow in B and C). (D) Delayed phase images showing contrast within the centre of the lesion with washout from the periphery representing the peripheral washout sign. Other common findings include capsular retraction, satellite nodules and macroscopic vascular invasion. These lesions usually encase the portal veins and their branches rather than invade the lumen-like HCC. Atrophy of the involved segments may be seen which may be a consequence of either portal venous occlusion or long standing biliary obstruction. Resultant crowding of biliary radicals in the affected lobe is seen (Fig. 9.11.56). This sign may be a useful clue to the diagnosis of ICC (Table 9.11.52). TABLE 9.11.52 D/D Peripheral Washout Sign Washout of Contrast From the Enhancing Periphery Called the Peripheral Washout Sign – Suggestive of Malignant Disease • Metastasis • IHC • Combined HCC cholangiocarcinoma MRI Mass typically shows high signal intensity on T2-weighted imaging and low signal intensity on T1-weighted imaging. Fifty-two to seventy-five per cent of mass-forming ICCs show peripheral target-like diffusion restriction corresponding to the areas of hyper cellularity. This target sign on DWI is also useful for distinguishing ICC from HCC. On dynamic contrast-enhanced MRI with extracellular contrast material, the mass also exhibits prominent peripheral rim enhancement with centripetal or gradual progressive enhancement. Peripheral washout sign is seen on the delayed phase. This sign is highly specific for malignancy and is not seen in benign lesions (Fig. 9.11.57).

FIG. 9.11.57 MRI in ICC. (A and B) T2W1 images showing a large well-defined hyperintense lesion in left lobe extending into segment 8. Note: Lesion is causing distal biliary dilatation in segment 2 ( arrow in B). Late arterial phase shows peripheral and heterogeneous enhancement (arrows). Delayed phase shows peripheral washout sign with enhancement of central fibrotic component. On contrast MR with gadoxetate mass-forming ICCs may exhibit a pseudowashout pattern during the transitional phase (late dynamic phase between the portal venous and hepatobiliary phases) owing to progressive enhancement of normal background liver. They appear hypointense to the background on delayed phase as they lack OATP expression and hence the ability to take up hepatocyte-specific contrast. Most lesions, however, reveal heterogeneous appearance on hepatobiliary phase. Atypical enhancement patterns Small tumours less than 3 cm show diffuse arterial enhancement due to fibrous vascular stroma. These can mimic HCCs particularly in the setting of cirrhosis or chronic hepatitis B. Most important differential of ICC is HCC (Table 9.11.53). TABLE 9.11.53 D/D ICC and HCC ICC Rim enhancement during the arterial phase, with centripetal filling-in On hepatobiliary phase multilayered pattern with hypointense rim Ancillary features like distal biliary dilatation, lobar atrophy Encase portal vein Locoregional adenopathy common

HCC Homogeneous or in homogeneous arterial enhancement HCCs typically showed homogeneous hypointensity on hepatobiliary phase Usually not associated with distal biliary dilatation or ipsilateral lobar atrophy Invade portal vein Metastatic spread to nodes is uncommon

Periductal infiltrating. This is a rare type of ICC but the most common type of hilar cholangiocarcinoma. A combination of mass forming and periductal infiltrative tumours are more common in the liver periphery. Perineural and perilymphatic spread is seen along with the bile duct toward the porta hepatis. Periductal thickening with enhancement is seen on contrast-enhanced CT and MRI. On contrast-enhanced CT, periductal infiltrating ICCs appear as hyperattenuation relative to the liver parenchyma during both hepatic arterial and portal venous phase scans (Fig. 9.11.58). These may be difficult to distinguish from benign strictures such as those seen in IgG4-related biliary diseases. Distinguishing features are discussed in subsection on hilar cholangiocarcinoma and IgG4-related diseases.

FIG. 9.11.58 Periductal infiltrating C. Portal venous and parenchymal phases’ images showing an ill-defined hypodense minimally enhancing lesion along the biliary radicles in segment 8 of the liver. Involvement of anterior branch of right portal vein is seen. There is mild bilobar biliary dilatation ( arrows in C). Small cholangitic abscesses are seen in right posterior segments (yellow arrows). Intraductal growing intrahepatic cholangiocarcinoma. These lesions are seen as segmental or diffusely dilated bile ducts, with or without polypoid or papillary tumours. Multiplicity may be seen is these lesions. Imaging These are hypo- or isoattenuating lesions that show mild progressive enhancement on contrast study (Fig. 9.11.59). The degree of enhancement is lesser compared to other varieties of ICC. This is because intraductal growing ICC is usually confined to the bile duct mucosa with small fibrovascular stalks.

FIG. 9.11.59 Intraductal cholangiocarcinoma. Venous phase images showing heterogeneously enhancing polypoidal lesion within biliary radicles in segments 8, 5 and their branches extending into the right hepatic duct ( arrows in A and B). Resultant bilobar biliary dilatation is visualized. D/D of intraductal cholangiocarcinoma 1. Hepatolithiasis: These are hyperdense on nonenhanced CT. Associated enhancement of bile duct wall is smooth, unlike intraductal tumours which show irregular enhancement of bile duct walls. 2. HCC with bile duct invasion: A hepatic parenchymal mass contiguous with the bile duct is seen. A hyperenhancing lesion during the hepatic arterial phase with portal venous washout, and the presence of a fibrous capsule or pseudocapsule, suggest HCC with bile duct invasion. Intraductal growing ICC exhibits progressive enhancement during the hepatic arterial and portal venous phases.

Treatment Surgical resection is the treatment of choice. Patients may undergo preoperative drainage if required. Biliary drainage and portal vein embolization. Preoperative or palliative stenting may be done. The aim of biliary drainage is to improve liver function, liver regeneration and decrease the risk of postoperative liver failure. The main drawback of biliary drainage is cholangitis. Patients with a future liver remnant of at least 50% should probably undergo a resection without preoperative biliary drainage. Indication for portal vein embolization include resection of more than 75% of total liver volume in a healthy liver of more than 65% of total liver volume in a compromised (cirrhotic or fibrotic) liver. This results in hypertrophy of the future remnant. 2. Resection surgical treatment is the only potentially curative treatment in patients with ICC. A complete resection of the tumours requires a right/left hepatectomy often extended. Bile duct resection and reconstruction is also often required. Extrahepatic disease, including lymph node metastases beyond the regional basin (N2), is a contraindication for curative-intent surgery. Whereas HCC is commonly treated with orthotopic liver transplantation (OLT), ICC as an indication for OLT is still controversial. Systemic Chemotherapy Adjuvant Aim of adjuvant chemotherapy is decreasing the chance of tumour recurrence. Most common chemotherapeutic agent includes gemcitabine often in combination with cisplatin.

Nonepithelial malignant tumours Epithelioid haemangioendothelioma Epithelioid haemangioendothelioma is a rare low-grade malignant vascular tumour of endothelial origin. Epidemiology Sixty-two per cent of cases occur in women. Its aetiology is unknown; however, there appears to be an association with regular intake of oral contraceptives, exposure to vinyl chloride and prior history of trauma to the liver. Clinical features vary from asymptomatic to severe and include nausea, periodic vomiting, anorexia, weakness, jaundice, pain and hepatosplenomegaly. Pathology The diagnosis of HEH requires a biopsy and a histological diagnosis, showing endothelial cells with an epithelioid appearance. Immunohistochemical staining with antibodies to factor VIII, CD31 or CD34 are diagnostic. Biochemistry Concentrations of serum bilirubin, alkaline phosphatase and aspartate aminotransferase are typically significantly increased. Only a few cases exhibit slightly increased levels of CEA. Tumour markers most commonly used in clinical practice have no significant value for the diagnosis of HEH. US Predominantly hypoechoic at US, although occasional iso- to hyperechoic lesions with a hypoechoic rim also have been reported. CT Multiple homogeneously hypoattenuating peripheral foci are seen on unenhanced CT. Contrast-enhanced CT shows nonenhanced outer rim of avascular tissue and an enhanced inner peripheral rim. The lesional centre may be enhanced or unenhanced on delayed phase depending on dominance of myxoid and hyalinized elements and the degree of central fibrosis (Fig. 9.11.60).

FIG. 9.11.60 CT in epithelioid haemangioendothelioma. (A to C) CT abdomen in the late arterial and (D and E) parenchymal phase showing multifocal well-defined hypodense lesions with peripheral enhancement ( arrows in A and C) and gradual filling on parenchymal phase. This is a biopsy-proven case of multifocal epithelioid haemangioendothelioma. MR Multifocal coalescing nodules in subcapsular distribution causing capsular retraction and venous invasion are seen. The nodules are hypointense on T1W1 images and heterogeneously hyperintense on T2W1 images. Bright-dark ring sign has been described consists of a peripheral rim of high T1 from peripheral thrombosed vascular channels (Fig. 9.11.61). The lesions show multilayered enhancement with central hypointensity surrounded by a ring of increased enhancement and an outer hypointense rim. The central fibrous portion typically shows delayed enhancement. Welldefined peripheral tumours can have a portal or hepatic venous branch tapering or terminating at its periphery. This is referred to as the lollipop sign.

FIG. 9.11.61 Hepatic epithelioid haemangioendothelioma. T2W1 and postcontrast arterial, venous and delayed phases showing multiple coalescing T2 hyperintense lesions in entire left lobe and part of right lobe causing capsular retraction. Lesions cause peripheral enhancement on early phases and fill-in on delayed phase. Note the enhancing dotlike venous radical terminating at the lesional periphery called the lollipop sign ( arrows in D and E). Lungs, peritoneum, lymph nodes and bone are the most common sites of extrahepatic spread of HEH (Table 9.11.54). TABLE 9.11.54 Intrahepatic Tumours Showing Capsular Retraction • Epithelioid haemangioendothelioma • Intrahepatic peripheral cholangiocarcinoma • Confluent hepatic fibrosis • Treated HCC • Metastasis • Large atypical haemangiomas Differential diagnosis Epithelioid haemangioendothelioma may be misdiagnosed as metastatic disease, cholangiocarcinoma, angiosarcoma, sclerosing HCC, abscess, cirrhosis or veno-occlusive disease. Management Management strategies for HEH include liver resection, liver transplantation, TACE and palliative treatment. Angiosarcoma Angiosarcoma is a rare tumour but is the most common primary mesenchymal hepatic malignancy. Can be idiopathic or secondary to cirrhosis. Association with haemochromatosis and neurofibromatosis type 1 is seen. Male predominance is seen with peak incidence in the sixth decade. Symptoms include hepatomegaly, pain, ascites, jaundice, pain and rarely acute abdomen secondary to haemoperitoneum.

There are four main morphologic patterns: Multiple nodules, a dominant mass, a combination of a mass and nodules, or diffuse infiltration without definable mass.

Imaging The lesion appears hypointense on T1- weighted sequences and hyperintense on T2weighted sequences. Tumours with haemorrhage may reveal T1 hyperintense signal. Early phase shows rim enhancement with delayed centripetal enhancement. The peripheral arterial enhancement is usually heterogeneous while the delayed phase shows progressive enhancement that is irregular and bizarre in morphology. The enhancement pattern may be similar to that seen in haemangiomas. Persistent delayed enhancement, intratumoural haemorrhage and the presence of splenic or pulmonary metastasis are findings suggestive of angiosarcoma. Primary hepatic lymphoma Primary hepatic lymphoma is defined as lymphoma originating or confined to the liver and is a rare entity than secondary lymphomatous involvement of liver. Patients that are immunocompromised and those with increased exposure to viruses such as Epstein–Barr, hepatitis are at increased risk.

Imaging Unlike the commonly seen secondary lymphoma, primary hepatic lymphoma presents as a solitary mass compared. The lesions may be larger in size. Other less common patterns include multifocal masses or diffuse infiltration (Fig. 9.11.62). They appear hypointense and hyperintense on T1- and T2-weighted sequences, respectively. Patchy enhancement is seen in the arterial phase with progressive portal venous enhancement. Central heterogeneous signal and enhancement may also be present depending on the degree of necrosis, fibrosis and vascularity. Peripheral washout sign may also be seen (Fig. 9.11.63).

FIG. 9.11.62 Primary hepatic lymphomas. (A and B) CT abdomen plain and (C) postcontrast images in a 40-year-old male with marked fatty infiltration of the liver showing multiple minimally enhancing lesions which are hyperattenuating to background liver on nonenhanced CT ( arrows in A and B). This is a biopsy-proven case lymphomatous deposit in the liver.

FIG. 9.11.63 Primary hepatic lymphoma. (A and B) T2WI axial images showing well-defined lobulated heterogeneous intensity lesions in segments 7, 8, 4 and 2 of the liver (arrows). The lesion shows central hyperintensity with thick nodular T2 isointense periphery. Restricted diffusion is visualized within the lesion periphery ( arrow in C). (D) Arterial phase images reveal intense enhancement of the lesion periphery (arrow). On the delayed phase, there is filling-in of the centre of the lesion with contrast with washout from the periphery suggestive of peripheral washout sign ( arrows in G and H). This is a biopsyproven case of primary hepatic lymphoma. Malignant cystic masses Biliary cystadenoma/carcinoma Biliary cystic tumours (BCTs), such as biliary cystadenoma (BCA) and cystadenocarcinoma (BCAC), comprise less than 5% of all liver cysts. BCTs are typically slow growing lesions with a reported size that can range in diameter from 1.5 to 35 cm. Epidemiology Biliary cystadenoma occurs predominantly in females in 90%, BCAC is more evenly distributed between men and women. The mean age at presentation of BCA is 45, while carcinomas present a decade later. Histology Majority of biliary cystadenomas arise in the liver. Extrahepatic cystadenomas occur in only 10% of cases. Most tumours are multilocular with a propensity for the right lobe. BCAs have been hypothesized to arise from ectopic rests of embryonic bile ducts. However, 50% of BCTs contain endocrine cells suggesting possible origin from intrahepatic peribiliary glands. BCAC is thought to originate either de novo from formed biliary ducts induced by ischemia and carcinogens or from malignant transformation of a preexisting BCA. Malignant transformation in cystadenoma occurs even years after stability. Macroscopically tumours contain mucin and hence fluid containing. The papillae are usually flat or may less commonly protrude in the lumen. Classically, BCA has been characterized by ovarian-type stroma that typically expresses oestrogen and progesterone receptors (60%–100%). Wheeler and Edmondson have defined BCA

based on the presence of mesenchymal stroma. Three distinct layers have been described. These include an epithelial layer, undifferentiated mucin cell layer and dense layer of collagenous connective tissue. BCAC shows the presence of proliferating cytologically malignant epithelium. Multilayered epithelium, frequent mitotic figures and nuclear pleiomorphism are features that suggest malignancy. Presentation Many patients with BCT will be asymptomatic; other patients with BCT can present with nonspecific symptoms, most commonly abdominal pain and distention (55%–90%). Haemorrhage and cyst rupture are uncommon presenting complications of these lesions.

Lab investigations Elevated liver function tests are seen in 20% of patients. Obstructive jaundice and cholangitis are typically seen in extrahepatic BCT and do not necessarily indicate malignancy. Imaging Usg On USG, biliary cyst adenomas may be uni- or multilocular with posterior acoustic shadowing. The lesions may be anechoic or have low-level echoes depending on mucin content. Ultrasound is excellent in detection of intralesional septae. If septal or wall calcification is present then acoustic shadowing may be seen. Presence of mural nodules and papillary projections favours diagnosis of carcinoma. Colour Doppler may detect vascularity in nodules. CEUS may increase sensitivity in detecting enhancement of the nodules. CT On nonenhanced CT, BCAs appear as a well-defined homogeneously hypoattenuating cystic lesion is seen. Lesions may reveal hyperdense fluid level depending on mucin content. Septal or wall calcification may be common (Fig. 9.11.64). Intralesional septae may be seen on contrast study, although the sensitivity for detection nonnodular septae is

lower on CT when compared with USG or MRI. A less commonly seen honeycomb or sponge-like appearance has also been described.

FIG. 9.11.64 Biliary cystadenoma. Contrast-enhanced CT showing a well-defined cystic lesion is segments 2 and 3 with enhancing internal septae ( arrows in B and C). Note the attenuation of the left portal with involvement of segment 2/3 branch and left lobar atrophy ( blue arrow in C). Crowding of biliary radicals is seen in left lobe ( arrows in D). Solid component, mural nodules or nodular septae suggest the diagnosis of carcinoma. Contrast-enhanced scan reveals enhancement of papillary projections distal biliary dilatation is uncommon, but if present favours malignancy (Fig. 9.11.65). Lymph nodal metastasis are rare.

FIG. 9.11.65 Biliary cystadenoma. (A to D) Contrast-enhanced CT images showing a well-defined cystic lesion with internal septa in segment 4. Associated mild biliary dilatation is seen ( arrow in C). Previously done imaging diagnosed lesion as an abscess, hence lesion was pigtailed ( arrow in D). MRI done 2 weeks later shows increase in size of lesion with progression of biliary dilatation ( arrows in E). Patient was subsequently operated with final diagnosis of biliary cystadenoma. MRI Signal intensity of the cyst is variable on T1 and T2W1 images depending on the content. High signal intensity on T1W1 images helps in diagnosis and reflect presence of mucin or haemorrhage. Intralesional septae and papillary projections, if present, appear hypointense on T2W1 images are better seen compared to CT. Diffusion-weighted images may show restriction in the projections; however, cysts with high mucin content may appear hyperintense on diffusion, thus limiting specificity. Similar to contrast-enhanced CT, postgadolinium images show enhancement of papillary projections and septal nodules. Biliary dilatation, if present, is better detected on MRI (Fig. 9.11.65). MRI using hepatobiliary specific agents has been found useful in demonstrating biliary communication, which can be detected by demonstrating uptake of the CA within the lesion on delayed phase. This feature is, however, not exclusive to cystadenomas and has been documented in other complex cystic lesions such as hydatid, intraductal papillary neoplasm and embryonal sarcoma. Role of image-guided aspiration Aspiration of BCT often demonstrates bile tinged mucin and may sometimes allow differentiation from hydatid, haematoma or haemorrhagic cysts. The role of cyst fluid CEA, CA19-9 and serum tumour markers remains controversial. The sensitivity and specificity of intracystic CA19-9 is not high enough to differentiate a BCA from a BCAC. Fine needle aspiration (FNA) of suspected BCAC has been associated with pleural and peritoneal dissemination, hence routine FNA and core needle biopsy of suspected BCT should generally be avoided. D/D The differential diagnosis includes hydatid cyst, liver abscess, polycystic disease, haemorrhagic cyst, primary or metastatic necrotic neoplasm, atypical simple cyst and biliary intraductal papillary mucinous neoplasm (IPMN). Biliary dilatation alone should not be an imaging criteria to distinguish biliary cystadenoma from hydatid cyst. Hydatid cysts commonly communicate with biliary tree (Tables 9.11.55–9.11.56).

TABLE 9.11.55 Differentiating Features Between Simple and Complex Hepatic Cyst US Simple cyst

CT Anechoic, homogeneous, aseptate, thin and smooth margins Anechoic, homogeneous without internal septae

Complex cyst

Irregular border, hyperechogenic septations, loculations, shadowing beyond calcifications Irregular borders, septae, loculations, posterior acoustic shadowing due to calcification

MRI Nonenhancing, hypodense, smooth margins Well-defined hypodense with imperceptible walls, no enhancement

Multilocular, mural and septal enhancement, mural thickening and/or nodules, calcifications, debris containing fluid Multilocular with septae, mural nodules which show enhancement on contrast study, calcifications, debris.

CEUS

Nonenhancing

Nonenhancing

T1: Low signal

No enhancement

T2: High signal Well-defined light bulb bright on T2W1 images and hypointense on T1W1 T1: Hypointense cyst contents

Mural and septal enhancement

T2: Hyperintense with low signal border

Enhancement of septae and mural nodules.

Intralesional complexity with contents shows both hypo- and hyperintense signal on T1W1 images. Moral nodules and septae better perceived compared to CT with enhancement on contrast study.

TABLE 9.11.56 D/D Complex Cystic Lesions in Liver Necrotic Primary or Secondary Septated cyst Daughter cysts May have nonliquefied Areas of component necrosis in otherwise so lesion Wall and septal Nonnodular wall Wall enhancement with Thick irregu enhancement enhancement septal/cyst surrounding hypodensity nodular wall enhancement representing compressed enhancemen liver parenchyma peripheral washout may be seen Enhancing mural nodules No mural nodules No mural nodules Nodular projections may be prese along the wa T1 hyperintensity due to No T1 hyperintense signal No T1 hyperintense signal T1 mucin or proteinaceous hyperintense content signal usuall not seen Biliary Biliary No biliary Biliary communication/dilatation communication/dilatation communication/dilatation dilatation m be seen in cases arising from/involvi biliary radic Biliary Cystadenoma

Hydatid Cyst

Abscess

Treatment Resection is the treatment of choice. The surgery may vary from lobectomy to enucleation, nonanatomical resection, depending on tumour location and size. Extrahepatic BCTs will require complete resection along with resection of the bile duct followed by biliary by-pass. Fenestration, aspiration, sclerosis, internal drainage, marsupialization or partial resection with or without cavity ablation can result in recurrence rate as high as 80%–90% and should be avoided. Pecoma (perivascular epithelioid cell neoplasms) This neoplasm was described in 2002 by the World Health Organization as unusual mesenchymal tumours composed of histologically and inmunohistochemically distinctive PECs. Presently this subgroup comprises of different entities such as AML or lymphangioleiomyomatosis (LAM). PEComas have been reported throughout the body. The hepatic PEComas develop mostly in women, with median age of 50 years and no history of chronic hepatic disease. Imaging The imaging appearance depends on the quantity of adipose tissue and the SMCs that the tumour contains. In a noncontrast CT, a well-defined subcapsular mass with heterogeneous low density is seen. Fat is often seen within these lesions. Arterial hyperenhancement is seen, with variable appearance in venous phase (Fig. 9.11.66). The lesion is hypo- or isoattenuating on delayed phase. The lesion appears hypointense on T1W1 and hyperintense on T2W1 images. The lipid component may be hyperintense on T1W1 images. The mass shows arterial enhancement which may persist in portal venous phase.

FIG. 9.11.66 Hepatic PEComa. (A) Nonenhanced scan showing a well-defined subcapsular lesion in segment 4 with intralesional fat (arrow). Intense enhancement is seen in arterial phase ( arrow in B). The hepatic PEComas are typically benign, but there have been reported some malignant cases with metastases at the diagnoses. These although rare are increasingly recognized entities and should be considered when a well-defined subcapsular hypervascular mass with lipid is seen in a healthy liver.

Metastatic liver disease Metastases are the most common malignant liver lesions and the most common indication for hepatic imaging. Hepatic metastasis can manifest as focal (more common) or diffuse forms (Tables 9.11.57–9.11.58). TABLE 9.11.57 Classification of Metastasis Based on Enhancement Pattern • Hypervascular • Peripherally enhancing • Hypovascular • Diffuse infiltrative TABLE 9.11.58 Hypervascular Metastases to the Liver • Neuroendocrine tumours (such as carcinoid, pheochromocytoma, and islet cell tumours), • Renal cell carcinoma • Melanoma • Choriocarcinoma • Thyroid carcinoma • Breast carcinoma

Imaging Hypervascular metastasis These lesions are hypodense on nonenhanced CT. They are usually hyperintense on T2WI images. Arterial enhancement is seen both on CT and MRI and is homogeneous in small lesions but heterogeneous in large metastasis, for example, neuroendocrine tumours (Fig. 9.11.67). Washout of contrast is seen in the portal venous phase. ‘Peripheral washout’ sign is seen in which lesion tends to wash out contrast from the periphery on delayed contrast-enhanced images and show a target appearance (Fig. 9.11.68). This is a specific sign of malignancy and has been reported in metastasis in addition to ICC, mixed HCC – IHC (Fig. 9.11.69 and Table 9.11.59).

FIG. 9.11.67 Hypervascular metastasis in HCC. K/c/o neuroendocrine tumour of uncinate process ( arrow in F) shows multiple varying size heterogeneously hypervascular lesions in both lobes.

FIG. 9.11.68 Peripheral washout sign in metastasis from rectal cancer. (A and B) T2W1 images show multiple well-defined hyperintense lesions in both lobes. The larger lesion in segments 8 and 7 shows peripheral enhancement in late arterial phase ( arrows in C) with peripheral washout in delayed phase ( arrow in F).

FIG. 9.11.69 Peripheral washout sign in metastasis from neuroendocrine tumour. K/c/o neuroendocrine tumour showing a welldefined lobulated lesion in segments 8 and 4 showing peripheral arterial enhancement with central scar-like structure ( arrow in B). Delayed phase shows peripheral washout ( yellow arrow in C) with filling-in of the central scar-like structure (arrows). TABLE 9.11.59 D/D Hypervascular Metastasis Flash Haemangiomas Rapid enhancement on arterial phase postcontrast images and Rapid enhancement on increased T2 signal arterial phase postcontrast images and increased T2 signal Hypervascular metastases tend to wash out Tend to remain enhanced during the portal venous phase No perilesional halo on late arterial phase Reveal a perilesional halo on late arterial phase Tend to wash out contrast from the periphery on delayed No peripheral washout contrast-enhanced images and show a target appearance, with seen the rim appearing hypointense relative to the centre – ‘peripheral washout’ sign Hypervascular Metastasis

D/D hypervascular hepatic metastasis The peripheral washout sign: This target appearance has been reported to be highly specific for hypervascular metastasis and is frequently seen in metastases from neuroendocrine and carcinoid tumours.

Peripherally enhancing/cystic metastasis This pattern of metastasis is seen in hypervascular metastatic tumours with rapid growth, which leads to necrosis and cystic degeneration like metastases from neuroendocrine

tumours, sarcoma, melanoma and certain subtypes of lung and breast carcinomas. Cystic metastases may also be seen with mucinous adenocarcinomas, such as colorectal or ovarian carcinoma. Imaging Target-like pattern of enhancement is seen (Figs. 9.11.70 and 9.11.71). The enhancing tumour periphery may be thick or thin. High signal on T1W1 images can be seen in some metastatic lesions like metastases from melanoma (melanin, extracellular methemoglobin), colonic adenocarcinoma (haemorrhage or coagulative necrosis), ovarian adenocarcinoma (protein), multiple myeloma (protein) and pancreatic mucinous cystic tumour.

FIG. 9.11.70 Ring-like enhancing metastasis from colorectal cancer. Multiple ring-like enhancing lesions in both lobes of liver suggestive of metastasis.

FIG. 9.11.71 Cystic metastasis in a patient with rectal cancer. K/c/o mucinous carcinoma of the rectum showing innumerable cystic peripheral ring-like enhancing lesions in both lobes. Ring-like enhancing lesions in an adult with no history of sepsis or locoregional ablation should be considered as metastasis. D/D of ring-like enhancing liver lesions: 1. Multiple abscesses • History of cholangitis usually present 2. Atypical HCC 3. Post-RFA HCC • History of ablation present 4. ICC • Usually shows centripetal filling-in with positive peripheral washout

Hypovascular metastasis Colon, lung, breast and gastric carcinomas are the most common causes of hypovascular liver metastases. These are best seen on the portal venous phase and show minimal enhancement.

Diffuse hepatic parenchymal metastasis Diffuse infiltrative tumour invasion into the liver is a less common form of metastatic disease. This pattern is seen in haematological malignancies, breast, lung, stomach, colon, pancreatic, nasopharynx, urothelial, uterine and malignant melanoma.

Imaging Most frequently seen finding is hepatomegaly without obvious identifiable nodule. Heterogeneous enhancement of liver parenchyma on contrast-enhanced CT and MRI is seen. Multiple tiny nodules replacing parenchyma may be seen.

FIG. 9.11.72 Diffuse metastasis in case of breast carcinoma. K/c/o metastatic Ca breast with deranged LFTs. Contrast-enhanced MRI showing gross hepatomegaly with heterogeneous enhancement suggesting diffuse infiltrative metastasis.

Hepatic capsular retraction in metastasis Since metastases are the most common form of hepatic malignancy, they constitute the most common cause of focal capsular retraction, even though only a small percentage of hepatic metastases demonstrate this sign. Capsular retraction usually occurs adjacent to subcapsular metastases after treatment with chemotherapy, radiation therapy or RFA. Untreated metastasis can also cause capsular retraction, especially from tumours that contain or induce substantial fibrosis, such as lung, breast and colon carcinomas, and carcinoid tumour. Extreme capsule retraction with pseudocirrhosis appearance has been reported in both untreated and treated breast cancer metastases.

DWI in hepatic metastasis Low b value DWI acquisition (60% should be treated according to type of shunt. Patients with type 1 shunts should be transplanted. Patients with type 2 shunts should be treated with shunt closure – either via embolization or surgical. Liver transplantation is considered when medical and surgical methods fail especially in patients with complications.

Congenital intrahepatic portosystemic shunts Intrahepatic portosystemic shunts are rare. They may be congenital or result from trauma or portal hypertension. They develop due to persistent communications between vitelline and umbilical systems. Intrahepatic shunts These are communications between the branches of the PV and inferior vena cava (IVC). Park et al. classified these 1990 in four types. Type 5 was added later, these are classified in Table 9.12.4.

TABLE 9.12.4 Parks Classification of Intrahepatic Shunts • Type 1 – Single tube-like vessel connecting the right branch of PV to IVC • Type 2 – Localized peripheral shunt in which one hepatic segment has communications between the peripheral branches of the PV and the hepatic veins • Type 3 – Aneurysmal communication between peripheral PV and hepatic vein • Type 4 – Multiple intrahepatic shunts in both lobes of liver • Type 5 – Persistent ductus venosus (suggested later) Type 2 shunt with or without a focal varix is the most common type reported. Another classification system is proposed by Kanasawa et al. based on correlation with severity of portal hypoplasia (mild, moderate and severe) with portal venous pressure, histopathological findings, postoperative portal venous flow and hepatic regeneration. Associations and clinical course Associated anomalies such as cardiovascular, hepatobiliary, urogenital and gastrointenstinal can be seen. Complications such as portopulmonary hypertension are seen in 13%–66% children. As a consequence of long-term shunting, hepatic encephalopathy, and hepatopulmonary syndrome are the most common symptoms. Tumours such as FNH and regenerating nodular hyperplasia can be seen. These shunts may close spontaneously within the first 2 years of life or may remain asymptomatic and undetected for several years. When chronic shunting persists into adulthood, patients most often present with encephalopathy. Imaging USG and colour doppler The feeding (afferent) and draining (efferent) vessels of the shunt appear as enlarged, tubular, anechoic structures that are contiguous with the portal and hepatic veins. Antegrade flow is seen on colour Doppler images. Focal varix if present appears as an abnormal, rounded cystic structure with turbulent flow. Doppler study can also calculate the shunt ratio (total blood flow volume in the shunt divided by the blood flow in the portal vein). Shunt ratios greater than 60% should be corrected to prevent complications. Loss of normal undulating waveform of afferent

portal vein branch with increased flow velocity and phasic waveforms owing to transmitted cardiac pulsations can be seen. The efferent hepatic vein branch of the shunt can show continuous flow with flattening of the Doppler waveform due to increased portal venous inflow. CT/MRI Communication between intrahepatic portal venous and peripheral hepatic venous radicals can be demonstrated easily on both contrast-enhanced CT and MRI. Similar to extrahepatic shunts CT is preferred over MRI in documentation of shunts. The afferent portal vein branch and the efferent hepatic vein branch are enlarged. Venous varices can be seen. The draining hepatic vein branch opacifies earlier than other hepatic veins (Fig. 9.12.6 and Table 9.12.5).

FIG. 9.12.6 Case of congenital intrahepatic portosystemic shunt. Contrast-enhanced CT in venous phase showing shunts between portal vein and hepatic veins (arrows). TABLE 9.12.5 Congenital Intrahepatic Portosystemic Shunts • Rare shunts due to persistent communications between vitelline and umbilical systems • Type 2 shunt with or without a focal varix is the most common type • Association with other anomalies maybe seen • Hepatic encephalopathy and hepatopulmonary syndrome are the most common symptoms. Patients may also develop hepatic tumours • Shunts may spontaneously close or remain asymptomatic • Feeding (afferent) and draining (efferent) vessels of the shunt can be documented on imaging. Shunt ratios can be calculated on USG • Treatment can be medical or involve shunt ligation

The liver may show fatty degeneration and atrophy, but when the anomaly is corrected, fatty replacement disappears and liver size increases. Treatment Conservative medical therapy including restriction of protein and ingestion of lactulose. Symptomatic intrahepatic portosystemic shunts can be managed conservatively or with transcatheter embolization, surgical ligation or partial hepatectomy.

Patent ductus venosus The connection between the left umbilical vein and right hepatocardiac vein (future IVC) in the foetal circulation is called ductus venosus. This vessel is responsible for carrying nutrient-rich blood from placenta to the right atrium directly by bypassing the sinusoidal plexus of the liver. The umbilical vein and ductus venosus close at birth and form the ligamentum teres and ligamentum venous, respectively. The time interval following birth for closure of ductus venosus is variable ranging from few minutes after birth to 18 days in term neonates and as late as 37 days in premature infants. Patent ductus venosus is an intrahepatic portocaval shunt causing partial or complete diversion of portal blood to the systemic circulation and may present with hyperammonemia. Imaging Patent ductus venosus is seen on Doppler sonography as a vascular tubular structure in the left lobe of the liver, continuing from the umbilical vein and connecting the portal vein to the inferior vena cava. The foetal ductus venosus show waveforms similar to IVC corresponding to the cardiac cycle with a systolic and diastolic component. This diphasic waveform is seen in preterm and term infants and becomes monophasic as ductus closes. CT and MRI also accurately detect the shunt and patency. Associated hepatic lesions seen in patients with portosystemic shunts can be diagnosed and characterized better. Treatment Treatment (closure) is recommended in cases with complications or to prevent complications if the shunts persisted beyond 2 years of age.

Shunt closure can be performed surgically or endoscopically. The complex nature of the shunt can pose problems during surgical closure. Transvenous and balloon occlusion have been done successfully.

Portal venous thrombosis Occlusion of portal vein can occur due to a variety of conditions. The aetiologies of portal venous thrombosis in the neonatal age group include umbilical vein catheterization, omphalitis, dehydration or neonatal sepsis. Older children develop occlusion secondary to intraabdominal infections and portal hypertension. Other aetiological factors include prothrombotic states such as hereditary deficiency of protein C or protein S and factor V Leiden deficiency, vascular injury, trauma, stasis and congenital anomalies such as webs. Clinical presentation Acute portal vein thrombosis can be asymptomatic, or the patient may present with abdominal pain, ascites or fever. Chronic portal vein thrombosis presents as ascites, encephalopathy, varices and upper gastrointestinal bleeding. Imaging Acute thrombus appears hypoechoic filling defect on USG with absent flow on Doppler. There is distension of the thrombosed vein (Fig. 9.12.7).

FIG. 9.12.7 USG in portal vein thrombus. Grey scale USG showing echogenic thrombus occluding the lumen of the main portal vein (arrows). CT and MRI with contrast will detect filling defect in the vein with distension. T2W1 images may show absence of flow void. Acute thrombus may appear hyperintense on T1W1 images. Tumour thrombus reveals signal similar to tumour on all sequences with diffusion restriction (Fig. 9.12.8).

FIG. 9.12.8 MRI showing malignant portal venous thrombus. T2W1 (A) showing hyperintense thrombus within the lumen of the right portal vein and its branches (arrows). Thrombus appears as filling defect on portal venous phase (arrows in B). T2 hyperintense portal thrombi are usually malignant, particularly in the setting of cirrhosis.

Chronic thrombus may present as eccentric filling defect, attenuation of vein or less commonly calcification of vessel wall. Collaterals are often seen in chronic portal vein thrombosis. Treatment usually involves combination of anticoagulation and intervention depending on age of thrombus. An acute portal venous thrombus may undergo partial or complete spontaneous resolution. 4. EHPVO – extrahepatic portal venous obstruction The commonest cause of paediatric portal hypertension in the developing world is extrahepatic portal vein obstruction (EHPVO). It is also the second most common cause of portal hypertension in the western world. EHPVO is a condition characterized by obstruction of the extrahepatic portal vein (as the name suggests) with or without associated involvement of the intrahepatic branches, splenic vein (SV) or superior mesenteric vein (SMV). The hallmark of this chronic longstanding condition is carvernomatous transformation of the portal vein. Acute and chronic portal vein thromboses occurring in the setting of liver cirrhosis or HCC are not included in this disorder. EHPVO is an important cause of noncirrhotic portal hypertension with preserved liver structure and function till late in course of the disease. Proposed aetiologies include infection or prothrombotic event occurring early in life (in genetically predisposed individuals), leading to portal venous occlusion (Table 9.12.6). TABLE 9.12.6 Aetiologies of EHPVO

Clinical presentation Patients with EHPVO typically present in the first two decades with symptomatic PHT most commonly with upper gastrointestinal bleed. Biliary complications (portal cavernoma cholangiopathy), hypersplenism, neurocognitive dysfunction due to subclinical hepatic encephalopathy and growth retardation are other symptoms (Fig. 9.12.9).

FIG. 9.12.9 Diagram showing occlusion of the main portal vein with collaterals in the periportal and peribiliary regions with biliary dilatation. 1. Venous changes in EHPVO Portal venous thrombosis leads to development of cavernoma. These extensive portoportal collaterals develop in an attempt to preserve hepatopetal flow. The collaterals are formed via the two well-formed venous plexi of the bile ducts: paracholedochal and epicholedochal plexi of Petren and Saint, respectively. These collaterals are however, insufficient to bypass the entire splenomesenteric inflow resulting in development of portal hypertension with formation of portosystemic shunts (primarily via the left gastric vein and the perisplenic veins) and splenic enlargement. Since portal hypertension occurs in the presence of a functionally and morphologically normal liver it is termed Non cirrhotic portal hypertension (Flowchart 9.12.4).

FLOWCHART 9.12.4 Portal venous thrombosis leads to development of cavernoma. These extensive portoportal collaterals develop in an attempt to preserve hepatopetal flow. The collaterals are formed via the two wellformed venous plexi of the bile ducts: paracholedochal and epicholedochal plexi of Petren and Saint, respectively. These collaterals are however, insufficient to bypass the entire splenomesenteric inflow resulting in development of portal hypertension with formation of portosystemic shunts (primarily via the left gastric vein and the perisplenic veins) and splenic enlargement. Since portal hypertension occurs in the presence of a functionally and morphologically normal liver it is termed noncirrhotic portal hypertension. 2. Biliary changes Anatomical contact between the biliary tree and portal venous cavernoma predisposes to a high incidence of biliary changes, seen in 70%–100% cases. Biliary involvement occurs either due to extrinsic mechanical compression or ischaemic insult with subsequent fibrosis of the biliary tree (Fig. 9.12.10).

FIG. 9.12.10 Diagram showing occlusion of main portal vein with periportal, para and epicholedochal collaterals with biliary dilatation. The biliary changes seen secondary to cholangiopathy includes extrinsic indentations, luminal narrowing ± upstream dilatation, bile duct thickening, angulation/displacement of the extrahepatic duct, choledocholithiasis and hepatolithiasis. The suprapancreatic common duct is the most commonly involved, and the stenosis can be either short segment (25 mm). 3. Hepatic changes Since EHPVO is primarily a prehepatic disorder, and the liver size, architecture, volume and echotexture remain normal. Compromised portal perfusion over a long period of time leads to smooth hepatic atrophy. Poor peripheral perfusion leads to subcapsular atrophy with nodular liver contours. 4. Splenic changes Patients with EHPVO have a hyperdynamic circulation with increased splenic blood flow and consequent moderate to massive splenomegaly (average size, 11 cm below the costal margin). The presence of Gamma–Gandy bodies on imaging is an indication of longstanding PHT. 5. Arterial changes

Splenic artery aneurysms can be seen as a result of splenic hyperkinetic state, and are often large at presentation. Those >2 cm are at high risk of rupture and should be treated. Imaging USG Ultrasound–Doppler has a high sensitivity and specificity (>95%) for establishing EHPVO. Portal cavernoma is seen as multiple hypoechoic vessels in the hepatoduodenal ligament, porta hepatis, peripancreatic or pericholecystic region with possible extension into the liver hilum. The portoportal collaterals show monophasic hepatopetal flow with loss of normal respiratory undulations. Dilatation of intrahepatic biliary radicals representing changes of biliopathy can be seen. Liver parenchymal changes, heterogeneous echotexture, splenomegaly can be accurately diagnosed (Fig. 9.12.11).

FIG. 9.12.11 USG showing EHPVO. Grey scale ultrasound image (A) showing multiple anechoic channels in periportal region (arrows). Colour Doppler images (B) showing collaterals (arrows). CT/MRI CT/MRI allows assessment of the exact extent of obstruction of the portosplenomesenteric axis. Typical findings seen include nonvisualization of main portal vein and or its right, left branches. Cavernoma is well visualized and seen as multiple flow voids/enhancing venous collaterals (Figs. 9.12.12 and 9.12.13). Concomitant SV/SMV thrombosis should be looked for as it may alter treatment. Identification of shunts should be done providing a roadmap for interventional and surgical procedures. For a surgical anastomosis to be successful and satisfactory decompression of the portal system, the shunt should be of sufficient size (at least 10 mm in diameter).

The renal vein and inferior vena cava patency should be assessed (Fig. 9.12.14).

FIG. 9.12.12 Classic cavernoma formation in EHPVO. Contrast-enhanced portal venous phase images (A,B) shows occlusion of portal vein with cavernoma formation (arrows). Note that despite patient having longstanding portal occlusion, the liver is not cirrhotic.

FIG. 9.12.13 C/o EHPVO with portal cavernoma formation. Contrast-enhanced CT in portal venous phase showing cavernoma with collaterals in periportal, pericholecystic and pericholedochal regions. Note the gross splenomegaly which is classically seen in patients with EHPVO.

FIG. 9.12.14 EHPVO with predominantly leftsided collaterals. Portal venous phase images (A to C) in a patient with EHPVO showing large left-sided, peripancreatic collaterals. Note the paracholedochal collaterals around the CBD (arrows). In addition, apart from confirming the diagnosis, cross-sectional imaging allows exclusion of tumoral PVT and other possible causes of portal vein obstruction tumour-like cavernoma. Variable degrees of dilatation of biliary radicals can be seen with collaterals along wall of ducts. In the chronic phase the collaterals there is development of fibrosis and the collaterals decrease in number. This fibrosis also leads to biliary narrowing with proximal dilatation. Fibrosis classically appears as T2 hypointense plaque-like wall thickening along the ducts and shows enhancement on delayed phase (Fig. 9.12.15).

FIG. 9.12.15 Portal biliopathy. k/c/o EHPVO showing multiple periportal collaterals with cavernoma formation (arrows from A–C). Note the extensive paracholedochal collaterals causing biliary dilatation (arrows in D–F). MRCP is the modality of choice in diagnosing changes of biliopathy. The three types of portal cavernoma cholangiopathy have been described. These include varicoid type, fibrotic type and mixed type. In the varicoid variety of PCC paracholedochal venous plexus of Petren cause mechanical compression over the biliary tree. This leads to wavy contour of the bile ducts. Decompression of splanchnic system may lead to reversal of changes. The fibrotic variety is caused by Epicholedochal collaterals of Saint. These lead to ischaemia and fibrosis of the bile ducts with resultant structuring. The narrowed biliary segments show enhancement on contrast study which progresses on delayed phase. These don’t revert following shunt surgery. The mixed variety is caused by both Plexi of Petren and Siant and shows a combination of both extrinsic compression and ischaemic fibrosis. Imaging shows both biliary undulations and strictures showing progressive delayed enhancement. Response to shunting is variable (Figs. 9.12.16 and 9.12.17).

FIG. 9.12.16 Longstanding EHPVO with fibrotic cavernoma cholangiopathy. Contrastenhanced CT in portal venous phase (A–D) showing plaque-like enhancing fibrosis around the bile ducts (arrows in A–C) T2WI images in axial and coronal plain (F–G) showing hypointense soft tissue around the bile ducts (arrows). Not the stenosis of the mid CBD secondary to fibrosis on MRCP images (H,I).

FIG. 9.12.17 Longstanding EHPVO with portal biliopathy. T2W1 images (A, B) showing hypointense plaque-like fibrosis around the bile ducts (arrows). MRCP images (C,D) showing stricture in the CBD and right duct at confluence (arrows). Contrast-enhanced venous phase shows occluded portosplenic system with collaterals postcontrast coronal images show plaque-like enhancement of the fibrotic cholangiopathy. Heterogeneous enhancement of the liver, with relative hypoenhancement of the periphery without changes of cirrhosis can be seen. CT/MR can accurately diagnose splenic artery aneurysms. Treatment A multidisciplinary approach is needed that includes the management of variceal bleed, portal biliopathy and massive splenomegaly. Treatment options include medical management, endoscopic variceal ligation, endotherapy (biliary stenting±sphincterotomy, stone extraction etc.) and surgical methods such as portosystemic shunting and splenectomy. Surgical shunts such as splenorenal or mesentericocaval anastomosis or Rex shunt (mesenterico – left portal vein bypass) can decompress the portomesenteric axis. Rex shunt is preferable in children, due to the fact that it is more physiological (Fig. 9.12.18 and Table 9.12.7).

FIG. 9.12.18 Shunt procedures in EHPVO.

TABLE 9.12.7 EHPVO • Important cause of noncirrhotic portal hypertension and commonest cause of portal hypertension in children in developing world • Cavernomatous transformation of portal vein is seen, pericholedochal and epicholedochal collaterals • Morphologically and functionally normal liver • Biliary anomalies include extrinsic indentations, luminal narrowing ± upstream dilatation, bile duct thickening, angulation/displacement of the extrahepatic duct, choledocholithiasis and hepatolithiasis and involve suprapancreatic segment of CBD most commonly • Liver size, morphology and echotexture remain normal • Splenomegaly with aneurysms may be seen. • Collaterals are well seen on imaging modalities • Biliary changes are bets evaluated on MRCP • In late phase fibrosis may replace collaterals and show plaquelike enhancement • Multimodality treatment involving conservative medical therapy, endoscopic variceal ligation, endotherapy (biliary stenting ± sphincterotomy, stone extraction etc.) to surgical intervention

Portal vein stenosis Narrowing of a segment of portal vein is not uncommon and can be secondary to various conditions Aetiologies • Tumour encasement by pancreatic carcinoma, cholangiocarcinoma, hepatocellular carcinoma and metastases • Acute pancreatitis • Postsurgical complications of liver transplantation, partial hepatectomy and Whipple procedure • Radiation therapy USG Focal area of vessel narrowing with colour aliasing on Doppler. At duplex Doppler US, accelerated flow across the stenosis may be seen with spectral broadening of the waveform suggesting poststenotic turbulence. Extensive portosystemic collaterals can however lead to dampening of venous flow to the extent that

neither accelerated flow velocity nor poststenotic turbulence can be seen. CT/MRI Focal narrowing of the portal vein can be, with or without poststenotic dilatation. Portal vein stenosis may lead to portal venous hypertension. Treatment Treatment if needed includes percutaneous venoplasty with or without stent placement.

Pylephlebitis Pylephlebitis, also known as acute suppurative thrombophlebitis of the portal venous system is a rare condition occurring as a complication of intraabdominal infections affecting portal venous drainage territories such as diverticulitis, appendicitis, pancreatitis or inflammatory bowel disease. Contiguous extension of a periportal infection from infectious source is the aetiology. Gram-negative bacilli are the usual microorganism, and patients present with nonspecific abdominal pain and sepsis. Untreated, this condition has a high mortality of approximately 50% due to bowel ischaemia, hepatic abscesses and sepsis. Imaging USG An acute thrombus appears hyperechoic, and gas within the portal venous system appears as hyperechoic shadowing foci. CT CT is the modality of choice owing to its ability to identify the source, features of thrombophlebitis and secondary complications. On contrast-enhanced CT images, an infected portal thrombus appears as a hypodense filling defect that expands the portal vein or its tributaries Portal pyaemia may appear fluid density in the postal venous thrombus with air fluid levels. Periportal fat stranding can be seen. Treatment Systemic antibiotic therapy with or without percutaneous drainage of hepatic abscesses and portal pyaemia.

Portal venous gas Rare entity, which is increasingly recognized now due to widespread use of imaging. Aetiologies include a. bowel ischemia b. inflammatory bowel disease c. bowel distension d. intraabdominal sepsis USG Hyperechoic mobile foci are seen in the lumen of the portal vein. Comet tail artefact can be seen as a result of gas locules in the hepatic periphery leading to heterogeneous hepatic appearance. Sharp high-amplitude bidirectional spikes can be seen on duplex Doppler. On CT portal venous gas is seen as air density linear, branching or ovoid structures. Portal vein gas is often seen in the hepatic periphery predominantly in the left lobe, as opposed to pneumobilia which is more central (Fig. 9.12.19).

FIG. 9.12.19 Portal venous gas. Contrastenhanced CT in portal venous phase showing gas in the portal vein (arrows).

Varix Varix or aneurysm of the portal venous system is localized saccular or fusiform dilatation of the portal vein with diameter substantially greater than rest of the vessel, and is usually more than 2 cm in diameter. An intrahepatic portal venous diameter greater than 0.7 cm in healthy liver or more than 0.85 cm in cirrhotic liver also constitutes a varix. The most commonly affected vein includes the extrahepatic portal vein, followed by the splenomesenteric venous confluence, intrahepatic portal vein, splenic vein, SMV and inferior mesenteric vein. Portal hypertension is discussed in details in chapter 9.9.

Hepatic arterial 1. Hepatic arterial thrombosis Thrombosis of the hepatic artery is the commonest posttransplant complication. This condition can also occur following other hepatobiliary surgeries such as Whipple’s procedure. Thrombosis usually occurs within first 4 months of transplantation and is a significant cause of retransplantation (Fig. 9.12.20).

FIG. 9.12.20 Hepatic arterial thrombosis. Contrast enhanced CT showing occluded hepatic artery. The intrahepatic artery is seen reforming through collaterals. Imaging is discussed in chapter on liver transplant.

2. Hepatic artery stenosis This is also usually seen the setting of liver transplantation. USG Focal peak velocity of greater than 200 cm/sec in the hepatic artery is considered diagnostic. Tardus parvus waveform is seen in the intrahepatic vessels, which is characterized by prolonged acceleration time of greater than 80 msec and a low resistance index of less than 0.5 (Fig. 9.12.21).

FIG. 9.12.21 Hepatic artery stenosis on Doppler. Contrast-enhanced CT in arterial phase in a patient who underwent liver transplant shows stenosis of hepatic artery (arrows in A) with elevated peak velocities. Dampening of intrahepatic waveform is seen (arrow in B). CT/MR angiography CT/MR angiography will show area of stenosis in the vessel accurately. Narrowing of the vessel with or without post stenotic dilatation can be seen. 3. Hepatic arterial aneurysms Hepatic artery aneurysms are classified as true aneurysms or pseudoaneurysms. True aneurysms contain all three vessel wall layers, while pseudoaneurysms consist of only one or two vessel wall layers. Causes of aneurysms • Fibrodysplasia (such as neurofibromatosis 1)

• medium-vessel vasculitides such as Kawasaki disease and polyarteritis nodosa Causes of pseudoaneurysms • Trauma (blunt, penetrating, or iatrogenic), and are typically extrahepatic at the arterial anastomotic site. Intrahepatic pseudoaneurysms are less common and can result from percutaneous procedures. • Infection (mycotic pseudoaneurysms) Clinical findings. True hepatic artery aneurysms are typically clinically silent and are detected at imaging, while pseudoaneurysms typically manifest with abdominal pain, haemorrhage and/or haemophilia. A triad of epigastric pain, haemophilia and obstructive jaundice (Quincke triad) is seen in up to one-third of cases. Imaging Focal dilatation of the hepatic artery with bidirectional flow and yin–yang pattern of flow is seen on colour and spectral Doppler. Haematoma and peripheral calcification can be seen on nonenhanced CT. Contrast-enhanced CT and MR show focal dilatation of the hepatic artery (Figs. 9.12.22 and 9.12.23).

FIG. 9.12.22 Hepatic artery aneurysms in a patient with polyarteritis nodosa.

FIG. 9.12.23 Hepatic artery pseudoaneurysm in a patient with blunt abdominal trauma. Contrast-enhanced axial late arterial phase (A) and reformatted coronal images (B) show pseudoaneurysm of the hepatic artery (arrows). Note the large contusion/laceration in the liver with haematoma. Air foci are the result of surgical packing with gauze to achieve tamponade. Endovascular treatment is indicated for symptomatic aneurysms larger than 2 cm.

Hepatic venous anomalies Budd–chiari syndrome This is a rare disorder characterized by obstruction of hepatic venous outflow anywhere from the small hepatic veins to the IVC– right atrium junction. BCS can be classified as primary, when the blockage is intrinsic to the vein (i.e. thrombosis or phlebitis), or as secondary, when the obstruction or compression originates external to the vein (i.e. compression or invasion by a tumour or a benign mass, such as an abscess or cyst). Budd–Chiari syndrome can be classified according to the duration of disease (Table 9.12.8).

TABLE 9.12.8 Classification of Budd Chiari Syndrome Based on Duration of Disease Type Duration Fulminant Patients present within 8 weeks of development of jaundice with features of encephalopathy Acute Short duration (6 months). Complications of chronic liver disease, cirrhosis are seen in addition to features of chronic liver disease

Epidemiology and demographics Epidemiology depends on ethnicity. In Western countries, women are more commonly affected (approximately 2/3 of cases). In Asia, men are slightly more affected (approximately 1.5/1). In Western countries, presentation is usually in the third and fourth decades of life, with the median age being 35–50 years. In Asia, presentation is usually at a median age of 36 years. Aetiologies Approximately 80%–87% of patients have one prothrombotic risk factor, and approximately 50% have multiple. The aetiological factors usually involve prothrombotic state and have been described in Table 9.12.9.

TABLE 9.12.9 Etiologies for Budd–Chiari Syndrome

Pathophysiology Occlusion of the hepatic veins leads to elevated sinusoidal pressure causing hepatic congestion and increased lymphatic infiltration. Once the capacity of lymphatic drainage is exhausted the proteinaceous fluid exudes through the hepatic capsule resulting in ascites. Elevation of sinusoidal pressure along with impaired venous drainage leads to development of intra or extrahepatic collaterals. Discrepancy in time intervals for development of hepatic venous obstruction (asynchronous involvement) leads to coexistence of atrophic and hypertrophic segments. This results in the ‘hepatic dysmorphy’. The most characteristic feature of ‘hepatic dysmorphy’ is irregular liver contours. Without treatment, irreversible liver abnormalities progressively develop such as centrilobular fibrosis. Subsequently there is decrease in portal venous flow with compensatory, hepatic hyperarterialization, leading to liver regeneration in the form of focal nodular hyperplasia or regenerative nodules with a typical periportal distribution. Pathophysiology of BCS (Flowchart 9.12.5) BCS can also be classified based on level of obstruction into four types, depending on whether there is involvement of only hepatic veins, IVC or both with thrombosis or webs (Table 9.12.10).

FLOWCHART 9.12.5 Pathophysiology of BCS. TABLE 9.12.10 Classification of BCS Based on Level of Obstruction Type 1 Type 2 Type 3 Type 4

Hepatic vein obstruction or thrombosis without IVC obstruction or compression Hepatic vein obstruction or thrombosis with IVC obstruction or thrombosis Isolated hepatic venous webs Isolated IVC webs

Clinical presentation The classic presentation of Budd–Chiari syndrome includes hepatomegaly, ascites and right upper quadrant pain. Presentation is variable according to the degree, location, acuity of obstruction and presence of collateral circulation.

1. Acute/fulminant – (25%): These patients present with severe right upper abdominal pain, fever, nausea, vomiting, mild jaundice, hepatomegaly with ascites. Marked elevation in serum aminotransferases (AST/ALT > 5 times the upper limit of normal), elevation of alkaline phosphatase to 300– 400 IU/L, serum–ascites albumin gradient ≥ 1.1 with total protein > 2.5 g/dL, coagulopathy are seen. Variceal bleeding, encephalopathy occur within 8 weeks of onset of jaundice, renal failure. 2. Subacute/Chronic – (60%): Vague abdominal discomfort, gradual progression to caudate lobe hypertrophy with atrophy of the rest of the liver can be seen. Subacute disease may also have features of portal hypertension with or without cirrhosis and its sequelae. Mild to moderate elevation in aminotransferases, bilirubin and alkaline phosphatase, hepatorenal syndrome, hepatopulmonary syndrome and rarely, encephalopathy can occur. 3. Asymptomatic – (20%): Discovered incidentally by abnormal liver function tests or imaging done for other reasons.

Imaging USG Grey scale Sonography is the first investigation in patients with BCS and provides diagnostic and haemodynamic information. A membrane or web is seen as an echogenic crescent-shaped focus constricting the lumen. Thrombus is seen as a hyperechogenic cord-like can be seen occluding the vessel. Large hepatic vein may indicate downstream stenosis usually involving the ostium of the hepatic veins or due to intrahepatic collateralization. In advanced disease, there is attenuation with poor visualization of the hepatic veins (Fig. 9.12.24 and Table 9.12.11).

FIG. 9.12.24 Thrombosed echogenic cord-like RHV. Grey scale ultrasound showing hypoechoic thrombosed cord-like right hepatic vein (arrows). (Source: Courtesy of Dr Nitin Chubal.) TABLE 9.12.11 USG Findings in Budd-Chiari Syndrome • Membrane/web/thrombus seen as echogenic structures • Venous stenosis, attenuation, intrahepatic collaterals well seen • Collaterals can hockey– ‘stick’, ‘comma’, ‘undulated’, ‘H-shaped’, or ‘inverted U-shaped’ • Dilated inferior right hepatic vein and caudate vein • Abnormalities of hepatic contour and enlarged caudate lobe The other vessels that should be imaged include inferior right hepatic vein and caudate vein are. The right inferior hepatic vein serves as the main drainage vessel of the right lobe in patients with right hepatic venous occlusion. The drainage of the caudate lobe via the caudate vein is preserved in Budd–Chiari syndrome. A caudate vein more than 3 mm is seen in 50% patients and may raise suspicion of BCS. Intrahepatic collaterals are seen in 90% patients with BCS. These intrahepatic collaterals connect the patent portion of the obliterated hepatic vein with a normal vein. These collaterals have various configurations such as hockey stick, comma, undulated, H- or inverted U-shaped. Caudate lobe hypertrophy is a feature commonly seen in BCS owing to preserved drainage. A mean anteroposterior diameter greater than 35 mm is seen. The inferior vena cava may show narrowing due to compression by enlarged caudate lobe. Ascites is commonly seen in BCS.

Colour doppler Flow pattern in IVC or hepatic veins or both changes from phasic to absent, continuous, turbulent or reversed. Reversal of portal flow can also be seen. Thrombus or webs can be identified as absence of flow in affected veins. Intrahepatic collaterals is well identified (Figs. 9.12.25–9.12.30).

FIG. 9.12.25 Turbulent flow in IVC. Grey scale (A) and Doppler images (B) showing stenosis of IVC (yellow arrows) with turbulent flow on Doppler. (Source: Courtesy of Dr Nitin Chubal.)

FIG. 9.12.26 Narrowing of IVC with turbulent flow. Grey scale USG images (A) showing IVC stenosis (yellow arrows). Turbulent flow is seen on Doppler (arrows) with high velocities and loss of phasicity. (Source: Courtesy of Dr Nitin Chubal.)

FIG. 9.12.27 Hepatic venous aneurysm in Budd–Chiari syndrome. Grey scale and colour doppler images show aneuysmal dilatation of right hepatic vein (arrows). (Source: Courtesy of Dr Nitin Chubal.)

FIG. 9.12.28 Narrowing with ectasia Of the IVC. Case of Budd–Chairi syndrome showing areas of narrowing with ectasia in the hepatic veins. (Source: Courtesy of Dr Nitin Chubal.)

FIG. 9.12.29 Turbulent flow in hepatic veins. Case of Budd–Chiari syndrome showing turbulent flow in the left hepatic vein (arrows). (Source: Courtesy of Dr Nitin Chubal.)

FIG. 9.12.30 Dampened flow in hepatic veins. Dampening of flow in hepatic veins with loss of phasicity in Budd–Chiari syndrome. (Source: Courtesy of Dr Nitin Chubal.) Doppler can also be used in post-TIPSS setting to accurately detect patency.

MRI MR imaging is preferred as a second line of investigation. MRI findings in BCS can be divided into 1. Imaging of liver parenchymal, morphology changes 2. Imaging of hepatic nodules associated with BCS 3. Imaging of veins 1. Imaging of liver parenchymal, morphology changes (Table 9.12.12) The MRI signal intensity depends on the variations in perfusion, necrosis, hypertrophy and atrophy. a. Acute phase – MRI shows hepatomegaly with decreased T1weighted and slightly elevated T2-weighted signals in the central liver. There is increased enhancement within caudate lobe on arterial phase which persists on delayedphase images, due to its separate venous drainage. Enhancement of liver periphery is heterogeneously decreased throughout early, late and delayed-phase images due to lack of venous collaterals. The central portions of liver reveal enhancement in arterial phase. A ‘flip–flop’ pattern of enhancement is seen in the portal venous phase, with low attenuation of the central part of the liver because of washout and gradually increase in attenuation in the

peripheral part of the liver due to accumulation of contrast material from capsular veins (Figs. 9.12.31 and 9.12.32). b. Subacute stage – Enhancement differences throughout the hepatic parenchyma are minimal. After the formation of intra- and extrahepatic collateral veins, more stable hepatic perfusion occurs with resultant homogeneity of enhancement. The caudate lobe reveals normal signal on all sequences, while the hepatic periphery shows heterogeneously decreased and increased signal on T1- and T2-weighted images, respectively. c. Chronic stage – Progression to cirrhosis may occur with presence of regenerating nodules. Changes in liver morphology maybe seen. Differential signal intensities and enhancement are more subtle in chronic stage. In Budd– Chiari syndrome, hypertrophy of caudate lobe is found in 60%–87% of all cases. TABLE 9.12.12 MRI in Budd-Chiari Syndrome • Signal intensity of liver depends on stage. Acute stage showing significant heterogeneity of signal and enhancement with flip–flop pattern • Signal and enhancement becomes progressively more homogeneous in subacute and chronic stage • Adequate delays on poststudy needed for accurate depiction of venous anatomy and avoiding false-positive results • Type and extent of venous occlusion, intrahepatic and extrahepatic collaterals are well identified • BCS-related regenerating nodules, HCC can be diagnosed • Morphological changes in liver, caudate hypertrophy, features of portal hypertension can be accurately detected. • Both CT/MR venography provide crucial information and roadmap in guiding intervention therapy

FIG. 9.12.31 Heterogeneous liver enhancement in acute BCS. Case of Budd– Chiari syndrome showing hepatomegaly with caudate hypertrophy (arrows in A). Note heterogeneous enhancement of the liver in the arterial phase with early hyperenhacement of the central portion (arrows in C). Washout of contrast is seen in venous phase (flip–flop pattern). The hepatic veins are not seen and multiple collaterals are identified (yellow arrow).

FIG. 9.12.32 Acute Budd–Chiari with heterogeneous liver enhancement. Postcontrast MRI (A to C) showing morphological changes in the form of patchy decreased enhancement in the liver periphery (yellow arrow), while central portions and caudate lobe enhance normally (white arrows). Parenchymal phase images (D) show thrombus in hepatic veins (blue arrows). Note multiple intrahepatic collaterals in E (red arrows). 2. Imaging of liver nodules Parenchymal lesions such as benign regeneration nodules, perfusion disorders can be seen. These patients are also at risk for development of HCC. Benign regenerative nodules are typically multiple (>10), smaller than 4 cm and hypervascular. These usually appear hyperintense on T1-weighted images, iso–/hypointense on T2-weighted images and show intense arterial enhancement on dynamic imaging. Number of these nodules progressively increases during the consecutive phases of MR angiography and their enhancement persists until the late venous phase (Fig. 9.12.33).

FIG. 9.12.33 Case of chronic Budd–Chiari syndrome with cirrhosis. T21W1 (A and B) showing changes of cirrhosis of liver with gross splenomegaly. T1W1 images (C and D) showing multiple large hyperintense nodules in both lobes (arrows). Postcontrast T1W1 images in portal venous phase shows mild enhancement of these nodules (yellow arrows) (confirmed on subtraction images) with multiple other hypoenhancing nodules in both lobes (blue arrows). Venous phase images reveal abnormal configuration of the hepatic veins (arrows) with intrahepatic collaterals. Note stenosis of the IVC on coronal T1W1 images (arrows). It is important to distinguish benign regenerative nodules from HCC. The signal intensity of HCC is usually hyperintense on T2W1 images. Areas of haemorrhagic necrosis within a nodule also help in differentiating. HCC has been regarded as one of the major complications of BCS. The incidence is high in Japan (41%), South Africa (48%) and the United States (25%). Hepatic venous outflow obstruction can lead to hepatic necrosis, fibrosis and cirrhosis, which contribute to the pathogenesis of HCC in patients with BCS.

Patients with longstanding inferior vena cava block are at higher risk of developing HCC than those with pure hepatic vein block.

Imaging of veins Postcontrast phases may need modification in patients with BCS due to slow circulation. Hence late venous phase should be obtained to visualize venous anatomy. Hepatic veins with sluggish flow may be missed if inadequate delay time is used. Aetiology of hepatic venous or IVC occlusion, that is thrombosis or web can be diagnosed accurately. The type of obstruction (intrinsic or extrinsic), evaluation of vessel proximal or distal to occlusion as well as the condition of the surrounding tissues can be depicted by MR venography (Fig. 9.12.34).

FIG. 9.12.34 A 32-year-old male with Budd– Chiari syndrome. T2W1 images (A and B) show hepatomegaly with changes of cirrhosis and gross ascites. Postcontrast T1W1 images (C and D) showing marbled pattern of enhancement (arrows). Postcontrast coronal T1W1 image showing stenosis of IVC (arrows) and axial images showing ostial stenosis of MHV and LHV (arrows). Budd–Chiari syndrome leads to smooth narrowing of the IVC secondary to extrinsic compression the result of enlarged caudate lobe. This pattern is distinct from IVC stenosis due to other causes. Collaterals can be intrahepatic or extrahepatic. Intrahepatic collaterals can form between two or more hepatic

veins, hepatic veins and pericapsular veins, hepatic veins and IVC and hepatic veins and veins of caudate lobe. These form in the chronic phase of the disease to decongest the liver parenchyma and are specific for the diagnosis (Figs. 9.12.35 and 9.12.36).

FIG. 9.12.35 Venous changes in Budd–Chiari syndrome. Axial images showing thrombosis of right hepatic vein (blue arrows). Multiple intrahepatic collaterals are seen with abnormal configuration (arrows in E). Stenosis of IVC is seen because of enlarged caudate lobe (arrows in F and G).

FIG. 9.12.36 T2W1 (A) and postcontrast venogram images (B–D) showing nonvisualization of hepatic veins with multiple intrahepatic collaterals (arrows in B and C). Coronal image (D) showing mild compression over intrahepatic IVC (arrows). The locations of extrahepatic collateral veins in Budd–Chiari syndrome are usually different from those seen in cirrhosis. Extrahepatic systemic venous collateral routes in Budd–Chiari syndrome mainly develop in the retroperitoneum. Most common collateral routes include deep and central tributaries of the systemic circulation (i.e. ascending lumbar veins, vertebral venous plexus, azygous and hemiazygous veins).

CT

Triple-phase CT is another useful tool to diagnose BCS. It is also useful to illustrate vascular anatomy in cases where transjugular intrahepatic portosystemic stent shunting (TIPSS) is planned. In the acute phase, CT shows the absence of hepatic vein opacification. Similar to MRI however care should be taken regarding optimal time delay to avoid false-positive results. A hypertrophied caudate lobe may be found in 75% of the cases. On CT, the liver may have a mottled appearance due to increased central enhancement, particularly in the caudate lobe with associated hypoenhancing periphery secondary to sinusoidal and portal vein stasis. In chronic BCS the liver is shrunken with the exception of caudate lobe and shows intrahepatic collaterals. Extrahepatic collaterals can also be seen predominantly in the retroperitoneum Regenerating nodules may appear hyperdense on nonenhanced CT and reveal enhancement in both arterial and portal phase imaging. Persistent hyperdensity can be seen in subsequent phases. These nodules are usually multiple in numbers and their size range from 0.5 to 4 cm (Fig. 9.12.37). HCC in setting of BCS should be considered when nodules are larger than 4 cm with heterogeneous appearance and presence of central necrosis (Fig. 9.12.38). Conversely secondary Budd–Chiari syndrome can also be caused by infiltration of HCC into lumen of the hepatic veins and IVC (Fig. 9.12.39).

FIG. 9.12.37 Contrast-enhanced CT in Budd– Chiari syndrome. Contrast-enhanced CT showing multiple peripherally enhancing nodules in left lobe of liver (biopsy-proven regenerating nodules), heterogeneous enhancement of the liver is seen with stenosis at RHV insertion (arrows). Rest of the hepative veins are not seen.

FIG. 9.12.38 Case of chronic Budd–Chiari syndrome with multiple HCC. Contrastenhanced CT in arterial phase (A,B) showing cirrhotic liver with large neovascular lesions in left lobe and segment 7 (arrows). Venous phase images (C–G) shows nonvisualization of hepatic veins with stenosis of IVC (arrows in D,F,G). Note heterogeneous enhancement of the liver with marbled appearance the result of longstanding venous occlusion.

FIG. 9.12.39 BCS secondary to HCC with tumour thrombus in IVC and hepatic veins. Contrast-enhanced CT in the late arterial phase shows ill-defined heterogeneous lesion in segment 4a and 8 (yellow arrows) invading into the lumen of the hepatic veins (blue arrows). Resultant enhancing thrombus is seen extending up to the right atrium (blue arrows in C and D). The liver shows heterogeneous enhancement.

Treatment A stepwise strategy should focus on (1) Preventing further venous occlusion; (2) Managing the clinical sequelae of venous obstruction (such as ascites); (3) Portal decompression to prevent progression to cirrhosis. Therapeutic options include: • Diuretics and anticoagulants

• Thrombolysis • Percutaneous transluminal angioplasty/ stenting (PTA/S) • Transjugular intrahepatic portosystemic shunting (TIPS) • Direct intrahepatic portocaval shunting (DIPS) • Surgical options of portosystemic shunting • Liver transplant.

Medical therapy Anticoagulation is standard in BCS unless contraindicated by bleeding risk, but this serves only to prevent propagation of thrombosis and does not reverse established venous obstruction. Ascites and hepatic encephalopathy should be managed similar to other patients with end-stage liver disease with salt restriction, appropriate use of diuretics.

Interventions Endovascular treatment is the most important therapeutic option in patients with BCS. The aim of interventional procedures is reduction of hepatic congestion and associated sequelae such as portal hypertension. Cross-sectional imaging including CT and MR venography play an important role in patient selection and treatment planning. A. Angioplasty and stenting – Patients with short segment stenosis or membranous occlusions are ideal candidates. Balloon angioplasty maybe required for residual stenosis. B. Mechanical thrombolysis – is indicated in acute BCS with thrombus to restore deteriorating liver function. C. TIPSS – patients in whom all the HV are replaced by intrahepatic collaterals are candidates for TIPSS. D. DIPS – This is an alternate endovascular approach to decompress the BCS liver in cases where no adequately patent or suitable hepatic vein is present. DIPS procedures involve creation of an endovascular shunt through the hepatic parenchyma which passes directly from IVC into the portal vein and does not require patency of the hepatic vein. Details and techniques of these have been separately discussed in chapter on hepatobiliary intervention.

Liver transplantation Indications

• For the rare patient who presents with fulminant hepatic failure secondary to BCS, LT is usually the only curative treatment option. • In the 10%–20% of patients who show progression of BCS despite all other therapies, LT is also the only remaining therapeutic option. • In patients who develop hepatic venous thrombosis secondary to metabolic defects localized to the liver (e.g., antithrombin III deficiency, protein C deficiency), LT offers the singular benefit of being curative. • Chronic hepatic venous outflow obstruction who have cirrhosis. Transplantation in BCS is associated with technical challenges which have been discussed in chapter on liver transplant.

Sinusoidal obstructive syndrome (venoocclusive disease) Is a rare liver disease characterized by the nonthrombotic obstruction of the sinusoids and is associated with considerable morbidity and mortality. The underlying process in venoocclusive disease is subendothelial sclerosis of the hepatic veins and sinusoids.

Aetiologies This entity was firstly described in patients after the ingestion of herbal teas (“bush tea disease”) or foodstuffs contaminated with pyrrolizidine alkaloids, especially in protein-malnourished individuals and is still the major cause of SOS in many parts of the world. In Western countries, myeloablative conditioning (highdose chemotherapy or chemotherapy plus irradiation) prior to hematopoietic cell transplantation (HCT) has caused the highest incidence of SOS. It is also seen following treatment with other chemotherapeutic drugs not necessarily related to HCT. Patients undergoing allogeneic transplantation, older age, female gender, underlying liver disease are high-risk factors for development of SOS in setting of HCT. SOS also occurs in patients with colorectal liver metastases that receive neoadjuvant oxaliplatin-based chemotherapy. An autosomal recessive condition termed hepatic venoocclusive disease with immunodeficiency (VODI) has also been described.

Pathogenesis SOS is initiated by injury to liver sinusoidal endothelial cells and the lack of repair of these cells. This subsequently leads to sinusoidal occlusion.

Clinical features The characteristic features are right upper quadrant pain, hepatomegaly, weight gain (due to fluid retention/ascites), and hyperbilirubinemia. Diagnostic Seattle and Baltimore criteria have been proposed in the setting of HCT and include criteria such as hepatomegaly, hyperbilirubinemia, ascites and weight gain.

Imaging Findings are nonspecific such as hepatomegaly, ascites, splenomegaly and periportal oedema. Doppler findings include reversal of portal venous flow, monophasic flow in hepatic veins, attenuation of hepatic venous flow and a high hepatic arterial resistance. CT scan is not recommended due to the toxicity of contrast agents. Noncontrast MRI may show hepatosplenomegaly with attenuation of hepatic veins. Findings are however not classic like those seen in BCS. A transjugular liver biopsy with hepatic venous pressure gradient is the gold standard for diagnosis. In the setting of stem cell transplantation, a hepatic venous pressure gradient of greater than 10 mm Hg has a specificity greater than 90% and positive predictive value greater than 85% (Table 9.12.13).

TABLE 9.12.13 Sinusoidal Obstructive Syndrome – Venoocclusive Disease • Nonthrombotic obstruction of the sinusoids caused by subendothelial sclerosis of the hepatic veins and sinusoids • Ingestion of foodstuffs contaminated with pyrrolizidine alkaloids and myeloablative conditioning prior to hematopoietic cell transplantation (HCT) are implicated aetiologies • Imaging findings are nonspecific and include hepatomegaly, ascites, splenomegaly and periportal oedema, reversal of portal venous flow, monophasic flow in hepatic veins, attenuation of hepatic venous flow and a high hepatic arterial resistance • Transjugular liver biopsy with hepatic venous pressure gradient is the gold standard for diagnosis • Spontaneous recovery, antifibrotic measures, supportive therapy and liver transplantation are described treatments

Treatment The majority of patients with SOS recover spontaneously over a 2to 3-week period. However, severe SOS carries a high mortality, usually due to multiorgan failure with renal and pulmonary failure. Supportive care includes management of fluid and electrolyte balance, diuretics. Role of antifibrotic drug defibrotide has been recently validated in severe SOS. TIPSS is not effective in SOS. Liver transplantation maybe considered in those developing SOS secondary to HCT for a benign disorder or selective malignancies associated with good outcome.

Passive hepatic congestion This condition occurs as a result of underlying cardiac disease leading to stasis of blood in hepatic veins. Elevated right heart pressures lead to increased central venous pressure with resultant absence of normal triphasic waveforms in hepatic veins on Doppler. Overtime the hepatic veins can show a unidirectional, low-velocity continuous flow waveform. Enhancement of the hepatic veins and IVC in the arterial phase due to reflux of contrast medium from the right heart is seen on contrast-enhanced CT and MRI. Heterogeneous mottled enhancement of the liver is seen in venous phase and is termed as nutmeg liver. Other features include hepatomegaly, periportal oedema and ascites. Changes of cardiac failure such as cardiomegaly, pleural and pericardial effusion aid in diagnosis (Fig. 9.12.40).

FIG. 9.12.40 Passive hepatic congestion. Contrast-enhanced CT in arterial phase (A,B) shows reflux of contrast from the right atrium into the IVC and hepatic veins (arrows). The liver is enlarged in size and shows mottled enhancement pattern called nutmeg liver (arrows). Associated cardiomegaly is seen (arrows in D).

IVC occlusion/torsion and stenosis IVC obstruction is a rare but serious complication of orthotopic liver transplantation (OLT), with a prevalence of 1%–6%. There are a few reports of IVC torsion following OLT. Most of the cases are due to stenosis at either the level of IVC or one of the hepatic veins (Fig. 9.12.41).

FIG. 9.12.41 Posttransplant IVC obstruction. Contrast-enhanced CT in a patient with history of liver transplantation shows filling defect in hepatic vein (arrows). An air containing abscess is seen adjacent to the cut surface of liver (yellow arrow). Ribbonlike narrowing of the IVC is seen at venography. The presentation depends on level of IVC obstruction and can include Budd–Chiari like presentation, graft dysfunction, ascites, portal hypertension, renal dysfunction, low cardiac output and limb oedema.

Vascular shunts Hereditary haemorrhagic telangiectasia Previously known as Osler–Weber–Rendu syndrome, this is a rare autosomal dominant condition. Clinical manifestations are the result of arteriovenous malformations (AVMs) involving the mucocutaneous tissues, lung, brain and liver. Two types HHT1 and 2 have been described. Mutations in ENG and ALK1/AcVRL1 result in HHT type 1 and HHT type 2, respectively. It has been suggested that 41%–84% patients with HHT-related hepatic AVMs can be asymptomatic, while symptomatic hepatic AVMs are seen in 5%–14%. Higher risk for peripheral arteriovenous shunts and larger hepatic artery diameter secondary to shunts is more common in patients with HHT type 2.

Imaging Hepatic telengiectasias are seen as small (2.5 mm. More commonly, there is stricturing of lower CBD and the presence of diffuse gallbladder wall thickening, absence of liver parenchymal changes, pancreatic and renal involvement and steroid responsiveness (Table 9.15.17).

TABLE 9.15.17 Differentiation Between IgG4 and PSC • Biliary ductal abnormality • Pancreatic involvement • Multiorgan involvement HISTOLOGY • Morphology • IgG41 plasma count in liver biopsy • IgG4/IgG ratio TREATMENT • Steroids

PSC Beading, short band-like strictures, peripheral pruning 80%

Associated ulcerative colitis is suggestive of PSC. IBD is present in only 0%-6% of patients with IgG4-SC. 2) Cholangiocarcinoma The infiltrating variety of cholangiocarcinoma mimics IgG4-SC on imaging. Solitary lesion with irregular margins, short segment eccentric narrowing occluding bile duct lumen, gross proximal dilatation, contrast enhancement and an abrupt transition between the normal and the involved bile duct are features more suggestive of cholangiocarcinoma (Table 9.15.18). TABLE 9.15.18 Differentiation Between Cholangiocarcinoma and IgG4 Disease Cholangiocarcinoma Focal short segmental stricture Eccentric asymmetric wall thickening with irregular margins Gross proximal dilatation Abrupt cut-off

IgG4 Disease Continuous long segmental involvement Symmetric smooth wall thickening Mild upstream dilatation Patent lumen

3) Recurrent pyogenic cholangitis MRCP features of RPC include intrahepatic biliary dilatation with hepatolithiasis, presence of biliary strictures without much wall thickening, atrophy of left lateral and posterior segments or hypertrophy of caudate lobe and medial segments. 4) Others Ischaemic cholangiopathy is usually seen in the clinical setting of hepatic arterial injury (liver transplant and biliary or pancreatic surgeries) and mostly involves hilar ducts or mid CBD. In AIDS cholangiopathy, papillary stenosis and long segment and multifocal strictures with enhancing walls are present. AIDS cholangiopathy is seen in patients with a CD4 count lower than 100 cells/mm3. Eosinophilic cholangitis (EC) may be diagnosed in patients with peripheral eosinophilia, long segment bile duct stricture and wall thickening of the cystic duct and gallbladder.

Treatment

The mainstay of treatment for patients with ISC is corticosteroids, which produce good results. MRCP shows improvement in the biliary involvement and strictures on therapy. When the diagnosis is uncertain, a steroid trial is started after exclusion of malignancy and response is assessed within 1–2 weeks using liver function tests, serum IgG4 level and MRCP. *IgG-SC is almost always responsive to steroids. If lesions do not respond to steroids, reevaluation to rule out malignancy should be performed. Biliary drainage (endoscopic or percutaneous) may be required for those with a bilirubin level higher than 5 mg/dL, cholangitis or both. Other organ involvement in igG4-SC (Tables 9.15.19 and 9.15.20) TABLE 9.15.19 Other Organ Involvement in IgG4-RD Organ Kidney Prostate Mesentery Lymph nodes Submandibular and parotid gland Orbit Aorta Thyroid disease Lung and pleural disease Skin disease Breast CNS Pericardium

Manifestations Inflammatory pseudotumours, membranous nephropathy, chronic sclerosing pyelitis Prostatitis Sclerosing mesenteritis Lymphadenopathy Sclerosing sialadenitis Dacryoadenitis, orbital pseudotumours, orbital myositis Aortitis and periaortitis Riedel’s thyroiditis Pseudotumours and interstitial pneumonia, visceral or parietal pleural thickening Like cutaneous pseudolymphoma Sclerosing mastitis and inflammatory pseudotumours of the breast IgG4-related hypophysitis, pachymeningitis Constrictive pericarditis

TABLE 9.15.20 IgG4 Disease – Points to Remember

Autoimmune pancreatitis Autoimmune pancreatitis is the pancreatic manifestation of IgG4-related sclerosing disease and is characterized by periductal infiltration with IgG4-positive plasma cells, which leads to periductal and interlobular fibrosis. Men are affected at least twice as often as women, with a reported male-to-female ratio as high as 15:2. More than 80% of patients with IgG4SC are associated with autoimmune pancreatitis and IgG4-related sclerosing cholangitis is present in as many as 88% of patients with autoimmune pancreatitis. Other organ involvement IgG4-RD is an immune-mediated fibroinflammatory condition that is capable of affecting multiple organs.

AIDS cholangitis Introduction AIDS cholangiopathy is a form of sclerosing cholangitis believed to be of infectious aetiology seen in severely immunocompromised AIDS patients.

Aetiology and pathogenesis Opportunistic infections of the biliary tree associated with immunosuppression in AIDS are believed to be the most common cause of AIDS cholangitis – Table 9.15.21.

TABLE 9.15.21 Infections Causing AIDS Cholangiopathy • Infections causing AIDS cholangiopathy • Cryptosporidium parvum (Most common) • Cytomegalovirus • Enterocytozoon bieneusi • Isospora • Histoplasma capsulatum • Giardia • Mycobacterium avium intracellulare • Cyclospora cayetanesis Cryptosporidium parvum is the most common pathogen associated with AIDS cholangiopathy followed by cytomegalovirus (CMV).

Clinical features Patients may be asymptomatic or present with right upper quadrant pain. Patients with papillary stenosis usually have severe abdominal pain. Ten to twenty per cent patients present with fever and jaundice. Serology AIDS cholangiopathy is usually seen in patients with a CD4 count well below 100/mm3. Almost all patients have markedly raised (5–7 times above normal limits) serum ALP levels. The other most common biochemical abnormality is increased gamma-glutamyl transferase (GGT). Serum bilirubin may remain normal or elevated. Liver biopsy Microscopically, the changes of AIDS cholangiopathy are usually severe inflammatory changes consistent with sclerosing cholangitis. Imaging features US Dilatation of intra- and extrahepatic biliary radicals is the most frequent abnormality on ultrasound. Other abnormalities include biliary wall thickening, beading and oedema at ampulla appearing as an echogenic nodule at the distal end of the CBD. CT CT of the abdomen can demonstrate dilated intrahepatic biliary better than ultrasound. Papillary stenosis may be seen; however, sensitivity is lower than MRCP. It also rules out any external compression from malignant masses causing biliary dilatation. MRCP Combination with intrahepatic ductal irregularities with papillary stenosis is present in up to 75% of patients and is diagnosed when a dilated (8–11 mm) CBD and shows smooth tapering at its terminal portion. This feature is well depicted on MRCP. Contrast-enhanced T1-weighted fat-saturated images show the enhancement and thickening of the bile duct walls. The characteristic ‘beaded’ appearance of intrahepatic sclerosing cholangitis-like pattern without extrahepatic bile duct abnormalities is observed in 20% of patients. Left ductal system is disproportionately more severely involved. The other cholangiographic pattern includes 1–3 cm segmental extrahepatic biliary stricture with or without intrahepatic involvement (Fig. 9.15.14).

FIG. 9.15.14 HIV cholangiopathy. (A and B) MRCP images showing narrowing of the distal CBD (arrow) with proximal biliary dilatation. The tapering of the distal CBD is smooth and likely the consequence of papillary stenosis. ERCP ERCP is not usually performed unless there is need for therapeutic procedures, such as brushing, sphincterotomy or placement of stents due to biliary. Cello identified four patterns of cholangiographic features based on ERCP (Table 9.15.22). TABLE 9.15.22 ERCP Features of AIDS Cholangitis Types Type 1 Type 2 Type 3 Type 4

Patterns Papillary stenosis alone

Incidence 20%

Combined intrahepatic and extrahepatic sclerosing cholangitis without papillary stenosis Combined papillary stenosis and sclerosing cholangitis

15%–20%

Long extrahepatic bile duct strictures with or without intrahepatic involvement

6%–15%

50%

Management Although infection is the most common cause of AIDS cholangiopathy, antimicrobial therapy directed against C. parvum, Microsporidium or CMV is usually ineffective and does not influence symptoms or cholangiographic abnormalities. The mainstay of treatment for HIV/AIDS cholangiopathy is restoring the immune function through the introduction of HAART, whereas patients already on therapy may require change in their medications regimen. Patients who have abdominal pain, cholangitis or jaundice associated with papillary stenosis show marked symptomatic relief after sphincterotomy. The relief can be long lasting. Isolated or dominant CBD strictures can be treated with endoscopic stenting.

Complications The primary complications reported to be caused by AIDS-related cholangiopathy are development of cholangiocarcinoma and progression of sclerosing cholangitis despite appropriate treatment. Differential diagnosis The typical imaging findings of PSC include ductal wall thickening, segmental ectasia, multifocal strictures and beaded appearance of the intrahepatic and extrahepatic bile ducts. Biliary strictures in AIDS cholangiopathy are indistinguishable from PSC. However, the combination of papillary stenosis and intrahepatic ductal

strictures appears relatively unique to AIDS cholangiopathy; this combination is not found in PSC. Clinical history may help to distinguish one from the other. Another differential is pyogenic cholangitis. The clinical picture is setting of sepsis with microabscesses and perfusion defects in liver on imaging. These features are not seen in AIDS cholangitis. Other associated features seen in AIDS • Acalculous cholecystitis : The most common manifestation of gallbladder disease in HIV-infected patients • Gallstones • Pancreatitis • Lymphadenopathy • Kaposi’s sarcoma and primary Burkitt’s lymphoma of biliary ducts • Pancreatic duct dilatation

Eosinophilic cholangitis EC is an extremely rare benign disorder of the biliary tract which can result in biliary obstruction and mimic cholangiocarcinoma. It is a part of spectrum of disorders which involve eosinophilic infiltration of tissues and organs with or without concomitant peripheral eosinophilia. Patients with biliary tract involvement usually have multiorgan affection. No clear relationship between EC and hypereosinophilic syndrome has been established in literature. Diagnosis of EC is based solely on histological findings as follows: (1) Wall thickening or stenosis of the biliary system. (2) Histopathological findings of eosinophilic infiltration. (3) Reversibility of biliary abnormalities without treatment or following steroid treatment. Lab investigations Peripheral eosinophilia is usually seen. There is no elevation of tumour markers like CA199, unlike cholangiocarcinoma. Imaging Imaging modalities can provide information regarding the level of obstruction, extent of biliary dilatation and the presence of other causes of biliary obstruction. Segmental or diffuse thickening of the bile duct wall is seen with mild enhancement. Findings are nonspecific and not associated with stone disease. Vascular involvement like that seen in cholangiocarcinoma is not seen on this entity (Fig. 9.15.15).

FIG. 9.15.15 Biopsy proven case of eosinophilic cholangitis. (A) Contrast-enhanced CT in arterial, (B and C) portal venous, (D) venous and (E) delayed phases showing ill-defined hypodensity in segment 7 of liver. Few rounded hypodense structures are seen within ( red arrows in C and D). The vessels are seen coursing through the abnormality. There is attenuation of right posterior portal vein (blue arrows). Invasive imaging modalities such as ERCP and/or cholangioscopy aid in obtaining tissue for diagnosis by means of brush cytology and biopsy in order to exclude malignancy. Precise preoperative diagnosis of EC is not always possible and surgery is usually necessary to exclude CCA. EC may be a self-limiting disease. Oral corticosteroids are effective treatment.

Ischaemic cholangitis Ischaemic bile duct strictures are usually seen following liver transplantation. These may occur because of iatrogenic injury, hepatic arterial thrombosis or stenosis, prolonged preservation time, recurrence of primary liver disease, chronic rejection, cholangitis or cholangiocarcinoma. Thrombosis of the hepatic artery occurs in 4%–8% of liver transplants and is the cause of up to 50% of nonanastomotic strictures. Because of poor collateral supply, the bile ducts are solely responsible on hepatic arteries for blood supply. Nonanastomotic bile duct strictures and leaks should suggest the diagnosis of hepatic arterial thrombosis (Fig. 9.15.16).

FIG. 9.15.16 Postliver transplant nonanastomotic biliary stricture. (A and B) T2W1 axial images showing dilated radicals in transplanted liver not extended up to the cut surface. (C) Postcontrast T1W1 axial images showing biliary radical dilatation with peribiliary enhancement. Patient had hepatic arterial stenosis postliver transplant, leading to nonanastomotic biliary stricture. Hepatic arterial thrombosis can be accurately diagnosed on USG. Multiple intrahepatic strictures are seen on CT and MRI. Vascular occlusion and extent islets are seen on CT angiography. This entity has been discussed in detail in the chapter 9.14 on liver transplant.

Choledocholithiasis The presence of a stone or stones within the CBD is known as choledocholithiasis. Epidemiology Approximately 10%–15% of the population is found to have gallstones. Of these, 10%–20% of cases are found to have concomitant CBD stones. The gallbladder stones are concomitantly found in 50%–70% of CBD stone cases. The ratio of women to men with CBD stones is 0.89:1, although the prevalence of gallbladder stones is higher in women than in men. Incidence increases with age with the mean age of CBD stone patients is 67 years. Primary and secondary CBD stones The CBD stones are usually migrated stones from the gallbladder. These are known as secondary stones. The stones which develop in the CBD itself are known as primary biliary stones. Pathogenesis of primary CBD stones Parasitic infestation by liver flukes (Opisthorchis veverrini, C. sinensis) of the biliary tree leads to stasis of bile and subclinical infection that result in stone formation. The infecting organisms are mainly E. coli, Bacteroides and Clostridium species which breakdown the conjugated bilirubin into unconjugated bilirubin. This is often predisposed by preexisting conditions like choledocal cysts, biliary strictures (sclerosing cholangitis, benign and

malignant strictures) hepaticojejunostomies and foreign bodies (retained T-tubes, parasites, sutures and blocked stents).

TABLE 9.15.23 Differential Diagnosis of Sclerosing Cholangitis PSC Geographic distribution

RPC

IgG4-Related Sclerosing Cholangitis

AIDS Cholangiopathy

Northern Europe and USA

East Asia

Worldwide

Developing countries

Fourth to fifth decades

Sixth to seventh decades

Seventh decade (mean age: 63 years)

Fourth to fifth decades

M:F = 2–3:1

Equal sex incidence

M:F = 8:1

Variable

Clinical symptom

Variable

Epigastric pain, fever and jaundice

Obstructive jaundice

Variable

Associated disease

IBD

Parasitic infestation including clonorchiasis

Autoimmune pancreatitis or other IgG4-RD

Advanced AIDS

Periductal fibrosis (‘onion skin type’) around mediumsized to large bile ducts

Bilirubinate stones and fibrous thickening of ectatic large ducts

Lymphoplasmacytic infiltration with abundant IgG4positive plasma cells and storiform fibrosis

Severe inflammatory changes with occurrence of squamous metaplasia of the bile ducts

p-ANCA

None

IgG4

CD4 counts/100 mm3

Typically ‘beaded’ appearance involving both intraand extrahepatic bile ducts

Bile duct dilation

Prominent bile duct wall thickening with visible lumen

Long segment extrahepatic bile duct

Stricture in intrapancreatic bile ducts

Stricture

Age

Gender

Microscopic findings

Specific lab work MRCP findings

Diverticular outpouching Pruned-tree appearance at chronic stage

Hepatolithiasis

Multifocal intrahepatic bile duct strictures

PSC MRI findings

Atrophy of the posterior right and lateral left hepatic segments with hypertrophy of the caudate lobe

RPC T1hyperintense pigmented stones Atrophy of the left hepatic lobe and/or right posterior segment

IgG4-Related Sclerosing Cholangitis

AIDS Cholangiopathy

Findings of autoimmune pancreatitis or other IgG4-related systemic disease

Bile duct thickening and enhancement Peribiliary enhancement Papillary stenosis

Pathogenesis of secondary CBD stones Secondary CBD stones are migrated stones from the gallbladder. Bile duct stone composition is biochemically identical to that of gallbladder stones. Thus pathogenesis of secondary CBD stone is thus same as gallstone.

Clinical features Right upper quadrant colicky pain radiating to the right shoulder, intermittent jaundice, pale stools and dark urine constitute the symptom complex. Choledocholithiasis is the most frequent cause of Charcot’s triad, characterized by jaundice, biliary colic and sepsis suggests cholangitis. Patients may also present with epigastric pain radiating to back suggesting acute pancreatitis. On physical examination, the gallbladder is usually not distended in contrast with patients having neoplastic obstruction of CBD and ampulla (Courvoisier’s law). Serology Serum alanine aminotransferase (ALT), AST, and gamma-glutamyl transpeptidase concentrations are elevated in biliary obstruction in a cholestatic pattern. Elevation of serum bilirubin greater than 3–4 mg/dL in a patient with cholelithiasis suggests choledocholithiasis. Amylase and lipase should also be checked to assess for gallstone pancreatitis. One-third of patients, however, may have normal laboratory data. The American Society for Gastrointestinal Endoscopy estimation of risk of carrying CBD stones in patients with symptomatic cholelithiasis is based on clinical predictors (Table 9.15.24). TABLE 9.15.24 Predictors of Choledocholithiasis in Patients With Cholelithiasis PREDICTORS OF CBD STONES CBD stone on US Cholangitis Bilirubin level >68.4 mmol/L Strong: Dilated CBD on US (>6 mm with gallbladder in situ) Bilirubin level 30.8–68.4 mmol/L Moderate: Abnormal liver biochemical test other than bilirubin Age >55 years Clinical gallstone pancreatitis LIKELIHOOD OF CBD STONES High Presence of at least one very strong predictor or two strong predictors Low No predictors present Intermediate All other patients Very strong:

Imaging features USG Transabdominal ultrasonography is a good initial investigation in picking up stones in the gallbladder but it is not the ideal imaging modality to image the CBD. Biliary stones appear as intraluminal echogenic and round focus within the CBD. Unlike the gallbladder stone, CBD stone only produce acoustic shadow in about 20% of cases. In a meta-analysis, US had a sensitivity of 73% and specificity of 91% for detecting a CBD stone. US can reliably detect a dilated extrahepatic bile duct, typically a CBD >6 mm, which is an indirect sign of choledocholithiasis. Largely, due to its poor sensitivity, a negative US does not rule out choledocholithiasis (Fig. 9.15.17).

FIG. 9.15.17 USG in choledocholithiasis. Grey scale USG showing a large calculous with posterior acoustic shadow in the CBD with proximal biliary dilatation. CT A CT scan is frequently obtained in the evaluation of abdominal pain. Many gallstones are similar in density to surrounding bile and lack calcium, which limits CT conspicuity and hence sensitivity. The radiopacity of stones differed significantly according to stone type. Black pigment and mixed cholesterol stones are more detectable than brown and pure cholesterol stones. Various signs are described namely target sign (the stone is seen as a central density surrounded by hypoattenuating bile or ampullary soft tissue), rim sign (one can see a faint rim of increased density along the margin of a low-density area) and crescent sign (a calculous with increased density that is surrounded by a crescent of hypoattenuating bile) (Figs. 9.15.18 and 9.15.19).

FIG. 9.15.18 Choledocholithiasis on CT. (A to C) Unenhanced CT multiple calculi in the gallbladder (yellow arrow) with large calculi in the CBD (red arrows).

FIG. 9.15.19 CT in choledocholithiasis. Unenhanced CT showing calculous in distal CBD (yellow arrows) with mild proximal biliary dilatation (red arrow). Similar to US, CT is able to detect biliary ductal dilation, a secondary sign of choledocholithiasis. Stones are more difficult to see at CT than at MRI. The reported sensitivity of CT for choledocholithiasis is between 72% and 88% (Table 9.15.25). TABLE 9.15.25 Imaging Modalities in Choledocholithiasis Modality Imaging Features USG

CT MRCP

EUS ERCP

• Intraluminal echogenic and round focus • Acoustic shadow Variable attenuation raging from heavily calcified to gas attenuation • T2 hypointense filling defect • Variable intensity on T1 Same as USG Radiolucent filling defects

Accuracy Sensitivity of 73% and specificity of 91%

Sensitivity is between 72% and 88% Sensitivity of 81%–100% and a specificity of 92%–100% Sensitivity of 81%–100% and a specificity of 92%–100% Gold standard

MRCP MRCP is the preoperative investigation of choice for detection of CBD stones. MRCP provides excellent anatomic detail of the biliary tract and has a sensitivity of 81%–100% and a specificity of 92%–100% in detecting choledocholithiasis (Figs. 9.15.20 and 9.15.21).

FIG. 9.15.20 Choledocholithiasis. Reconstructed coronal MRCP images showing filling defect in distal CBD (arrows) with proximal biliary dilatation.

FIG. 9.15.21 MRI in choledocholithiasis. T2W1 axial and coronal images showing calculi in the CBD (arrows) with proximal biliary dilatation. Note crescent sign seen on axial images with bile outlining the dependent calculous. Calculi appear hypointense to bile on T2W1 images. An impacted biliary stone will appear as a rounded filling defect with a crescent of bile. Additionally, signs of inflammation such as periductal oedema, biliary epithelial thickening and mural enhancement may be seen due to local irritation caused by stones, or to associated cholangitis. Stones have a more variable appearance at T1-weighted imaging. Intrahepatic stone burden can also be readily diagnosed with MRCP. Hepatobiliary specific agents with biliary excretion can provide better visualization of stones in patients with ascites. The accuracy of MRCP in diagnosing CBD stones is comparable with that of ERCP and intraoperative cholangiography (IOC). A recent meta-analysis showed that there is no statistically significant difference in sensitivity (93% vs 85%) and specificity (96% vs 93%) between EUS and MRCP. However, it is probably less sensitive than EUS for detecting CBD stones smaller than 5 mm. Endoscopic ultrasound EUS is sensitive for stones smaller than 5 mm, and has a much lower complication rate (0.1%–0.3%) than ERCP. Sensitivity of EUS ranges from 88% to 97%, with a specificity of 96%–100%. However, because of moderately invasive nature of EUS, cost, the need for an endoscopic theatre, sedation, including instrumentation, personnel and expertise, MRCP has superseded its use. Endoscopic retrograde cholangiopancreatography ERCP was once considered as a gold standard for the preoperative detection of CBD stones. ERCP has added therapeutic benefits allowing stone extraction. Complications are,

however, seen in 15% patients and include pancreatitis, cholangitis, perforation of duodenum and bile duct. The ERCP mortality rate is 0.2%–0.5%. This makes MRCP a more acceptable and safe diagnostic procedure. Intraoperative cholangiography and intraoperative ultrasound IOC involves injection of biliary tree with radiographically visible water-soluble agent to detect choledocholithiasis and detect calculi. It is a highly specific and sensitive modality (99%) in detection of cholelithiasis. Its use is, however, debatable and currently is not performed routinely. Intraoperative ultrasound is a safer modality not requiring ductal cannulation or use of contrast and radiation. It allows direct visualization of cholelithiasis and some studies have shown superiority over MRCP in detection of stones less than 5 mm, with sensitivity of 100%. Percutaneous transhepatic cholangiography PTC is an invasive procedure that involves the cannulation of the biliary tree under fluoroscopic guidance. It provides information similar to ERCP, however, due to its invasive nature is not routinely used for diagnosis. Its role is reserved for patients requiring interventions when ERCP is not feasible.

Management CBD clearance by endoscopy, surgery or lithotripsy is the treatment. Cholecystectomy should be performed following stone extraction, since most cases of choledocholithiasis result from gallstone migration.

Endoscopy ERCP is the preferred choice in dealing with CBD stones. Endoscopy is capable of treating 90% of choledocholithiasis. Endoscopic sphincterotomy (ES) and endoscopic papillary balloon dilation (EPBD), in conjunction with stone extraction (with balloons and baskets), are the primary treatment methods for choledocholithiasis. Lithotripsy Lithotripsy is stone fragmentation and can be performed in several ways (mechanical, electrohydraulic, laser and extracorporeal shock wave). Mechanical lithotripsy is a commonly employed technique. Endoscopic mechanical lithotripsy is usually performed after ES for CBDs that cannot be removed through a Dormia basket or balloon catheter. The success rate for biliary stone clearance is 80%–90%.

Surgical techniques Nowadays, open surgery is regarded as the last resource or obsolete therapy of CBDs. CBD exploration may be performed laparoscopically, if needed.

Choledochal cysts Congenital cystic dilatation of any portion of bile duct is known as choledochal cysts. the prevalence is more in Asia compared to the Western countries, with most reports from Japan. The incidence in England is about 1 in 2 million as opposed to 1 in 13,000 in Japan. Classification According to the Todani classification, choledochal cysts are classified in Table 9.15.26.

TABLE 9.15.26 Classification of Choledochal Cysts Type IA Type IB Type IC Type II Type III Type IVA Type IVB Type V Type IA Type IB Type IC

Todani Classification of the Bile Duct Cysts Cystic dilatation of the extrahepatic bile ducts

Incidence 50%–80%

Extrahepatic distal focal – segmental biliary dilatation Extrahepatic fusiform biliary dilatation Extrahepatic biliary diverticula

2%

Intraduodenal portion of the CBD dilatation (choledococele)

1.4%–4.5%

Multiple cystic dilatation of the intrahepatic and extrahepatic bile duct 15%–35% Multiple cystic dilatation of the only extrahepatic bile duct Cystic dilatation of the intrahepatic bile ducts (Caroli’s disease)

20%

REVISION IN TYPE 1 CYSTS BY TODANI ET AL.BASED ON AUPBD Cystic dilatation of the extrahepatic bile duct

Segmental dilatation with no presence of anomalous union of pancreaticobiliary duct (AUPBD) Fusiform, diffuse or cylindrical dilatation of the extrahepatic bile duct with AUPBD NEW PROPOSED ADDITIONS TO TODANI SYSTEM Type Characterized by dilation of the cystic duct in addition to dilated CBD ID (type I) resulting in a bicornal configuration of the cyst Type Isolated dilation of the cystic duct without CBD or CHD involvement VI

‘Forme fruste’ choledochal cyst The form fruste of choledochal cysts has been described by Lilly and colleagues. These patients present with abdominal pain and jaundice, have an anomalous pancreaticobiliary union but lack biliary dilatation. The symptoms, histology and malignancy potential is however similar to those with choledochal cysts. Aetiopathogenesis The most widely accepted hypothesis in pathogenesis is the Babbitt’s theory. The activated enzymes then cause inflammation and destruction in the wall of the biliary tract, causing dilatation. However, according to another theory, high choledochal pressure contribute to choledochal malformation rather than pancreatic reflux. Anomalous union of pancreaticobiliary duct junction A close association exists between cholecochal cyst with anomalous union of the pancreaticobiliary duct junction (APBDJ). The common channel is formed by the union of the CBD and pancreatic duct in the sphincter of Oddi and measures approximately 0.2 to 1 cm in length. Anomalies in this union have been implicated as an aetiology in diagnosis of choledochal cysts. One feature is long length of the common channel which is a consequence of union of the PD and the CBD outside the duodenal wall. The other feature is the angle of union between the ducts. Normally, this angle is acute since the ducts converged as they are enclosed within the sphincter. The prevalence of long common channel in choledochal cyst ranges from 96% to 100% in paediatric series and from 68% to 94% in adult series.

Anomalous pancreaticobiliary ductal union (APBDU) has been classified by Komi et al. The classification is mentioned in Table 9.15.27. TABLE 9.15.27 Komi’s Classification of APBDU CLASSIFICATION OF APBDU BY KOMI ET AL. Type IA Right angle between the ducts without dilatation of the common channel Type IB Right angle between the ducts with dilatation of the common channel Type IIA Acute angle between the ducts without dilatation of the common channel Type IIB Acute angle between the ducts with dilatation of the common channel Type IIIA Classic pancreas divisum with biliary dilatation Type IIIB Absence of the Wirsung’s duct Type IIIC1 Tiny communicating duct between the main duct and the accessory ducts Type IIIC2 Common channel made up of common and accessory ducts of equal calibre Type IIIC3 Total or partial dilatation of the ductal system

Choledochal cyst and APBDJ association Clinical course Choledochal cyst may remain asymptomatic for many years and diagnosis may be made incidentally, when asymptomatic patients undergo imaging studies for unrelated process. Approximately 85% of children have at least two features of classic triad, whereas only 25% of adults present with at least two features of the classic triad. The classic clinical presentation includes triad of abdominal pain, jaundice and palpable mass. This triad is however seen in only 20% of cases. At least two features of classic triad are seen in approximately 85% of children and only 25% of adults. Clinical findings of choledochal cyst also develop secondary to ascending cholangitis and pancreatitis, which occur due to biliary stasis, development of gallstones, inflammation and development of secondary inflammation and are more common in adults. Patients with a choledococele (type III) are usually asymptomatic but rarely can present with gastric outlet obstruction or duodenal obstruction. Blood investigations Laboratory tests have not been proven to be useful in establishing a diagnosis. Raised serum amylase and lipase indicate pancreatitis. Raised CA 19-9 should raise the suspicion of malignancy in adults with CCs. Associations Various associations have been described and include colonic atresia, imperforate anus, duodenal atresia, pancreatic arteriovenous malformation, ventricular septal defect, aortic hypoplasia, pancreatic divisum, focal nodular hyperplasia, congenital absence of the portal vein, heterotopic pancreatic tissue and familial adenomatous polyposis. Choledochal cysts: Adults versus paediatric patients The classic triad of jaundice, abdominal pain and abdominal mass was often seen in paediatric patients than in adults. Adult patients were prone to have the symptom of abdominal pain, while paediatric patients tended to have jaundice. Children commonly have higher association with APBJ anomalies, adults have lower incidence of PBJ anomalies. Low perioperative and long-term postoperative complications are seen in paediatric patients as compared to adults.

Imaging features USG USG is the first modality for diagnosis. Choledochal cysts is seen as a large cystic mass in the right upper quadrant separate from gallbladder. Demonstrable biliary communication

clinches the diagnosis. Ultrasound has a sensitivity of 71%–97% in diagnosing choledochal cysts. Hepatobiliary scintigraphy check Choledochal cysts appear as a photopenic area on initial phase of hepatobiliary scintigraphy using technetium-99 hepatobiliary iminodiacetic acid (HIDA). Subsequent filling of cysts is seen on delayed phase with delayed emptying into bowel. Ultrasound has a high sensitivity of 100% in diagnosis of type 1 choledochal cysts. Sensitivity is however lower in type IVA cysts due to poor delineation of intrahepatic radical dilatation. Spontaneous rupture of cysts can be seen as dye entering the peritoneal cavity. HIDA can also distinguish between choledochal cyst and biliary atresia. CT CT is a useful modality in demonstrating the cyst, classifying the type and demonstrating biliary communication. Relationship to adjacent structures and associated malignancy can be diagnosed. Imaging of the intrahepatic bile ducts, distal bile duct and pancreatic head is better compared to ultrasound. In patients with type IVA cysts and Caroli’s disease, intrahepatic dilatation and extent of disease can be accurately depicted. ERCP ERCP has been reported to be the most sensitive imaging modality for choledochal cysts and its best in visualizing pancreaticobiliary junction. Technical challenges such as difficult cannulation of the ampulla going to repeated inflammation and scarring are however a hindrance. Added to that the fact that the procedure is invasive and associated with complications such as cholangitis and pancreatitis make it less preferred as a diagnostic modality. Incidence of post-ERCP complications like cholangitis and pancreatitis is higher in patients with choledochal cysts. MRCP Given the concerns regarding ERCP, MRCP is now considered to be the gold standard. Assessment of cyst anatomy, type, site, size, shape of bile duct dilatation and detection of APBDU make it the preferred modality. Unlike ERCP, the procedure is noninvasive with no complications. Sensitivity for diagnosis has been reported to be as high as 90%–100%. MRCP is 84% sensitive for imaging of postoperative anastomosis. Unfortunately, sensitivity for assessing the pancreaticobiliary junction is as low as 46%–60% and some authors advocate the preimaging administration of secretin, which will increase pancreatic secretion and dilate the duct.

Imaging features of individual types Type 1 Type 1A: Cystic dilatation of extrahepatic biliary tree is seen in patients with type 1A choledochal cysts The intrahepatic radicals are normal and the cystic duct opens in a dilated CHD. (Fig. 9.15.22) Type 1B: In this subtype, focal segmental dilatation of the extrahepatic biliary tree is seen. The ductal dilatation is typically distal, though can be located anywhere. The opening of the cystic duct is usually in normal calibre extrahepatic tree because dilatation is usually distal. No dilatation of intrahepatic radicals is seen. Type 1C: Regular fusiform dilatation extending from the pancreaticobiliary junction into the intrahepatic biliary tract is seen in this subtype. Type II: This type is characterized by a diverticulum from the extrahepatic tree connected to tract via a narrow stalk. Type III: This is also called choledochocele and is characterized by cystic dilatation of the distal duct within the duodenal wall. Owing to their intramural nature, imaging abnormalities in choledochoceles are subtle, and the correct diagnosis is made preoperatively as little as 30% of the time. The cysts are usually too small to visualize, and the normal diameter of the CBD makes connection to the biliary tree

difficult to identify. Endoscopy and ERCP will show smooth bulging of the papilla, and cannulation will opacify the dilated intramural CBD.

FIG. 9.15.22 Type I choledochal cyst. (A and B) MRCP images showing cystic dilatation of CBD with long common channel suggesting APBDU (red arrows). Type IVA choledochal cysts Type IVA involves multiple cysts in both the intrahepatic and extrahepatic bile ducts. Intrahepatic dilatation affects both lobes, although the left lobe is predominantly involved. These cysts are further classified by Todani as cystic–cystic, cystic–fusiform or fusiform– fusiform according to the shape of the intrahepatic and extrahepatic dilatations. The type IVA cyst is often accompanied by a primary ductal stricture around the hepatic hilum, which probably leads to either cystic or fusiform dilatation of the intrahepatic duct (Figs. 9.15.23–9.15.25).

FIG. 9.15.23 Type IVA choledochal cysts. (A) T2W1 coronal image showing cystic dilatation of extrahepatic duct (red arrow). (B) MRCP image showing associated dilatation of left hepatic duct with long common channel (red arrow).

FIG. 9.15.24 Type IVA choledochal cyst. T2W1 axial and coronal images showing fusiform of intrahepatic and extrahepatic ducts. Reformatted MRCP images showing the same ( arrow in G and H).

FIG. 9.15.25 Type IVA choledochal cyst. Contrast-enhanced CT showing cystic dilatation of intra- and extrahepatic biliary radicals (arrows). Calculi are seen in the extrahepatic tree ( arrow in E). Air within the radicals (yellow arrow) was secondary to recent ERCP. Type IVB: Multiple cystic dilatations of only the extra hepatic tree is seen. The appearance resembles beads or bunch of grapes. Type V: This variant is also known as Caroli’s disease and is characterized by multiple saccular or cystic dilatations of the intrahepatic tree. Caroli’s disease implies isolated biliary dilatations, whereas Caroli’s syndrome describes biliary dilatations in association with congenital hepatic fibrosis and kidney disease. Caroli’s disease is discussed in detail in chapter 9.11 on focal liver lesions. Complications Among all, formation of stones (cystolithiasis, choledocholithiasis and hepaticolithiasis) and related inflammation and infections (calculous cholecystitis, cholangitis and intrahepatic abscess) are the common complications. Patients with type IVA choledochal cyst disease have the highest incidence of hepatolithiasis. This is owing to the presence of membranous or septal stenosis or segmental bile duct near main biliary convergence (Tables 9.15.28 and 9.15.29).

TABLE 9.15.28 Cholangiocarcinoma in Choledochal Cyst • Cholangiocarcinoma in choledochal cyst • Choledochal cyst is premalignant condition • Incidence is 10% to 15% which increases with age • Can happen even after excision • Most common site is extrahepatic biliary tree followed by gallbladder • Synchronous cholangiocarcinoma is also possible TABLE 9.15.29 Complications of Choledochal Cyst COMPLICATIONS • Biliary stones • Biliary strictures • Cholangiocarcinoma • Ascending cholangitis • Pancreatitis • Secondary biliary cirrhosis • Spontaneous cyst rupture • Intrahepatic abscess • Calculous and acalculous cholecystitis In addition, the coexistent congenital hepatic fibrosis in patients with type V CCD predisposes to portal hypertension and oesophageal varices. Patients with CBD stones are also predisposed to biliary pancreatitis. Cyst rupture has been reported in 1%–2% of cases and occurs due to increased fragility of cyst wall secondary to distal obstruction and increased intracystic pressures. Junction of the cystic duct and the main hepatic duct, which has the weakest blood supply in the biliary tract is a common site of rupture. The major concern is the risk of malignant transformation. Choledochal cyst is a premalignant condition. Chronic inflammation leading to dysplasia, recurrent cholangitis and pancreatic reflux are factors that predispose to malignancy. The risk of malignancy associated with a choledochal cyst has been reported to be 10% to 15% in the overall population; however, this rate increases with increasing age. The entire biliary tree is at a high risk for malignancy. Malignant CA arose in the dilated bile duct, remnant nondilated biliary ducts and even gallbladder. Malignancies affect the extrahepatic biliary tract in 50% to 62% of cases, the gallbladder in 38% to 46%, the intrahepatic biliary tract in 2.5% and the liver and pancreas in 0.7%. The forme fruste form also has a high incidence of malignancy of 12%–39% with gallbladder cancer being the commonest site. Risk of malignancy remains unchanged in patients with prior cystoenterostomy and incomplete cyst excision (Fig. 9.15.26).

FIG. 9.15.26 Malignancy in patient with choledochal cysts. (A to C) Contrast-enhanced CT in portal venous phase showing a large polypoidal enhancing mass in the gallbladder ( yellow arrow in A). There is a cystic dilatation of the extrahepatic biliary tree suggestive of choledochal cyst ( yellow arrows in B and C).

On the basis of Asian literature, malignancy occurs more often in types I and IV cysts and rarely in types II and III.

Management Management is usually surgical. Most cysts are treated with complete excision with Rouxen-Y hepaticojejunostomy and cholecystectomy (Table 9.15.30). TABLE 9.15.30 Management of Choledochal Cyst Type 1 Type II Type III Type IVA Type IVB Type V Forme Fruste

Complete excision with Roux-en-Y hepaticojejunostomy Simple cyst excision usually preferably with cholecystectomy ES Wide hilar hepaticojejunostomy with segmental resection of liver or liver transplantation depending on degree of involvement Complete excision with Roux-en-Y hepaticojejunostomy Segmental resection of liver or liver transplantation depending on degree of involvement • At least cholecystectomy • Excision of the malformed ductal tissue with biliary reconstruction

Bile duct injuries Laparoscopic cholecystectomy is considered as the gold standard for the treatment of gallstone disease since its introduction. There has, however, been an increase in incidence of bile duct injuries from 0.06% to 0.3%. The incidence of bile duct injuries remain unchanged despite preventive manoeuvres to avoid ductal injury during laparoscopic cholecystectomy. The nature of injuries after laparoscopic cholecystectomies tends to be more complex than after open approach. Patients can also have associated vascular injuries particularly of the right hepatic artery.

Aetiologies Classification of bile duct injury Various classification systems have been described. The systems as well as their limitations have been discussed below. Bismuth classification This is a simple most widely used classification of bile duct injuries and is based on the location of the injury in the biliary tree. Five types of bile duct injuries are classified on the basis of their distance from bile duct confluence, involvement of confluence and injuries to right posterior sectoral duct (Table 9.15.31). TABLE 9.15.31 Bismuth Classification of Bile Duct Injuries • Type I involves the CBD and low CHD >2 cm from the hepatic duct confluence. • Type II involves the proximal CHD 180°) OF THE HEPATIC ARTERY (HA) HA0 No portal involvement HA1 Proper hepatic artery HA2 Hepatic artery bifurcation HA3 R Right hepatic artery HA3 L Left hepatic artery HA4 Right and left hepatic arteries LIVER REMNANT VOLUME (V) V0 No information on the volume needed (liver resection not foreseen) V% Indicate Percentage of the total volume of a putative remnant liver segments after resection Underlying liver disease Fibrosis (D) Nonalcoholic steatohepatitis PSC LYMPH NODES (N) N0 No lymph node involvement N1 Hilar and/or hepatic artery lymph node involvement N2 Periaortic lymph node involvement METASTASES (M) M0 No distant metastases M1 Distant metastases (including liver and peritoneal metastases) Laboratory investigations Serum bilirubin is often greater than 10 mg/dL and averages 18 mg/dL, patients with obstruction from benign diseases have lower bilirubin levels. Carcinoembryonic antigen (CEA) and CA19-9 are used for the diagnosis, treatment and monitoring of HC with 89% sensitivity and 86% specificity when combined with other diagnostic modalities. CA19-9 is, however, not secreted in 10% of patients. CA19-9 have a sensitivity and specificity of 79% and 98%, respectively, at serum concentration >129 U/mL in patients with PSC. While patients without PSC, a CA19-9 > 100 U/mL has

sensitivity of 76% and a negative predictive value of 92% compared to those with benign strictures. Biopsy and endobiliary procedures ERCP and PTC have similar sensitivity (75%–85%) and specificity (70%–75%) with regard to their ability to attain a tissue diagnosis. A negative biopsy, however, cannot be considered definitive and cholangiocarcinoma should always be suspected in the right clinical setting regardless of the biopsy results. Intraductal ultrasonography has acceptable sensitivity when compared with histologybased staging, although this technique is also operator dependent and its accuracy can vary. Transperitoneal FNA should be avoided when curative resection is being considered due to higher rate of peritoneal seedling. Preoperative staging and resectability Surgery remains the only curative treatment for HCA. Preoperative staging using imaging should evaluate longitudinal extent of tumour along biliary tree and involvement of adjacent vasculature. Nodal and distant metastatic disease should be looked for. USG Typically, HC appears hypoechoic relative to surrounding liver parenchyma. Small masses and malignant strictures may not be well seen. Biliary dilatation is seen and level of obstruction may be identified. Ultrasound is, however, not an accurate modality in determining type of hilar block or radial extent of tumour. Evaluation of metastatic disease to nodes, liver or peritoneum is also not as accurate as CT and MRI. MDCT MDCT is usually the initial modality of choice in diagnosis and staging of hilar cholangiocarcinoma. Thinly sliced (2–5 mm) MDCT correlates well (greater than 90%) with local tumour extension when compared with operative and pathological findings. These tumours usually appear as circumferential hypodense wall thickening involving the bile ducts showing gradual enhancement which persists on delayed phase. The delayed enhancement may be the result of fibrotic nature of the lesion. Resultant biliary dilatation is seen upstream to the level of neoplasm (Figs. 9.15.35 and 9.15.36).

FIG. 9.15.35 CT appearance of hilar cholangiocarcinoma. Contrastenhanced CT showing circumferential wall thickening with enhancement involving the primary confluence extending along the proximal CBD.

FIG. 9.15.36 Hilar cholangiocarcinoma. Contrast-enhanced CT in venous phase showing enhancing lesion at the hepatic hilum ( arrows in A, B, C and E) involving the CHD and primary confluence with resultant stricturing. Note the collapsed gallbladder ( blue arrows in D) which is often a feature in hilar cholangiocarcinoma as opposed to gallbladder neck malignancy. MDCT is excellent in delineating vascular involvement associated with cholangiocarcinoma. Owing to the fibrotic nature of these tumours, they tend to encase blood vessels and do not typically cause thrombosis. Involvement of vessels can be classified as abutment (≤180°) or encasement (>180°). MIP images should not be used in isolation to comment on degree of vascular involvement, as they may be misleading.

Polypoidal lesions may show arterial enhancement and distend the lumen of the affected duct. Ni et al. showed sensitivity, specificity and overall accuracy of MDCT assessment of 83.3%, 75.9% and 80.5%, respectively. MDCT is also an excellent modality for imaging nodal and distant metastasis. Complications like cholangitic abscess can be diagnosed. MRI MRCP is an accurate modality for evaluation of biliary tree. Extent of tumour can be accurately determined in 71%–96% of cases (Fig. 9.15.37). HC appears as a hypointense signal on T1-weighted images and high signal intensity of T2 imaging. Diffusion-weighted images may show restriction within the neoplasm. The tumour generally appears hypovascular in relation to adjacent hepatic parenchyma. Irregular, mildly enhancing wall thickening of the bile duct wall with upstream dilation of intrahepatic bile ducts is seen. Postcontrast dynamic scan has high accuracy in diagnosing vascular involvement. Similar to CT features such as lobar atrophy and metastasis are well delineated. MR may be superior to CT in distinguishing cholangitic abscesses from metastasis, both of which may occur in this clinical setting.

FIG. 9.15.37 MRI with MRCP in hilar cholangiocarcinoma (Bismuth type I). T2W1 images showing bilobar biliary dilatation with irregular nodular thickening involving the CHD ( arrow in D). (D and E) MRCP images show stricturing of the CHD without involvement of the primary confluence. Longitudinal extension of cholangiocarcinoma: Biliary staging. Biliary involvement is best evaluated with MRCP. Classification of cholangiocarcinoma into Bismuth subtypes is best done with MRCP. Recent studies using MDCT have also reported high diagnostic accuracy. Choi et al. reported an approximate 80% accuracy for the diagnosis of tumour spread at the level of the secondary biliary confluences. The reported accuracy for MRCP in determining the extent of bile duct tumours ranges from 71% to 96%. Thus, the accuracy of MRCP and MDCT in assessing the longitudinal tumour spread is comparable. MRCP has demonstrated similar

efficacies to PTC and ERCP in identifying anatomic extension of tumours (Figs. 9.15.38– 9.15.41).

FIG. 9.15.38 Type II Bismuth. (A to D) T2W1 axial and coronal images showing mass involving the CHD and the primary confluence with nonunion of the right and left hepatic ducts (red arrows). Note the partly distended gallbladder with large calculous at neck. MRCP images clearly show the CHD stricture. This is proven of hilar cholangiocarcinoma causing type II block.

FIG. 9.15.39 Type II Bismuth block with variant biliary anatomy. (A and B) T2W1 axial images showing a mass involving the confluence (arrows) showing diffusion restriction ( arrow in c). The right posterior sectoral duct is aberrant and opens into CHD ( arrow in D) and shows narrowing with irregularity with resultant proximal dilatation, the result of involvement ( arrows in E)

FIG. 9.15.40 Type IIIB Bismuth. (A to C) T2W1 and (D to E) postcontrast venous phase showing enhancing wall thickening with stricturing involving the CHD, primary confluence and secondary confluence on left (red arrows). Note the nonunion of biliary radicals in left lobe (yellow arrow). The mass also involved the left portal vein (blue arrow).

FIG. 9.15.41 Bismuth 1V block. (A to C) T2W1 images and (D and E) postcontrast venous phase images showing large heterogeneous mass involving the CHD, primary confluence and infiltrating into the left lobe (red arrows). The mass also invades into the right lobe involving the confluence of right and left ducts (yellow arrows) suggesting a type IV. Radial extension of cholangiocarcinoma: Vascular staging

Vascular extension is either assessed with MDCT or gadolinium-enhanced dynamic MRI. This hilar neoplasm can involve portal vein, hepatic artery, hepatic vein and inferior vena cava. The vessel is considered to be infiltrated if it is occluded, stenosed, deformed adjacent to the tumour contact, and/or more than 180° of its circumference is involved. Tumour causing complete encasement or occlusion of the main portal vein and hepatic artery proximal to the bifurcation, atrophy of one hepatic lobe with encasement of contralateral vessel and involvement of secondary biliary confluence on one side and encasement of contralateral vessel is considered unresectable. Unilateral portal vein or hepatic artery occlusion, vascular compression, unilateral hepatic metastasis and infiltration of fat planes adjacent to nonvascular structures are not a contraindication to surgical resection. Short segment invasion of less than 20 mm in length of the main portal vein is also not a contraindication for resection (Tables 9.15.39 and 9.15.40). TABLE 9.15.39 Criteria for Unresectability in HCCA • Liver metastasis • Distant lymph node metastasis • Bilateral arterial or portal invasion • Significant occlusion of main portal vein or hepatic artery proximal to bifurcation • Unilateral vascular invasion and contralateral lobar atrophy • Involvement of secondary biliary confluence on one side and encasement of contralateral vessel TABLE 9.15.40 Not Considered Unresectable • Parenchymal invasion because a right or left hepatectomy can be performed • Bismuth stage IV • Unilateral portal vein or hepatic artery occlusion • Vascular compression • Unilateral hepatic metastasis • 95%) and sensitivity (95%) for stones larger than 2 mm. CT Calcified gallstones are easily detected at CT (Fig. 9.15.53). Noncalcified gallstones are often isoattenuating to the surrounding bile and hence difficult to visualize on CT. Upon degeneration of stones, nitrogen can collect in central fissures and create the so-called Mercedes-Benz sign.

FIG. 9.15.53 CT in cholelithiasis. Unenhanced CT showing distended with gallbladder with multiple dense calculi (red arrows). Dual energy CT allows data acquisition at two different energy spectra – at high kilovolt peak (140 kvp) and a low kilovolt peak (80–100 kvp). Cholesterol containing gallstones are more conspicuous on higher and lower kiloelectron volt virtual monochromatic images than conventional CT or 70 keV dual-energy CT. Noncalcified cholesterol containing gallstones appear to have lower attenuation than bile on low-energy 40 keV images, but are hyperattenuating on high-energy 190 keV images. the contrast between noncalcified stones and surrounding bile is maximal at low kiloelectron volt virtual monochromatic imaging energy levels (Fig. 9.15.54).

FIG. 9.15.54 Dual energy CT in gallstones. (A) Conventional CT image showing distended gallbladder without stone. (B and C) Dual energy CT with low and high keV showing cholesterol stones appearing hypodense to bile on 40 keV images and hyperdense on 190 keV images. CT is however inferior to ultrasound at assessing the gallbladder. CT, however, can be very effective at assessing extrabiliary gallstone pathology and complications arising from gallstone pancreatitis and cholecystitis. MRI Gallstones usually appear hypointense on T2 and T1W1 images. MR imaging can also help distinguish between different types of gallstones. Pigment stones appear hypointense on T2W and hyperintense on T1W1 images. Cholesterol stones are hypointense on T1 and T2W1 images. The composition of the stones may affect management. Pigment stones being softer are amenable to removal with endoscopic lithotripsy, on the contrary cholesterol stones are harder and hence difficult to treat endoscopically. (Figs. 9.15.55 and 9.15.56).

FIG. 9.15.55 Cholelithiasis. T2W1 and MRCP showing a hypointense calculous in the gallbladder (arrows).

FIG. 9.15.56 Pigment stones. (A and B) T2W1 and T1W1 images showing gallbladder calculi appearing hypointense on T2W1 and hyperintense on T1W1 images (arrows). Complications 1. Choledocholithiasis: Approximately 10%–20% of patients who undergo cholecystectomy are found to have choledocholithiasis. Stones larger than 5 mm frequently do not pass and can obstruct the CBD, resulting in abdominal pain, cholangitis and pancreatitis, while smaller stones may pass off. Preoperative identification and treatment of CBD stones are critical prior to cholecystectomy due to high postoperative morbidity. Complications such as cystic stump blow out with bile leaks can be seen in patients with retained CBD stones. Choledocholithiasis is easier to detect when there is concomitant biliary duct dilatation. one-half of patients with choledocholithiasis will be found to have nondilated ducts at imaging. MRCP is the gold standard in diagnosing stone disease with high sensitivity of 90%–94% and specificity of 95%–99%. It has replaced ERCP which carries an increased risk of complications such as pancreatitis and involves use of ionizing radiation. Choledocholithiasis has been discussed in details earlier in this chapter. 2. Calculous cholecystitis: Inflammation of the gallbladder wall caused by irritation from gallstones is called calculous cholecystitis, and can be an acute or chronic. USG is the modality of choice in acute cholecystitis. Complications of acute cholecystitis like emphysematous changes, perforation are better diagnosed with CT (Fig. 9.15.57). 3. Gallbladder mucocele: When a stone obstructs the cystic duct causing the gallbladder to become distended with bile. This distended gallbladder forms a mucocele. Infection within the contents leads to empyema formation and increases morbidity. 4. Mirizzi syndrome: In this condition, an impacted stone in the gallbladder neck or cystic duct causes extrinsic compression over the CHD with resultant proximal biliary dilatation and jaundice. This entity has been discussed in detail later in the chapter. 5. Ascending cholangitis: Stasis of bile secondary to obstructed biliary drainage may lead to infection and cholangitis. Fever, right upper quadrant pain, jaundice, hypotension and altered mental status, described as Reynolds’ pentad are classic clinical features seen in patients with cholangitis. 6. Gallstone pancreatitis: Impacted calculous at ampulla may obstruct drainage of pancreatic fluid resulting in gallstone pancreatitis. This occurs more frequently with larger stones. 7. Cholecystoenteric fistula: Chronic irritation from a large gallstone can erode through the gallbladder wall with fistulization into small bowel. Air seen within the gallbladder or biliary tree on imaging. 8. Gallstone ileus: When a gallstone passes through the fistula into the small bowel, this can result in intestinal obstruction. The ileocecal valve is the narrowest point in the small bowel, hence most stones get obstructed in this region.

FIG. 9.15.57 Calculous cholecystitis. (A and B) T2W1 images showing distended gallbladder with multiple calculi (red arrow) with surrounding inflammatory changes in form of fat standing (yellow arrows) suggesting acute cholecystitis. On X-ray, pneumobilia is seen in the right upper quadrant with dilated loops of bowel consistent with bowel obstruction. CT shows features bowel obstruction, pneumobilia or demonstrate the presence of a cholecystoenteric fistula. Bouveret’s syndrome represents a syndrome in which a stone obstructs the upper GI tract proximally at the level of duodenum or gastric outlet (Figs. 9.15.58–9.15.60). 9. Dropped gallstones: Dropped stones at time of laparoscopic cholecystectomy can have a delayed presentation with postoperative complications such as intraabdominal abscess formation. 10. Stump cholecystitis or retained cystic duct stump: These findings result from incomplete cholecystectomy and can be identified on imaging.

FIG. 9.15.58 Gallstone ileus. (A) Unenhanced and (B to D) contrastenhanced CT showing large calculous in gallbladder ( red arrow in A) eroding into the duodenum ( arrow in B) suggesting a cholecystoduodenal fistula. Dilatation of small bowel loops is seen with calculous in the ileum (yellow arrow).

FIG. 9.15.59 Gallstone ileus. (A) Contrast enhanced and (B) showing collapsed gallbladder with thick walls and air within its lumen, which is likely the result of cholecystoduodenal fistula. Large calculous is seen in the ileum with resultant proximal small bowel obstruction (arrows).

FIG. 9.15.60 Gallstone ileus. (A to C) T2W1 axial images and (D and E) coronal images showing a cholecystoduodenal fistula with air within the gallbladder lumen (red arrows). Dilatation of small bowel loops is seen with calculous on the ileum (yellow arrow). (F) MRCP image showing all the fistula, stone and obstruction. Treatment Asymptomatic gallstones can be left alone. Cholecystectomy is the treatment for symptomatic patients. Most cholecystectomies are performed laparoscopically unless complications are anticipated or in cases of complicated cholecystitis. Ursodeoxycholic acid should be used only for occasional symptomatic patients with small stones presumably formed from cholesterol or proven gallbladder sludge.

Gallbladder polyps Introduction Gallbladder polyps are lesions that project from the gallbladder wall into the lumen. In the majority of instances, diagnosis is incidental in a routine abdominal ultrasound or following cholecystectomy for gallstones or biliary colic. Gallbladder polyps are classified as benign or malignant. Malignant gallbladder polyps are gallbladder carcinomas. It is important to differentiate between benign polyps and malignant or premalignant polyps, which are associated with poor prognosis. Epidemiology Gallbladder polyps are relatively common, with a reported prevalence of 3%–7% at abdominal ultrasound and 2%–12% in cholecystectomy specimens. Some reports mention male prevalence. Cholesterol polys are more prevalent in women. Aetiology/genetics The formation of gallbladder polyps is associated with fat metabolism. Patients with congenital polyposis syndromes such as Peutz–Jeghers and Gardner syndrome can also develop gallbladder polyps. Patient risk factors for malignant gallbladder polyps include age greater than 60 years, presence of gallstones and PSC. Clinical features Polys are often asymptomatic and detected incidentally. They are picked up on transabdominal ultrasounds done for right upper quadrant pain. Most commonly, symptoms include right upper quadrant pain, nausea, dyspepsia and jaundice.

Classification Gallbladder polyps may be classified as benign nonneoplastic, benign neoplastic and malignant based on histology. Most common benign nonneoplastic polyps are cholesterol polyps. Others include inflammatory and adenomyomatosis. A. Benign nonneoplastic polyps i. Cholesterol polyps: These are the most common polyps, accounting for 60%– 70% of such lesions in some studies. They are formed due to deposition of triglycerides and cholesterol esters within macrophages in the lamina propria. These polyps predominantly occur in middle-aged women. These are typically multiple and may not be associated with gallstones. Strawberry gallbladder is the name given to gross appearance of cholesterolosis and describes a bright red mucosa with intervening yellow lipid. Cholesterol polyps have no malignant potential. ii. Adenomyomatosis: This accounts for 25% of all polypoidal lesions of the gallbladder. Adenomyomatosis is not premalignant but may be seen in chronically inflamed gallbladders, which have a higher risk for developing cancer. iii. Inflammatory polys: These represent 10% of all gallbladder polyps are usually small and multiple. Inflammatory polyps occur secondary to gallstones and chronic inflammation,. which leads to mucosal irritation formation of granulation and fibrous tissue. Inflammatory polyps may lead to mucosal epithelial dysplasia. However, there is no definitive evidence that inflammatory gallbladder polyps have an increased risk for adenocarcinoma. B. Neoplastic polyps Epithelial lesions like adenoma and adenocarcinoma are the most important aetiologies. Benign tumours which contribute to less than 1% of all gallbladder polyps include leiomyomas, lipomas and neurofibromas. Polypoidal gallbladder masses are rarely seen as a manifestation of lymphoma and metastasis. Adenomas These are rare, accounting for 4%–7% of polyps. Role of adenoma in the pathogenesis of carcinoma is controversial. They are most frequently seen in patients with PSC and gastrointestinal polyposis syndromes, such as Peutz–Jeghers and Gardner syndromes. Adenomas may be sessile, pedunculated or just polypoid projections, and most are accompanied by gallstones. Histologically, they can be tubular, papillary or tubulopapillary. Adenocarcinoma Fifteen per cent of gallbladder carcinomas are polypoidal. These are, however, larger and have distinct imaging appearances and have been discussed in detail subsequently. Metastatic disease and lymphoma: May sometimes present as polyps. Imaging features have been discussed in subsection on malignant biliary masses. Imaging USG (Table 9.15.48) US is the modality of choice in diagnosis. Gary-scale imaging, colour and spectral Doppler should be included in the protocol. Patients should be imaged in more than one position. USG features of polyps include small size 1 cm, particularly >1.5 cm • Age >50 years • Sessile polyp • Solitary polyp • Associated gallstones • Clinical setting of PSC • Associated focal gallbladder wall thickening

TABLE 9.15.48 Imaging Pearls GB Polyps • Can be neoplastic or nonneoplastic • USG is the modality of choice • Signs favouring malignancy should be looked for CT and MTI • Patients with larger polyps, high risk stigmata and those in setting of PSC should be operated EUS EUS is as a superior modality to transabdominal US for imaging gallbladder lesions because of its use of high-frequency probes. EUS can predict features of benignity such as cystic spaces or comet tail artefact, which may be appreciated on transabdominal scanning. A scoring system to predict malignancy has been devised on EUS. The polyp size, internal echo pattern and hyperechoic spotting are criteria used with specificity and sensitivity of 78% and 83%, respectively. FDG–PET FDG uptake within a gallbladder polyp greater than that in the background liver is an indication of malignancy. Mimics of gallbladder polyps Stones or sludge adherent to the gallbladder wall may mimic polyps. Obesity may further hamper visualization of posterior acoustic shadowing. Adherent tumefactive sludge mimics a polypoidal mass. Contrast-enhanced CT and MRI may help in showing no enhancement in tumefactive sludge. Management Factors influencing management decisions in gallbladder polyps. a. Size – polyps larger than 10 mm should be operated. b. Polyps 6–10 mm in size, should be followed up on imaging after 6 and 12 months and, if they are stable an annual follow-up US should be performed. If an increase in size up to 10 mm is seen on imaging they should be resected. c. Polyps less than 5 mm in size can be left alone. d. Surgical management should be considered in patients over the age of 50 years, those with associated cholelithiasis and those with focal wall thickening at base of more than 3 mm. Polyps in patients with PSC should be treated with cholecystectomy irrespective of their size.

Acute cholecystitis (Table 9.15.50) Acute cholecystitis, an acute inflammatory condition of the gallbladder, remains a common cause of right upper quadrant pain in patients presenting at the emergency department. Epidemiology and aetiopathogenesis: 95% of cases of acute cholecystitis are due to an obstructing calculous in the gallbladder neck or cystic duct. Approximately 10%–20% of people in Western societies have cholelithiasis and that one-third of those with gallstones will develop cholecystitis. Obstruction of the cystic duct leads to overdistension of the gallbladder. Along with cholesterol-supersaturated bile, the increased pressure triggers an acute inflammatory response. Secondary bacterial infection is present in 20% of cases of acute cholecystitis. Increased intraluminal pressure may also lead to mural ischaemia causing complications such as gangrenous cholecystitis and perforation. Acalculous cholecystitis accounts for 5%–10% of all acute cholecystitis. Four stages of acute cholecystitis are seen at imaging – oedematous (2–4 days), necrotizing (3–5 days), suppurative (7–10 days), and finally chronic cholecystitis.

Clinical features Symptoms include pain in right upper quadrant and a positive Murphy’s sign (in which inspiration is inhibited by pain on palpation). Patients with acute cholecystitis may have a history of attacks of biliary colic or they may have been asymptomatic until the presenting episode. Complicated cholecystitis can present with features of fever and jaundice.

Imaging The recent World Society of Emergency Surgery (WSES) guidelines recommend abdominal ultrasound as the first-line modality for the diagnosis of acute calculous cholecystitis. ACR preparedness guideline also mentions USG as the modality of choice in initial evaluation of patient with pain in right upper quadrant. CT is excellent in detection of complications of acute cholecystitis and for evaluation of other causes of pain in right upper quadrant. Ultrasonography US is the preferred imaging modality for the diagnosis of acute cholecystitis. Findings on USG include cholelithiasis with distended gallbladder, gallbladder wall thickening, a positive US Murphy sign and presence pericholecystic fluid. Increased gallbladder wall thickness of more than 3.5 mm suggests acute cholecystitis reliably. Associated gallstones increases the positive predictive value to 95% in diagnosis of acute cholecystitis. Assessment of sonographic Murphy’s sign, defined as tenderness over gallbladder from pressure by the ultrasound probe is a chief advantage of USG, and has a sensitivity of 92%. The ACR preparedness guidelines mentions USG as the first modality of choice in patients presenting with right upper quadrant pain. Colour Doppler shows increased vascularity of the gallbladder wall. Thickening of the gallbladder wall is however not exclusive to cholecystitis and can be seen in a variety of systemic conditions such as liver, renal and heart failure. CT On CT, features of uncomplicated acute cholecystitis include a combination of overdistended gallbladder with thickened enhancing wall, pericholecystic fat stranding and fluid. Pericholecystic hyperaemic corresponds as a Transient hepatic attenuation difference (THAD) in adjacent hepatic segments (Fig. 9.15.63). Classically, a stone can be seen impacted in the gallbladder neck or cystic duct. The sensitivity of CT in diagnosing gallstones, even larger stones is lower than USG. Mural thickening of the gallbladder is however not specific and can be seen in a variety of conditions such as hepatitis, hypoproteinemia and heart failure.

FIG. 9.15.63 CT in acute cholecystitis. (A and B) Contrast-enhanced CT images showing a distended gallbladder with stone disease with thickened oedematous wall and surrounding inflammation ( arrow in B). CT scan is usually not indicated in patients with uncomplicated cholecystitis. It is however excellent in diagnosing complications of cholecystitis, which have been discussed later in the chapter. Patients with right upper quadrant pain not showing features suggestive of cholecystitis on USG should undergo CT to diagnose other causes of pain. MRI MRI with MRCP are not commonly used in the diagnosis of acute cholecystitis. The most important setting in which MRCP is used when patient has clinical or laboratory features suggestive of choledocholithiasis (Fig. 9.15.64). MRI is superior to CT in diagnosis of gallstones and is superior to US in the depiction of cystic duct and gallbladder neck calculi. Features of acute cholecystitis include distended gallbladder with mural thickening and surrounding fat standing. Additionally, comment on intrahepatic biliary anatomy can be made on MRI. Aberrant ducts in the Calot’s triangle should be reported to avoid inadvertent biliary injuries, leading to catastrophic complications.

FIG. 9.15.64 MRI in acute cholecystitis. (A) T2W1 and (B and C) contrast-enhanced MRI images showing distended gallbladder with stones and sludge. The gallbladder walls are thickened and pericholecystic inflammatory changes are seen with THAD in adjacent liver segments (red arrows in B). The lack of widespread availability of MRI and the relatively high cost prohibits its primary use for now.

Imaging of complications (Table 9.15.49)

TABLE 9.15.49 Complications of Acute Cholecystitis Diagnosis Acute calculous cholecystitis

CT Findings Gallstone in the gallbladder neck or cystic duct, thickened (≥ 0.3 cm) and enhancing wall, pericholecystic fat stranding with or without pericholecystitic fluid, reactive enhancement in the adjacent liver Gangrenous Nonenhancing wall, sloughed membrane, mural striation, irregular cholecystitis enhancing wall with defect, with or without gallstone, pericholecystic fat stranding and fluid (more than that seen in uncomplicated cholecystitis) Emphysematous Similar findings as acute cholecystitis, with presence of gas in cholecystitis gallbladder wall (intraluminal gas can be due to fistula formation or other causes of pneumobilia) Perforated Similar findings as acute cholecystitis, with focal defect in cholecystitis gallbladder wall, contiguous pericholecystitic fluid or hepatic abscess TABLE 9.15.50 Imaging Pearls Acute Cholecystitis • Ultrasound is the first-line modality for the diagnosis of acute calculous cholecystitis. • Ultrasound has the best sensitivity and specificity for evaluating patients with suspected gallstones. • Gallbladder wall thickness of >3.5 mm has been found to be a reliable and independent predictor of acute cholecystitis. • Evaluation of complications may require cross-sectional imaging techniques, namely CT or MR imaging. • CT has a relatively low sensitivity in detecting gallstones due to the variable composition of the stones. • MR cholangiography is superior to US in the depiction of cystic duct and gallbladder neck calculi at the evaluation of cystic duct obstruction. 1. Gangrenous cholecystitis is a complication of acute cholecystitis, associated with higher morbidity and mortality. It occurs in up to 39% of patients with acute calculous cholecystitis. Elderly patients and patients with a history of diabetes mellitus are at an increased risk of having gangrenous changes at presentation. Additional features on ultrasound include membranes within the gallbladder lumen which representing mucosal shredding, wall defects and collections in relation to gallbladder. CT is the modality of choice and shows poorly enhancing walls, intraluminal membranes, reduced mural enhancement, focal mural defects and pericholecystic abscesses. These findings have a high specificity close to 90% in the diagnosis of gangrenous cholecystitis (Figs. 9.15.65 and 9.15.66).

FIG. 9.15.65 Gangrenous cholecystitis. Contrast-enhanced CT showing distended gallbladder with thickened walls (red arrow) with mucosal irregularity and shredding (yellow arrows) suggestive of gangrenous changes. Pericholecystic inflammatory changes are seen (blue arrow).

FIG. 9.15.66 MRI gangrenous cholecystitis. (A and B) T2W1 axial images showing distended gallbladder with inclusion defect (red arrows). Sloughing of mucosa is seen with intraluminal membranes (yellow arrows). (C) MRCP image showing the mucosal splitting (arrow) with appearance of fluid level. 2. Perforation: Perforation of gallbladder wall is often seen in the setting of gangrenous cholecystitis. Focal mural defect with contiguous pericholecystic fluid suggests perforation in the gallbladder, which can result in pericholecystic abscess, intrahepatic abscess or peritonitis, depending on the site of perforation (Figs. 9.15.67, 9.15.68 and 9.15.70).

FIG. 9.15.67 Gallbladder perforation with empyema. (A to C) T2W1 images showing overdistended gallbladder with breech of wall in the fundic region (red arrows). Resultant multiple walled-off collections are seen around the fundus (yellow arrows). The contents of the gallbladder reveal diffusion restriction ( arrow in D) suggesting empyema.

FIG. 9.15.68 Gallbladder gangrene with fundic perforation. A to E) Contrast-enhanced CT showing thickened gallbladder wall with mucosal sloughing ( red arrow in B) suggesting gangrenous changes. Defect in fundic wall is seen ( yellow arrow in D) with resultant pericholecystic collection ( yellow arrow in E).

FIG. 9.15.69 Emphysematous cholecystitis. (A to C) Nonenhanced CT images showing a distended gallbladder with air in the wall in fundic region suggestive off emphysematous changes.

FIG. 9.15.70 Perforated gallbladder with biliary peritonitis. (A to C) Contrast-enhanced CT venous phase axial showing perforated gallbladder ( arrow in A) with extensive biliary peritonitis ( red arrow in C). 3. Emphysematous cholecystitis: This is defined as air in the gallbladder wall and may occur secondary to infection by Clostridium welchii. Patients with diabetes are at higher risk and may be clinically silent initially. Radiolucent gas lining the gallbladder wall is seen on X-ray. USG shows hyperechoic nondependent foci along the wall. CT scan unequivocally shows air densities with feature of acute cholecystitis (Fig. 9.15.69). 4. Pericholecystic abscess: Acute cholecystitis is complicated with pericholecystic abscess formation in 3%–19% of cases. Peripheral rim-like enhancing clustered lesions may be seen on CT in the intramural region, extending into the pericholecystic space and involving adjacent liver parenchyma (Fig. 9.15.72).

FIG. 9.15.71 Haemorrhagic perforation. (A to C) T2W1 axial images and (D) coronal images showing hypointense contents of the gallbladder extending into pericholecystic space (red arrows). (E and F) Nonenhanced CT images showing hyperdensity in the gallbladder lumen extending into the pericholecystic space (arrows).

FIG. 9.15.72 Gallbladder perforation with localized abscess in liver. Contrast-enhanced CT in venous phase showing perforated gallbladder with stones ( red arrows in A). Note the breech in fundic wall with localized hepatic abscess ( arrow in B). 5. Vascular complications: Inflammatory vessel wall destruction associated with acute cholecystitis results in gallbladder haemorrhage, which appears as hyperdensity in the gallbladder lumen on nonenhanced CT and show signal intensity of blood on MRI. Portal vein thrombosis and cystic artery pseudoaneurysm are also occasionally seen as sequelae of local vascular inflammation from acute or chronic cholecystitis (Fig. 9.15.71).

Management Most patients with acute cholecystitis respond to conservative, first-line management. About 20% of patients with acute cholecystitis need emergency surgery. Laparoscopic cholecystectomy is usually the surgical procedure. Patients with complicated cholecystitis may undergo open cholecystectomy or require conversion from laparoscopic to open Percutaneous cholecystostomy is a minimally invasive procedure that can benefit patients with serious comorbidities who are at high risk for cholecystectomy.

Chronic cholecystitis (Table 9.15.51) TABLE 9.15.51 Pearls Chronic Cholecystitis • Chronic cholecystitis almost always arises in the setting of cholelithiasis • Most common cross-imaging findings of chronic cholecystitis are cholelithiasis and gallbladder wall thickening • Complications related to chronic cholecystitis include acute cholecystitis and gallbladder carcinoma Chronic cholecystitis is a common inflammatory condition affecting gallbladder. It almost always arises in the setting of cholelithiasis. Recent studies have also raised a possible connection between chronic cholecystitis and infection with Helicobacter pylori. Clinical manifestation Patients may have a history of recurrent acute cholecystitis or biliary colic. Some patients may, however, be completely asymptomatic. Complications Patients with chronic cholecystitis can develop complications such as acute cholecystitis and gallbladder carcinoma. Another uncommon complication is the development of biliary enteric fistula causing gallstone ileus. Imaging Contracted gallbladder showing thickened enhancing walls. The pattern of wall enhancement is usually single-layered type. No surrounding inflammation is seen. Cholelithiasis is almost invariably present (Fig. 9.15.73).

FIG. 9.15.73 Chronic calculous cholecystitis. (A to C) T2W1 images showing slit- like contracted gallbladder (red arrows) with calculi in neck ( yellow arrow in C). The feared complication of chronic cholecystitis is associated gallbladder carcinoma. Early T1 carcinomas may be indistinguishable on imaging, hence patients with chronic cholecystitis should undergo resection. Management: Uncomplicated chronic cholecystitis is generally managed with elective cholecystectomy. Gallstone ileus carries a high mortality rate (20%–40%) and is treated surgically.

Xanthogranulomatous cholecystitis (Table 9.15.52) TABLE 9.15.52 Pearls Xanthogranulomatous Cholecystitis • Intramural hypoechoic (on USG) or hypoattenuating (on CT) nodules or bands may suggest the specific diagnosis of XGC • May mimic gallbladder carcinoma on cross-sectional imaging • Patients with XGC also may be at increased risk of gallbladder malignancy XGC is a rare gallbladder inflammatory disorder characterized by abnormal intramural nodules.

These nodules are thought to form when the Rokitansky–Aschoff sinuses become occluded and rupture. This leads to extravasation of bile into the gallbladder wall causing an inflammatory reaction. Superimposed infection is also frequently present. This condition is most commonly observed in elderly patients. Imaging USG Cholelithiasis and gallbladder wall thickening are the most common findings. Mural thickening may be focal or diffuse. Intramural hypoechoic nodules suggest the diagnosis of XGC. CT Wall thickening, which maybe may be focal or diffuse. Pericholecystic inflammatory changes may also be present. Intramural hypoattenuating nodules or bands may suggest the specific diagnosis of XGC. There may be associated biliary obstruction secondary to extrinsic compression of the bile duct and associated Mirizzi syndrome. The gallbladder often becomes adherent to adjacent organs and may be associated with fistula formation. On occasion, XGC may mimic gallbladder carcinoma on cross-sectional imaging. Five features useful to distinguish from carcinoma include continuous mucosal enhancement, intramural hypoattenuating nodules, diffuse mural thickening, absent hepatic invasion and absent intrahepatic duct distension (Fig. 9.15.74).

FIG. 9.15.74 Complicated XGC. (A to D) Contrast-enhanced axial CT showing stones within the gallbladder lumen ( arrows in A). Multiple hypodense nodules are seen in gallbladder wall ( red arrow in B and C). The gallbladder appears mass like and is adhered to the hepatic flexure, which is grossly thickened ( arrow in D). The gallbladder is also causing biliary obstruction with resultant intrahepatic biliary dilatation. Complications include gallbladder perforation, hepatic abscess, biliary ductal stricture with or without biliary obstruction, ascending cholangitis and biliary fistula. Management: Treatment is typically elective open cholecystectomy because laparoscopic cholecystectomy is often unsuccessful due to adhesions and adjacent fibrosis. Adenomyomatosis (Table 9.15.53)

TABLE 9.15.53 Imaging Features Favouring Adenomyomatosis • Echogenic foci in wall with comet-tail artefact on USG • Hypodense cystic spaces in wall on contrast-enhanced CT • Focal intramural calcifications • Pearl necklace sign on MRI multiple rounded hyperintense intraluminal cavities on T2 Gallbladder adenomyomatosis is a benign condition caused by exaggeration of the normal invaginations of the luminal epithelium (Rokitansky–Aschoff sinuses) with associated smooth muscle proliferation. Thickening of the gallbladder wall with internal cystic spaces is seen on imaging. This condition is relatively common and identified in at least 5% cholecystectomy specimens. No sex predilection is seen. It is not a premalignant condition and does not require treatment. Most patients with adenomyomatosis are asymptomatic. Rarely, however, patients may get pain, which gets relieved with cholecystectomy. Adenomyomatosis may be focal or diffuse. The focal form most commonly involves the fundus. Imaging USG The most common appearance on sonography is tiny, echogenic foci in the gallbladder wall that create comet-tail artefacts, caused by either the cystic space itself or the internal debris Prominent mass-like focal areas of adenomyomatosis, called adenomyomas, are the next most common manifestation. This finding may mimic a neoplasm; however, presence of cystic spaces with comet-tail artefact or twinkling artefact on Doppler appearance allows the entities to be distinguished. Twinkling artefacts appear as rapidly alternating red and blue colour Doppler signals, ‘comet-tail’ shaped, and are better appreciable using low-frequency probes. Focal adenomyomatosis is most common in the gallbladder fundus, less often narrowing the midportion of the organ, called hourglass gallbladder. CT Contrast-enhanced CT is required for the diagnosis of adenomyomatosis. Nonspecific signs include wall thickening and enhancement. CT rosary sign has been described formed by enhancing epithelium within intramural diverticula surrounded by the relatively unenhanced hypertrophied gallbladder muscularis. The accuracy of CT in differentiating adenomyomatosis from gallbladder carcinoma is between 40% and 75% and a confident diagnosis of GA is possible only if large (at least 3–4 mm) RAS are present. Focal intramural calcifications are virtually pathognomonic for GA, but are not commonly seen. MRI MRI shows gallbladder wall thickening and reveals Rokitansky–Aschoff sinuses as intramural lesions that are hyperintense on T2-weighted images, hypointense on T1weighted images, and not showing enhancement on contrast study. The ‘pearl necklace sign’ describes the characteristically arrangement of multiple rounded hyperintense intraluminal cavities visualized at T2-weighted MR imaging and MR cholangiopancreatography. MRI is the imaging modality that offers the highest accuracy in diagnosing adenomyomatosis and, in particular, in differentiating GA from gallbladder carcinoma (accuracy 93%) (Fig. 9.15.75).

FIG. 9.15.75 MRI in adenomyomatosis. T2W1 axial images showing features of calculous cholecystitis ( red arrow in A) with choledocholithiasis ( yellow arrow in E). Multiple tiny bright cavities are seen in gallbladder wall ( red arrows B and D) representing Rokitansky–Aschoff sinuses. This is pearl necklace sign. Mirizzi syndrome Mirizzi syndrome is a rare complication in which a stone embedded in the neck of the gallbladder or cystic duct extrinsically compresses the CHD, with resulting jaundice, bile duct obstruction and in some cases a fistula. Mirizzi syndrome is classified according to the Csendes classification into four subtypes (Tables 9.15.54 and 9.15.55). TABLE 9.15.54 Csendes Classification of Mirizzi’s Syndrome Type 1 Type 2 Type 3 Type 4

Extrinsic compression over the CHD by impacted calculous in gallbladder neck or cystic duct Cholecystobiliary fistula with diameter one-third of the circumference of the CHD Cholecystobiliary fistula with diameter over two-thirds of the circumference of the CHD Cholecystobiliary fistula involving entire circumference of the CHD

TABLE 9.15.55 Imaging Pearls – Mirizzi’s Syndrome • MRCP is the modality of choice • Dilated intrahepatic biliary tract, with extrinsic compression over CHD secondary to impacted calculous • Fistula, if present, can be graded on MRCP • Stenosis of bile ducts accurately seen on MRCP • CT shows dilated biliary radicals with narrowing at level of CHD, stone may or may not be seen depending on composition • ERCP is an excellent modality to diagnose and grade Mirizzi’s syndrome

Clinical presentation Mirizzi syndrome is rare, occurring in about 1% of all patients who undergo cholecystectomy. Most patients present with repeated bouts of pain, fever and jaundice. Imaging US reveals gallstones with a contracted gallbladder and moderate intrahepatic ductal dilatation with normal extrahepatic biliary anatomy. MRCP is the modality of choice. The typical findings are a dilated intrahepatic biliary tract, with extrinsic compression over CHD secondary to impacted calculous. The CBD is usually normal in calibre. Surrounding inflammation may be seen. The stone may be seen eroding into the CHD. The size of the fistula cannot be accurately diagnosed on MRCP. Ductal strictures can however be well seen on MRI. Associated inflammatory changes in the gallbladder are readily diagnosed (Figs. 9.15.76 and 9.15.77).

FIG. 9.15.76 Mirizzi’s syndrome. (A) Unenhanced CT and (B and C) contrast-enhanced CT showing a large calculous in the gallbladder neck eroding into the CHD (arrows). (D and E) T2W1 and (F) MRCP images showing calculous partly within the gallbladder and partly in the CHD with intrahepatic biliary dilatation.

FIG. 9.15.77 Mirizzi’s syndrome. (A) T1W1 and (B and C) T2W1 images showing multiple calculi in gallbladder next compressing upon and eroding into the CHD (arrows). (D) MRCP images showing narrowing of CHD (yellow arrow) in the region of calculous with proximal biliary dilatation (red arrow). The appearance of the obstruction and surrounding inflammation may be confused with a Klatskin tumour. The clinical picture and presence of impacted stone help in excluding malignancy. CT shows dilated biliary radicals with narrowing at level of CHD. Stone may or may not been depending on degree of calcification and content. Features of concomitant cholecystitis can be accurately diagnosed. ERCP is an excellent modality for diagnosing and staging Mirizzi’s disease. The fistula between the gallbladder and CHD can be seen and graded. Treatment is traditionally by an open cholecystectomy, although endoscopic stenting and laparoscopic cholecystectomy have been performed successfully. Preoperative diagnosis of Mirizzi syndrome is important so that bile duct injury can be avoided. Acute hepatitis-related gallbladder changes Patients with acute hepatitis may show inflammatory changes around the gallbladder. Such gallbladder changes are likely reactive because of adjacent hepatic inflammation. A direct correlation has been reported between the level of elevation of serum liver transaminases and the degree of gallbladder wall thickening on sonography. Imaging USG findings seen include marked gallbladder wall thickening, oedema, contracted gallbladder and echogenic bile. The gallbladder wall may also show three distinct layers with central hypoechogenicity. Oedema can be seen in adjacent liver which appears hypoechoic with prominent echogenic portal triads (the so-called starry-sky appearance). CT may show diffuse gallbladder wall thickening with oedema. Surrounding fat stranding may be seen. Changes of hepatitis can be visualized in the liver parenchyma in the form of hepatomegaly with periportal cuffing. The most important role of imaging is to distinguish hepatitis-related wall thickening from cholecystitis. The clinical setting plays an important role. Patients with cholecystitis typically present with severe right upper quadrant pain, while those with hepatitis present

with dull pain, jaundice and deranged LFTs. If a patient with cholecystitis has deranged LFTs, it indicated choledocholithiasis, which typically presents with biliary colic, a feature not seen with hepatitis. Imaging findings in hepatitis include hepatomegaly with periportal cuffing, enlarged periportal nodes. The gallbladder wall appears oedematous and may show layered enhancement without significant surrounding fat standing. As opposed to this, cholecystitis appears as diffuse thickened enhancing wall with surrounding inflammation and fluid. Pericholecystic THAD in the adjacent liver segments is a feature that aids in diagnosis. Findings resolve on treatment of hepatitis (Fig. 9.15.78).

FIG. 9.15.78 Acute hepatitis-related gallbladder wall oedema. (A and B) T2W1 images in a patient with acute hepatitis A showing gallbladder wall oedema (arrows). This finding should not be misconstrued as cholecystitis. Ceftriaxone-associated gallbladder pseudolithiasis Ceftriaxone (CTRX) is a third-generation cephalosporin antibiotic used for treating bacterial infections.. It can cause transient cholelithiasis (also referred to as pseudolithiasis). The incidence of CTRX-associated biliary pseudolithiasis has been reported to be relatively high (approximately 10.1%–46.5%) in children, but some studies have reported the occurrence of CTRX-associated biliary pseudolithiasis in adults. CTRX shows biliary excretion with concentration in bile 20–150-fold greater than that in serum. When biliary concentration of the drug exceeds a threshold, it precipitates by binding to calcium ions. Most patients are asymptomatic, gallstone pancreatitis or acute cholecystitis have however also been reported. High daily dosages (over 2 g daily) and a long-term duration of drug therapy increase risk for developing CTRX-associated GB sludge or stone. Radiologically, the most common abnormality seen is biliary sludge. However, the sludge may serve as the nidus and can form gallstone. Sonographic abnormalities showed echogenic material with/without acoustic shadowing in gallbladder and high attenuation contents on CT scan. CTRX-associated biliary pseudolithiasis has been reported to resolve within approximately 2 months after CTRX therapy cessation.

Gallbladder volvulus Gallbladder volvulus is a rare disease. It mainly occurs in elderly woman, with clinicradiological findings mimicking acute cholecystitis. It is a surgical emergency, and the diagnosis is usually made intraoperatively. Eighty-five per cent of cases occur between the ages of 60 and 80 years. The disease is more prevalent in females with a female-to-male ratio of 3:1. Volvulus characterized by mechanical clockwise or counter clockwise organoaxial torsion along the longitudinal axis of the gallbladder involving cystic artery and cystic duct. It can be classified into complete and incomplete forms. In complete torsion, gallbladder undergoes rotation greater than 180°, whereas in incomplete, the rotation is less than 180.

There are five positions of the gallbladder in relation to the liver. These include intrahepatic, close attachment to liver by peritoneum, complete mesentery but held closely to liver, complete mesentery that is long allowing the gallbladder to hang freely and an incomplete mesentery attached to cystic duct allowing the gallbladder to hang freely. The last two positions predispose to torsion. Though the variation in peritoneal attachment of the gallbladder is congenital, the predisposing factor that are more commonly acquired include age >70 years, female sex, weight loss, liver atrophy, and loss of visceral fat which results in the elongated gallbladder mesentery necessary for torsion to occur. No obvious association with gallstones is seen. Preoperative diagnosis of gallbladder volvulus remains difficult because the symptoms and signs are analogous to those of an acute cholecystitis. Blood tests are usually nonspecific. LFTs are not deranged because CBD is usually nonobstructed. On US features suggestive of gallbladder torsion include a diffusely thickened and hypoechoic gallbladder wall. The gallbladder is floating not appearing attached to the gallbladder fossa. A conical structure is seen at the gallbladder neck with multiple linear echoes converging toward the tip of the cone. CT scan and MRCP scan show abnormal anatomical position and ‘floating gallbladder’ with associated wall thickening and signs of ischaemia in the form of absent wall enhancement. Once diagnosed, the appropriate treatment is emergency derotation and cholecystectomy often performed by laparoscopy. Vicarious excretion of intravenous contrast medium in the gallbladder The term vicarious excretion of a contrast medium refers to the excretion of the contrast medium from a route other than the normally expected. In general, intravenous contrast media are mainly excreted by the renal glomeruli. However, 1.5%–2% of dose can be excreted by alternative routes including biliary tract, gastrointestinal tract and glandular epithelium. Excretion can occur with normal renal function and large doses of contrast agents or with impaired renal function or obstruction. The time for the visualization of the contrast medium in the gallbladder may vary from 20 minutes to 72 hours Structurally, there is no change in the gallbladder, though on imaging the luminal contents appear slightly radiopaque. The diagnosis is based usually on CT scan which shows hyperdense contents on delayed phase (Fig. 9.15.79).

FIG. 9.15.79 Vicarious excretion of contrast. Delayed phase (1 h) shows layering of IV contrast in the gallbladder (arrows). Factors related to contrast media can be responsible for vicarious excretion. Omnipaque has the highest rates of hepatobiliary excretion. In another study by Gillespie et al., the authors concluded that the gallbladder opacification is dose related. No treatment is required as vicarious excretion is of no clinical significance; however, abnormal renal function or renal injury must be ruled out.

Dysfunctional gallbladder Also known as gallbladder dyskinesia, chronic acalculous gallbladder dysfunction, acalculous biliary disease and functional gallbladder It refers to biliary-type abdominal pain (also termed biliary colic) in the context of a structurally normal gallbladder. Pain of biliary origin is typically steady, severe epigastric or right upper quadrant pain that might radiate through to the back and right infrascapular regions, lasting for at least 30 minutes but less than 6 hours and can be associated with nausea and vomiting, Its functional nature should be supported by an absence of markers of organic disease: Normal liver and pancreatic biochemistries, and negative diagnostic imaging. Functional biliary disorders have been most prominently linked to abnormal motility of the gallbladder and/or sphincter of Oddi. Organic pathologies of the gallbladder like stones on imaging and abnormalities in upper GI tract on endoscopy are typically absent in functional disease of gallbladder. Assessment of gallbladder emptying by cholecystokinin–cholescintigraphy is crucial in diagnosing functional gallbladder disorder. Normal gallbladder ejection fraction should be ≥38%, according to a recent consensus conference. The medical options for management of functional biliary disorders are quite limited. Although there may be a rising tide of cholecystectomies being performed for biliary dyskinesia, the literature does not yet support cholecystectomy being done routinely for this disorder.

Gallbladder malignancies Gallbladder carcinoma This malignancy arises from the epithelial lining of the gallbladder and cystic duct and is the most common biliary malignancy worldwide. Geographic and ethnic variations influence the incidence of the malignancy. In India, North, East, Northeast and Central regions are among the high incidence areas for gallbladder. The incidence in North India is 10–22/100,000 population. The incidence of gallbladder carcinoma has been rising in India among women as well as men. Risk factors for GBC (Table 9.15.56) TABLE 9.15.56 Risk Factors for Carcinoma Gallbladder • Geographical region • Female gender • Gallstones • Obesity • Parity • Family history • Lower socioeconomic status • H. pylori • S. typhi infection • Smoking • Structural biliary abnormalities • Preexisting benign conditions 1. Geographical region In India, the incidence of GBC is 10 times higher in north India compared to the southern Indian states. Untreated sewage, industrial waste, bacteria like Salmonella typhi in Gangetic water are associated with pathogenesis of GBC.

Mustard oil consumed by poor population, is a known carcinogen. 2. Age and gender The mean/median age is usually 50–55 years. In India, the mean age for diagnosis is lower than the west by approximately 15–20 years. Increasing age is associated with increasing risk for GBC. Incidence is higher in females with ratios varying from 3:1 to 4.5:1 in various Indian series. 3. Gallstones Gallstone are present in 70%–90% of patients with GBC. Gallstones cause local mucosal irritation and chronic inflammation resulting local production of carcinogens. 4. Obesity Obesity, body mass index (BMI) of >30, is associated with twofold increased risk for GBC. 5. Parity Higher parity is associated with increased risk with GBC globally as well as in India. 6. Family history History of GBC or GSD in first-degree relatives has been associated with increased risk for GBC by five times. 7. Socioeconomic status Lower socioeconomic status has been associated with increased risk for GBC in Chile as well as in India. 8. H. pylori All studies from India have shown a definite but small risk of H. pylori in the causation of GBC. 9. Smoking Smoking has been seen to be associated with increased risk of GBC in various studies globally as well as in India. 11. Structural biliary abnormalities Anomalous pancreaticobiliary junction with or without choledochal cysts results in reflux of pancreatic juice into the gallbladder causing chemical irritation in gallbladder mucosa and predisposing to carcinoma. 12. Pre-existing benign conditions Presence of large polyps (>10 mm), sessile polyps, solitary polyps, associated gallstones, older age and rapidly increasing size are features favouring malignancy Other premalignant conditions include chronic cholecystitis, porcelain gallbladder, choledochal cyst and PSC. Pathology Approximately 60%, 30% and 10% tumours originate in the fundus, body and neck of the GB, respectively. Over 90% of cases of gallbladder cancer are adenocarcinomas, with the majority related to chronic inflammatory metaplasia and dysplasia. Gallbladder adenocarcinoma is divided into multiple subtypes, the most common of which is the papillary form, although signet ring and mucinous adenocarcinomas, also occur. Squamous cell carcinomas is the second most common histologic type of gallbladder carcinoma, representing up to 3% of all gallbladder primary malignancies. Researchers also divide gallbladder carcinoma into metaplasia and nonmetaplastic types. The two types of metaplastic variety include the pseudopyloric and intestinal types. They are associated with chronic inflammation and cholelithiasis.

K-ras gene mutations have been found in 39%–59% of GBC, whereas p53 mutations have been reported in 35%–92% of patients having GBC. Patterns of gallbladder carcinoma 1. Mass occupying or replacing the gallbladder lumen: This pattern may be present in 40%–65% of patients with gallbladder carcinoma at initial detection. 2. Focal or diffuse asymmetric wall thickening: Gallbladder carcinoma may present as focal or diffuse asymmetric wall thickening in 20%–30% of cases. 3. Intraluminal poly: The initial detection of gallbladder carcinoma as a polypoid lesion occurs in 15%–25% of cases. Clinical presentation Patients are often asymptomatic early in the course of disease. Nonspecific symptoms include right upper quadrant pain, weight loss and anorexia. Once the mass enlarges, clinical presentation depends on the direction in which the mass extends. In cases where the mass extends into hilum jaundice the presenting symptom is jaundice. If the malignancy is located in the body or fundus of the gallbladder and extends into the liver or adjacent colon or small bowel can lead to local pain or bowel obstruction, respectively. Tumour markers CA242, CA15-3, CA19-9 and CA125 are the tumour markers used. CA242 and CA125 when utilized together have the best sensitivity and specificity. CEA more than 4 ng/mL has a sensitivity of 50% and specificity of 93%. CA19-9 is frequently increased in the presence of biliary obstruction; therefore, it is less specific. Serum ALP, direct bilirubin (conjugated bilirubin), and AST concentrations are usually deranged in more than 50% of cases. Routes of spread Gallbladder carcinoma spreads via vascular, lymphatic, intraperitoneal, neural and intraductal routes. Loco regional spread in GC is more common than distant metastasis. Incidence of nodal and hepatic metastasis is high seen in 60% and 76%–86% cases, respectively. Intraperitoneal spread is common with ascites, omental nodules and peritoneal implants. Pattern of nodal spread is important in carcinoma gallbladder and correlated with lymphatic drainage of the gallbladder. Pathways of nodal spread (Fig. 9.15.80) 1. Primary route is called cholecystoretropancreatic pathway. The cystic duct and pericholedochal nodes are first to be involved, followed by nodes posterior to the head of the pancreas and then interaortocaval lymph nodes. 2. The retroportal and right celiac nodes constitute the secondary route of drainage and this pathway is called the cholecystoceliac pathway. 3. The third route is called cholecystomesenteric route and involves nodes posterior of gallbladder with spread to the aortocaval lymph nodes.

FIG. 9.15.80 Diagrammatic representation of pathways of nodal spread of gallbladder carcinoma. Carcinoma of the gallbladder, particularly around the neck may infiltrate into the hepatic hilum involving the right and left hepatic ducts and presenting with hilar block and jaundice. This variety needs to be differentiated from hilar cholangiocarcinoma. The hilar variety often involved the right hepatic artery and portal vein which lie posterior to the neck. Internal fistulation is seen. Cholecystoduodenal type (61%–77%) is the most common communication, followed by cholecystocolonic (14%–17%) and cholecystogastric (6%). Metastases can occur to liver, lymph nodes, adrenal, kidney, spleen, brain, breast, thyroid, heart and uterus. Bone metastasis are rare and when seen are usually lytic. Staging The eighth edition of AJCC classification is currently used in the staging. Tumour (T) TX: The primary tumour cannot be evaluated. T0 (T plus zero): No evidence of cancer was found in the gallbladder. Tis: This refers to carcinoma (cancer) in situ, which means that the tumour remains in a preinvasive state and its spread, if any, is very confined. T1: The tumour is only in the gallbladder and has only invaded the lamina propria (a type of connective tissue found under the thin layer of tissue covering a mucous membrane) or muscle layer. • T1a: The tumour has invaded the lamina propria. • T1b: The tumour has invaded the muscle layer. T2: The tumour has invaded the perimuscular connective tissue (the layer between the muscle layer and the serosa) but has not extended beyond the serosa (the outer layer) or into the liver. • T2a: The tumour has invaded the perimuscular connective tissue on the peritoneal side.

• T2b: The tumour has invaded the perimuscular connective tissue on the side of the liver but has not spread to the liver. T3: The tumour extends beyond the gallbladder and/or has invaded the liver and/or one other adjacent organ or structure, such as the stomach, duodenum (part of the small bowel), colon or pancreas. T4: The tumour has invaded the main portal vein or hepatic artery or has invaded more than one organ or structure beyond the liver. Node (N) NX: The regional lymph nodes cannot be evaluated. N0 (N plus zero): There is no regional lymph node metastasis. N1: There is regional lymph node metastasis. According to the seventh edition, metastasis to the nodes along the cystic duct, CBD, hepatic artery and/or portal vein. According to eighth edition, metastasis in 1–3 regional lymph nodes. N2: There is distant lymph node metastasis. Metastasis to the periaortic, pericaval, superior mesentery and/or celiac artery lymph nodes. According to the eighth edition, metastasis in 4 regional lymph nodes artery. Metastasis (M) The ‘M’ in the TNM system describes whether the cancer has spread to the other parts of the body. M0 (M plus zero): There is no distant metastasis. M1: There is metastasis to one or more other parts of the body. Imaging USG Mass forming carcinomas appear as a heterogeneous lesion with irregular margins and intralesional necrosis. Coexistent stones, wall calcification appear as echogenic foci with acoustic shadowing. Intralesional vascularity is seen on colour Doppler. Sonographically demonstrating that the intraluminal mass is immobile with changes in patient position allows one to distinguish tumour mass from tumefactive sludge. Irregular nodular focal wall thickening is another manifestation of carcinoma. It must be distinguished from wall thickening secondary to benign aetiologies, which are usually diffuse and non nodular without internal vascularity. Polypoidal carcinoma is seen a solitary, sessile polyp with focal wall thickening at base measuring more than 3 mm with coexisting stone disease. At colour and spectral Doppler US, linear colour signals at the polyp base and an increased resistive index. Diffuse or branched pattern of enhancement is seen in malignant lesions on contrast-enhanced US and has a sensitivity of 100%, specificity of 76.9% and accuracy of 84.5%. These lesions in addition show persistent time– intensity enhancement curve. The gallbladder lacks muscularis mucosa and submucosa and has direct venous drainage through the liver into the hepatic veins. This allows large masses to directly invade the liver. Sonography is not useful in staging of gallbladder carcinoma. Studies have reported that 30% of early carcinomas may be missed by ultrasound. The sensitivity and accuracy of US in advanced GC are 85% and 80%, respectively. Vascular involvement and surgical planning require additional contrast-enhanced CT or MRI. EUS improves accuracy in both characterizing local disease and identifying regional nodal spread versus conventional ultrasound. Sonography can however differentiate between carcinoma and chronic cholecystitis with a sensitivity of 44% in early stages of disease. CT/MRI Ct is most commonly used modality for staging. Imaging features depends on the morphology of thickening. 1. Mass forming

This type appears as a hypoattenuating or isoattenuating mass in the gallbladder fossa possibly invading into the liver parenchyma. These masses show enhancement in arterial phase predominantly in the periphery with retention of contrast during the portal venous and delayed phase, owing to fibrous stromal components of gallbladder carcinoma. Heterogeneity of enhancement and central areas of necrosis can be seen. The mass can infiltrate into the hilum causing a biliary involvement with resultant bilobar biliary dilatation. Although any pattern of biliary obstruction can be seen, gallbladder carcinomas most frequently cause a type 2 Bismuth biliary block. On MRI, gallbladder carcinoma usually shows hypo- to isointense signal on T1-weighted and moderately hyperintense signal on T2-weighted sequences. Enhancement pattern is similar to that on CT. Diffusion restriction may be seen in the mass (Figs. 9.15.81–9.15.83).

FIG. 9.15.81 Mass forming cholangiocarcinoma. (A and C) T2W1 and contrast-enhanced venous phase images showing a large T2 heterogeneously hyperintense mass in the gallbladder fossa replacing it ( arrows in A and C). The mass infiltrates into adjacent hepatic segments and the hilum ( red arrow in B) with resultant bilobar biliary dilatation.

FIG. 9.15.82 Mass forming gallbladder carcinoma causing hilar block. (A to C) Contrast-enhanced CT images showing a large mass replacing the gallbladder (red arrows) infiltrating into the hilum causing biliary dilatation.

FIG. 9.15.83 Mass forming gallbladder carcinoma. (A to C) T2W1 images showing a large heterogeneously hyperintense mass arising from the gallbladder and infiltrating into adjacent hepatic segments 5 and 4B (yellow arrows). Note metastatic nodal disease around the portal vein (red arrows).

The differential diagnosis of mass in central liver in region of gallbladder lumen includes HCC, cholangiocarcinoma and metastatic disease. The features of these masses is discussed in the following table (Table 9.15.57). TABLE 9.15.57 D/D Mass Forming Mass Forming Gallbladder Carcinoma HCC

Intense arterial enhancement with washout and capsule appearance, occurs more commonly in setting of cirrhosis. Not associated with hilar block. Cholangiocarcinoma Mass forming lesions show centripetal enhancement pattern with peripheral washout and can be associated with distal biliary dilatation with vascular involvement and atrophy. Metastatic disease. Associated multiple lesions, known primary, variable enhancement pattern depending on primary. 2. Wall thickening This pattern can mimic acute and chronic inflammatory cholecystitis on imaging and hence poses a diagnostic challenge. Asymmetric, irregular, focal or extensive thickening showing intense arterial phase that persists or becomes isodense or isointense to the liver during the portal venous phase should suggest malignancy. Focal wall thickening or enhancement should also raise possibility of early carcinoma. Wall thickening >1 cm with associated mural irregularity, asymmetry should also raise concerns for malignancy. Associated lymphadenopathy, soft-tissue extension into the liver, metastatic disease favours the diagnosis of malignancy (Figs. 9.15.84–9.15.86).

FIG. 9.15.84 Wall thickening type of gallbladder carcinoma. T2WI images showing irregular wall thickening involving the gallbladder wall infiltrating into the liver (red arrows). Note the metastatic retroperitoneal adenopathy (yellow arrow).

FIG. 9.15.85 Wall thickening pattern of gall bladder with hepatic infiltration. (A) T2W1 and (B) postcontrast venous phase image showing irregular enhancing thickening involving the gall bladder wall (red arrows). A large mass contiguous with gallbladder wall is seen infiltrating into the adjacent hepatic segments ( red arrow in C) with metastatic nodes (yellow arrow) along the cholecystoceliac pathway encasing the CHA (blue arrow).

FIG. 9.15.86 Contrast-enhanced CT in late arterial phase showing intensely enhancing plaque-like eccentric wall thickening involving the gallbladder wall (arrows). Such intense arterial enhancement is not seen in benign biliary conditions. Kim et al. described five patterns of gallbladder wall thickening. In his paper, he has distinguished gallbladder pathologies based on pattern of enhancement of the gallbladder wall. Enhancement was classified as one of five patterns: Type 1 was a one-layer pattern, and types 2–5 were two-layer patterns. Type 1 pattern – one layer heterogeneously enhancing wall thickening or indistinguishable layering of the gallbladder wall. Type 2 pattern – thick strongly enhancing inner layer and poorly enhancing or nonenhancing inner layer. Type 3 pattern – cystic spaces in the inner layer which shows borderline enhancement and thickness with a nonenhancing outer layer Type 4 patterns – thin weekly enhancing inner layer with nonenhancing thin outer layer. Type 5 pattern – thin weekly enhancing inner layer with nonenhancing thick outer layer. According to them features suggestive of malignancy include thick enhancing inner layer ≥2.6 mm, greater enhancement of the inner layer compared to the liver, thin outer layer ≤3.4 mm, irregularity of thickened wall with focal involvement. Based on these features patterns, 2 and 1 are most commonly associated with malignancy. The other patterns were more commonly seen in adenomyosis and cholecystitis. Jung et al. classified the layered pattern of thickened wall into four patterns on MRI. Type 1 shows two layers with a thin hypointense inner layer and thick hyperintense outer layer. Type 2 has two layers of ill-defined margin. Type 3 shows multiple hyperintense cystic spaces in the wall. Type 4 shows diffuse nodular thickening without layering. Type 1 was seen in chronic cholecystitis, acute cholecystitis corresponded to type 2, adenomyomatosis showed type 3 and the gallbladder carcinomas showed type 4. Differential diagnosis of wall thickening pattern including acute and chronic cholecystitis, XGC and adenomyomatosis (Table 9.15.58).

TABLE 9.15.58 D/D Wall Thickening Type of Gallbladder Carcinoma Acute cholecystitis

Chronic cholecystitis

XGC

Presentation with pain, pericholecystic inflammation and collections. THAD in adjacent hepatic segments. On contrast study frequently show a weakly enhancing thin inner layer representing inflamed or sloughed mucosa, and the nonenhancing thick outer layer due to oedema. Gallbladder wall is not as thickened and irregular as seen in malignancy. Most common pattern of wall enhancement is isoattenuation of the thin inner layer. This feature will however not allow detection of early T1 or T2 neoplasm in the setting of chronic cholecystitis. Enhanced continuous mucosal line in a thickened gallbladder wall, in association with gallstones in a patient with chronic gallbladder disease, are highly suggestive of XGC. Intramural hypoattenuated nodules in the thickened wall also strongly suggests XGC. Hepatic infiltration, involvement of pylorus, duodenum can be seen in both malignancy and XGC. Distinguishing the two entities may sometimes be difficult (Fig. 9.15.87).

Adenomyomatosis

Focal wall thickening and gallstones can be seen in both. Intramural diverticula help in diagnosis. Gallbladder wall thickening with cystic spaces in the gallbladder wall is classic for adenomyomatosis (Fig. 9.15.88).

FIG. 9.15.87 Xanthogranulomatous cholecystitis. Contrast-enhanced CT showing thickened gallbladder wall with multiple hypoattenuating nodules ( arrows in A). Associated marked thickening of adjacent bowel is seen. This is a case of XGC which can mimic gallbladder carcinoma.

FIG. 9.15.88 (A and B) T2W1 axial and (C) coronal images showing focal thickening of the gallbladder fundus with intramural cysts representing dilated Rokitansky–Aschoff sinuses. This is a case of fundic adenomyomatosis and may mimic gallbladder cancer if thickening is focal and cysts are less conspicuous. 3. Polyp This is the least common variety of carcinoma and appear as well defined, round or oval shape on cross-sectional images. The tumour may be hypoattenuating or isoattenuating on nonenhanced CT scans. Malignant lesions are usually larger than 1 cm in diameter and have focal wall thickening at base. Enhancement may be intense in the arterial phase. Infiltration into adjacent liver may be seen on imaging. Malignant polyps show variable hyperintensity on T2W1 images, diffusion restriction and contrast enhancement (Figs. 9.15.89 and 9.15.90).

FIG. 9.15.89 Malignant gallbladder polyp. T2W1 images showing a hyperintense polypoidal mass in the gallbladder lumen (red arrows). Multiple large metastasis nodes are seen encasing the CBD along the cholecystoretroperitoneal pathway (yellow arrows) (nodes along cystic duct and pericholedochal region) causing biliary dilatation.

FIG. 9.15.90 Malignant gallbladder polyp. Contrast-enhanced CT showing a large polypoidal enhancing mass in the gallbladder lumen (arrows). Benign lesions like adenomatous or hyperplastic cholesterol polyps and malignancies like carcinoid and metastasis are differentials for polypoidal gallbladder mass. Features suggestive of malignancy in a polyp have been discussed in the chapter previously. Polypoidal metastasis can be distinguished on the basis of history and presence of other metastatic lesions. Lymphoma presenting as a polyp will often be associated with lymphomatous masses elsewhere. EUS EUS has an overall accuracy of 91.9% in differentiating neoplastic from nonneoplastic masses and have been widely used in the perioperative diagnosis. Carcinoma is seen as a hypoechoic mass with or without gallbladder wall calcification.

Radiological evaluation of staging The reported accuracy of MDCT in determining T-stage is approximately 84% while that in predicting resectability is 85% (Table 9.15.59).

TABLE 9.15.59 Radiological T-Staging Proposed by Kim et al. T1

T2

T3

Polypoid lesions without focal thickening of the gallbladder wall

Nodular or flat lesions with mucosal enhancement or focal thickening of the inner enhancing layer of the gallbladder wall with clear, lowattenuated outer wall

Nodular or sessile lesions associated with focal thickening of the gallbladder wall at what was considered to be attachment sites and with the presence of an apparently smooth fat plane separating the adjacent organs

Diffuse wall thickening with heterogeneous enhancement

Lesions showing loss of a fat plane separating the lesions from a single adjacent organ, indicating tumour involvement (≤2 cm into the liver)

Tumour perforates the serosa (visceral peritoneum) and directly invades the liver or one other adjacent organ or structure (such as the stomach; duodenum; colon or pancreas, omentum or extrahepatic bile ducts)

Apparent nodularity on the serosal aspect, indicating serosal exposure of the tumour T4

Lesions involving two or more adjacent organs or extending into the liver more than 2 cm

Diffuse wall thickening with strong, thick inner wall enhancement and weak enhancement of the outer layer (two-layered pattern) Focal wall thickening with outer surface dimpling at the tumour base

Tumour invades main portal vein or hepatic artery or invades multiple extrahepatic organs or structures

Using criteria proposed by Kim et al., the accuracies of MDCT in terms of differentiating T1 from ≥T2 and ≤T2 from ≥T3, were 94.1% and 89.8%, respectively. The sensitivity of MCCT sensitivity in detecting hepatic invasion is 65% if 2 cm. MR has a variable reported sensitivity between 67%–100% for hepatic invasion, although the depth of invasion is underestimated in approximately 10% of cases. CT sensitivity for nodal spread has been reported as 36% for N1 and 47% for N2 disease; there is 99% specificity for nodes >10 mm.MR sensitivity for lymphadenopathy has been reported between 56%–92%. Overall studies have found CT to be 85% precise in evaluation locoregional spread of gallbladder malignancy. Hwang et al. evaluated the added benefits of MRI in T-staging of CA gallbladder with emphasis on hepatic invasion. They showed, liver invasive was best seen in hepatocyte phase using HPB specific agent. The infiltrated liver appears hypointense to the background liver and this feature is not hampered by accompanying hyperaemia in the gallbladder bed of the liver due to accompanying cholecystitis. CT and MRI accurately show extension into hepatoduodenal ligament which is seen as nodular or plaque-like hypodense soft tissue or matted nodes encasing the portal vein and hepatic artery causing attenuation in calibre. Biliary dilatation is a common finding in gallbladder carcinoma, occurring in 38% of patients in one series. This is commonly seen with carcinomas around the gallbladder neck causing a hilar block. This pattern of spread can mimic and be falsely diagnosed as hilar cholangiocarcinoma. The distinguishing features are discussed in Table 9.15.60. Infiltrative tumour growth with spread along the cystic duct to the extrahepatic bile duct, lymph node enlargement and intraductal spread of tumour are other causes of biliary obstruction.

TABLE 9.15.60 Gallbladder Carcinoma Versus Hilar Cholangiocarcinoma CA Gallbladder Biologically aggressive Distended gallbladder Mass on imaging, relation to gallbladder neck Features of gastric outlet obstruction

Hilar Cholangiocarcinoma Less aggressive Gallbladder often collapsed Stricture Involvement of the long segment of bile ducts

The nodal metastasis are very common in gallbladder carcinoma. the nodal pathways have been discussed previously and progress from the gallbladder fossa through the hepatoduodenal ligament to nodes near the head of the pancreas. The most common nodes involved as surgery include the cystic and pericholedochal nodes and form a pathway to involvement of coeliac, superior mesenteric and paraaortic nodes (Fig. 9.15.91). The node of the foramen of Winslow, the superior pancreatoduodenal node, and the posterior pancreatoduodenal nodes are the most common nodes demonstrated by CT.

FIG. 9.15.91 Metastatic paraaortic nodes in advanced gallbladder carcinoma. (A to C) T2W1 images showing enlarged hyperintense paraaortic nodes ( red arrows in B and C). Large mass is seen in the gallbladder lumen ( red arrow in A). Other modes of spread include intraperitoneal, intraductal and neural spread. The most common organ involved by direct contiguous spread is the liver (65% of cases), followed by the colon (15%), duodenum (15%) and pancreas (6%). Treatment Management of carcinoma of gallbladder (Table 9.15.61) TABLE 9.15.61 Imaging Pearls, Gallbladder Carcinoma • Commonest biliary tumour in Northern and Eastern parts of India • Mass forming, wall thickening type and polypoidal mass are common morphological types • High propensity for perineural, lymphatic invasion • Imaging characteristic depend on morphological type • Mass forming variant is the commonest and seen as a large enhancing mass replacing the gallbladder • Hyperenhancement of inner layer or entire wall are commonest enhancement patterns in wall thickening variety • Polypoidal variety presents as a large hypervascular mass more than 1 cm projecting into the lumen • Along with Klatskin tumour it is an important differential of malignant hilar block

There are three common clinical scenarios for gallbladder cancer: (1) identified by final pathology after routine cholecystectomy; (2) discovered intraoperatively and (3) suspected before surgery. CaGB discovered during at or immediately after a routine cholecystectomy are usually early tumours. In a study of 498 patients with incidentally detected CaGB, 48% had T1 disease and 42% had T2 disease. If suspected intraoperatively, a frozen section analysis of the GB wall should be performed. If malignancy is confirmed, the surgeon should be prepared for a partial liver resection along with portal lymphadenectomy. Referral to a specialized hepatobiliary centre is acceptable if the surgeon is not comfortable with the extent of resection. For CaGB detected on histopathological examination after routine cholecystectomy, complete staging workup of the patients is a must. For T1a tumours with negative margins, a simple cholecystectomy alone is curative in 85%–100% of cases. For tumours with T1b and greater level of invasion reresection is indicated. If the cystic duct margin is positive, excision of bile duct and hepaticojejunostomy should be performed. For CaGB suspected preoperatively, complete staging workup with cross-sectional imaging should be performed. In a medically fit patient with operable disease, surgery should begin with a staging laparoscopy to identify occult metastatic disease. The extent of surgical resection is dictated by the stage of the disease and the location of the tumour and is discussed below. Extent of surgical resection by stage Factors determining the extent of surgical resection are the location of the tumour, T-stage and margin status (if prior cholecystectomy has been performed). Risk of morbidity of extensive resections should be weighed carefully against the long-term survival benefit. Since the body and fundus of the gallbladder lie at a distance from the major inflow structures to the liver, a limited segmental resection (segment IVb/V) is adequate to resect most tumours arising from this area. Neck-type CaGB often involve portal structures and formal hepatic resections with bile duct resections are usually required to achieve R0 resections. For T1a tumours, a standard cholecystectomy is adequate and liver resection does not add any survival benefit. In T1b tumours, a wedge resection of the liver at the GB fossa is needed for a negative margin; in addition, lymphadenectomy at the porta must be performed. A negative cystic duct margin must be ensured with resection of the bile duct, if necessary. For T2 and T3 tumours, en block resection of segment IVb and V is needed to ensure complete clearance. If the tumour is involving the inflow structures of the right liver, a right or extended right hepatectomy may be needed. This can be performed in a medically fit patient with no evidence of systemic disease. Bile duct excision is usually required. Careful preoperative evaluation may require preoperative biliary drainage and portal vein embolization prior to resection. It is important to examine the distant nodes (retropancreatic and aortocaval) and abandon the resection if they show evidence of metastatic disease. In patients with isolated extrahepatic organ involvement (stomach, duodenum or colon), a local resection may be performed. There has been controversy over routine excision of laparoscopic port sites in incidentally detected CaGb. In a study of 113 patients with incidental CaGB who presented for definitive resection after laparoscopic cholecystectomy, 69 patients had port sites resected and 44 did not. The incidence of port site metastasis was 19% and was associated with peritoneal disease recurrence. Port site recurrence is a marker of aggressive disease, and empiric resection of port sites during reexploration for CaGB is not advised. Results of surgery Though the survival has been improving, the overall outlook for patients with CaGb is dismal. Two-thirds of patients have inoperable disease at diagnosis. In a study of 435 treated patients, median overall survival was 10.3 months (95% CI, 8.8–11.8 months) with a median follow-up of 26.6 months. In a study that analysed patients with incidental CaGB undergoing reexploration and complete resection, those with residual disease had a median disease-free survival of 11.2 months compared to 93.4 months for those without

residual disease. Factors associated with poorer disease-specific survival were positive lymph nodes, tumour grade and presence of residual disease at any site. Five-year survival of 85%–100% has been reported after complete resection of T1 CaGB. T2 tumours are associated with lymph node metastases in nearly one-third of cases. Hence, an extended cholecystectomy is needed to achieve an R0 resection. Survival of 40%–70% has been reported with extended cholecystectomy for T2 disease. Patients with T3/T4 tumours were historically thought to have poor survival. Recent series with extended resections have shown that long-term survival is possible in a limited number of patients with locally advanced disease. The most important prognostic factor is lymph node positivity. Patients with nodal involvement beyond the hepatoduodenal ligament rarely have long-term survival and should not undergo a resection. Adjuvant therapy Gemcitabine with or without a platinum-based agent is usually given for adjuvant treatment in patients with advanced disease (T3/T4) lesions, those with node positivity and in those with positive margins. In a study of 149 patients with locally advanced or metastatic CaGB who received Gemcitabine plus cisplatin, showed significantly better overall survival. Palliative management Most patients with CaGB eventually need palliative care. The common symptoms to palliate are pain, jaundice or bowel obstruction. Palliation of jaundice in gallbladder cancer can be complex and depends on the location and extent of biliary obstruction. Endoscopic or percutaneous interventions are the preferred approach for palliation and minimizing morbidity. Percutaneous stenting has higher success rate but also has more complications. Intestinal bypass can be performed for symptomatic bowel obstruction. Other tumours of gallbladder 1. Gallbladder metastasis. Approximately 98% of gallbladder malignancies represent primary carcinoma. The next most common malignancy is metastases. Most common tumour to metastasize to gallbladder is malignant melanoma. Imaging On USG melanoma metastases appear as hyperechoic mural masses >1 cm in diameter. On CT lesions appear as a polypoid enhancing mass or irregular wall thickening. The typical MR appearance is that of a T1 and T2 hyperintense mass. The T1 hyperintense may be the result of paramagnetic effects of melanin as well as haemorrhage. Because of the precontrast T1 hyperintensity, postcontrast imaging may not be helpful. Other reported metastases to the gallbladder include renal cell carcinoma and HCC. 2. Squamous/adenosquamous carcinoma. These are rare, and the incidence ranges from 1.4% to 12.7%. They arise from the gallbladder fossa show rapid and invasive growth with direct invasion into the liver and adjacent organs. Nodal metastasis and peritoneal disease is however not common, instead liver metastases are more frequently seen. 3. Gallbladder lymphoma. Gallbladder lymphoma probably occurs in the setting of chronic inflammation because lymphoid tissue is not normally found in the gallbladder. Diffuse large B-cell and mucosa associated lymphoid tissue (MALT) lymphoma are the common subtypes of lymphoma that involve the gallbladder. Lymphoma may appear as a homogenously enhancing polypoidal mass in the bladder lumen. Imaging appearance may however be variable. 4. Sarcomas. Primary gallbladder sarcomas, include Kaposi sarcoma, malignant fibrous histiocytoma, angiosarcoma, leiomyosarcoma and rhabdomyosarcoma. These often appear as large

heterogeneous masses showing central areas of necrosis. Nodal metastasis are uncommon; however, haematogenous spread of the disease occurs. 5. Small cell carcinoma. Small cell carcinoma of the gallbladder is a distinct but very rare tumour. It is more common in women and usually associated with cholelithiasis. These tumours are often large mass at presentation show extensive necrosis, and a propensity for submucosal growth. It tends to metastasize in the early stage, which results in death shortly after diagnosis. Conclusion Imaging plays a vital role in diagnosis, characterization, staging and follow-up of patients with both benign and malignant biliary disorders. MRCP has revolutionized imaging in biliary pathologies and has largely replaced more invasive procedures like ERCP and PTC, which are used mainly in patients requiring intervention. Approach to jaundice When evaluating a patient with jaundice, the initial task is to establish whether jaundice is secondary to nonobstructive or obstructive causes. Clinical evaluation, including blood tests, makes this distinction in a majority of patients. Nonobstructive jaundice occurs in conditions like diffuse liver disease, cirrhosis and inflammation, to a congenital or metabolic condition. Obstructive jaundice also called as ‘surgical’ jaundice occurs due to biliary obstruction at the major intrahepatic or extrahepatic duct level. When imaging a patient with obstructive jaundice, the first step would be at establishing the level of obstruction. Once level of obstruction is established the approach should be based on combination of clinical features, lab investigations and imaging appearance (Tables 9.15.62–9.15.70).

TABLE 9.15.62 Classification of Biliary Pathologies Based on Level of Obstruction Intrahepatic PSC RPC

Porta Hepatis Dominant hilar stricture in PSC Mirizzi’s disease

Suprapancreatic Pancreatic Cholangiocarcinoma Pancreatic adenocarcinoma Metastatic disease /nodes

Distal CBD cholangiocarcinoma

IgG4 cholangitis

Pancreatic Hilar carcinoma cholangiocarcinoma

Periampullary carcinoma

Intrahepatic cholangiocarcinoma

Carcinoma gallbladder neck

Choledocholithiasis

Metastasis

Chronic pancreatitis

TABLE 9.15.63 Painless Progressive Jaundice – Usually Secondary to Neoplasms 1. Carcinoma gallbladder 2. Hilar cholangiocarcinoma 3. Periampullary tumours 4. Pancreatic adenocarcinoma 5. Metastasis TABLE 9.15.64 D/D – Jaundice With Overdistended Gallbladder on Imaging 1. Carcinoma gallbladder neck 2. Distal CBD/periampullary tumours 3. Metastatic nodal disease causing biliary compression 4. Stones at GB neck 5. Choledocholithiasis TABLE 9.15.65 D/D – Beading of Biliary Radicals With or Without Jaundice 1. PSC – most common 2. RPC – usually has associated stone disease 3. IgG4-related cholangiopathy 4. HIV cholangiopathy TABLE 9.15.66 D/D – Hepatolithiasis 1. RPC – commonest 2. PSC 3. Choledochal cyst TABLE 9.15.67 D/D – Jaundice With Long Segment Smooth Circumferential Biliary Enhancement 1. IgG4-related cholangiopathy 2. HIV cholangiopathy 3. PSC –rarely

TABLE 9.15.68 D/D – Jaundice With Short Segment Biliary Strictures 1. Bile duct carcinoma 2. Carcinoma gallbladder neck causing hilar block 3. PSC 4. IgG4-related cholangiopathy TABLE 9.15.69 D/D –Jaundice With Hilar Stricture 1. Carcinoma gallbladder 2. Klatskin’s tumour 3. Dominant hilar stricture in PSC 4. IgG4-related cholangiopathy 5. Mirizzi syndrome TABLE 9.15.70 Jaundice With Hilar Mass 1. Carcinoma gallbladder 2. Hilar cholangiocarcinoma 3. Metastasis

9.16: Paediatric pancreatic pathologies Priscilla Joshi, Mangal Subhash Mahajan, Vandana Jahanvi

Introduction Imaging is important in paediatric patients with pancreatic pathologies which can be congenital, pancreatitis or neoplastic. Congenital pancreatic anomalies predispose the children to recurrent attacks of pancreatitis and other complications. Paediatric pancreatic tumours are uncommon but when they do occur imaging is essential for their diagnosis, staging and posttreatment follow-up.

Pancreas divisum Aetiopathogenesis Pancreas divisum is the most common congenital pancreatic anomaly. It occurs in approximately 4%–14% of population. Failure of fusion of dorsal and ventral pancreatic ducts results in pancreatic divisum. Three variants of pancreatic divisum are known: 1. Type I or classical type: There is complete failure of fusion of ventral and dorsal pancreatic ducts. Majority of pancreatic drainage is through persistent duct of Santorini which drains into minor papilla. The duct of Wirsung drains the dorsal part of pancreatic head and uncinate process and joins the CBD before draining into the duodenum through major papilla. 2. Type II: Dorsal drainage is dominant in this type with absence of duct of Wirsung. 3. Type III: It is an incomplete divisum in which a small communicating branch is present. In most cases, pancreatic divisum is asymptomatic. However, it may give rise to recurrent episodes of pancreatitis. Pancreatitis is

believed to occur due to inadequate drainage of pancreatic secretions by the duct of Santorini. Imaging findings (Fig. 9.16.1)

FIG. 9.16.1 MRCP image of a patient with pancreas divisum. Dorsal pancreatic duct (white arrow) is seen crossing the CBD and draining into the minor papilla of the duodenum. The patient also had gallstone (asterisk) in the neck of GB which was compressing the common hepatic duct causing upstream biliary dilatation suggestive of Mirizzi syndrome. Pancreatic divisum is easily identified on MRCP (magnetic resonance cholangiopancreatography) which is a noninvasive technique and therefore is now increasingly being performed over ERCP to avoid ERCP-induce pancreatitis. Secretin-induced MRCP improves the visualization of the pancreatic ducts. The dorsal duct can be seen passing the CBD anteriorly and superiorly on imaging. This entity can also be identified on MDCT if the pancreatic duct is visualized. Rarely, it may be associated with cystic dilatation of terminal portion of duct of Santorini which is called Santorinocele.

Annular pancreas Aetiopathogenesis

Failure of rotation of ventral bud along with the duodenum results in encasement of duodenum by a rim of pancreatic tissue and this entity is known as annular pancreas. The band of pancreatic tissue encircling the duodenum could either completely or partially surround the duodenum and is in continuity with pancreatic head. Demographics It occurs in approximately 1 in 20,000 population. Clinical presentation Not all cases of annular pancreas present in childhood. In paediatric age group, it can present as neonatal duodenal obstruction because of associated duodenal stenosis. Children and adults with annular pancreas may also present with recurrent pancreatitis, postbulbar duodenal ulcerations or biliary obstruction. Imaging findings On upper gastrointestinal studies (barium meal), characteristic narrowing of second part of duodenum is seen. CT and MRI may show rim of pancreatic tissue encircling the duodenum. In partial annular pancreas (Fig. 9.16.2), pancreatic tissue is seen extending posterolateral or anterolateral to the duodenum with the pancreatic tissue giving a ‘crocodile – jaw’ configuration. This in the presence of gastric outlet obstruction helps in the diagnosis of incomplete annular pancreas. MRCP shows the pancreatic duct encircling the second part of the duodenum and entering it over its right lateral aspect. The pancreatic duct draining the annular segment usually drains into the main pancreatic duct. It can also drain into the intrapancreatic portion of common bile duct, the duct of Wirsung or the duct of Santorini. Secretin-induced MRCP because of its ability to demonstrate ductal anatomy well may become the best noninvasive imaging modality for diagnosis of pancreatic ductal variants including annular pancreas.

FIG. 9.16.2 CECT abdomen axial image (A) of a 12-year-old child showing pancreatic tissue (white arrowheads) partially encircling the second part of duodenum giving ‘crocodile–jaw appearance’ in partial annular pancreas. (B) Image shows the annular pancreatic duct (black arrow) and the CBD (white arrow). Differential diagnosis Other causes of paediatric duodenal obstruction should be kept in mind while diagnosing annular pancreas. Other than annular pancreas, the presence of duodenal narrowing on barium study in neonates, should raise the possibilities of duodenal atresia, duodenal web and Ladd’s bands. In duodenal atresia, the contrast does not pass beyond the obstruction and no air is seen on radiograph beyond the atretic segment. Whereas, in annular pancreas, intestinal gas is seen distal to the involved segment. And on upper gastrointestinal studies, the duodenal bulb is distended with slow transit of oral contrast through the stenosed duodenal segment distally. In duodenal web classical ‘wind–sock’ diverticulum is seen due to distal stretching of the web forming an intraluminal pseudodiverticulum. On barium studies, thin radiolucent membrane is seen due to filling of barium within the lumen and around the diaphragm.

Agenesis of pancreas and pancreatic hypoplasia The mutation in the developmental protein IPF1, results in pancreatic agenesis. It is very uncommon as it is incompatible with life. Anomalies associated with this condition are: foetal growth restriction, agenesis of gallbladder and polysplenia. Hypoplasia or partial agenesis occurs due to nondevelopment of dorsal or ventral pancreatic bud. Partial agenesis of the dorsal

pancreas is more common than agenesis of the ventral portion. However, complete dorsal pancreatic agenesis is rare. Dorsal pancreatic agenesis is often associated with heterotaxia syndrome. Partial dorsal pancreatic agenesis is more common than partial ventral agenesis. Complete dorsal pancreatic agenesis is however rare. In partial dorsal agenesis, short rounded head of pancreas is seen adjacent to the duodenum with absence of pancreatic neck, body and tail; however, remnant of duct of Santorini and minor duodenal papilla are generally present. In complete dorsal agenesis, both the minor duodenal papilla and the duct of Santorini are absent. The distal pancreas contains the islet cells, hence those with dorsal agenesis are at a higher risk of developing Diabetes Mellitus.

Accessory lobe of pancreas This uncommon condition is diagnosed when there is an accessory lobe of pancreatic parenchyma originating from the main gland and draining through an aberrant duct. The accessory lobe may be of varying size and may drain into the main pancreatic duct through a narrow or a wide communication. Association with gastric duplication cyst is known and if present the aberrant duct communicates with the gastric duplication cyst and the main pancreatic duct. Accessory pancreatic lobe may present as acute pancreatitis which is believed to result from obstruction of the pancreatic duct by viscus secretions, ulcer bleeding or biliary sludge.

Ectopic pancreas (Table 9.16.1)

TABLE 9.16.1 Location of Ectopic Pancreas Serial No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Sites Stomach Duodenum Jejunum Meckel’s diverticulum Colon Oesophagus Gallbladder Bile ducts Liver Spleen Umbilicus Mesentery Mesocolon Omentum

Ectopic pancreatic tissue can be seen in 0.6%–13.7% of population. It is most commonly seen in the stomach or duodenum. The ectopic tissue is generally located in the submucosa. Although, usually asymptomatic, it presents as stenosis, ulceration, gastrointestinal haemorrhage or intussusception.

Pancreaticobiliary maljunction Introduction Pancreaticobiliary maljunction is a congenital abnormality in which the main pancreatic and common bile ducts join outside the duodenal wall that forms a common channel. It was first described by Arnolds in 1906. Women are more frequently affected than men with a female to male ratio of 3:1. It is predominantly present in young women. Its incidence is 0.9%–6.2% on ERCP and 61.8%– 70% on autopsy. Although few familial cases have been reported whether pancreaticobiliary maljunction is hereditary remains unclear. It is diagnosed on the basis of radiological findings or anatomical findings at surgery or autopsy. Hence, radiologist play crucial role in making diagnosis of this entity. Aetiopathogenesis Pathogenesis of pancreaticobiliary maljunction is controversial. Several studies have proposed that anomalous development of the ventral pancreas with abnormal fusion between the bile duct and branches of the ventral pancreatic duct is responsible for development of pancreaticobiliary maljunction. Normally, the main

pancreatic duct and common bile duct open either separately or join to form a common channel that opens in second part of duodenum. Length of the common channel varies between 1 and 12 mm normally. Sphincter of Oddi is present at the distal end of pancreatic and common bile ducts. It regulates outflow of pancreatic and bile juice. The sphincteric control at the pancreaticobiliary junction is important for the regulated drainage of bile and pancreatic juice. In maljunction, as the union of the bile duct and the pancreatic duct is outside the duodenal wall, the sphincter of Oddi is unable to regulate the flow of pancreaticobiliary juices resulting in bidirectional regurgitation of juices (Graphic 9.16.1). It produces various pathological conditions in the biliary tree and pancreas.

GRAPHIC 9.16.1 Aetiopathogenesis of pancreaticobiliary maljunction. Types (Table 9.16.2)

TABLE 9.16.2 Types of Pancreaticobiliary Maljunction (A) Based on dilatation of common bile duct

1. Pancreaticobiliary maljunction with biliary dilatation 2. Pancreaticobiliary maljunction without biliary dilatation

(B) New Komi classification

1. Type I (bile duct type) – Common bile duct joins the pancreatic duct at right angle a. IA – Absence of the common channel dilatation b. IB – Presence of the common channel dilatation 2. Type II (pancreatic duct type) – Pancreatic duct joins the common bile duct at an acute angle a. IIA – Absence of the common channel dilatation b. IIB – Presence of the common channel dilatation 3. Type III (complex type) a. IIIA – Identical to pancreatic divisum with biliary dilatation b. IIIB – Characterized by absence of duct of Wirsung c. IIIC i. IIIC1 – Thin communicating duct between the main and accessary ducts is present ii. IIIC2 – Common channel is made up of common and accessary ducts of equal calibre iii. IIIC3 – Complex network of enlarged ducts that join each other by total or partial dilatation of the ductal system

(C) Japanese Study Group classification

(1) Stenotic type: The common channel is joined by the distal CBD with stenosis (2) Nonstenotic type: The common channel is joined by the distal CBD without stenosis (3) Dilated common channel type: As the name suggests, the common channel is dilated

(4) Complex type: A complicated pattern is formed by the pancreaticobiliary junction On the basis of dilatation of common bile duct, pancreaticobiliary maljunction is divided into that with biliary dilation and without biliary dilatation. The former is more common and present in 77% of cases. The latter is less common and present in remaining 23% of cases. New Komi classification (Graphic 9.16.2) is based on how the pancreatic and common bile ducts join. It takes into account presence or absence of the common channel dilatation and the concept of pancreatic divisum. Type I union is bile duct type, in which the common bile duct joins the pancreatic duct at right angle. It has single papilla. It is subclassified into type IA and IB based on absence or presence of the common channel dilatation respectively. Type II union is pancreatic duct type, in which the pancreatic duct joins the common bile duct at an acute angle. It also has single papilla. It is subclassified into type IIA and IIB based on absence or presence of the common channel dilatation, respectively. Type III is complex type, in which the two ducts join in complex configuration. It has two papillae. It is subclassified into type IIIA, IIIB and IIIC. Type IIIA is similar to pancreatic divisum with biliary dilatation. Type IIIB is characterized by absence of duct of Wirsung. Type IIIC is further subclassified into IIIC1, IIIC2 and IIIC3. A thin communicating duct between the main and accessary ducts is present in type IIIC1. A common channel is made up of common and accessary ducts of equal calibre in type IIIC2. There is complex network of enlarged ducts that join each other by total or partial dilatation of the ductal system in type IIIC3. Japanese Study Group on Pancreaticobiliary Maljunction proposed a new classification (Graphic 9.16.3) in 2015 on the basis of formation of pancreaticobiliary maljunction. According to this new classification, pancreaticobiliary maljunction is divided into four types: (1) Stenotic type: The common channel is joined by the distal CBD with stenosis, (2) Nonstenotic type: The common channel is joined by the distal CBD without stenosis, (3) Dilated common channel type: As the name suggests, the common channel is dilated and (4) Complex type: A complicated pattern is formed by the pancreaticobiliary junction.

GRAPHIC 9.16.2 New Komi classification of pancreaticobiliary maljunction.

GRAPHIC 9.16.3 Japanese Study Group classification of pancreaticobiliary maljunction.

Diagnosis Pancreaticobiliary maljunction with congenital biliary dilatation have higher incidence of symptoms in neonatal and infantile period and manifest as jaundice and abdominal mass. Less common symptoms include abdominal pain, vomiting and fever. Dilatation of common bile duct is an important finding on ultrasonography and further imaging with magnetic cholangiopancreatography is recommended to look for the status of common channel. Pancreaticobiliary maljunction without congenital biliary dilatation is more difficult to diagnose because of less frequent symptoms and less remarkable imaging findings. These patients are frequently asymptomatic but may presents as abdominal pain and hyperamylasaemia in adulthood. Many adult patients may show signs of biliary cancers. Focal or diffuse gallbladder wall thickening may be an early clue for the diagnosis. Hence, pancreaticobiliary anatomy should be assessed by magnetic resonance cholangiopancreatography when no specific cause of gallbladder wall thickening is established. Diagnostic criteria (Table 9.16.3)

TABLE 9.16.3 Diagnostic Criteria for Pancreaticobiliary Maljunction Imaging diagnosis

Anatomical diagnosis

Supplementary diagnosis

1. An abnormally long common channel of the pancreatic duct and the CBD; or an abnormal union between the pancreatic and bile ducts seen on an investigation which directly images these structures. These include endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography or intraoperative cholangiography, magnetic resonance cholangiopancreatography or three-dimensional drip infusion cholangiography computed tomography 2. When the common channel is relatively short, it is crucial to confirm that the effect of the papillary sphincter does not extend to the junction with direct cholangiography 3. Demonstration of pancreaticobiliary junction outside the duodenal wall on endoscopic ultrasound or multiplanner reconstruction images of multidetector row computed tomography 1. Pancreaticobiliary junction must be present outside the duodenal wall at surgery or autopsy 2. Union of pancreatic or bile duct must be abnormal at surgery or autopsy 1. Elevated amylase level in bile within in the bile duct or gallbladder obtained immediately after laparotomy 2. Extrahepatic biliary dilatation

Imaging diagnosis The diagnosis of pancreaticobiliary maljunction is made when there is an abnormally long common channel of the pancreatic duct and the CBD; or there is an abnormal union between the pancreatic and bile ducts seen on an investigation which directly images these structures. These include endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography or intraoperative cholangiography, magnetic

resonance cholangiopancreatography or three-dimensional drip infusion cholangiography computed tomography (CT). However, when the common channel is relatively short, it is crucial to confirm that the effect of the papillary sphincter does not extend to the junction with direct cholangiography. There is no clear definition of a long common channel. Few authors suggest 8 mm or longer while others suggest 15 mm or longer as a long common channel. It can also be diagnosed if the pancreaticobiliary junction is demonstrated outside the duodenal wall on endoscopic ultrasound or multiplanner reconstruction images of multidetectorrow CT. Anatomical diagnosis Pancreaticobiliary junction must be present outside the duodenal wall or the union of pancreatic or bile duct must be abnormal at surgery. Supplementary diagnosis Elevated amylase levels in the bile within the bile duct and gallbladder obtained immediately after laparotomy and presence of extrahepatic biliary dilatation strongly suggest the existence of pancreaticobiliary maljunction. Rarely, the amylase levels are close to or below the normal serum value in these patients. When cystic, fusiform, or cylindrical dilation is present in the extrahepatic bile ducts, detail workup is necessary to determine whether pancreaticobiliary maljunction is present. To diagnose biliary dilatation, maximum calibre of the common bile duct is measured. Diagnosis of bile duct dilatation is age-dependent (Table 9.16.4).

TABLE 9.16.4 Diagnosis of Common Bile Duct Dilatation on Ultrasound Age in Years 0

Dilatation in Millimetres 3

5

3.9

10

4.5

15

5.0

20–29

5.9

30–39

6.3

40–49

6.7

50–59

7.2

60–69

7.7

70

8.5

Imaging modalities Ultrasound is used as screening tool and alone may not be enough to detect an anomalous pancreaticobiliary junction. Extrahepatic bile duct dilation or gallbladder wall thickening are the clues to make early diagnosis of pancreaticobiliary junction. Endoscopic ultrasound demonstrates the pancreatic and bile duct junction outside the duodenal wall and help to diagnose pancreaticobiliary maljunction. Magnetic resonance cholangiopancreatography is an accepted noninvasive imaging tool to demonstrate the pancreaticobiliary anatomy. It is preferred over ERCP. Source images and maximum intensity projection images of 3D MRCP are very useful to delineate the pancreaticobiliary anatomy. Its sensitivity is 75% in adult and 44%–65% in children. Fig. 9.16.3 shows a case of Pancreaticobiliary maljunction with Choledochal cyst. Secretin-stimulated dynamic MRCP and time-spatial labelling inversion pulse (Time-SLIP) can be used to identify the pancreaticobiliary reflux. Secretin stimulates the exocrine pancreas to secrete fluid. This increase of fluid content within the lumen of pancreatic duct improves visualization. In pancreaticobiliary maljunction, there is enlargement and retrograde increase in signal intensity of the common bile duct. Time-SLIP MRI allows direct visualization of pancreaticobiliary flow by placing the inversion pulse at the head and body of pancreas and suppressing the background. Gadoxetic acid-enhanced MRI is used to identify biliopancreatic reflux. Gadoxetic acid is a hepatobiliary specific contrast agent. It is taken up by hepatocytes and excreted into the

bile. In pancreaticobiliary maljunction, there is retrograde increase in signal intensity of the pancreatic duct. Multiplanar reconstruction images of the contrast-enhanced high-resolution multidetector CT scan can demonstrate the communication of the pancreatic and bile ducts and help to diagnose pancreaticobiliary maljunction. Its sensitivity is 58%–100% in adults and 20% in children. Drip infusion CT cholangiography involves intravenous injection of biliary contrast agent. It demonstrates details of pancreaticobiliary anatomy; however, it sometimes fails to demonstrate the pancreatic duct preventing the diagnosis of pancreaticobiliary anatomy. Endoscopic retrograde cholangiopancreatography confirms lack of effect of the sphincter of Oddi on the pancreatic and bile duct junction. Its sensitivity is 75%. Main advantage of ERCP is that it allows bile and tissue sampling and therapeutic procedures.

FIG. 9.16.3 Thick slab MPR–MRCP image showing pancreaticobiliary maljunction with long common channel (white arrow) and type I choledochal cyst. Complications Regurgitation of pancreatic juice and formation of protein plugs In pancreaticobiliary maljunction, the Oddi sphincter fails to regulate the pancreaticobiliary junction. Normally, hydrostatic pressure within the pancreatic duct is higher than that in the bile

duct. Hence pancreatic juice often refluxes into the bile duct. There is increased pressure in the bile and pancreatic duct secondary to obstruction of the common channel or primary stricture of distal bile duct. Obstruction or stricture is caused by impaction from a protein plug. It is often a temporary process because these protein plugs are fragile and resolve spontaneously. It causes transient and intermittent symptoms like abdominal pain, vomiting, and jaundice. Protein plugs consist of lithostathine. It is a soluble protein secreted by pancreas. They are often depicted at ERCP but not at CT or MRCP. Pancreatitis Incidence of acute pancreatitis in pancreaticobiliary maljunction is 30% in children and 9% in adults. Chronic pancreatitis is present in 3% of these patients. In majority, the changes are less severe but can be recurrent. Protein plugs are believed to be one cause of acute pancreatitis. Pancreatic calcifications are usually absent in chronic pancreatitis with pancreaticobiliary maljunction. Biliary calculi Common bile duct and gallbladder calculi occur more often in adults than in children. Its incidence is 23% in adults and 9% in children. Calculi formation appears to be related to bile stasis because pigmented calculi are more commonly detected than cholesterol calculi in patients with pancreaticobiliary maljunction. Biliary cancers (Graphic 9.16.4)

GRAPHIC 9.16.4 Pathophysiology of development of biliary cancers in pancreaticobiliary maljunction. Patients with pancreaticobiliary maljunction are at higher risk of developing biliary cancers. Average age of cancer development is 15–20 years earlier than in patients without pancreaticobiliary

maljunction. There occurs chronic inflammation secondary to reflux of pancreatic juice into the biliary tree. Phospholipase A2 in refluxed pancreatic juice is activated in the biliary system. Phospholipase A2 converts phosphatidylcholine in bile to lysophosphatidylcholine. Both phospholipase A2 and lysophosphatidylcholine are cytotoxic agents. They stagnate in the gallbladder or dilated bile ducts and irritate the epithelium that results in chronic inflammation, epithelial hyperplasia and dysplasia. The gene mutations are simultaneously induced in the biliary epithelium. In the early phase, there is mutational activation of the Oncogene KRAS, whereas in the late phase there is inactivation of the tumour suppressor gene, TP53. This supports the theory of hyperplasia–dysplasia–carcinoma sequence in the bile ducts of patients with pancreaticobiliary maljunction. Recent studies suggested that Helicobacter bilis, a gram-negative organism, might be associated with biliary carcinogenesis. Management Once the patient is diagnosed with pancreaticobiliary maljunction, risk-reducing surgery is recommended regardless of presence of symptoms to avoid complications like biliary cancers. Biliary cancers are present in gallbladder or dilated bile duct in patients with pancreaticobiliary maljunction with biliary dilatation. Hence, removal of the gallbladder and extrahepatic bile duct is considered as the standard surgery. Most biliary cancers are resent in gallbladder in patients with pancreaticobiliary maljunction without biliary dilatation. Hence, resection of the gallbladder is recommended.

Congenital and hereditary pancreatic lesions • Congenital Pancreatic cysts: Congenital cysts of pancreas are rare and show a female preponderance. They generally present as asymptomatic abdominal masses or may present with abdominal pain, jaundice or obstruction depending on abdominal structures compressed by the cysts. These are commonly located in tail and body of pancreas. Multiple congenital cysts are noted in association with Von Hippel Lindau (VHL) disease and hepatorenal polycystic disease. • Von Hippel Lindau disease: VHL disease is an autosomal dominant disorder with incomplete penetrance. Pancreatic involvement may vary from cysts to tumours as listed in Table 9.16.5. Other nonpancreatic pathological entities seen in VHL are enlisted in Table 9.16.6.

TABLE 9.16.5 Pancreatic Pathologies Seen in VHL Serial No. 1. 2. 3.

Pancreatic Manifestations of Von Hippel Lindau Disease Single cyst Cystic replacement of pancreas Tumours • Serous cystadenoma • Neuroendocrine tumour • Adenoma • Adenocarcinoma • Haemangioblastoma

TABLE 9.16.6 Nonpancreatic Pathologies Associated With VHL Serial Pathological Lesions Associated With VHL No. 1 Common lesions: • Retinal angiomatosis • Renal cysts and renal cancer • Cysts within pancreatic parenchyma • Pheochromocytoma–paraganglioma • Cystadenoma of the epididymis 2

Uncommon lesions: • Liver: Adenoma; angioma; carcinoma; cysts • Spleen: Angioma; cysts • Lungs: Angioma; cysts • Cutaneous: Skin-angiomas • Pancreas: Adenoma of the pituitary; pancreatic tumours • Thyroid: Medullary Ca • Carcinoid • Neuroblastoma • Spine: Hydrosyringomyelia • Inner ear: Endolymphatic sac tumour • CNS tumours: Ependymoma; astrocytoma; meningioma; choroid plexus papilloma

Pancreatitis in children

A. Acute pancreatitis Aetiopathogenesis Pancreatitis can occur in any age group including infants. Though there can be many causes for pancreatitis, commonest type of pancreatitis seems to be biliary pancreatitis. Various causes of pancreatitis are enlisted in Table 9.16.7. TABLE 9.16.7 Causes of Acute Pancreatitis Serial Causes of Pancreatitis in Children No. 1. Biliary pancreatitis: i. Gallstones ii. Biliary sludge iii. Congenital biliary tree anomalies (pancreas divisum, choledochal cyst, pancreaticobiliary maljunction and aberrant biliary ducts) 2. 3. 4.

Traumatic pancreatitis Autoimmune pancreatitis Metabolic disorders: i. Cystic fibrosis ii. Hyperlipidemia iii. Hypercalcemia

5. 6.

Drug-induced pancreatitis (by valproic acid, lasparaginase, prednisolone and 6-mercaptopurine. Multisystem conditions: i. Reye syndrome ii. Sepsis and shock iii. Haemolytic-uremic syndrome

7. 8. 9. 10.

Viral infection Systemic lupus erythematosus Hereditary pancreatitis Idiopathic causes

Imaging findings Radiological features consistent with acute pancreatitis include oedema, haemorrhage or necrosis within pancreatic parenchyma, peripancreatic fat stranding and intrapancreatic or peripancreatic collections. The presence of peripancreatic collection indicates

recurrent episodes of pancreatitis. Various imaging modalities have different roles to play in paediatric pancreatitis, as discussed below. Transabdominal ultrasound. For screening children with suspected pancreatitis and biliary anomalies, ultrasound is the modality of choice. Lack of ionising radiation, easy availability and nonrequirement of sedation makes ultrasound the preferred initial imaging modality. But due to certain constraints including interobserver variation and obscuration of pancreas due to bowel gases, sensitivity of ultrasound to detect pancreatitis is slightly low. One of the studies found the sensitivity to be 79.4%. On ultrasound, normal pancreatic parenchyma in infants is hyperechoic to liver, owing to the presence of prominent intralobular septae and significant amount of glandular tissue. After the neonatal period, echogenicity of pancreatic parenchyma is variable, hence size and greyscale characteristics are not reliable features to diagnose pancreatitis. Pancreas can be isoechoic to slightly hyperechoic in postneonatal children and may show speckled appearance. On ultrasound, a reliable characteristic of acute pancreatitis is pancreatic duct dilatation (Table 9.16.8). The evaluation of pancreatic duct should be performed with high-frequency probe (15 MHz) as far as possible. Ill-defined pancreatic contour, peripancreatic collections, and ascites can be seen on ultrasound in acute setting. Presence or absence of septae, internal debris and thickness of pseudocyst wall as determined on ultrasound decides the amenability to percutaneous drainage. Causes of pancreatitis including cholelithiasis, choledocholithiasis, biliary sludge and choledochal cysts can also be identified on ultrasound. In older children, grossly increased echogenicity of pancreatic parenchyma is attributed to fatty infiltration and can be seen in kids with cystic fibrosis, obesity or children on steroid therapy. TABLE 9.16.8 Criteria for Pancreatic Duct Dilatation in Children Criteria for Pancreatic Duct Dilatation (in Millimetres) in Children 1–6 years >1.5 7–12 years >1.9 13–18 years >2.2 Computed tomography. CT is more sensitive in diagnosing pancreatitis and identifying pancreatic necrosis and peripancreatic collections. Intravenous contrast is mandatory while performing CT and is required to determine pancreatic necrosis and vascular patency. Finding

suggestive of acute pancreatitis on CT include enlarged pancreas, parenchymal heterogeneity, abnormal pancreatic contour, and signs of peripancreatic inflammation as implied by peripancreatic fat stranding and thickening of retroperitoneal fasciae. Peripancreatic collections can be seen anywhere including retroperitoneal space, within the peritoneum or they may even extend into the mediastinum. CT is also useful in diagnosing complications of pancreatitis including vessel thrombosis, arterial aneurysms, fistula formation and peripancreatic abscess formation. Presence of air within any peripancreatic collection is suggestive of superadded infection. Pancreatic calcifications indicative of chronic pancreatitis, fatty infiltration of pancreas and hyperdense gallbladder calculi are all easily identified on CT. It can also be used for grading of pancreatitis using CT severity index (CTSI) score; however, the use of CTSI in grading acute pancreatitis in children still needs further research. Inability to evaluate pancreaticobiliary ductal anatomy and exposure to ionising radiation are main disadvantages of this modality. MRI and MRCP. MRI is difficult to perform in paediatric age group because of small body size and requirement of sedation for prolonged time. This difficulty can be overcome by using the appropriate coils (phased– array or surface coils), using ultrafast sequence for MRCP and selecting an appropriate slice thickness according to body size (3–5 mm). In neonates and infants, slice thickness should not be more than 2 mm. As MRCP can evaluate pancreaticobiliary ductal anatomy well, it should be performed when congenital anomalies are suspected. Secretin administration further enhances the visualization of smaller pancreatic ducts. On T1W-images, pancreatic parenchyma is inherently homogeneously hyperintense due to high protein content and presence of paramagnetic substances (manganese). In pancreatitis, the pancreas shows loss of this hyperintense signal and heterogeneity, which is best seen on T1W-fat-saturated images. On T2W-images, pancreatic parenchyma shows increased signal in the setting of pancreatitis. Peripancreatic fluid and oedema is well appreciated on T2W-fatsaturated images. In case of pancreatic necrosis, the pancreatic parenchyma may exhibit increase T1-signal owing to haemorrhage. Acute peripancreatic fluid collection and acute-necrotic collection can also be differentiated well on MRI, as acute necrotic collection demonstrates heterogeneous signal on T2W-images. Presence of restricted diffusion within the collection indicates superadded infection. Disadvantages of pancreatitis include longer imaging time and hence sedation requirement for longer period, higher cost, and nonavailability in smaller health centres. Fig. 9.16.4 shows a case of focal pancreatitis in a 5-years-old child mimicking as neoplasm.

FIG. 9.16.4 Focal pancreatitis mimicking as neoplasm. Sagittal USG image (A) through the region of the pancreas in a 5-year-old boy with abdominal pain revealed a mass measuring approximately 4 cm in diameter in the region of the pancreatic head. This was predominantly isoechoic to the pancreas and showed few hypo and anechoic areas within. The mass was seen causing CBD and diffuse pancreatic duct dilatation (B). HPE later revealed the mass to be focal pancreatitis. On follow up the lesion showed regression in size. Role of imaging in identifying cause of pancreatitis: • Biliary pancreatitis: Common bile duct obstruction due to stone, biliary sludge or pancreaticobiliary maljunction can cause pancreatitis. While gallbladder stones and sludge can be identified on ultrasound, obscuration by bowel gases may many a time hinder visualization of choledocholithiasis and CBD sludge. Intraductal filling defects due to stones or sludge are easily identified on MRI. Similarly, pancreaticobiliary anomalies including pancreas divisum, annular pancreas, pancreaticobiliary maljunction, aberrant biliary ducts and choledochal cysts are best diagnosed on MRI. • Traumatic pancreatitis: In the emergency setting, ultrasound and CT are most useful to identify

posttraumatic acute pancreatitis because they are readily available. However, ductal injury and pancreatic duct transection are better assessed on MRI. • Auto-immune pancreatitis: It is rarely seen in children and is a part of IgG4 systemic disease. On CECT, sausage-like diffuse enlargement of pancreas is seen without significant peripancreatic fat stranding. The pancreatic parenchyma appears hypoechoic on USG and hypodense on CT with typical enhancement on delayed phase. A capsule-like hypodense rim along the periphery of the gland can be seen. Focal involvement may show hypodensity in pancreatic head associated with obstructive jaundice, thus mimicking neoplasm. On MRI, pancreas appears hypointense on T1W-images and hyperintense on T2Wimages and shows significant enhancement on venous phase without obvious enhancement on arterial phase. Complications of acute pancreatitis: • Acute peripancreatic collections and pseudocysts: Acute peripancreatic fluid collections do not have a distinct wall and demonstrate homogeneous attenuation on CT and uniform signal intensity on MRI. Pseudocysts that are formed as sequelae to acute peripancreatic fluid collections have a well-defined wall and should not contain any solid component on imaging. They at times can be intrapancreatic. Nonresolution of acute peripancreatic collections or pseudocysts should raise the possibility of communication with the pancreatic duct. • Acute necrotic collections and walled-off necrosis: Acute necrotic collections arise within 4 weeks of onset of acute necrotising pancreatitis. Just like acute peripancreatic fluid collections, they do not possess a distinct wall however they contain solid material within, which can be identified on cross-sectional imaging. On CT, they show heterogeneous attenuation while MRI shows T2W-hypointense material within the hyperintense collection. Wall-off necrosis develops after 4 weeks, contain solid material within and have enhancing inflammatory capsule. They may get infected, and presence of air indicated abscess formation. • Vascular complications: Arterial pseudoaneurysms – Extravasated pancreatic enzymes due to breakdown of pancreatic parenchyma may erode the vessel wall. This results in pseudoaneurysm formation. On ultrasound, typical ‘Ying – Yang’ sign can be seen due to ‘to and fro’ flow of blood. On postcontrast imaging, these generally appear as contrast filled outpouchings from vessel wall

with attenuation similar to abdominal aorta on all phases. Pseudoaneurysms differ from true aneurysms in that they are not covered by vessel wall layers. They are generally difficult to differentiate from true aneurysms but usually have an irregular wall and are surrounded by hematoma. Venous thrombosis – Venous thrombosis may also occur and splenic vein is the most common vein to be affected. • Fistulas: Internal pancreatic fistula formation may occur in pancreatitis and results in pancreatic ascites and pancreaticopleural fistulas. They occur due to disruption of pancreatic duct and leakage of pancreatic enzymes. Duct disruption anteriorly results in pancreatic ascites. On the other hand, if the duct disrupts posteriorly, pancreaticopleural fistulas may form. The pancreaticopleural fistulas may also develop if the wall of pseudocyst is not well-formed or it ruptures through the aortic or oesophageal hiatus. They should be suspected in presence of persistent or recurrent ascites and pleural effusion. Reporting checklist for acute pancreatitis is mentioned in Table 9.16.9.

TABLE 9.16.9 Reporting Checklist in Acute Pancreatitis Serial Acute Pancreatitis No. I. Pancreatic parenchyma: 1. Size 2. Contour 3. Presence of pancreatic duct dilatation and pancreatic calculi 4. Fat/calcification/haemorrhage/necrosis II.

Peripancreatic changes: 1. Fat stranding 2. Collection 3. Peripancreatic collection/pseudocyst 4. Peripancreatic necrotic collection/walled-off necrosis

III.

Hepatobiliary system: 1. Gallstones/sludge 2. Associated cholecystitis 3. Biliary dilatation

IV.

Extrapancreatic: Ascites

V.

Extraabdominal: Pleural effusion

VI.

Complications: 1. Venous thrombosis 2. Arterial pseudoaneurysms 3. Fistulas 4. Pancreatic/peripancreatic abscess

Serial Acute Pancreatitis No. VII. Cause: 1. Biliary gallstone/biliary sludge/pancreaticobiliary maljunction/pancreatic anomalies 2. Traumatic–Pancreatic duct transection 3. Autoimmune: Sausage-like enlargement of pancreas, hypodense rim around pancreas, delayed enhancement B. Atrophic pancreas and chronic pancreatitis Atrophic pancreas is suggestive of chronic pancreatic scarring and volume loss, generally resulting from chronic pancreatitis. Causes of chronic pancreatitis and atrophic pancreas in children are multifactorial and are illustrated in Table 9.16.10. TABLE 9.16.10 Causes of Chronic Pancreatitis Serial No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 12. 13. 14. 15.

Causes of Chronic Pancreatitis Calcific chronic pancreatitis Juvenile tropical pancreatitis Hereditary pancreatitis Inborn errors of metabolism Hypercalcemia Hyperlipidemia Noncalcific chronic pancreatitis Congenital or acquired lesions of the pancreatic duct Trauma Cystic fibrosis Sphincter of Oddi dysfunction Sclerosing cholangitis Idiopathic fibrosing pancreatitis Renal failure

When pancreatic atrophy and fatty replacement of pancreatic parenchyma is present in a child with chest radiograph/CT suggestive of bronchiectasis, cystic fibrosis should be considered. Cystic fibrosis results from inherited defect in CFTR (cystic fibrosis transmembrane conductance regulator) gene located on chromosome 7. Faulty transmembrane transport of chlorine results in thick inspissated secretions from mucosal surfaces. Cystic fibrosis exhibits a multisystem involvement including respiratory, pancreaticobiliary and gastrointestinal systems. Pancreaticobiliary complications of cystic fibrosis include cholelithiasis, biliary

dilatation, fatty replacement (steatosis), atrophy of the pancreas and pancreatitis. Intestinal system involvement may manifest as neonatal meconium ileus and microcolon. Intestinal obstruction in meconium ileus due to inspissated contents occurs most commonly in the terminal ileum. On antenatal ultrasound, affected foetus shows echogenic small bowel. Postnatally, meconium mixed with gas gives a ‘bubbly’ appearance. Associated small bowel perforation and peritonitis if present manifest as peritoneal calcification. On contrast-enema examination, microcolon is appreciated. Outside neonatal period, cystic fibrosis may manifest as distal intestinal obstruction. Children with cystic fibrosis may also have appendiceal thickening and intussusception. Respiratory system involvement routinely shows cylindrical and cystic bronchiectasis with upper lobe predominance.

Pancreatic neoplasms in children Pancreatic neoplasms are relatively uncommon in the paediatric population. Only a small number of these are malignant. The clinical presentation differs in children and adults as does the outcome Malignancies affecting the paediatric population are quite different from those affecting adults. Pancreatic tumours in children have a different histologic spectrum and better clinical outcome as compared to adults. Paediatric pancreatic neoplasms can be divided into epithelial and nonepithelial lesions. The epithelial lesions can be further subdivided into exocrine and endocrine subtypes. The nonepithelial lesions include lymphatic malformations, malignant neoplasms such as lymphoma and intermediate lesions including inflammatory fibroblastic tumours. The acinar cell tumour pancreatoblastoma is the most common pancreatic tumour of young children.

Pancreatoblastoma This is the most common pancreatic tumour of young children. It is also called pancreaticoblastoma or infantile-type carcinoma of the pancreas. It is very rare. It occurs in the first decade with an age range of foetus to 9 years with a male preponderance. Clinical presentation These patients usually present with vague abdominal pain. Less often a very large mass may present as abdominal distension. Fatigue, lethargy, weight loss, anorexia diarrhoea or vomiting are other symptoms. Jaundice is not common. One-third of the

patients have raised alpha-fetoprotein levels which are also raised in hepatoblastoma and embryonal carcinoma. Patients with Beckwith–Wiedemann syndrome which is a genetic disorder may have congenital pancreatoblastoma. They may also develop other embryonal tumours like nephroblastoma, hepatoblastoma and rhabdomyosarcoma with a risk of malignancy of 4%. Other systemic manifestations like macroglossia, omphalocele and visceromegaly are also known. Pathology These are large, solitary masses 1.5–20 cm in size. Approximately half arise in the head of the pancreas. The tumour is a well-defined solid mass with lobulated margins. The cut surface is yellowish to tan with lobulations separated by fibrous bands. The mass may contain cystic spaces due to haemorrhagic necrosis and cystic degeneration. In most cases associated with Beckwith–Wiedemann syndrome, they may be cystic. Imaging Ultrasonography is the imaging modality of choice as it is easily available, inexpensive and not associated with radiation. The pancreatoblastomas are predominantly heterogeneous, welldefined complex masses with both cystic and solid components. On ultrasound, the cystic areas are hypoechoic to anechoic with internal septae. The mass may sometimes be a hypoechoic, solid mass. On CT the tumour is well or partially circumscribed. Rarely a margin maybe infiltrative. The tumour is smooth, may be multilobulated. The mass is heterogeneous due to internal cystic areas, corresponding to the areas of necrosis seen on pathology. Often the tumour appears multiloculated with enhancing septa. Small curvilinear punctate or clustered calcifications maybe identified. On images obtained after the administration of intravenous contrast the mass shows a fairly intense enhancement. Hepatic metastases are typically hypoattenuating at CT. Vascular encasement may occur by the tumour, at times mimicking a neuroblastoma. Biliary dilatation is rare. On MR imaging, the mass is hypointense to isointense to rest of the pancreas on T1-weighted images with the hypointense areas corresponding to the areas of necrosis. It is inhomogeneously hyperintense on T2-weighted images. The primary tumour shows fairly intense contrast enhancement with the hepatic metastasis showing similar enhancement as the primary tumour. The tumour may invade the surrounding pancreas, peripancreatic tissue and adjacent structures. Biliary invasion has

been reported. Vascular invasion with portal and mesenteric vein involvement is rare. Distant metastases to the liver and abdominal lymph nodes are seen in approximately 35% at presentation. Metastases to the lung and brain are less common. The tumour rarely metastasizes to the omentum, pelvic cul-de-sac, colon, spleen, kidney and adrenal glands. Differential diagnosis The tumours may be very large at the time of presentation and it may be difficult to determine the organ of origin. Common tumours of adjacent organs occurring in young children must be considered. These include: • Neuroblastoma • Wilms tumour • Hepatoblastoma • Other primary liver tumours Non-Hodgkin lymphoma involving the pancreas, especially Burkitt lymphoma. Pancreatoblastomas need to be differentiated form other paediatric pancreatic tumours which include (Table 9.16.11): 1. SPEN: The epidemiological features of the solidpseudopapillary tumours are different from a predominantly cystic pancreatoblastoma, though on imaging the two may mimic each other. Cystic pancreatoblastomas are seen in a younger age group with a predilection for males whereas SPEN is commoner in females in the second and third decades. 2. Acinar cell carcinoma: Imaging appearance is similar as pathology is also similar. It occurs in older age group (pancreatoblastoma 50% necrosis is given 6 points. Thus patients are graded on a scale of 0– 10. Those with a score of 0 or 1 showed no mortality or morbidity. Patients with a score of 2 had no mortality and only 4% morbidity. Patients with scores between 7 and 10 had 17% mortality and a 92% complication rate. Most complications of acute pancreatitis occur in Grade D and E patients. Modified CT severity index This is actually a minor modification of the CT severity index where rather than breaking the pancreatic necrosis into three categories 0–30, 30–50, more than 50%, it considers pancreatic necrosis as two categories, below 30% and above 30%. Pancreatic inflammation Normal pancreas – 0 Intrinsic pancreatic inflammation with no peripancreatic changes – 2 Peripancreatic inflammation- necrosis/collection – 4 Pancreatic necrosis No necrosis – 0 0%–30% necrosis – 2 30% and above necrosis – 4 Extra pancreatic complications – 2 points – Pleural effusion, ascites, vascular/GI complication 0–2 mild pancreatitis 4–6 moderate pancreatitis 8–10 severe pancreatitis There are minor changes between the two, both perform equally well so either is fine to use providing similar prognostication.

CTSI v/s Modified CTSI Characteristics PANCREATIC INFLAMMATION Normal pancreas

Grade CTSI MCTSI A

0

0

Focal or diffuse enlargement

B

1

2

Peripancreatic inflammation

C

2

2

Single acute fluid collection

D

3

4

Two or more fluid collection, retroperitoneal air PARENCHYMAL NECROSIS None

E

4

4

0

0

Less than 30%

2

2

b/w 30%–50%

4

4

More than 50%

6

4

EXTRA PANCREATIC COMPLICATION

0

2

One or more pleural effusion, ascites, vascular complication, GI tract involvement, parenchymal complication. Classification of Acute Pancreatitis According to Severity Index Score CTSI Score

Modified CTSI Score

Mild acute pancreatitis

1–3

2

Moderate

4–6

4–6

Severe

7–10

8–10

The clinical scoring systems such as the Ransons and APACHE are more sensitive to predicting systemic complications compared to the CT Severity Index, which is more sensitive than the clinical scoring systems in predicting pancreatic and peripancreatic complications. A combination of both the clinical scoring systems and the CT severity index provides an accurate prognostic indicator for both systemic and local complications. It must be remembered that the resolution of the CT features of pancreatic/peripancreatic inflammation lag behind clinical improvement.

Indications for initial CT study It is often confusing to the clinician when and how often to request for a CT study in acute pancreatitis.

It has been suggested that an initial CT study should be done. • In patients in whom the diagnosis is in doubt. • In patients with severe pancreatitis accompanied by fever, tenderness and leukocytosis or hypotension where a complication is suspected clinically. • In patients who do not improve within 72 hours of conservative treatment. • In patients with a Ransons score >3 or an APACHE II score >8. • In patients who show initial good improvement, but then rapidly deteriorate.

Follow-up CT study A follow-up CT study is performed as follows according to the patient’s grade or CTSI score. Grade A to C or CTSI of 0–2: Only if there is a clinical suspicion of a complication. Grade D or E and CTSI of 3–10: • After 7–10 days of the initial CT study. • If the clinical status at any time deteriorates or does not improve. • Final CT at the time of discharge as important complications may develop without clinical symptoms.

Other modalities Though CT is the modality of choice for evaluation of the pancreas, other modalities which may be used are sonography and MRI. Sonography is an excellent imaging modality, which can be performed at the bedside; unfortunately its role in imaging of acute pancreatitis is limited by its inability to demonstrate pancreatic necrosis which is an important diagnostic and prognostic indicator. Further the presence of intestinal gas, obesity and abdominal bandages may limit sonography in imaging the pancreas. The role of sonography in acute pancreatitis is limited to detecting the cause of pancreatitis, gallstones, in the follow-up of acute pancreatic fluid collections/effusions, and occasionally as a guide for aspiration of fluid collections. MRI is becoming a very viable alternative to CT. MRI has been found to be more sensitive than CT in detection of acute pancreatitis especially mild cases. Morphological changes are seen earlier on MRI than CT. Acute interstitial oedema is seen on T1WI fat sat images as a diffuse or focal enlargement of pancreas. The normal high signal intensity seen in the pancreas on T1WFS images

is lost. On T2W fat sat images there may be hyperintensity in the pancreas due to pancreatic oedema, peripancreatic hyperintensity in the form of peripancreatic inflammation and fluid collections. On contrast-enhanced images there is decreased and delayed enhancement. On MRCP the pancreatic duct may appear normal or compressed due to the pancreatic swelling. In necrotizing pancreatitis there may be focal, segmental, diffuse high signal intensity on T1WI from haemorrhage or decreased signal intensity due to necrosis. These areas of haemorrhage or necrosis will not enhance on the contrast studies. Complications such as pancreatic duct rupture and nonliquefied contents of pancreatic/peripancreatic collections are better demonstrated on MRI than CT. MRCP also helps determine the underlying cause of pancreatitis, which may be choledocholithiasis, neoplasm or abnormalities of pancreatic duct such as pancreas divisum. In patients with renal failure it is a useful alternative to CT as it demonstrates pancreatic oedema and peripancreatic collections very well. Atlanta classification This is a universally accepted classification for different manifestations of acute pancreatitis. The basic purpose of this classification is to define specific terms to facilitate understanding and correlation of findings to improve communication amongst clinical specialists, imaging and surgical colleagues. This improves clinical assessment and management. In 1992, the Atlanta Classification for acute pancreatitis was introduced. In 2012, the classification was modified to update the terminology and provide simple functional clinical and morphological classifications. Temporally, pancreatitis is divided into an early phase (first week) and a late phase (after first week). In the first week, SIRS and multiorgan failure predominate. Therefore only clinical parameters are important for treatment planning. Imaging is required in the first week only if diagnosis is in doubt or persistent multiorgan failure for 72 hours where sepsis needs to be excluded. In the early phase acute pancreatitis is divided into mild/severe based on duration of multiorgan failure; less than 48 hours is mild and more than 72 hours is severe. From an imaging perspective the different imaging findings are categorized into specific categories as the management for each varies depending upon on the category. The salient features of the classification from an imaging perspective are: 1) Dividing pancreatitis into two types interstitial and necrotising. 2) Classifying pancreatic/peripancreatic fluid collections based on contents and time line.

3) Within 4 weeks of onset of acute pancreatitis A) Acute peripancreatic fluid collections: which only contain liquefied components, no solid components. B) Acute Necrotic collections: containing nonliquefied components such as fat necrosis, solid peripancreatic necrosis, pancreatic necrosis and intrapancreatic fluid collections. 4) After 4 weeks of acute pancreatitis an enhancing capsule usually develops in relation, the peripancreatic fluid collection/neurosis. A) Pseudocyst: Acute pancreatic fluid collections which contain only liquefied components and are walled off. There should be no solid components such as fat necrosis. B) Walled of necrosis: Acute necrotic collections which are walled off after 4 weeks. 5) Any of these collections can be sterile or infected. The new Atlanta Classification makes a clear distinction between acute necrotic collections and acute pancreatic effusions based on the presence of any nonliquefied contents however small. Therefore, it is important to detect non-liquefied components in a fluid collection. Occasionally, performing CT may be difficult. In these situations where CT has difficulty, sonography or MRI may be useful to demonstrate nonliquefied components.

Chronic pancreatitis This is a chronic inflammatory disease that leads to progressive and irreversible structural damage to the pancreas, consequently leading to reduction in its exocrine and endocrine functions. Multiple aetiological factors have been implicated in the causation of chronic pancreatitis such as chronic alcohol abuse, hypertriglyceridemia, hypercalcemia, autoimmune factors, pancreatic ductal obstruction and genetic factors. However, the most common aetiological factor is chronic alcohol abuse. A small percentage of chronic alcoholics will develop chronic pancreatitis though chronic alcohol consumption is an aetiological factor in 70%–80% of cases of chronic pancreatitis. Consumption of more than 100 g of alcohol in day results in a decrease in pancreatic secretion, reduction in bicarbonate concentration, diffusion of calcium into pancreatic ducts, as well as increase in protein secretion. In view of the high protein content in the ducts, protein plugs form, with the high calcium content in duct fluid they calcify. There is also progressive destruction of pancreatic secretory parenchyma by necrosis/aptosis. Acinar cells disappear, duct cells

are injured, fibrosis sets in and consequently there is functional impairment of exocrine and endocrine function leading to malnutrition and diabetes. The fibrotic tissue produces duct strictures with upstream dilatation and stasis. This usually results in atrophy and ductal calculi. Patients present with chronic abdominal pain, diabetes and steatorrhea. Imaging is the key to diagnosis especially in the early stages of the disease. The hallmark of chronic pancreatitis is pancreatic ductal calcifications and ductal dilatation. Proteinaceous material is deposited in pancreatic ducts that form protein plugs, which subsequently calcify. These plugs lie in the secondary ductules of the main pancreatic duct or main pancreatic duct. These may cause obstruction or inflammation of the ductal wall resulting in periductal inflammation which causes strictures due to fibrosis to the duct with resultant downstream dilatation of the duct. These may be visualized on a plain radiograph of the abdomen however plain radiographs have a poor sensitivity, as only in 30% of chronic pancreatitis calcification may be visible on a radiograph. Rarely calcification in solid masses, cysts, vascular calcification may simulate calcification of chronic pancreatitis. CT is extremely sensitive in demonstrating calcific densities in the secondary and main pancreatic duct. The calcific plugs in the secondary ducts appear as calcific densities in the pancreatic parenchyma as the secondary ducts are not demonstrable on CT. Presence of ductal calculi in the main pancreatic duct is the most specific sign of chronic pancreatitis. The other findings are ductal dilatation and pancreatic glandular atrophy. Pancreatic ductal dilatation may involve only the MPD, side branches or both. The duct maybe smoothly dilated or beaded or irregular. Glandular atrophy is the third important component of chronic pancreatitis; this is usually present with ductal dilatation. Chronic pancreatitis can have episodes of acute pancreatitis, complicating chronic pancreatitis due to ductal obstruction by calculi or pancreatic strictures. This results in focal enlargement of the pancreas, pancreatic necrosis and peripancreatic fluid/necrotic collections. The peripancreatic fluid collections may progress to formation of pseudocysts. Nearly 25% of patients with chronic pancreatitis develop pseudocysts. These are visualized as thin walled well-defined homogeneous fluid density lesions in the peripancreatic region or in distant locations. There may be evidence of pancreatic/peripancreatic necrosis which may get complicated with sepsis or evolve to form walled off necrosis. The presence of acute pancreatic and peripancreatic inflammation can also lead to venous thrombosis of the splenic, superior mesenteric and portal veins. In chronic pancreatitis splenic vein thrombosis is seen in 11% of individuals. Venous thrombosis is well seen as hypodensity within the contrast-enhanced veins. There may be total occlusion of

the vessel with consequent portal hypertension and collateral vessels. Arterial pseudo aneurysms can also occur due to digestion of arterial walls by leakage of pancreatic enzymes into the peripancreatic regions. Pseudo aneurysms occur in the region of the head of the pancreas and splenic hilum. Commonly involved vessels are the gastroduodenal, pancreatodoudenal, splenic or middle colic artery. These pseudo aneurysms may be asymptomatic and detected incidentally at imaging or symptomatic following rupture of aneurysms with haemorrhage into the retroperitoneum, peritoneum or bowel. In arterial phase CT, pseudo aneurysms appear as fusiform dilatation of vessels or saccular structures arising from the parent artery. These aneurysms are treated by embolization, stenting or surgery. CT provides valuable information to decide on further treatment. Pancreatic fistula may occur due to rupture of main pancreatic duct or a peripheral duct with consequently pancreatic ascites or communication with the pleural space with resultant pancreatic pleural effusions. These collections have very high levels of amylase. MRI has a definite role in the evaluation of chronic pancreatitis as it is useful in demonstrating parenchymal changes and MRCP is very useful to demonstrate ductal changes (Fig. 9.17.14).

FIG. 9.17.14 Chronic Pancreatitis: CECT demonstrates dilated pancreatic duct with extensive calcific densities in pancreas. Parenchymal changes Early parenchymal changes are well demonstrated on MRI. In the initial stages of chronic pancreatitis as chronic inflammation and fibrosis sets in, there is loss of proteinaceous fluid in the pancreatic parenchyma. This results in reduction of normal T1-weighted hyperintense signal intensity of the pancreas. The normal pancreas enhances homogeneously in the late arterial phase and washes out

in the venous phase. In chronic pancreatitis there is decreased heterogeneous enhancement in the arterial phase with delayed increased enhancement in the venous phase. The enhancement pattern in chronic pancreatitis is opposite of the enhancement pattern of normal pancreas. These changes are probably due to arteriolar damage due to ongoing fibrosis. In the late stage of chronic pancreatitis, there is pancreatic parenchymal atrophy. The altered signal intensity and delayed enhancement, similar to as seen in the early stages of chronic pancreatitis is also visualized (Fig. 9.17.15).

FIG. 9.17.15 Chronic Pancreatitis: Coronal MIP of CECT demonstrates dilated pancreatic duct with extensive calcific densities in the head/uncinate process of pancreas. Ductal changes Pancreatic ductal abnormalities are the key findings, which help establish the diagnosis of chronic pancreatitis. MRCP is extremely useful as on heavily T2-weighted images the ductal system is very well demonstrated. In the early stages, there is dilatation and irregularity of the side branches. With progression, there is dilatation of the main pancreatic duct. The dilated main pancreatic duct may get complicated by strictures and intraductal calculi. Both which may cause further downstream dilatation of the main pancreatic duct and side branches. Intraductal calculi may be seen as hypointense filling defects within the hyperintense fluid of the duct. There may be also multiple retention cysts of varying sizes. These are usually small and lined by cuboidal epithelium. These

represent sequelae of repeated episodes of acute on chronic pancreatitis. MRCP may also demonstrate pancreas divisum, an important cause for chronic pancreatitis. This is as the main pancreatic duct drains into the minor papilla which has a smaller diameter than the major papilla. As a result there is back pressure in the main pancreatic duct resulting in repeated episodes of pancreatitis leading to chronic pancreatitis. One of the most common diagnostic dilemmas in chronic pancreatitis is when chronic pancreatitis presents on imaging as a focal mass lesion. This may resemble an adenocarcinoma. Patients with adenocarcinoma usually have a smooth dilated pancreatic duct as the pancreatic duct downstream is dilated, secondary to obstruction of the pancreatic duct by the adenocarcinoma. The duct is dilated due to obstruction and not disease as compared to chronic pancreatitis where the duct is diseased and manifests as an irregularly dilated duct; there also may be calculi in the duct as well as prominence of the side branches (Fig. 9.17.16).

FIG. 9.17.16 Chronic Pancreatitis: MRCP image demonstrates marked dilatation of pancreatic duct with prominent side branches, ductal calculi seen as filling defects in dilated main pancreatic duct and pancreatic ductal strictures. The morphology of the common bile duct also provides assistance in differentiating adenocarcinoma of the pancreas from chronic pancreatitis. In adenocarcinoma the common bile duct

reveals an abrupt cut off, whereas in chronic pancreatitis the CBD reveals a smooth tapering of its distal end due to benign fibrosis. Additional features such as vascular encasement can be an unreliable sign, as in both conditions there may be loss of fat plane between the mass and mesenteric vessels, due to peripancreatic inflammation. Though in some cases of pancreatitis a collar of fat is seen between the vessels and pancreas. The presence of liver metastases is helpful in establishing the diagnosis of adenocarcinoma of pancreas. In certain cases where there is still difficulty in differentiating, a EUS-guided biopsy would be required. IPMN also may resemble chronic pancreatitis, especially when there is main-duct IPMN. The main differentiator is the presence of intraductal calculi. Occasionally calcifications may occur in IPMN, these are usually small flaky calcifications. Pancreatic atrophy favours the diagnosis of chronic pancreatitis, but may also be seen in IPMN. If there is presence of a soft tissue density mass in the pancreatic duct then the possibility of IPMN is much greater. Though ERCP is the gold standard for demonstrating the pancreatic duct, MRCP has significant advantages over ERCP as it is noninvasive, provides a more physiologic estimate of ductal diameter as compared to ERCP, where the duct is distended by injection of contrast. In case of a ductal obstruction, often by a calculus, the distal pancreatic duct is not visualized on ERCP, whereas MRCP is able to evaluate it (Fig. 9.17.17).

FIG. 9.17.17 Acute on chronic pancreatitis: Chronic pancreatitis as evidence by calcific densities in pancreas with illdefined hypodensity in pancreatic head representing acute on chronic pancreatitis.

Groove pancreatitis This is an uncommon form of focal chronic pancreatitis affecting the pancreaticoduodenal groove, which is located between the head of the pancreas, duodenum and CBD. There are two forms, the pure form and the segmental form. In the pure form there is scar tissue between the duodenum and the head of the pancreas. In the segmental form there is scar tissue that involves the groove as well as pancreatic head. On imaging in the pure variety a sheet like tissue is seen between the duodenum and head of pancreas. This demonstrates delayed enhancement and small cysts representing pseudocysts may be seen along the duodenal wall. In the segmental form there is a sheet of tissue that is inseparable from the head of the pancreas that appears hypodense. There may be duodenal wall thickening and small pseudocysts. In addition, there may be pancreatic ductal dilation and consequently pancreatic atrophy. The main differentials for pure groove pancreatitis are groove carcinoma, groove neuroendocrine, duodenal or periampullary carcinoma. Differentiating these is difficult and the only sign that helps is the presence of cysts in the medial wall of the duodenum representing pseudocysts.

In the segmental form the most important differential is adenocarcinoma. The useful differentiating signs would be the presence of vascular encasement, metastases, sudden cut-off of CBD and smooth dilated pancreatic duct, which would favour a malignancy (Fig. 9.17.18).

FIG. 9.17.18 Groove Pancreatitis: Ill-defined inflammatory soft tissue between pancreas and duodenum representing groove pancreatitis.

Tropical pancreatitis This is a type of chronic pancreatitis seen in Asia, particularly India, predominantly in Kerala. These patients are young with a rapidly progressive course. Nearly two-thirds develop fibrocalcareous pancreatic diabetes in a decade after the onset of disease. These individuals also have a higher likelihood of developing adenocarcinoma, especially in the body and tail of pancreas. Twenty-five per cent of these patients die before the age of 45 years. The exact aetiology is unknown but considered to be due to protein malnutrition, cyanide toxicity, pancreatic duct anomalies and genetic mutations (SPINK1). On imaging the features are of a chronic pancreatitis. The pancreatic ductal calculi can measure unto 5 cm.

Autoimmune pancreatitis This is a chronic fibroinflammatory process, part of IgG4 immunoglobulin systemic disease manifesting as sclerosing pancreatitis. Other organs such as the salivary glands (sialadenitis), bile duct (sclerosing cholangitis), liver (autoimmune hepatitis), retroperitoneum (retroperitoneal fibrosis), bowel (inflammatory bowel disease) and renal system may be involved. Patients present with steatorrhea and diabetes due to deteriorating pancreatic function, may also present with obstructive jaundice due to associated biliary obstruction; rarely they present as a pancreatic mass as a result of focal pancreatic involvement. The pancreas may be involved focally (most common) or multifocally. AIP usually starts as a focal swelling progressing to a diffuse form. Consequently there is diffuse pancreatic swelling with loss of normal parenchymal lobulations. The pancreas appears sausage shaped. With further progression in disease there is pancreatic tail retraction with the pancreatic tail not present. The margins of the pancreas are smooth. On MRI a capsule may be seen which is hypointense on T1/T2WI and shows delayed enhancement. In the focal variety, a mass lesion is seen usually in the body or tail, which is hypodense on CT, hypointense on T1 mildly hyperintense on T2WI and shows delayed enhancement. This form is difficult to differentiate from pancreatic cancer as both present with hypodense mass lesions. The delayed enhancement is a feature helpful towards the diagnosis of AIP. Features that would indicate pancreatic carcinoma are vascular invasion/encasement, nodal/liver metastases and abrupt cut-off of CBD and MPD with gross dilatation of these ducts upstream. In AIP there may be changes involving the MPD and CBD. There may be diffuse or segmental narrowing of the MPD, however pancreatic duct dilatation is not to the same extent as seen in pancreas Ca. Sclerosing cholangitis is usually present in 88% of cases of AIP. This manifests as focal stenosis of the intrapancreatic CBD, with consequent upstream dilatation of CBD, less frequently multifocal intrahepatic biliary strictures. The treatment of AIP is corticosteroid therapy. Following treatment the gland regresses in size, the pancreatic duct changes also regress. In advanced disease as the swelling regresses there is residual atrophy (Fig. 9.17.19).

FIG. 9.17.19 Autoimmune pancreatitis: Typical appearance of bulky pancreas with absence of tail of pancreas and abrupt rounding off pancreatic body. D/D The diffuse form may mimic lymphoma or other diffuse infiltrative processes. In these diseases the pancreatic parenchyma is usually heterogeneous. The focal form may resemble adenocarcinoma. Lack of upstream dilatation of pancreatic duct, absence of vascular encasement, absence of parenchymal atrophy, vascular encasement and metastatic disease help differentiate.

9.18: Imaging in solid pancreatic masses Anirudh Kohli

Introduction This is probably the most dreaded form of cancer with a dismal outlook. It is the fourth most common cancer. The 5-year survival rate is 15% when the tumour is small and confined to the pancreas with no peripancreatic extension. The 5-year survival rate drops to 6.8% when there is peripancreatic invasion and 1.8% when distant metastases are present. The only option for cure is surgical resection, with a survival rate of 15%–27%. Unfortunately, only 10%–15% of patients with pancreatic adenocarcinoma are eligible for resection. Imaging is important to detect disease as well as to determine resectability. Most patients with recurrent disease following surgery recur due to inoperable disease. Ninety per cent of pancreatic adenocarcinomas present as a focal mass in the head of the pancreas. The remaining 5%–10% present as a diffuse involvement of the gland. A total of 60%–65% of these focal lesions arise in the head of the pancreas, while 20%–25% in the body and 5%–10% in the tail of the pancreas. The most frequent appearance is of a hypodense mass lesion relative to the normal enhancing pancreatic parenchyma on pancreatic phase of enhancement. The decreased attenuation is attributable to fibroblastic proliferation and decreased vascularity. There may be dilatation of the pancreatic duct distal to the mass lesion as the mass lesion obstructs the pancreatic duct. The pancreatic ductal dilatation is smooth and homogenous. Lesions in the head of the pancreas may obstruct the distal common bile duct with resultant upstream biliary dilatation. The distal common bile duct demonstrates a sudden cut-off. A few pancreatic tumours may be isodense; these are recognized only by secondary signs such as loss of lobular texture, contour change, dilatation of pancreatic or bile ducts. Small tumours in the uncinate process may be totally inconspicuous.

Resectability

In addition to detecting pancreatic adenocarcinoma, imaging plays a key role in assessing, if the neoplasm is amenable to resection. As the tumour is seated deep in the retroperitoneum, it typically infiltrates the adjacent superior mesenteric vessels, portal vein or mesenteric neural plexus. Presence of distant metastases also indicates inoperability. To determine vascular invasion, the venous system and arterial system needs to be studied in detail. Multidetector computed tomography (MDCT) with thin isotropic imaging is particularly suited. Images are obtained in the pancreatic phase to study the arteries and in the portal venous phase to study the porto-mesenteric system. The portal vein, splenic vein, superior mesenteric vein and the tributaries of the superior mesenteric vein are evaluated on axial and multiplanar reformation or reconstruction (MPR) images, especially the gastrocolic trunk, inferior mesenteric vein and first jejunal branch. Vascular invasion is seen as encasement of the vessel, that is tumour encircling the vessel totally or vessel coursing through substance of tumour, occlusion of the vessel or contact with vessel wall greater than 180 degrees. Positive predictability for unresectability for MDCT is 89%–100% and for resectability is 45%–79%. Since the only hope for a patient with adenocarcinoma of the pancreas is surgical resection, new techniques have been introduced to perform vascular resection along with tumour with re-anastomosis or placement of grafts. The techniques available are venous resection and reconstruction, hepatic artery segmental resection and/or reconstruction. Venous resections are performed with short segments of superior mesenteric vein, portal vein and/or splenoportal confluence excised and re-anastomosed. If sufficient length is not available, saphenous venous patches, interposition grafts from the jugular vein may be performed. Thus, patients with tumour encasing the vessel for a short segment or vessel contact greater than 180 degrees can be resected. The key to this is that the two venous ends to be joined should have only one lumen on either side, if the branches’ reconstruction is not possible. Most adenocarcinoma of the pancreas arise in the head of the pancreas; thus they tend to involve the gastroduodenal artery. Involvement of the gastroduodenal artery does not constitute inoperability as it would be resected in a Whipple surgery. The important aspect of gastroduodenal arterial involvement is that cephalad growth of tumour may occur along the gastroduodenal artery to involve the common hepatic artery. Additionally, if there are anomalous origins of the hepatic artery such as accessory or right hepatic artery or common hepatic artery arising from the superior mesenteric artery (SMA), these vessels course close to the posterior aspect of the pancreatic head and are commonly encased. These vessels can be excised for a short segment and primary

anastomosis done or if inadequate length available, excised and a reverse saphenous vein graft placed.

TNM staging Though not routinely used by radiologists in reporting, there is value in classifying pancreatic carcinomas by the TNM (“Tumor”, “Nodes”, “Metastases”) classification. Routinely radiology reports essentially cover two important aspects: vascular invasion and distant metastases, which determine operability. T staging • T1 and T2 tumours are determined based on size: • T1 tumours are less than 2 cm in size. • T2 tumours are larger than 2 cm in size. • T3 tumours extend into the peripancreatic soft tissue; however, there is no invasion of the celiac axis, mesenteric vessels and portal vein. • T4 tumours extend into the peripancreatic tissue with invasion of vascular structures. Generally T1–T3 tumours are resectable. N staging CT is not very accurate in N staging. This is due to the fact that the criteria for nodal involvement is size. Nodes larger than 10 mm in short axis are considered abnormal. Nodes that are less than 10 mm are considered normal on CT. However, metastases may be present in nodes less than 10 mm. Thus, CT is of limited value in detection of nodal metastases. Positron emission tomography–computed tomography (PETCT) and MRI are of great value in detecting lymph nodal metastases. Metastatic adenopathy smaller than the CT size criteria of 10 mm are detected as they are avid on Ffluorodeoxyglucose (FDG) and may show diffusion restriction/ADC on MRI. PETCT has a higher sensitivity than MRI. PETCT which should be considered as the gold standard for metastatic nodal detection. Nodes are classified based on location Infrapyloric, superior to pancreas, hilum of spleen, inferior to pancreas, pancreatoduodenal posterior, pancreatodoudenal anterior. Hepatic artery node is an important node. This node is located at the site of takeoff of the gastroduodenal artery. It is part of the coeliac drainage. Involvement of this node indicates a poor prognosis similar to prognosis when liver metastases are present.

M staging The most common site for metastatic disease spread is the liver. Small deposits to the liver and peritoneum may be missed on imaging. Hepatic metastases are seen as hypodense, hypovascular lesions, best demonstrated on the portal venous phase. Imaging-guided biopsy for establishing diagnosis CT is useful as a guide for performing CT-guided fine needle aspiration cytology (FNAC) of a pancreatic mass to obtain material for histopathology. The only care to be taken is not to transgress large bowel as coliform bacilli may be implanted into the pancreas resulting in secondary infection. Care also needs to be taken not to transgress a vascular structure. MRI. MRI is a very useful alternative to CT. MRI demonstrates pancreatic masses similar to CT, as well as is useful in determining resectability. MRI has the advantage of magnetic resonance cholangiopancreatography (MRCP) – therefore able to demonstrate the common bile duct and pancreatic duct very well. There is usually a sudden cut-off of the common bile duct by the pancreatic mass with upstream dilatation. There is also occlusion or narrowing of the pancreatic duct by the pancreatic mass with consequent smooth downstream dilatation of the pancreatic duct secondary to obstruction by the pancreatic mass. Chronic pancreatitis may present with a focal mass lesion in the head of the pancreas with associated pancreatic and biliary duct dilatation. MRCP helps differentiate between a mass lesion due to chronic pancreatitis and Ca pancreas. The pancreatic duct would be irregularly dilated, with possibly intraductal calculi and strictures in chronic pancreatitis as compared to Ca pancreas where the duct would be smoothly dilated. The common bile duct usually terminates abruptly in Ca pancreas as compared to chronic pancreatitis where due to a fibrous stricture there is smooth tapering of the common bile duct. The disadvantages of MRI are its longer acquisition time, slightly lower spatial resolution and inability to obtain material for histopathology. Solid pseudopapillary neoplasm of pancreas Previously known as solid and papillary epithelial neoplasm. Solid pseudopapillary neoplasms of the pancreas are tumours with a benign or a low malignant potential. These are rare tumours accounting for 9% of cystic pancreatic tumours. A total of 10%–15% of these have a malignant potential. They are usually discovered incidentally; large tumours may cause symptoms due to pain or mechanical obstruction. These tumours are mainly seen in young

females, generally in the 20–40 age group, earning their nickname daughter tumours, though they may occur in younger or older individuals. These tumours are usually larger than 3 cm in diameter with an average size of 9 cm, well-defined round encapsulated masses with a heterogeneous consistency. Internally there are haemorrhagic, necrotic, cystic and solid components, contributing to the heterogeneous appearance. On histopathology, they demonstrate psuedopapillary architecture and do not demonstrate exocrine or endocrine cells raising the possibility that these arise from primordial pancreatic stem cells. Progestrone receptors are seen in 81% of cases. On imaging the heterogeneity of these lesions is demonstrated. The solid components tend to be along the periphery and enhance after administration of contrast. An important feature is the capsule of the lesion which is hypointense on T1 and T2 weighted images and enhances densely on the arterial phase with progressive enhancement on the venous phase. Peripheral calcifications may be present; the presence of calcifications may be an indicator of a more aggressive tumour. Smaller SPNs tend to be more solid and homogenous in enhancement. On MRI, these lesions are heterogeneous with bright areas on T1 weighted images due to haemorrhage. The rest of the lesion is usually heterogeneously hypointense on T1 weighted images. On T2 weighted images, the lesion turns heterogeneously hyperintense. Similar to as seen on CT, the lesions have welldefined margins and demonstrate early enhancement in the solid portions with delayed enhancement in the noncystic/haemorrhagic regions. The presence of haemorrhage is a diagnostic feature of these tumours. A small proportion of these tumours may metastasize to the liver. Pancreatic metastases The pancreas may be a site for metastatic disease usually via hematogenous spread. Renal cell CA, lung, breast, ovarian, HCC, GI, thyroid, melanoma may metastasize to the pancreas. These lesions may be localized or multifocal masses resulting in diffuse enlargement of the pancreas. These resemble pancreatic neoplasms, when they are the sole site of metastases. On imaging, differentiation from pancreatic masses is not possible; differentiation can be done only at biopsy.

Pancreatic lymphoma Primary pancreatic lymphoma may occur but it is very rare. More commonly, the pancreas is involved secondarily as part of NonHodgkins lymphoma, involving the liver, spleen and lymph nodes. In Non-Hodgkins lymphoma, there is diffuse enlargement of the

pancreas. This is hypodense on CT with mild enhancement. Similarly, hypointense to normal pancreatic parenchyma on T1 and T2 weighted images. The diffuse pancreatic enlargement on imaging may mimic acute edematous pancreatitis. The lack of acute symptoms and lack of peripancreatic inflammation help to differentiate. Following treatment, the pancreatic gland reduces in size and calcific foci may be seen in the pancreas. Primary pancreatic lymphoma presents as a mass lesion in the pancreas with peripancreatic adenopathy. This is visualized on imaging as a hypodense mass lesion. There is no dilatation of the pancreatic duct distal to the mass helping to differentiate from adenocarcinoma of the pancreas. An additional feature of note is that there is no hepatosplenomegaly or focal lesions in the liver/spleen; though a biopsy would be required to establish the diagnosis. More commonly, the pancreas is involved secondarily as part of Non-Hodgkins lymphoma. In addition to focal pancreatic involvement, there is focal involvement in the liver/spleen/bowel/mesentery/adenopathy, etc. PETCT is very useful to demonstrate the multifocal involvement.

Pancreatic neuroendocrine tumours Neuroendocrine tumours (NET) are a heterogenous group of neoplasms which arise from the diffuse neuroendocrine system. These may be found throughout the body, in the lung, pancreas, gastrointestinal tract. Those arising in the pancreas are termed as pancreatic neuroendocrine tumours. Previously, they have been called islet cell tumours, but this is a misnomer as they arise from the ductal pluripotent cells rather than islets of Langerhans. These constitute 10% of all pancreatic tumours. There has been a substantial increase in the last few decades. All neuroendocrine tumours are potentially malignant but differ in their biological characteristics and probability of metastatic disease. Pancreatic NET occur sporadically but some may be associated with inherited genetic syndromes. They have no particular age or sex predilection but when they arise in younger individuals, they are usually part of a familial syndrome. The most common syndrome associated with pancreatic NET is MEN – 1. This syndrome has an autosomal dominant pattern of inheritance due to mutations on chromosome 11, characterized by tumours of the pituitary gland, parathyroid gland and NET of pancreas. Occasionally thyroid, adrenal and ovarian tumours also occur. Less commonly pancreatic NET are associated with VHL disease; this is also autosomal dominant in transmission due to mutation of chromosome 3. VHL is characterized by cerebellar and retinal haemangioblastomas, tumours and lymphoepithelial cysts of the

pancreas, kidney and epididymis. Fourteen per cent of patients with VHL have pancreatic NET of which 50% are multiple NET. These are mainly nonfunctional NET. Other syndromes are NF-1 and tuberous sclerosis complex. These are essentially divided into two groups, functional and nonfunctional. Functional tumours hypersecrete hormones such as insulin, gastrin, glucagon, vasoactive intestinal peptide or adrenocortical hormone. These secreted hormones manifest as clinical syndromes with typical features related to the excess production of these hormones. These are usually well-defined rounded neoplasms ranging from 1 to 5 cm. Nonfunctioning tumours do not secrete hormones; therefore these are usually clinically silent. Since they are clinically silent, they are usually large in size at presentation, symptoms arising due to mass effect on adjacent structures. Nonfunctioning tumours constitute 30%–40% of pancreatic NET. Pancreatic NET are much less aggressive than pancreatic adenocarcinoma but often metastasize to the liver. In fact, they are the second most common tumour to metastasize to the liver after colon carcinomas. Imaging is important in detection, staging, preoperative assessment to determine the ideal operative technique – Whipple surgery, distal pancreatectomy or enucleation. Intraoperative ultrasound is also very important to localize nonpalpable tumours for the surgeon, as well as demonstrate relationship between splenic artery, superior mesenteric vessels, CBD and pancreatic duct. Functional tumours are: • Insulinoma • Gastrinoma • Glucagonoma • Vipoma • Somatostatinoma Functional tumours become clinically evident at a smaller size and much earlier than other pancreatic neoplasms due to symptoms, as a result of their hormone release. These tumours are benign but as they grow in size, the likelihood of malignancy increases. Imaging of pancreatic NET MDCT is the first line investigation with an overall sensitivity of 84%. MDCT with its ability to image in the arterial phase has made a huge impact on the detection of pancreatic NET as these lesions enhance in the arterial phase. The sensitivity to detect insulinoma

on single slice CT was 29%, and with the introduction of MDCT, the sensitivity rose to 94%. MDCT studies are performed following administration of IV contrast at 3 mL/s in the pancreatic phase (approximately 30 seconds after injection) and in the portal venous phase (approximately 70 seconds after injection of contrast). Images are reconstructed using the narrowest collimation to provide isotropic 3D sets. MRI is also a useful first line modality with a similar sensitivity rate of MDCT of 85%. In fact, for lesions above 3 cm it rises to 100%. These lesions are hypointense on T1 weighted images and hyperintense on T2 weighted images. Multiphasic dynamic MRI is performed after injection of gadolinium at 0.1 mmol/kg body weight at 2 mL/s. The acquisition is a 3D vibe so as to produce 3D isotropic data sets. Other imaging modalities are EUS endoscopic ultrasound, which has a very high sensitivity as well as somatostatin receptor scintigraphy. These are useful second line investigations if MDCT or MRI has failed. Insulinoma This is the most common functioning pancreatic NET. These constitute approximately 50% of all pancreatic NET. Ninety-five per cent are benign at the time of diagnosis, 97% occur in the pancreas, 90% are less than 2 cm and 66% are less than 1.5 cm. Thus, these are very small lesions. Ten per cent are malignant with metastases to the peripancreatic nodes and liver and 10% are multifocal. Multifocal insulinoma (8% of all insulinomas) is usually associated with genetic syndromes such as MEN 1. Clinically they present with persistent episodic symptomatic hypoglycemia, typically in a fasting state or after exercise as compared to other causes of hypoglycemia, which occur postprandial. Hypoglycemia induced by insulinoma is rapidly relieved by administration of intravenous or oral glucose. The clinical presentation may occasionally be not so straightforward with patients presenting with neurological and cardiovascular symptoms such as dizziness, amnesia, confusion, personality changes, seizures, palpitations and chest pain. These subtle and nonspecific symptoms may delay the diagnosis and only on performing cross-sectional imaging, the diagnosis may be established. Insulinoma enhance densely on the late arterial/pancreatic phase and become isodense to pancreatic parenchyma on the venous phase. To detect insulinoma, it is essential to obtain early, late arterial phases as occasionally small insulinomas may enhance only in the early arterial phase; however, most of them enhance in the late arterial phase. On MRI similarly insulinoma are hypervascular.

They are usually iso- to hypointense on T1 weighted images and mildly hyperintense on T2 weighted images. Enhance densely on the arterial phases especially late arterial phase, becoming isodense on portal venous phase. Gastrinoma Gastrinomas are the second most common functioning pancreatic NET. These constitute 30% of all functioning pancreatic NET and 20% of all pancreatic NET. Thirty-five per cent are associated with MEN – 1. Gastrinomas hypersecrete gastrin causing hypersecretion of gastric acid resulting in peptic ulceration. Clinically, these present as Zollinger–Ellison syndrome, which constitutes peptic ulceration due to hypersecretion of gastric acid and pancreatic NET. These individuals also have diarrhoea due to the excessive volume of gastric acid secreted. The diagnosis of gastrinoma is based on demonstration of an elevated serum gastrin level. Secretin stimulation test can differentiate between Zollinger–Ellison syndrome and other causes of hypergastrinaemia. Fifty per cent of gastrinomas at time of detection have liver metastases. While 60% of gastrinomas are located in the pancreas, 30% are located in the duodenum. In fact 90% of gastrinomas are located in the gastrinoma triangle. This triangle is formed superiorly by junction of the cystic duct and CBD. Inferiorly by the junction of the second and third part of the duodenum and the medial margin is formed by the junction between head and body of pancreas. Gastrinoma are visualized on imaging as small 1–2 cm hypervascular homogenous lesions in the gastrinoma triangle. Multiphase MDCT and multiphase dynamic contrast enhanced MRI have a high sensitivity in detecting gastrinoma, though occasionally lesions in the duodenal wall may be difficult to detect. In these situations, a somatostatin receptor study with SPECT is useful, alternatively endoscopic ultrasound is a useful compliment. Glucagonoma Glucagonoma constitute 2%–5% of all endocrine pancreatic tumours and 8% of functional pancreatic tumours. Eighty per cent of these are malignant, with metastases found in 70% at the time of presentation. Glucagonoma hypersecrete glucagon resulting in 4D syndrome – this syndrome constitutes diabetes, dermatitis, deep venous thrombosis and depression. The dermatitis is usually the first to come to attention as erythematous plaques on the face, abdomen, groin and lower extremities. These plaques tend to coalesce with blistering and encrustation of their margins. Diabetes occurs in 75%–95% and deep venous thrombosis in 30%. The diagnosis is established with the combination of classical symptoms and elevated serum glucagon levels. Predominantly, these tumours occur in body and tail and are usually approximately

4 cm and larger in size at the time of detection. Hepatic metastases are seen in 50%; metastases also occur to the adrenals, lymph nodes, bones and lungs. Tumours larger than 5 cm have a 60%– 80% chance of being malignant. On multiphase MDCT, they are visualized as large hypervascular masses in the body and tail of pancreas. Somatostatin receptor SPECT and EUS are also useful to detect gastrinoma. VIPoma VIPoma constitute 8% of functional pancreatic NET of which 60% are malignant. VIPomas are caused by hypersecretion of vasoactive intestinal peptide. This intestinal peptide binds to receptors in the intestinal lumen causing secretion of sodium, potassium, chloride and water into the bowel lumen while increasing bowel motility. These actions lead to secretory diarrhoea, hypokalemia, achlorhydria and dehydration. Clinically referred to as Verner– Morrison syndrome, VIPoma are diagnosed by determining the fasting plasma vasoactive intestinal polypeptide level and stool analysis. Surgical debulking and use of octreotide are useful to control symptoms especially the diarrhoea and allow correction of metabolic derangements. At imaging, most VIPoma are larger than 3 cm, 90% occur in the pancreas with 75% in the tail of the pancreas. These are seen as large heterogeneous tumours in the pancreatic tail. A total of 60%– 80% are metastatic at the time of diagnosis. Less commonly, these arise in the colon, bronchus, adrenals, liver and sympathetic ganglia. Somatostatinoma Somatostatinoma is the rarest pancreatic NET constituting less than 1% of all endocrine tumours. However, 75% of these are malignant. These tumours secrete somatostatin, which actually functions in a paracrine role inhibiting secretion of insulin, gastrin and cholecystokinin. Clinically, these patients present with diabetes due to somatostatin inhibitory effect on insulin secretion, cholelithiasis due to inhibition of cholecystokinin and gall bladder contractility and steatorrhoea due to inhibition of pancreatic enzyme and bicarbonate secretion. Diagnosis is established by demonstration of elevated fasting levels of somatostatin. At imaging, most somatostatinomas are large bulky heterogeneous tumours. Most of these occur in the head of the pancreas. Seventy per cent occur in the pancreas, the rest occur in duodenum, ampulla or small bowel. The duodenal tumours are associated with NF1. The main differentials to a hypervascular pancreatic mass are pancreatic metastases from renal cell carcinoma, solid serous

cystadenoma, intrapancreatic accessory spleen. IPAS has imaging and enhancement characteristics that match the spleen. Heatdamaged technetium 99 red blood cell scintigraphy with SPECT is diagnostic as the intrapancreatic lesion picks up radiotracer similar to spleen. Nonfunctioning pancreatic NET These are the third most common pancreatic NET and constitute 15% of all pancreatic NET. These tumours are not associated with any syndrome related to hypersecretion, therefore considered nonfunctioning. However, these tumours may secrete high levels of pancreatic polypeptide, calcitonin or neurotensin. Secretions of these hormones produce no symptoms. Due to the lack of a hypersecreting clinical syndrome, these tumours come to attention only when they reach a large size to cause biliary and GI obstruction. They may also cause abdominal pain and weight loss. By then they are nearly always malignant (90%). They are also more commonly metastatic as compared to the functioning tumours: 60%–80% versus 25%. This impacts the survival of these patients – 3-year survival is 82% in patients with no liver metastases and 56% with liver metastases. Due to their large size they may demonstrate haemorrhage/necrosis. Large necrotic components may give the appearance of a cystic lesion but usually there is a thin hypervascular rim. Twenty per cent may demonstrate calcification which usually is an indicative of malignancy. They may obstruct the main pancreatic duct causing obstruction and downstream pancreatic ductal dilatation. They may spread locally to invade the retroperitoneum, spleen, stomach or duodenum or metastasize to the liver and or regional lymph nodes. However, the imaging features are nonspecific and differential diagnosis of adenocarcinoma, lymphoma, metastases should be considered. Functional imaging (Figs. 9.18.1–9.18.18)

FIG. 9.18.1 Hypodense mass lesion in the head and neck of pancreas representing primary neoplasm.

FIG. 9.18.2 Hypodense mass lesion in head of pancreas with consequent distal atrophy of body of pancreas.

FIG. 9.18.3 Hypodense mass lesion in head neck of pancreas encasing the origins of splenic artery with distal pancreatic duct dilatation.

FIG. 9.18.4 Mass lesion is pancreatic head encasing superior mesenteric artery from its origin.

FIG. 9.18.5 Mass lesion in pancreatic head encasing superior mesenteric artery, deviating artery to the right (A) Lower image reveals artery encased in the mass (B).

FIG. 9.18.6 Mass lesion in head of pancreas encasing Superior mesenteric artery and vein.

FIG. 9.18.7 Mass lesion in neck/body of pancreas representing a primary neoplasm, multiple focal hypodense hepatic lesions representing metastatic deposits.

FIG. 9.18.8 Large hypodense mass arising in pancreatic head with invasion of duodenum and obstructing common bile duct.

FIG. 9.18.9 Large solid and cystic mass arising from head of pancreas in a young female – biopsy solid and papillary neoplasm of pancreas.

FIG. 9.18.10 Arterial phase CT study demonstrates a large well defined hyper vascular mass in head of pancreas which was missed on portal venous phase CT – Biopsy Insulinoma.

FIG. 9.18.11 CT demonstrates bulky body of pancreas with multiple focal hyper vascular lesions – multicentric insulinoma.

FIG. 9.18.12 CT demonstrates multiple focal hyper vascular lesions in the pancreas (green arrows) multi centric neuroendocrine tumors.

FIG. 9.18.13 CT demonstrates multiple focal hyper vascular lesions in the head and tail of pancreas (green arrows) multi centric neuroendocrine tumors.

FIG. 9.18.14 Proven insulinoma on follow up – Focal hyper vascular lesion in body of pancreas which reveals progression in size on follow up scan after 3 years.

FIG. 9.18.15 DOTATEC scan reveals focal uptake in pancreatic tail representing neuroendocrine tumor.

FIG. 9.18.16 Coronal reformatted arterial CT images. Hypervascular mass lesion in body of pancreas with hyper vascular lesion in liver demonstrating primary neuroendocrine and metastatic deposits in liver.

FIG. 9.18.17 Metastatic neuroendocrine tumor – progression of lesions from first to second scan.

FIG. 9.18.18 Metastatic neuroendocrine tumor following resection of pancreatic neuroendocrine. (A) Focal hypodense lesions in liver on portal venous phase CT representing metastatic deposits. (B) FDG PET shows no uptake in liver lesions, however DOTTEC shows vivid uptake (C) A low grade tumor will show uptake on DOTATEC, high grade will show uptake on FDG PET. This helps categorise, prognosticate as well as plan further management. Patient was treated with somatostatin receptor blocking agents, follow up scan revealed complete elimination of lesions. Neuroendocrine tumours have a high expression of somatostatin receptor (SSTR). This is exploited by somatostatin receptor scintigraphy or PET scan. In somatostatin receptor scintigraphy, a synthetic somatostatin analogue octreotide is labelled with indium 111 to detect receptor positive lesions. Though the spatial resolution has been improved with single photon emission computed tomographic (SPECT) and planar imaging SPECT has significant limitations – lesions smaller than 1 cm cannot be picked up,

physiological uptake in bowel and gall bladder can obscure lesions, additionally SPECT is a 2-day study with imaging being performed 24 hours later. To overcome these limitations, PET scans utilize an octreotide analogue labelled with gallium 68 directly which directly binds to SSTR. Scanning can be done in 45–90 minutes after radiotracer injection. With hybrid CT, both PET and contrastenhanced MDCT can be obtained in the same sitting. One limitation of PET with gallium analogue is its inability to detect poorly differentiated lesions. Since these have a high metabolic requirement for glucose, they are detected on FDG PET. These features have also been exploited in the management of neuroendocrine lesions. Lesions with high SSTR which are inoperable can be managed by medical treatment with somatostatin analogues octreotide and or targeted radionucleide agents. These help control systemic symptoms in patients with functional symptoms or metastatic NET. Those with aggressive biology and poor SSTR expression require systemic chemotherapy. The first line of management of neuroendocrine tumours is surgical excision; however, this is dependent on lesion size, location and disease stage.

9.19: Cystic pancreatic masses Ritu K. Kashikar, Shrinivas B. Desai, Pooja Punjani Vyas, Nilesh Doctor, Vivek Shetty

Introduction Advancement and extensive use of imaging in recent times has to lead to increased detection and recognition of cystic pancreatic masses. Imaging however, plays a vital role in noninvasive diagnosis of these lesions, avoiding unnecessary intervention and planning management and follow up guidelines. The aetiology of pancreatic cysts ranges from primary cystic neoplasm to cystic degeneration of solid neoplasm to nonneoplastic cysts (Table 9.19.1). Cystic tumours of the pancreas comprise around 10%–15% of cystic lesions of the pancreas. The aim of this chapter is to educate the reader regarding imaging features of cystic lesions of pancreas, how to differentiate between cysts which can be left alone and those that require further management and also emphasize on latest international guidelines used in stratification of these lesions. TABLE 9.19.1 Classification of Cystic Pancreatic Masses

Imaging techniques Ultrasonography (USG) Cystic pancreatic lesions are often incidentally detected on USG abdomen performed for other reasons. Although USG is an excellent modality for evaluation of cystic lesions elsewhere, it is unable to adequately characterize pancreatic cysts due to retroperitoneal location of the organ and other confounding factors such as obesity and gases. Most lesions detected on USG require characterization with either MDCT or MRI with MRCP. CEUS improves accuracy in the differentiation between a solid and a cystic lesion and also in determining whether enhancing septa or nodules are present

within the cystic lesion. Currently USG also does not have a role in follow up algorithms of pancreatic cystic lesions. MDCT Multidetector CT evaluation of pancreatic lesions is best performed with a multiphasic technique (Table 9.19.2). The phases include a precontrast scan, an early arterial angiographic phase, a pancreatic parenchymal phase, and a portal venous phase. The precontrast scan is important for detection of calcification, which may be diagnostic of some lesions. Mucinous cystic neoplasms may be hyperdense on nonenhanced scan suggesting mucin content or haemorrhage. TABLE 9.19.2 MDCT Protocol Precontrast Scan Arterial phase Pancreatic parenchymal phase Portal venous phase

18–20 seconds 35–45 seconds 60–70 seconds

The arterial phase aids in detection of hyperenhancement neovascularity and arterial involvement in pancreatic masses. Optimal parenchymal enhancement of the pancreas is achieved at 35–45 seconds after initiation of injection of contrast agent. This is the pancreatic parenchymal phase. It is in this phase that the tumour pancreas contrast is maximum (Fig. 9.19.1, Table 9.19.3). Most hypoenhancing pancreatic lesions are best detected in this phase. The portal venous phase allows in detection of venous involvement and hepatic metastasis. Delayed phase is typically not required in cystic masses.

FIG. 9.19.1 (A) Normal CT imaging protocol of pancreas – Nonenhanced image a showing normal pancreatic density. B. Postcontrast early arterial phase showing mild enhancement of pancreas. Pancreatic parenchymal phase (C) showing good enhancement of gland. It is this phase that’s provides the best pancreas/lesion contrast. Venous phase images (D) is acquired to diagnose venous involvement and detection of liver metastasis. TABLE 9.19.3 MRI Protocol • T2-weighted single-shot fast spin-echo with and without fat suppression • T1-weighted in-phase and opposed-phase gradient echo • T2W1 MRCP • Diffusion-weighted imaging • Post contrast protocol includes dynamic three-dimensional T1-weighted fat-suppressed spoiled gradient-echo (in arterial, pancreatic and portal venous phases) MDCT has an accuracy of 56%–85% for characterization of cystic pancreatic lesions. MRI MR imaging affords the best noninvasive means for the evaluation of cystic lesions of the pancreas due to superior soft tissue resolution. The helpful distinguishing characteristics of cystic pancreatic lesions, morphology of septae, relation to pancreatic duct are easier to detect at MR imaging and MR cholangiopancreatography (MRCP) than at CT (Table 9.19.4).

Studies however indicate that MDCT and MRI are comparable in identifying malignant behaviour of cystic pancreatic lesions. TABLE 9.19.4 Advantages of MRI Over CT in Cystic Pancreatic Masses • Better delineation of cyst fluid content • Identification of internal septations and mural nodules is superior • Relationship between the cystic neoplasm and pancreatic duct is better demonstrated The MRI protocol for evaluation of cystic lesions of pancreas includes T2weighted single-shot fast spin-echo, T1-weighted in-phase and opposed-phase gradient echo, diffusion-weighted imaging, T2-weighted fat-suppressed fast spin-echo. Three-dimensional T1-weighted fat-suppressed spoiled gradientecho T2-weighted MRCP. Postcontrast protocol includes dynamic threedimensional T1-weighted fat-suppressed spoiled gradient-echo (in arterial, pancreatic and portal venous phases) (Fig. 9.19.2, Table 9.19.3).

FIG. 9.19.2 Normal precontrast MRI protocol of pancreas. TW1 T2W1 image (A) showing normal pancreas appearing isointense to liver. T1W1 image (B) showing pancreas as the most hyperintense structure in the abdomen. Other sequences include T1 in- and opposed-phase (C and D), diffusion (E) and MRCP (F). Postcontrast protocols are similar to MDCT. DWI has not found much utility in cystic neoplasms owing to overlap in ADC values. Some studies suggest role in distinguishing malignant from benign tumours in the case of mucinous cystadenoma and IPMN.

Secretin-enhanced MRI Secretin is a peptide hormone produced in the intestinal mucosa, which stimulates the secretion of bicarbonate-rich fluid into the pancreatic ducts and transiently increases the tone of the sphincter of Oddi. The increased fluid distention of the pancreatic duct allows better study of ductal anatomy and identifying communication of pancreatic cystic lesions with the pancreatic duct. EUS EUS is excellent in characterization of cystic lesions of pancreas. The proximity between the transducer and the lesions allows precise definition of the structural component of the cysts and components such as

small mural nodules are better visualized with EUS than with other modalities. The other advantage of EUS is that cysts fluid aspiration and cytology can be performed. Tumour markers, genetic markers can be evaluated in the aspirated fluid. This allows comprehensive evaluation of cystic lesion. EUS also has therapeutic advantages allowing endoscopic draining of pseudocysts. Recently endoscopic ablation of cysts has been performed. These advantages have led to increasing use of EUS in recent years. This modality is however not indicated in all lesions and imaging should be able to stratify lesions requiring further invasive investigations. PET CT Studies have found PET CT comparable to PET alone or CT to determine presence of malignancy in cystic lesions. False positive findings may however be problematic. There is however no consensus for routinely using PET CT in characterization of cystic pancreatic masses. Serum tumour markers Serum CA19-9 and CEA are routinely done in all pancreatic masses. Though role in cystic lesions is still controversial.

Serous cystadenoma Serous cystadenoma is a benign neoplasm composed of glycogenrich epithelial cells that form innumerable small thin-walled cysts containing serous fluid. It is the prototype microcystic pancreatic neoplasm. They occur frequently in older women (median age, 65 years) and is also called as grandmother lesion. Location Approximately 40% of pancreatic serous cystadenoma arise from the pancreatic head and uncinate process and 60% arise from the pancreatic body and tail. Clinical features Serous cystadenomas are usually discovered incidentally at imaging; however, those that are large may cause symptoms. Patients may present with abdominal pain, palpable mass, anorexia, fatigue/malaise, or weight loss. Rarely the patient may present with jaundice. Genetics Genetic alterations similar to those in VHL are seen in sporadic SCA and include tumour suppressor gene VHL mutations and overexpression of vascular endothelial growth factor (VEGF). Allelic loss in chromosome 3 have seen in up to 40% cases of sporadic SCA. Histopathology Gross appearance Serous cystadenomas are variable in size. The size ranges from 2 cm in size, giving it a macrocystic appearance (Fig. 9.19.4). These lesions also lack the central stellate scar, classic of the microcystic variant Owing to macrocystic appearance these often need to be differentiated form mucinous cystic neoplasm or IPMN. Distinguishing features that aids in diagnosis includes presence of external lobulations and absence of ductal dilatation. • Solid pattern: Rare cases of solid variant of serous cystadenoma have been described. These serous cystadenomas do not contain any cystic spaces on histopathology. • Aggressive behaviour of atypical serous cystadenomas: Aggressive features like direct invasion into large blood vessels, nerves, lymph nodes can be seen in a small subset. These however resemble typical serous cystadenomas on histology lacking cytological atypia.

FIG. 9.19.3 Classic shapes of serous cystadenoma. A. Classic lobulated appearance with microcystic appearance. B. depicts the central stellate scar.

FIG. 9.19.4 Appearance of oligocystic variety. This variety lacks the tiny innumerable cysts seen in the microcystic variety and is comprised of fewer larger cysts. Imaging appearance Ultrasound On USG the microcystic variant shows lobulated contour with multiple tiny anechoic cysts separated by septae. the central scar containing calcification can be seen if present. Extremely microcystic, honeycomb variant may resemble a solid lesion at conventional US. The macrocystic type, can be mixed type with multiple large (>20 mm) and small cysts, and the unilocular type, which is more difficult to differentiate from mucinous cystadenoma (MCA). Contrast-enhanced US Enhancement of the intralesional sepatations is seen on contrast-enhanced USG allowing better characterization of the lesion. The central scar can show homogenous enhancement. Honeycomb variety appears as a hypervascular lesion owing to its extremely microcystic morphology and may resemble solid masses like neuroendocrine tumours. CT

Pancreatic serous cystadenoma can have a varied appearance on CT depending on the morphologic patterns. Serous cystadenomas are typically solitary but may be multiple in von Hippel–Lindau disease, causing an appearance of disseminated involvement (Table 9.19.5). TABLE 9.19.5 CT Features of Serous Cystadenoma • Lobulated lesions with multiple small cysts >6 in number and 2 cm) cysts. Imaging Features include a lobulated contour, lack of a prominent thickened peripheral wall, and location in the head of the pancreas (Fig. 9.19.7).

FIG. 9.19.7 Oligocystic variety of serous cystadenoma. Contrast-enhanced CT showing well-defined lobulated lesion in head of pancreas with thin internal sepate. Not absence of microcysts within the lesion. MRI features Owing to its supreme soft tissue resolution, MRI is the modality of choice in diagnosis of serous cystadenomas. The classic MRI features of microcystic variant includes a lobulated lesion with multiple small T2 hyperintense and T1 hypointense cysts with intervening hypointense fibrous sepate. These lesions do not communicate with the pancreatic duct; hence no dilatation is usually seen. Dilatation of pancreatic duct has however been reported in larger lesions. After the administration of

gadolinium, the hypervascularization of the central scar and of internal septa may be seen. The morphology of the honeycomb pattern may also be better depicted on MRI. Multiple tiny T2 hyperintense cysts with intervening hypointense septae are seen (Fig. 9.19.8).

FIG. 9.19.8 MRI in classic serous cystadenoma. T2W1 axial images (A and B) showing a well-defined lobulated lesion in the pancreatic head composed of multiple tiny cysts T2W1 coronal image (C) showing central hypointense dot representing calcification (arrow). Note the duct (yellow arrow) causing posterior to the lesion without upstream dilatation. The oligocystic variant shows fewer larger T2 hyperintense and T1 hypointense cysts and can mimic mucinous cystadenoma. However, the lobulated contour, together with the absence of wall enhancement and a wall thickness less than 2 mm, suggest the correct diagnosis (Fig. 9.19.9) (Table 9.19.6).

FIG. 9.19.9 MRI showing combined oligocystic and microcystic serous cystadenoma. T2W1 axial images (A and B) showing well-defined lobulated lesion in the pancreatic head with multiple large and microcysts (blue and yellow arrow). Post contrast images (C) and (D) showing enhancement of septae within the microcystic portion. TABLE 9.19.6 MR Features of Serous Cystadenoma • Cysts appear hyperintense, surrounded by hypointense septa and sometimes with a hypointense central scar • Enhancement of septae and scar on contrast-enhanced images • No ductal dilatation or communication • Oligocystic variant shows lobulated contour, absence of enhancement and wall thickness less than 2 mm

Atypical imaging appearance 1. Giant serous cystadenoma with ductal dilatation: Giant cystadenoma are lesions larger than 10 cm in diameter. These tumours may present with complications such as rupture, compression and invasion of adjacent structures like bile ducts and postoperative recurrences. Lesions may present with pain, obstructive jaundice and often require treatment (Fig. 9.19.10). 2. Serous cystadenoma with haemorrhage: Rarely intratumoural haemorrhage has been reported in serous cystadenomas. This leads to heterogeneous appearance on imaging with haemorrhage, necrosis and cystic degeneration. These lesions may be difficult to differentiate from islet cell tumour and solid cystic papillary epithelial neoplasm (SPEN). (image) 3. Disseminated variant: Disseminated SCA have been described in setting of Von Hippel-Lindau disease. Fifty-six per cent cases with VHL syndrome have pancreatic lesions, which include cysts, serous cystadenomas and islet cell tumours. The lesions when present in combination lead to diffuse involvement with heterogeneous appearance of pancreas. 4. Solid Variant: There are few case reports in the literature of solid serous adenoma of the pancreas, a rare variant of serous cystadenoma. It is formed by the cells that line the cysts of other forms of serous cystadenoma but with an absence of any cystic spaces on histopathology. It has been reported on CT as having the appearance of an enhancing solid pancreatic mass.

FIG. 9.19.10 Giant cystadenoma with atypical features: contrast-enhanced CT showing a large combined micro and oligocystic serous cystadenoma in the pancreatic head with enhancing septae (blue arrow). Note the compression over the common bile duct with resultant biliary dilatation (yellow arrow in A and B). There is additionally compression over the pancreatic duct which is also dilated with distal glandular atrophy (blue arrow in A and B). Differential diagnosis The differential diagnosis of serous cystadenoma depends on the variety and are listed in Tables 9.19.7 and 9.19.8.

TABLE 9.19.7 Honeycomb Pattern Serous Cystadenoma Lobulated contour Multiple tiny cysts giving a sponge like appearance

Neuroendocrine Tumour Presence of hypervascular halo Centre may be necrotic

SPEN Presence of haemorrhage Thick enhancing capsule

TABLE 9.19.8 Oligocystic Variant Serous Pseudocyst Cystadenoma Lobulated Smooth contour external contour No Peripancreatic enhancing stranding septae or wall No calcification in this variant

Clinical history of pancreatitis

Mucinous Cystic IPMN Neoplasm Smooth external contour Pleomorphic and tubular external contour Relatively thick Communication enhancing wall, with main septations and mural pancreatic duct or nodule in the case of side-branch malignancy Peripheral calcifications Thick internal septations and nodularity suggestive of malignancy

Role for cyst fluid analysis Lesions with classic imaging features do not require further investigation or fluid analysis. The fluid in classic cystadenomas is yellow in colour and does not show elevated amylase, mucin or tumour markers. Approximately 20%–50% cases show cytological positivity for periodic acid-Schiff and cytokeratin AE1 and 3. Hemosiderin laden macrophages also do not have high diagnostic accuracy and are seen in only about 43% cases.

Management Current management guidelines suggest (Table 9.19.9). • If cystic lesion reveals classical imaging features of serous cystadenoma – no further investigations/fluid aspiration is needed • Size is no longer a criteria to decide treatment or resection • Resection is reserved only for truly symptomatic lesions

TABLE 9.19.9 Management Algorithm of Cystic Pancreatic Masses – Tanaka Guidelines

Surgery Resection involves distal pancreatectomy or Whipples, depending on location of the tumours and is currently reserved for truly symptomatic cases.

Mucinous cystadenoma Mucinous cystic tumours are a rare subset of cystic neoplasms, constituting approximately 2.5% of pancreatic exocrine tumours.

TABLE 9.19.10 Serous Cystadenoma – Pearls • Lobulated microcytic lesions • Less common variants include honeycomb, oligocystic, solid pattern • Common in older women, 60% occur in tail. • On imaging-lobulated lesions with multiple small cysts >6 in number and 5 mm without other cause for obstruction 5–9 mm: ‘worrisome feature’ ≥10 mm: ‘high-risk stigmata’ • Mixed-type IPMN: appears like an advanced branch-duct IPMN with main pancreatic duct dilatation (>5 mm) Higher frequency of malignancy, similar to the main-duct type

FIG. 9.19.17 Types of IPMN. A. Branch-duct type. B. Main-duct IPMN. C. Focal main-duct IPMN. D. combined main and branch-duct type. Main-duct IPMNs have been associated with higher histological grade and more rapid growth compared to branch-duct lesions.

The risk of developing high-grade dysplasia or invasive carcinoma within 5 years is 63% for main pancreatic duct IPMNs and 15% for branch-duct IPMNs.

Location IPMN particularly branch chain variety arises from uncinate process of pancreas in 70% cases, however can occur anywhere in pancreas. In 5%–10% of cases, IPMNs involve the entire pancreas. Presence of multiple lesions favours diagnosis of IPMN as this finding is not common in other cystic neoplasms.

Clinical features Symptoms for IPMN are vague and often nonspecific. Twenty-seven to forty per cent of patients with small (≤3 cm) lesions are asymptomatic. Common symptom is abdominal pain which may be the result of gradual distension of the pancreatic duct caused by excess mucin secretion. Patients with main-duct IPMN can present with pancreatitis. Those with malignant IPMN may present with features of pancreatic insufficiency like diabetes, steatorrhoea similar to chronic pancreatitis or with weight loss and recent onset jaundice similar to ductal adenocarcinoma. Uncommon presentations of IPMNs include invasion or fistulation of adjacent structures such as bowel loops or common bile duct, and rarely intraabdominal perforation resulting in pseudomyxoma peritonei.

Imaging USG On USG main-duct IPMN appears as pancreatic ductal dilatation. Branch-duct lesions appear as a well-defined pleomorphic cystic lesion. Ductal communication is usually not demonstrated and additional imaging with CT or MRI is required.

Main-duct IPMN CT Diffuse or segmental dilatation of the main duct is the commonly seen finding. Ductal filling defects representing papillary tumor, mural nodules, or mucin globule may be seen. Since the projections tend to be flat they are often not detected on CT. Enhancement is generally only appreciated in lesions containing nodular foci (Fig. 9.19.18).

FIG. 9.19.18 CT in main-duct IPMN. Dilatation of the MPD more than 5 mm in the absence of history of pancreatitis or any other plausible aetiology is the typical imaging feature. Presence of solid components, thick sepate and irregular wall thickening suggest malignancy. Solid components or mass in an IPMN are highly suggestive of invasive carcinoma, while mural nodules suggest carcinoma in situ (Figs. 9.19.19 and 9.19.20).

FIG. 9.19.19 Contrast-enhanced CT in malignant mainduct IPMN. Axial images (A, B, F) and coronal images g showing dilated main duct with gross glandular atrophy (arrows). Multiple mural nodules are seen within the dilated duct (yellow arrows). Solid component is seen in region of head, arrows in D and E.

FIG. 9.19.20 Malignant IPMN CT. Contrast-enhanced CT (A–E) showing diffuse grossly distended pancreatic duct with enhancing solid component (yellow arrow) with multiple metastatic lesions in liver (blue arrows). MRI

Diffuse or segmental dilatation of the main pancreatic duct (5 mm or greater as per international consensus guidelines) without identifiable obstructive lesion is the characteristic feature of main-duct lesions on MRI. Bulging of the duodenal papilla into the lumen of duodenum is a characteristic feature of diffuse form of IPMNParenchymal atrophy may be present depending on the severity of main-duct IPMNs. Main-duct IPMNs may thus resemble or even coincide with chronic pancreatitis. Segmental type may show focally dilated main duct and may mimic other cystic neoplasms. In cases with frank invasive carcinoma features of malignancy like vascular invasion, lymphadenopathy and metastatic disease is seen.

Branch-duct IPMN CT Branch-duct IPMNs are seen as unilocular or multilocular cystic dilatation of side branches. This lesion is most commonly seen in the uncinate process of pancreas (Fig. 9.19.21). The appearance and configuration of the cysts may be variable. In the case of malignant lesions, solid enhancing component may be identified. Lesions more than 3 cm in size are associated with higher risk of malignancy. Coronal and curved reformatted CT images may show dilated duct and ductal communication. MRI with MRCP is however superior in showing ductal relation.

FIG. 9.19.21 CT in branch chain IPMN. Contrastenhanced CT (A–E) showing hypodense lobulated cystic lesion in the uncinate process with cysts of different configurations (arrows). MRI MRI is superior compared with CT in showing the connection of a cyst to the pancreatic duct.) Branch-duct lesions may have variable morphology depending on the number of side branches affected, that distend due to production of copious mucin. When one or two side ducts are involved a clubbed finger like lesional morphology is seen. Involvement of three or more cysts results in pleomorphic appearance (Fig. 9.19.22).

FIG. 9.19.22 MRI – branch chain IPMN. T2W1 image (A– C) and contrast-enhanced image (D) showing a well-defined lobulated cystic lesion in the uncinate process (arrows). The main pancreatic duct is not dilated. Note the multiplicity of the lesions (arrows in E), a feature favouring IPMN. The cysts are also of variable sizes and configurations. Lesions may thus be lobulated or round in appearance and the clue to diagnosis is establishing ductal communication. Contrast-enhanced scan can show septal enhancement and solid components. Secretin MRCP may aid in distinguishing a side branch IPMN from other cystic pancreatic lesions including main-duct IPMN and mucinous cystic neoplasms (Table 9.19.17).

Combined type Combined IPMNs show features of both branch-duct and main-duct IPMNs. Diffuse or segmental dilatation of main pancreatic duct along with one or more dilated side branches are seen (Figs. 9.19.23 and 9.19.24).

FIG. 9.19.23 CT combined main and branch IPMN. Contrast-enhanced CT (A –C) showing dilated main duct (blue arrows) with dilated side branches in the distal body and tail (yellow arrows).

FIG. 9.19.24 MRI with MRCP of combined main and branch-duct IPMN. Large pleomorphic cystic lesion in the pancreatic head with dilated main duct. Note the features of chronic pancreatitis in the distal gland in the form of atrophy and ductular dilatation. Image E shows bulging ampulla, a characteristic feature seen in main-duct IPMN. The International Association of Pancreatology published guidelines in 2012 (with minor update in 2017), regarding management of mucinous lesions. This guideline distinguishes between “high risk stigmata”, which mandate surgical resection and ‘worrisome features’, which require surveillance and endoscopic ultrasound evaluation. Both of these are however correlated with an increased risk of malignancy (Table 9.19.16).

TABLE 9.19.16 CT Features of IPMN • Dilatation of main duct >5 mm in diameter without history of pancreatitis. ductal involvement may be diffuse or segmental • Branch chain type may appear uni-or multilocular cystic dilatation of side branches and is most commonly seen in the uncinate process of pancreas • Malignant lesions may reveal solid enhancing components • Reformatted coronal images demonstrate ductal relation TABLE 9.19.17 MRI Features of IPMN • Dilatation of the main pancreatic duct >5 mm in a diffuse pattern or a segmental portion without an identifiable obstructive lesion or stenosis, seen in main-duct type. • Bulging duodenal papilla is diagnostic • Morphology of branch-duct IPMN is variable depending on number of side branches involved • Contrast-enhanced scan shows enhancement of septae, mural nodules Worrisome features in IPMN – tanaka guidelines (Table 9.19.21) • cyst ≥3 cm • thickened and enhancing cyst wall • enhancing mural nodule 7 mm and lesional size > 2.5 cm as high risk stigmata. Follow up protocol is also mentioned (Tables 9.19.22 and 9.19.23).

TABLE 9.19.22 ACR 2017 Guidelines for Management of BD – IPMN

TABLE 9.19.23 IPMN – Pearls • Commonest cystic neoplasm • Common in males, with peak incidence 60–70 years • Mucin secreting tumour • Main duct, branch duct and mixed type • Dilated main duct focally or segmentally, mural nodules may be seen in main-duct IPMN • Bulging papilla diagnostic in the case of main-duct IPMN • Branch-duct type can be variable in shape and show communication with branch duct • Patients with high risk features should undergo upfront surgery • Patients with worrisome features should be stratified with EUS

SPEN SPEN is a rare is usually a benign or a low-grade malignant tumour slowgrowing pancreatic neoplasm and occurs almost exclusively in women (85%), with most being found in younger women (mean age 25 years; age range 8–67 years). Previously these tumours were known by various names like Hamoudi tumour or Franz tumour.

Histology These tumours lack exocrine and endocrine differentiation and hence probably arise from primodial pancreatic stem cells. Histopathological analysis of SPNs varies with tumour size. Small SPNs show predominantly solid sheets of cells and degenerative changes. Solid, cystic and pseudopapillary components with intratumoural haemorrhage are seen in larger lesions. These lesions are solid when small and develop cystic and haemorrhagic degeneration as they enlarge. The cystic components are not true cysts represent a degenerative or necrotic process due to solid components outgrowing the blood supply. Similar to histopathology the imaging features of larger lesions are more typical with solid cystic appearance, while those in smaller lesions are those of homogenous enhancement, hence atypical (Fig. 9.19.27).

FIG. 9.19.27 Morphologic appearance of SPEN. Predominantly solid cyst with necrotic cystic areas.

Location The tumour reportedly arises in the pancreatic tail most commonly. This finding is however not consistent across case series. Some studies report equal incidence in head and tail. The lesion and has a tendency to displace structures rather than invading them.

Presentation The tumour is generally asymptomatic. Larger tumours cause compression over adjacent structures and are usually symptomatic. The average tumour size at presentation is 9.3 cm. These lesions usually displace surrounding vessels and nerves rather than invade them; however, encasement has been reported.

Imaging USG The lesion may appear as solid hypoechoic mass with well-defined margins. Larger tumours may be more heterogeneous due to areas of haemorrhage and cystic degeneration. In rare cases, an upstream dilated main duct could be

found if lesion is located in the pancreatic head. CEUS could show a heterogeneous pattern of enhancement in larger lesions and characteristic capsule rim enhancement due to the presence of a pseudocapsule of compressed normal pancreatic parenchyma. CT On nonenhanced scan the lesion appears hypodense but may show hyperdense areas representing haemorrhage. Peripheral calcification is present in up to 60% of cases, and central dystrophic calcifications may occur in areas of haemorrhage. On contrast study the lesion usually reveal heterogeneous enhancement pattern. Solid areas are usually located in the periphery while cystic regions are located centrally. The thick capsule and solid areas show gradual enhancement from pancreatic to venous phases, while the haemorrhagic, necrotic and cystic areas appear avascular. Smaller lesions are more homogenous and show arterial enhancement with fewer areas of necrosis (Fig. 9.19.28).

FIG. 9.19.28 Plain (A) and contrast-enhanced CT (B and C) showing a well-defined slightly hyperdense mass in pancreatic tail with heterogeneous enhancement pattern. The mass involves the splenic vein congruent with its locally aggressive nature. Combination of a central area of internal haemorrhage and cystic degeneration, and peripheral rim of solid components is considered hallmark Large SPEN can be locally invasive and hence MDCT plays an important role in surgical planning, particularly with respect to vascular involvement. The tumour may be adhered to or in rare cases encase both major arterial and veins. This information is critical prior to surgery for better planning and avoiding incomplete resection (Fig. 9.19.29) (Table 9.19.24).

FIG. 9.19.29 Locally invasive SPEN. Contrast-enhanced axial CT images (A–C) showing a well-defined solid cystic mass in the head of pancreas with exophytic extension. Reformatted images (D–F) showing encasement of CHA (yellow arrows) with anterior displacement of the portal vein with narrowing of confluence (blue arrows). TABLE 9.19.24 SPEN, CT Features • Lesion appears hypodense on plain scan but may show hyperdense areas representing haemorrhage • Calcification central or peripheral can be seen • Solid areas are located at the periphery and show heterogeneous enhancement • Combination of a central area of internal haemorrhage and cystic degeneration, and peripheral rim of solid components is considered hallmark MRI Overall MRI is better in diagnosing the lesion and identifying characteristic, particularly in small lesions (Fig. 9.19.30).

FIG. 9.19.30 MRI in SPEN. T2W1 images (A and B) showing well-defined homogenously hyperintense lesion in the pancreatic body. The lesion appears hypointense to gland on T1W1 images (C). Lesion shows mild homogenous enhancement (D and E) with diffusion restriction. MRI scores over CT in identifying intratumoural haemorrhage. Areas of haemorrhage show signal depending on stage of blood products. In the late subacute stage haemorrhagic are hyperintesne on T1W1 images, while in the chronic phase these areas show hypointense signal on both T1 and T2W1 images. Fluid-fluid level or blood flow level is seen in 10%–20% cases. After contrast administration, the solid (peripheral) components of SPENs show heterogeneous enhancement during the arterial phase and progressive enhancement in the portal and delayed phase. A key diagnostic finding of is the presence of a fibrous capsule that encompasses and surrounds the tumour (image). The cystic and necrotic components do not enhance. Rarely distal ductal dilatation and glandular atrophy can be seen. Signs of location invasive can be accurately diagnosed on post contrast images (Fig. 9.19.31) (Table 9.19.25).

FIG. 9.19.31 MRI showing Large SPEN. T2W1 images (A– D) showing a well-defined solid cystic mass in pancreatic head (arrows). T1W1 images (E) shows intratumoural haemorrhage (arrows). Diffusion weighted images (F) showing restriction with mass due to solid contents and haemorrhage. Note the aggressive nature of the lesion with flattening of the confluence and abutment of the SMV (yellow arrows). TABLE 9.19.25 MR Features of SPEN • Haemorrhage is best seen on MRI • Solid (peripheral) components of SPENs show heterogeneous enhancement during the arterial phase and progressive enhancement in the portal and delayed phase • Presence of a fibrous capsule diagnostic

Malignancy in SPEN SPEN is considered as a benign albeit locally invasive lesion. Malignant behaviour occurs in 10 to 15% of cases. Age >40 years and male gender are more commonly associated with malignancy. Distant metastases develop in up to 15% of cases. They are most commonly present at diagnosis but can develop with a latency of several years even after primary resection. Common sites for metastatic disease are the liver, omentum, peritoneum and lymph node. However if diagnosed and resected they have a 5 year survival of 96% (Fig. 9.19.32).

FIG. 9.19.32 Malignant change in SPEN with liver metastasis. Contrast-enhanced CT in a patient with history of surgery for SPEN in head 2 years ago, shows a welldefined enhancing lesion in segment 8 of liver, which was not previously seen (arrows). Heterogeneously enhancing recurrent mass also noted in pancreatic head (arrows). Imaging features suggesting malignant change include pancreatic duct dilation vessel encasement and Local invasion of the peripancreatic tissue. These features can however be seen in large benign tumours as well and hence the only radiologically definite sign of malignancy is distant metastatic disease. D/D The differential diagnosis of SPEN depends on the size. Smaller tumours are solid and show homogenous enhancement mimicking neuroendocrine tumours (Table 9.19.26). TABLE 9.19.26 Differentiation Between SPEN and Neuroendocrine Tumours SPEN Seen in younger patients

Neuroendocrine Tumours Rarely seen younger than 30 years Haemorrhagic areas may be seen on imaging No haemorrhage is seen Early arterial enhancement which progresses Early arterial enhancement in in venous and delayed phase. Peripheral either a diffuse or ring-like enhancing capsule seen. enhancement pattern Larger tumours have variable solid cystic component and require differentiation from mucinous cystadenoma and rarely ductal adenocarcinoma.

Role of preoperative biopsy (Table 9.19.27)

TABLE 9.19.27 Differentiation Between SPEN, Mucinous Adenocarcinoma and Adenocarcinoma Mucinous Adenocarcinoma Cystadenoma/Adenocarcinoma Seen in younger Common in middle aged patients Seen in middle patients aged and older patients with no gender predilection for females Haemorrhage Haemorrhage rare No haemorrhage common seen Solid cysts masses Septated cystic masses. Solid Hypovascular with areas of component in malignant cases masses arterial usually seen as small nodules along hyperenhancement wall or septae Ductal dilatation Ductal dilatation rare Ductal dilatation rare almost always present Local invasion in Local invasion occurs in malignant Local invasive large masses cases features common SPEN

Preoperative biopsy is not necessary in most cases. Radiological finding of large solid cystic mass in young female are usually diagnostic.

Treatment Treatment is usually surgical resection. Surgery depends on location of tumour. Vascular reconstruction may be needed in cases with vessel wall involvement. There is a role of postoperative radiotherapy in patients with incomplete resection.

Management protocols in cystic pancreatic neoplams Cysts 5 mm in size, a pancreatic protocol CT or contrast-enhanced MRI with MRCP is recommended (Table 9.19.29). TABLE 9.19.29 Cystic Pancreatic Masses – Summary of Management and Follow-Up Algorithms – International Consensus Guidelines

Serous cystadenoma Classical imaging features – no further investigations

No treatment, size is no longer a criteria Resection for truly symptomatic lesions

Resection recommended for All main-duct IPMNs All other IPMNs with high-risk stigmata All mucinous cystic neoplasms

EUS Cysts with worrisome features All cysts ≥3 cm without worrisome features • if inconclusive, then close surveillance with alternating MRI and EUS every 3–6 months • strongly consider surgery in young patients

Follow-up • Largest cyst 55 years), due to the fact that the success rate is superior in younger individuals. Key components of the assessment include determining the presence of renal, cardiac, peripheral vascular, cerebro-vascular and psychiatric diseases. The pretransplant work-up consists of extensive laboratory, infectious and physiologic testing. Chest radiography is required for preoperative fitness of recipient. The extent of aorto-iliac calcification of recipients, a factor in choice of implant site, is evaluated with unenhanced CT.

Assessment, procurement and implantation of the pancreatic graft for transplantation Assessment Donor factors such as age, sex, body mass index, cause of death, donation after cardiac death, serum creatinine and preservation time (cold ischaemia) can influence the outcome of pancreas transplantation. Usually, evaluation of donor pancreas is best done by the pancreatic transplant surgeon intraoperatively. Visual inspection of pancreas in terms of its size, texture, colour, fibrosis, fatty infiltration and its vascular supply is essential. There is very little role for preoperative imaging in the setting of deceased organ donation. Procurement and implantation The donor’s pancreas is harvested en bloc with its respective vascular support and a variable duodenal segment that contains the ampulla of Vater. The most common technique consists placing the pancreatic graft intraperitoneally in the right pelvic region with the duodenal segment facing cephalad and the renal graft in the left iliac fossa, extraperitoneally. Whole pancreatic graft transplantation can be performed with a duodenal segment; in this type of transplantation, donor’s duodenum is anastomosed with the recipient’s small bowel loop for enteric exocrine drainage and grafted portal vein is anastomosed with common iliac vein or inferior vena cava for systemic endocrine drainage (Fig. 9.20.1). Another way of restoring the endocrine drainage, grafted portal vein may be anastomosed with the recipient’s portal venous system and for exocrine drainage duodenal segment may be anastomosed with the urinary bladder. Duodenoenterostomy done by side to side anastomosis of donor’s duodenal segment to the recipient’s small bowel loop. Arterial supply is established by using the donor’s aortic patch, containing the splenic artery and the superior mesenteric artery (SMA), which

is anastomosed to the recipient’s common or external iliac artery. Native pancreas of patient is left untouched in the upper abdomen.

FIG. 9.20.1 Illustration of the pancreas transplantation technique. Duodenoenterostomy for exocrine drainage and systemic endocrine drainage. Recipients common iliac artery is anastomosed with the donor’s aortic patch (dAP) along with the origin of the superior mesenteric artery (dSMA) and the splenic artery (dSA); the donor’s portal vein (dPV) is anastomosed to the recipient’s common iliac vein. PG – pancreatic graft, dD – donor’s duodenum, rSmall bowel – recipient small bowel, IVC – inferior vena cava, A – aorta.

Intraoperative imaging of pancreatic graft

After placement of pancreatic graft by surgeon, pancreatic graft Doppler evaluation should be done intraoperatively. Intraoperative ultrasound probe is directly put on anastomotic artery and vein which show normal colour flow without evidence of thrombosis. In the case of occlusion, there is no evidence of colour flow. In the case of occlusion, surgeon does re-anastomosis of vessels once thrombi are removed. Due to its superficial location in pelvis and visualization of pulsation of vessels, visual inspection is sufficient for patency of vessels. So most of the time intra-operative Doppler study is not necessary.

Posttransplant pancreatic graft imaging Postoperative imaging of pancreas transplantation is a challenge for the radiologist because of the altered surgical anatomy, identifying the pancreatic graft from adjacent structures and various postoperative complications that may arise posttransplantation. Imaging evaluation of the pancreas transplant grafts is commonly performed by a multitechnique approach. The most commonly utilized scanning techniques include US, CT and MR imaging. DSA and radionuclide study are routinely not performed nowadays.

Ultrasound Ultrasound usually represents the first line imaging method in the assessment of the pancreatic graft, due to its portability, repeatability for ill and unstable patients in the immediate postoperative period, lack of ionizing radiation, and it provides a real-time vascular flow map which may allow detection of vascular anastomotic stenosis and reduced pancreatic graft perfusion. Its evaluation may, however, be limited due to the intraperitoneal position of the pancreas graft, in particular with the portal enteric approach with the organ in the right upper abdomen and intestinal gas overlap. Unless abnormally dilated, the duodenal component often cannot be separately evaluated by ultrasound. Additionally, ultrasound may be fundamental in guiding the percutaneous biopsy. Although the lack of an organ capsule generally results in an ill-defined appearance, the pancreatic transplant can be identified by its relatively cylindrical shape. In greyscale B-mode, the normal pancreatic graft presents homogeneous echotexture, lower than the native pancreas and the surrounding mesenteric or epiploic fatty tissue (Fig. 9.20.2). Colour and power Doppler US play a vital role in demonstrating pancreas transplant perfusion and vascular anatomy. We would also be able to visualize the Y arterial graft, graft vein, splenic artery and vein (Fig. 9.20.3A and B). Venous structures demonstrate a monophasic waveform within an anechoic lumen and velocities ranging between 10 and 60 cm/s. Normal arterial waveform exhibits a sharp systolic upstroke and a continuous diastolic flow. In the immediate postoperative period, the velocities of the arterial anastomosis may be very high as 400 cm/s due to possible postoperative oedema and/or due to kinking of the anastomosis. Usually in both the cases, the arterial anastomotic velocities gradually decrease on in follow-up. The resistive index (RI) may be of limited use to diagnose graft rejection, as the values may be as high as 0.9 and are variable throughout the gland. Due to the presence of renal capsule in a transplanted kidney, there is elevated vascular resistance when there is intrarenal oedema; however, due to the absence of capsule in the transplanted pancreas, the vascular resistance will be normal in spite of oedema secondary to pancreatitis or rejection.

FIG. 9.20.2 Normal USG appearance of a pancreas transplant; longitudinal greyscale image of the head (HOP), body (BOP), and tail (TOP) of a pancreas allograft shows a welldefined, homogeneous hypoechoic structure.

FIG. 9.20.3 A: Colour Doppler image of the vascular pedicle demonstrates flow within the patent donor Y-graft artery (curved arrow), bifurcating into the splenic artery (straight arrow) and SMA (arrowhead). B: Colour Doppler image of venous drainage of the pancreas transplant demonstrating the confluence of the donor splenic vein (straight arrow) and donor superior mesenteric vein (white arrowhead) to form the portal vein (curved arrow).

Computed tomography CT is generally required after an abnormal ultrasound or whenever the patient presents unexplained fever, abdominal pain or when

abnormal laboratory data are found. Contrast-enhanced CT helps to evaluate the graft parenchyma, the enteric and vascular anastomosis and in diagnosing postoperative complications such as focal collections, vascular thrombosis or pneumoperitoneum. In noncontrast CT scan, pancreatic graft appears as a homogeneous isodense soft tissue organ. It is more difficult to differentiate between pancreatic graft and nonopacified and nondistended small bowel loop in plain/noncontrast CT scan. But you can always make out the surgical clips which are stapled on duodenal stump, which can be helpful for localization of pancreatic graft. Nonenhanced images should be acquired with the goal of locating the graft and possible early thrombus or haematoma. The protocol used should include (positive) enteric contrast that allows identification of intestinal loops adjacent to the graft and distinction from possible liquid collections (Fig. 9.20.4A). The donor’s duodenum is frequently collapsed and may fill (or not) with the given oral contrast. IV contrast material is administered infrequently, to avoid the risk of nephrotoxicity, if native renal function is impaired. About 120–150 mL of contrast medium greater than 350 mg iodine per millilitre is injected at the rate of 4– 6 mL/s. Late arterial phase can be obtained with the bolus-tracking technique located in the common iliac artery (attenuation value of 150 HU) and is very useful in the assessment of parenchymal enhancement and arterial anastomosis; 50 seconds after the administration of intravenous contrast material, the portal venous phase evaluates the respective drainage and possible associated venous complications (Fig. 9.20.4B). CT images are evaluated by axial, multiplanar reformats and three-dimensional maximum intensity projection (MIP) and volume-rendered techniques. The normal pancreatic parenchyma will enhance uniformly more in the arterial phase than in the venous phase. The iliac arterial graft, peripancreatic and intrapancreatic arterial vasculature, as well as the anastomosis of the donor portal vein to the recipient iliac or superior mesenteric vein, should be delineated. Coronal reformats are the best to illustrate the intestinal anastomosis and to determine if the graft is placed inferiorly for a systemic venous drainage or superiorly for a portal venous drainage.

FIG. 9.20.4 A: Coronal unenhanced maximum intensity projection CT image shows the duodenal stump (*) distended with contrast and the surgical staple lines (arrows) along it. The pancreas transplant (arrowhead) is clearly visible. Extensive aortic and iliac arterial calcification are also noted. B: Coronal

reformatted MDCT image shows homogeneous enhancement of the pancreatic (white asterisk) and renal grafts (black asterisk) after SPK transplantation. The pancreas is placed laterally in the pelvis, on the right side, with the attached donor’s duodenal segment facing cephalad (black arrowhead), which anastomoses to the recipient’s jejunum. Surgical staples are present at the extremities of the duodenal segment (white arrows).

Magnetic resonance imaging and magnetic resonance angiography MR is usually indicated in young patients in which cumulative radiation is an essential consideration. Contrast-enhanced MR angiography is used for evaluating the arterial and venous anatomy of pancreatic graft; however, it is difficult to access the enteric anastomosis and postoperative complications due to low spatial resolution. Also, it is a challenge to image sick patients requiring intense monitoring and those with metallic clips. An appropriate protocol includes axial T1-weighted (T1WI) (precontrast; in-phase and out-of-phase), coronal T2-weighted (T2WI) fast-spin-echo and axial T2-weighted fat-suppressed sequences. Furthermore, images after intravenous contrast administration (gadolinium-based) should be acquired in arterial and venous phases. Unenhanced MR imaging readily helps distinguish the pancreatic allograft from adjacent structures and is superior to CT without intravenous contrast material. In plain MRI of abdomen, pancreatic graft appears hyperintense as compared to liver and appears as homogenous structure on T1-weighted images. Normal pancreatic graft’s signal intensity is between that of fluid and muscle on T2-weighted images. Various pathologic process of graft pancreas is more related to increased glandular water content, so T2-weighted images are more sensitive to diagnose graft pathology (Fig. 9.20.5A). Axial and coronal images are useful in displaying pancreatic and peripancreatic graft oedema, as occurs in pancreatitis, and in characterizing peritransplant fluid collections (haematoma/seroma). The MR angiography helps to access the arterial and venous anatomy and can diagnose arterial or venous stenosis and venous thrombosis. The normal pancreas graft enhances briskly and homogeneously in the late arterial phase (Fig. 9.20.5B). Gadolinium-based contrast agents may pose the risk of

nephrogenic systemic fibrosis in selected patients with advanced renal dysfunction. The normal pancreatic duct is generally not visible with US or CT but may be observed as a thin (≤3 mm) smooth line on T2W MRI.

FIG. 9.20.5 A: Coronal T2-weighted MR image shows a pancreas transplant (arrow), which has signal intensity between that of muscle and fluid. A nondilated segment of pancreatic duct is visible (arrowhead). B:

Coronal postcontrast dynamic image shows normal enhancement of a pancreas transplant (arrowhead) with portal venous-enteric drainage. Normally enhancing renal transplant (arrow) is seen.

Angiography Angiography primarily used to confirm or clarify suspected vascular thrombosis, anastomotic stricture, or pseudoaneurysm detected by other imaging techniques. Both intraarterial and IV digital subtraction techniques can be used to evaluate graft vasculature or when endovascular therapy (venous thrombectomy, stent placement, venous thrombolysis, real-time fluoroscopy) is sought.

Radionuclide study Several scintigraphic techniques can be used to differentiate normal from abnormal pancreas grafts. 99mTc-sulphur colloid, 111lnlabelled platelets and 99mTc-DTPA have some value in differentiating rejection from other pathologic changes in the graft. 99mTc-DTPA is used frequently to study pancreas transplants because it can be used for perfusion studies and because study of coexisting renal transplants frequently is needed. PO INT S T O R E ME MB E R • Ultrasound is first line imaging method – due to its portability, repeatability for ill and unstable patients in the immediate postoperative period, lack of ionizing radiation • Colour and power Doppler US – provides a real-time vascular flow map, demonstrate pancreas transplant perfusion and vascular anatomy; the Y arterial graft, graft vein and splenic artery and vein • Contrast-enhanced computed tomography (CECT) – excellent evaluation of the graft’s parenchyma, vascular and enteric anastomosis and detects several postoperative complications • Magnetic resonance imaging (MRI) and MR angiography – rarely used for examination of pancreatic graft-related complications because of its lower spatial resolution, creating difficulties in the assessment of the enteric anastomosis

• Angiography – primarily used to confirm or clarify suspected vascular thrombosis, anastomotic stricture or pseudoaneurysm detected by other imaging techniques • Radionuclide study – 99mTc-DTPA is used frequently to study pancreas transplants and study of coexisting renal transplants

Imaging of pancreas transplant complications Postoperative complications can be categorized as early or late, with most early complications being surgical or technical. Primary technical failure occurs in 8% of cases. Minimal perigraft fluid collection, donor’s duodenal wall thickening, peripancreatic fat stranding or mild pancreatic duct dilation are some of the immediate posttransplant complications. These imaging findings are usually self-limited, normally seen to be resolving spontaneously on follow-up examinations. Surgical complications include anastomotic breakdown with bowel leak, haemorrhage, infection and vascular thrombosis. Nonsurgical complications are usually immunologic, with rejection being the single most common cause of graft loss. Primary nonfunction occurs in 0.5%–1% of cases and is defined by the exclusion of other causes of early graft failure. List of pancreas transplantation complications are:

Pancreas graft parenchymal complications Pancreatitis Most pancreatitis cases occur in the early postoperative period (5 weeks

Pain Anorexia Nausea Vomiting

Vascular damage/injury

Variable

Variable

Prophylactic coil embolization

Proton inhibito

MAA study Hold any systemic chemotherapy 3 weeks prior, including bevacizumab

Variabl

TARE is used in the treatment of patients with unresectable early, intermediate and advanced HCC for the purposes of bridging to liver transplantation, to downstage for transplant eligibility or for palliation. Compared to cTACE, TARE has been shown to provide a longer time to progression for unresectable HCC patients. Some evidence suggests radiation lobectomy/segmentectomy may be an alternative curative option for some HCC patients, despite surgical resection being considered the gold standard. TARE is also routinely used for patients with unresectable liver only or liver dominant metastatic colorectal cancer. Lastly, TARE has shown promise for other malignancies arising from within or metastatic to the liver, including intrahepatic cholangiocarcinoma, neuroendocrine tumours, ocular melanoma and breast cancer. Although 90Y is the prevailing radionuclide for the majority of TARE, several other radionuclides that have been developed for treatment of hepatic tumours which are summarized in Table 9.25.19. Of note, a unique advantage of 166-Ho is that it may be used as an MRI contrast agent by virtue of its paramagnetic properties.

TABLE 9.25.19 Properties of Radionuclides used for TA Therapy for Liver Tumours Radionuclide Decay

Primary Physical HalfProduction Life (hours) Method Reactor 64.2

Yttrium-90 (90Y)

β-

Iodine-131 (131I) Rhenium-188 (188Re)

β-, γ

192.5

Reactor

β-, γ

16.9

Generator

Radiopharmaceutical Formulation Glass or resin microsphere 131I-Lipiodol 188Re-Lipiodol 188Re-Human

Serum Albumin microsphere Holmium-166 (166Ho)

β-, γ

26.8

Reactor

166Ho-chitosan 166Ho-poly-L-lactic

acid loaded microsphere

Combinatorial therapy Over recent years considerable effort has turned towards combining TA therapies with other modalities to improve outcomes. To date, most of the clinical studies have focused on patients with HCC. Treatment of patients with sequential TA therapy followed by ablation has been performed. Investigators hypothesized that improved response rates may be achieved by performing complementary approaches. Limited small prospective studies in patients with unresectable HCC have demonstrated that TACE or DEB-TACE combined with radiofrequency ablation (RFA) appear to provide higher rates of treatment response than RFA alone. After clinical studies established sorafenib, a small molecule tyrosine kinase inhibitor, as an effective first-line treatment option for patients with advanced HCC, investigators focused efforts on combining sorafenib with TA therapy. Unfortunately, most clinical studies combining TACE plus sorafenib have failed to demonstrate benefit in HCC patient in terms of overall survival or progression-free survival. In two large trials studying patients with advanced HCC, sorafenib plus 90Y-TARE failed to provide an overall survival benefit. Other studies have been conducted evaluating the combination of stereotactic body radiation therapy (SBRT) combined with TACE. A retrospective investigation suggests SBRT followed by TACE may provide a survival advantage in patients with unresectable HCC. Other work has shown that TACE plus SBRT is more effective than SBRT alone in unresectable HCC patients. Lastly, many other trials are ongoing aimed at combining TACE and/or TARE with the other agents, such as the approved immune checkpoint inhibitors, including nivolumab or pembrolizumab (NCT04472767 and NCT04246177).

Future of transarterial therapy The future of TA therapy is as exciting as ever. Some of the newest innovations utilize targeted gene delivery, oncolytic viruses, immune modulation and nanoparticle formulations. Given many genes are somatically mutated in cancer, some investigators have focused efforts towards correction of such alterations in tumours. Alternatively, efforts have been directed toward restoration of normal signalling pathways in tumours. An example is the tumour suppressor gene TP53, which is frequently somatically mutated in HCC. Studies have evaluated cTACE plus the an adenovirus expressing wildtype TP53. Other efforts have focused on combining TA therapies with promising oncolytic viruses, most notably pexastimogene devacirepvec (Pexa – Vec).

9.26: Interventions in portal hypertension Amar Mukund, Shaleen Rana

Portal hypertension Portal hypertension (PH) is an inevitable complication of chronic liver disease. Chronic liver disease results in increased vascular resistance due to fibrosis and increased sinusoidal tone. Associated increase in portal flow is seen due to hyperdynamic circulation and expanded plasma volume which is a result of splanchnic vasodilatation and neoangiogenesis. Splanchnic vasodilatation further activates the vasoactive pathways secondary to systemic underfilling, resulting in ascites and renal derangement. As the portal pressure increases there is a transition from the subclinical to the clinical phase. Increasing portal pressure causes a gradient between the portal vein and inferior vena cava (IVC) known as the portal pressure gradient (PPG). The increasing gradient coupled with neoangiogenesis opens up portosystemic collaterals and formation of varices. The asymptomatic stage is called compensated cirrhosis (CC) or compensated advanced chronic liver disease. The patients with hepatic venous pressure gradient (HVPG) between 5 and 10 mm Hg are labelled as mild PH while those with HVPG >10 mm Hg are labelled as clinically significant portal hypertension (CSPH). The onset of CSPH is associated with various complications of PH. The causes of PH have been classified into (1) Prehepatic (portal, splenic or mesenteric vein thrombosis), (2) Intrahepatic (diseases like viral/alcoholic hepatitis) and (3) Posthepatic (Budd–Chiari syndrome). Complications of PH like ascites, encephalopathy and variceal bleeding increase the morbidity and mortality in patients with chronic liver disease and are directly proportional to the increasing portal pressure. Early recognition and diagnosis of PH and its types can help to prevent development of complications in an asymptomatic patient and to treat the complications in a symptomatic patient.

Assessment of portal hypertension

Clinical examination Subclinical PH usually has no positive signs on examination. Presence of splenomegaly, abdominal wall collaterals, ascites and spider naevi suggest advanced disease. Laboratory investigations Various parameters like albumin, international normalized ratio (INR), platelets and liver function tests have been used in various combinations (Fibroindex, AST – platelet ratio index and Fibrosis – 4) and attempts have been made to correlate with progression of fibrosis and PH with reasonable degree of success. Imaging Ultrasound and contrast-enhanced CT/MRI are good in depicting the complications of chronic liver disease however none of the modalities measures the HVPG and do not correlate well with HVPG. Transient elastography (TE) TE can be used as a tool for assessing liver stiffness in patients with chronic liver disease. Baveno VI consensus workshop recommends that TE values >15 kPa suggests CC and screening endoscopy can be avoided in patients with liver stiffness 1,50,000 as these patients have very lower risk of varices. The above-mentioned noninvasive modalities lack the sensitivity and specificity of HVPG and none of these modalities directly measure the HVPG.

HVPG HVPG is an invasive technique which helps in determining portal pressure using a catheter placed in one of the hepatic veins. When a catheter is wedged in the hepatic vein the proximal column of blood reflects the pressure within the hepatic sinusoids. In cirrhosis, there is loss of normal connections within the sinusoids and the wedged hepatic venous pressure (WHVP) represents the portal pressure. Hepatic vein pressure gradient (HVPG) is calculated by subtracting free hepatic venous pressure (FHVP) from the WHVP. HVPG measurement is currently considered the gold standard for measurement of portal venous pressure in chronic liver disease. HVPG is helpful in diagnosing and measuring the severity of PH. HVPG predicts the severity of cirrhosis, clinical course in chronic hepatitis B and C infections and the development of complications. It is a surrogate clinical marker and has been used for prognostication and treatment response. HVPG >10 mm Hg is associated with formation of oesophagal varices while HVPG >12

mm Hg is associated with increased risk of variceal bleeding and ascites. A baseline HVPG of ≥16 is associated with increased risk of death irrespective of presence or absence of varices with no bleeding. Patients with HVPG ≥20 mm Hg presenting with variceal bleeding are more likely to have early rebleeding or inability to control bleeding than patients with HVPG 10 mm Hg). HVPG also predicts recurrence or onset of hepatitis C cirrhosis in transplant patients and HVPG >6 mm Hg in these patients is associated with disease progression. HVPG measurement via hepatic vein catheterization is simple, safe and reproducible technique with immense clinical benefit. Indications • Diagnosis of the degree of PH • Prognostic information • Measurement of response to therapy • Assessment of the risk of developing hepatocellular carcinoma • Predictor of response to antiviral therapy • Clinical trials for investigation of new therapies. Contraindications • Severe cardiac or pulmonary disease • Hypersensitivity to contrast agents • Pregnancy • Active encephalopathy. Technique Hepatic vein catheterization is done under conscious sedation in a daycare setting with continuous monitoring of the vitals during the procedure. The patient should be fasting for minimum 6 hours. Venous access (Internal jugular, femoral or ante cubital vein) is secured under local anaesthesia. A balloon-tipped catheter is

advanced into the right hepatic vein through the internal jugular vein (IJV) or IVC over a guidewire. Contrast is injected through the balloon catheter to confirm the position of the catheter and the diameter of the vein. FHVP is measured by letting the catheter tip float freely in the hepatic vein for at least 15 seconds within 5 cm of the hepatic vein ostium. WHPV is measured by inflating the balloon so that it is well opposed to the venous walls and the pressure tracing is stable for a minute (Fig. 9.26.1). After measuring the pressure adequate occlusion of the vein is confirmed by injecting 3–5 mL contrast slowly which should result in a wedge sinusoidogram, no reflux via collateral veins, absence of venous waveform and no blood on applying suction through the catheter. In the event of inadequate occlusion, the pressure is measured again and occlusion is verified again. Three readings are taken if the variation is ≤1 mm Hg and a mean of the values is considered. Permanent recording of the tracing using a multichannel recorder is done. The HVPG is calculated by subtracting FHVP from the WHVP. The advantage of measuring the gradient is that it is unaffected by changes in abdominal pressure, ascites or the hydration status of the patient. Venous pressure should also be measured in the IVC and the right atrium (RA). The IVC pressure should be measured at the level of the hepatic vein ostia because the pressure may be higher inferiorly due to compression of the IVC by hepatic parenchymal hypertrophy. The gradient between the hepatic veins and the RA should not be more than 2 mm Hg. If the gradient is >2 mm Hg then one must suspect a narrowing or a web in the hepatic vein or the IVC. Using RA pressures for HVPG measurement has the advantages of easy reproducibility and that it measures the actual portosystemic gradient. WHVP should be separately mentioned as it represents the pressure of blood in the varices and hence risk of variceal rupture. Patients coughing, movement or talking should also be recorded as it may cause artefacts while recording a trace. After successfully measuring the pressures the catheter and the sheath is removed and manual compression of the puncture site is done till the oozing stops followed by immobilization of the part for at least 4 hours.

FIG. 9.26.1 Contrast injection after inflation of a balloon (black arrow) to ensure adequate hepatic vein (blue arrow) occlusion during HVPG measurement. Some points to be kept in mind while measuring HVPG. 1. Check vitals prior to skin puncture. 2. Ultrasound-guided Right internal jugular puncture is to be done if a transjugular liver biopsy (TJLB) is planned. 3. Vein puncture should preferably under ultrasound guidance. 4. Liberal infiltration of local anaesthetic at the puncture site reduces pain and improves compliance. 5. Keep arrhythmias in mind while crossing the guidewire through the RA. 6. Calibration of the pressure monitor should be done. 7. Transducer should be kept at the level of the RA in the midaxillary line. 8. Always make a permanent recording. 9. Take three pressure recordings and use the mean. 10. Measure FHVP, IVC and RA pressures in addition to the WHVP. 11. FHVP should be measured within 5 cm of the ostium. 12. Allow the tracing to stabilize before recording any pressure (1 minute for WHVP and 15 seconds for FHVP). 13. Check adequate occlusion after measuring WHVP and measure the values again if there is a variation of >1 mm.

14. Postprocedure the vitals are to be recorded again and adequate compression of the puncture site to be done. Complications HVPG measurement is a safe procedure with no major complication or mortality. Puncture site leakage and hematoma of the access vessel are the common complications. Rare complications are vasovagal syncope and arteriovenous fistula formation. Most of the complications can be avoided by using ultrasound for puncture of the access vessels and adequate postprocedural compression. Self-limiting supraventricular arrhythmias may be seen when the wire or the catheter traverses the RA.

Transjugular liver biopsy Introduction TJLB was introduced to reduce the complications associated with percutaneous liver biopsy (PLB) in patients with ascites, coagulopathy or in patients whose percutaneous biopsy had failed. Transjugular biopsy is now an acceptable and established technique for obtaining biopsy from the liver with no incidence of major complications. Indications • Ascites • Coagulopathy • Morbid obesity • Small shrunken liver • Failure of percutaneous biopsy • Hereditary haemorrhagic telangiectasia • Early postoperative live donor liver transplantation graft dysfunction Relative contraindications • Right IJV thrombosis • Hepatic veins thrombosis • Hydatid cyst of the liver Technique TJLB is done as a daycare procedure. Patient has to be fasting for 6 hours and an informed consent should be taken. The patient is shifted to a procedure room/cath-lab and the right neck is cleaned and draped. Continuous monitoring of the vitals is done throughout the procedure. Under local anaesthesia right IJV is accessed and a

10 F vascular sheath is introduced. Through the sheath, right hepatic vein is accessed using a 5F catheter and J tip floppy guidewire (Terumo, Japan). A contrast run is taken to confirm the position of the catheter in the right hepatic vein. The floppy guidewire is exchanged with a 0.035-inch stiff guidewire over which a curved stiff TJLB cannula is advanced. The stiff TJLB cannula is wedged against the wall of the hepatic vein. Wedging prevents the needle from slipping while taking a tissue core. This is followed by introduction of the semiautomatic coaxial biopsy gun (Fig. 9.26.2). Two to three cores are taken. The needle should be directed anteriorly when taking a biopsy from the right hepatic vein and laterally while taking biopsy from the middle hepatic vein. A contrast run is taken postprocedure. Postprocedure the neck access site is compressed manually and patient is monitored for 4–6 hours. If patient complains of severe pain not relieved by analgesics or if there is any tachycardia/fall in blood pressure, ultrasound should be done to rule out hemoperitoneum.

FIG. 9.26.2 Transjugular biopsy being performed with metal cannula in the right hepatic vein. The semiautomatic biopsy gun tip (black arrow) is seen protruding into the hepatic parenchyma. Following important steps not to be overlooked.

1. Avoid air embolism by using a saline-filled syringe for puncture. 2. Patient may be asked to hold breath after deep inspiration if there is any difficulty in cannulation of the hepatic vein. 3. A contrast run is taken after cannulation of the vein to confirm the position. 4. Always wedge the stiff TJLB cannula against the vessel wall and ask the patient to hold breath before taking a core. 5. The sample should be taken from middle third of a hepatic vein so that there is adequate hepatic parenchyma surrounding the vein. 6. At least two passes should be taken. 7. Always take postbiopsy contrast run to rule out any vascular injury/peritoneal extravasation of contrast. Though vary rare, if any vascular injury and contrast extravasation is seen then embolization of the injured vessel should be performed. Discussion Liver biopsy is an essential procedure for evaluation of liver diseases and is considered the ‘gold standard’. There are various methods by which tissue can be obtained from the liver like percutaneous, transvenous and laparoscopic routes. Percutaneous (blind or image-guided) is the most common route for liver biopsy. PLB is cheap, fast and easier procedure. Percutaneous biopsy gives a good unfragmented specimen for histopathological examination. Perihepatic haemorrhage is the most common and significant complication of PLB which can occur due to injury to the hepatic artery, portal tracts or the intercostals artery. There are a few contraindications for PLB, most important being perihepatic fluid and coagulopathy. These conditions increase the risk of lifethreatening bleeding after percutaneous biopsy. Transvenous biopsy tends to overcome these limitations by avoiding intraperitoneal bleeding in patients with ascites and deranged coagulation parameters as the hepatic capsule is not breached. The blood drains back into the venous system even if bleeding occurs after TJLB. Earlier there were concerns regarding adequacy of the tissue sample as the tissue obtained in TJLB was fragmented and at least 11 portal tracts or a sample length of at least 2 cm is needed to make an accurate diagnosis. But with improvement in hardware and advent of tru-cut needles the adequacy of tissue has become comparable to PLB. Plugged liver biopy uses gelfoam to plug the biopsy tract and been used in patients with deranged coagulation with biopsy specimen length comparable to TJLB and similar rates of complications. Right transjugular is the most common access site. TJLB scores over PLB due to the fact that there is no increase in complications despite taking multiple passes in patients with and without coagulopathy. It can also be performed concomitant to

HVPG measurement in patients who require both with no additional puncture. The tissue yield has been better with tru-cut needles and if the tissue is fragmented then more passes can be taken. Complications Major complication is hemoperitoneum due to transgression of the hepatic capsule. Postprocedural contrast run of the hepatic vein can show leakage of contrast into the peritoneum and an immediate embolization can be performed. Though, hepatic artery injury or biliary fistulas are rare complications, if any vascular injury and hemoperitoneum is suspected computed tomography (CT) hepatic angiography should be performed to confirm the findings. If the hemoperitoneum is present with active extravasation of contrast, catheter angiography should be done to look for the injured vessel and embolization should be done. Other complications like arrhythmias during wire manipulation are transient. Puncture site hematomas or bleeding can be managed by manual compression. Advances In cases of right IJV thrombosis, the biopsy can be performed via the left internal jugular or the right femoral transcaval routes. Trans femoral transcaval biopsy has also been used in liver transplant patients where TJLB could not be performed due to acute angulation between the hepatic veins and the IVC. Right external jugular approach has also been used for TJLB. As the external jugular vein is superficial the access to this vein is easy and potentially reduced complications associated with a deeper puncture. These routes should be used only by experienced interventional radiologists.

Transjugular intrahepatic portosystemic shunt Transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneous interventional procedure in which a stent is placed within the liver parenchyma creating an artificial shunt between the portal vein and the systemic venous system, thereby reducing portal venous pressure. PH leads to hepatofugal flow in the portal vein and results in the development of complications like variceal bleeding, ascites, encephalopathy, hydrothorax and hepatorenal syndrome. PH is managed in the early stages by pharmacologic therapy. However, in case of refractory or severe complications of PH TIPS has an important role. Since the introduction of TIPS in 1988, there has been a steady innovation in technique and hardware leading to improvement in outcomes and reduced

complications. The role TIPS has evolved from salvage procedure in acute variceal bleeding to treatment of other complications of PH. Indications Indications of TIPS are: • Acute oesophageal variceal bleeding a. Salvage procedure in acute variceal bleeding. b. Early TIPS after oesophagal variceal bleeding. c. Secondary prophylaxis of oesophagal variceal bleed • Acute gastric variceal bleeding in gastro-oesophagal varices type 2 and isolated gastric varices type 1. • Refractory ascites • Refractory hydrothorax • Hepatorenal syndrome • Budd–Chiari Syndrome Contraindications Absolute • Congestive cardiac failure • Severe triscuspid regurgitation • Severe pulmonary hypertension • Sepsis • Unrelieved biliary obstruction • Multiple hepatic cysts Relative • Portal vein thrombosis • Severe coagulopathy • Severe thrombocytopenia • Encephalopathy • Hepatic vein obstruction • Moderate pulmonary hypertension • Centrally located liver mass • Primary prophylaxis of variceal bleeding Preprocedural evaluation A multiphasic CT or a contrast-enhanced MRI is helpful to assess the anatomy of the portal vein, the hepatic veins and the IVC. Echocardiography is done to assess pulmonary hypertension as placement of TIPS shunt increases the right heart pressures and can precipitate cardiac failure. Liver and kidney function tests, Child-Pugh score and MELD scores are calculated prior to the procedure. Patients with high MELD score have a higher mortality.

Patients with high Child-Pugh/MELD scores, high serum creatinine, hyponatremia and low albumin levels are more likely to present with hepatic encephalopathy post TIPS. Technique (Figs. 9.26.3 and 9.26.4) TIPS is done under controlled sedation with the vitals being monitored throughout the procedure. Right IJV access is obtained and right atrial and IVC/HV pressures are measured. Preferably, the right hepatic vein is cannulated but in cases of right lobe atrophy/dysmorphic liver the middle hepatic vein may be used to create TIPS. The direction of puncture varies in each of the veins due to different spatial relationship of the veins with the portal vein. Ultrasound guidance (transabdominal/intravascular) can be used as it is real-time and facilitates easy puncture. A long sheath and stiffening cannula from RUPS/RTPS set (Cook, In) is advanced in the hepatic vein and the puncture needle is directed towards the right branch of the portal vein (Left branch of portal vein if middle hepatic vein is cannulated). After a successful puncture a guide wire is advanced into the portal vein up to the splenic/superior mesenteric vein. The portal venous pressure is recorded. Portal venogram is done which serves the purpose of defining the anatomy and variceal identification. The parenchymal tract is dilated using 8/10 mm balloon catheter. Later, a marker pigtail catheter (Cook, In) is advanced in the main portal vein and venogram is performed with simultaneous contrast being injected to the pigtail catheter and the sheath (in the IVC). This combined angiographic image is used to ascertain the length of the TIPS stent to be deployed. After deployment of the stent a contrast run is taken and if any large varix is seen then it may be embolized. Post procedural pressures are measured in the portal vein, IVC and the RA to see if pressures have been adequately reduced.

FIG. 9.26.3 Diagrammatic representation of TIPS procedure. (A) Diagram showing hepatic veins, IVC and the portal vein. (B) Puncture of the right portal vein via the right hepatic vein. (C) Balloon dilatation of the hepatic parenchymal tract over a wire with its tip in the splenic vein. (D) Postprocedure which shows TIPS stent, proximal covered part of the stent reaching just up to the right portal vein and the distal uncovered part of stent extending into the portal vein.

FIG. 9.26.4 (A) Hepatic venogram with a catheter placed in the right hepatic vein. (B) Portal venogram performed after portal puncture and placement of a catheter in the portal vein. (C) Balloon dilatation of the parenchymal tract up to the portal vein over the wire. (D) Post TIPS venogram shows good flow of the contrast into the RA via the stent. An additional technique has been described in patients with small or occluded hepatic veins called ‘Gun sight technique’. In this technique two snares are placed in the portal vein and the IVC, respectively. A percutaneous needle is passed through both the snares via a lateral approach in way that both the snares overlap each other. After confirming the tip of the needle in the IVC a guide wire is passed. This guidewire is retrieved using a snare and is used to create a connection with the portal system. Once the communication is established TIPS can be performed. Complications Percutaneous access site complications include hematoma/bleeding and it can be prevented by proper compression at the puncture site. Other complications like arteriovenous fistula, arterial puncture, pneumothorax or haemothorax can be markedly reduced by using ultrasound guidance for puncture of the jugular vein. Arrhythmias usually are transient and occur when the wires or the hardware cross the RA. Operators should be careful while traversing the heart and care should be taken to prevent the wires or the catheters from coiling inside the cardiac chambers. Hepatic capsule puncture resulting in hemoperitoneum is one of the complications related to the hepatic vein puncture and

transgression of the liver capsule. This can be avoided by carefully reading the preprocedural CECT or CEMR so that the right hepatic vein is cannulated instead of the accessory vein. Also, the portal puncture should neither be too distal nor too central. Care should be taken to puncture the intrahepatic part of the portal vein branch. Biliary fistula is a rare complication and has markedly reduced after introduction of covered stents. Injury to the hepatic artery causing hemoperitoneum needs to be managed by embolization. Sometimes the bleeding may stop on placement of TIPS stent also. Loss of arterial supply may result in ischemic injury to the liver. Stent related complications are thrombosis, occlusion, migration and tipsitis. Thrombosis and occlusion of the stent is treated by balloon angioplasty within the stent. Anticoagulants may be administered to prevent any further thrombosis. Tipsitis is usually bacterial infection of the stent and is managed by vigorous administration of antibiotics. Complications related to portosystemic shunting are hepatic encephalopathy and hepatic ischemia. These complications may be treated by reduction in calibre of the shunt. Discussion TIPS has proven to be beneficial in controlling upper gastrointestinal bleeding. TIPS by reducing the portosystemic gradient is used in the treatment of acute variceal bleeding after failure of pharmacotherapy and endoscopic treatment. TIPS has been effective in controlling bleeding in approximately 90% patients. MELD and Child-Pugh scores are predictors of mortality in these patients and TIPS is unlikely to be beneficial in MELD scores 14–15. Early TIPS performed within 72 hours of acute oesophagal variceal bleed has been found superior than pharmacotherapy/endoscopic therapy in terms of controlling variceal bleeding. Patients who have undergone early TIPS are less likely to rebleed or present with failure to respond to treatment. Also, they are less likely to develop new ascites or present with worsening of already existing ascites. TIPS has been used in secondary prophylaxis of oesophagal variceal bleeding in patients who have multiple rebleeding events or have oesophagal varices which are likely to bleed. Child-Pugh B patients are more likely to benefit from TIPS than Child-Pugh C patients. TIPS has also been used for treatment of bleeding GOV2 and IGV1 varices however there have been varying outcomes and TIPS was not found to offer a better survival benefit than endoscopic therapy though the chances of rebleed were reduced; however, BRTO may offer a better outcome in IGV1 bleed. TIPS has shown promise in treating other complications of PH besides bleeding. Refractory ascites has a good response to TIPS

placement. Budd–Chiari syndrome is another disease in which TIPS/DIPS is performed and a liver transplant may be avoided if a shunt is placed. Shunt placement in Budd–Chiari syndrome has excellent long-term outcomes and the morbidity associated with a surgery can be avoided. Portal vein thrombosis which is a relative contraindication for TIPS placement is now being treated with TIPS. Use of covered stents has result in better stent patency rates. They have also reported a better-improved survival and reduced risk of encephalopathy than bare-metal stents. Advances Use of intravascular ultrasound for puncture of the portal vein Puncture of the portal vein branch is one of the most important steps of TIPS. USG guidance of puncture of portal vein has resulted in reduced bleeding complications, reduced procedure time and reduced radiation dose. Intravascular ultrasound has also been used to guide portal vein puncture with similar benefits. The IVUS transducer is placed in the IVC via the right femoral vein. IVUS due to its excellent resolution also reduces inadvertent biliary punctures. Transsplenic portal vein recanalization and TIPS Accessing the splenic and then the portal vein via collateral vein within the splenic parenchyma has been used in splenic and portal vein thrombosis. After accessing the portal vein a TIPS is performed by snaring the wire through the right hepatic vein. The splenic and the portal vein then can be recanalized and balloon angioplasty can be performed. Patent TIPS stent restores the flow towards the heart and prevent portal/splenic vein thrombosis.

Balloon occluded retrograde transvenous obliteration Introduction Gastric variceal bleeding is one of the many complications of chronic liver disease. Endoscopy is the most important investigation for diagnosing and simultaneous treatment of gastric varices. Gastric varices mostly end up forming a portosystemic shunt (gastro/lieno-renal shunt). In BRTO the gastric varices are accessed retrogradely through the gastro/lieno-renal shunt which opens into the left renal vein and after cannulating the shunt a balloon catheter is used to occlude the outflow of the shunt and sclerosant is injected within the shunt to thrombose and obliterate

the varices (Figs. 9.26.5 and 9.26.6). This is how the procedure got its name. Previously, TIPS was used in variceal haemorrhage not responding to initial pharmacologic and endoscopic therapy but TIPS is more effective in controlling oesophagal variceal bleeding rather than gastric variceal bleeding as the gastric varices bleed at a lower pressure. TIPS controls the variceal bleed by reducing the portal pressure by connecting the high pressure portal system with low-pressure systemic venous circulation, but in an already low pressure system further reducing the portal pressure is not very effective. In BRTO the bleeding varices is obliterated by filling it with sclerosant after occluding the outflow of portosystemic shunt opening in the left renal venal vein. Balloon occluded retrograde transvenous obliteration (BRTO) is being increasingly used for treatment of gastric varices. This procedure is relatively less invasive as compared to TIPS and has potential of increasing portal flow with less rate of rebleeding. As a result, BRTO has resulted in improvement of hepatic encephalopathy and can be used in patients with poor hepatic reserve.

FIG. 9.26.5 (A) Diagrammatic representation of the venous system showing the splenic vein (black arrowhead), left renal vein (white arrow) and the gastrorenal shunt (black arrow). (B) A balloon inflated within the proximal part of the gastrorenal shunt via the left renal vein. (C) Instillation of the sclerosant into the shunt.

FIG. 9.26.6 (A) Contrast venogram showing long sheath placed within the gastrorenal shunt. (B) Balloon occlusion of the shunt dune using a compliant balloon (black arrows) to prevent reflux of sclerosant. (C) Post BRTO image shows sclerosant within the gastric varices showing adequate variceal opacification (white arrows). Indications • Bleeding gastric varices • Refractory hepatic encephalopathy Contraindications relative • Severe oesophagal variceal bleeding • Uncorrectable coagulopathy • Splenic vein thrombosis • Portal vein thrombosis Technique (Figs. 9.26.5 and 9.26.6) A review of the preprocedural multiphasic CT scan is beneficial in understanding the anatomy of the gastric varices and its afferent and efferent vessels. Further, it is also helpful in ascertaining the route for access. The procedure is mostly done under conscious sedation. After understanding the venous anatomy, a suitable venous access is secured either via femoral or the IJV. The left renal vein is cannulated and a long sheath is placed in the renal vein. The catheter is then used to cannulate the gastrorenal shunt and if possible, the sheath is further advanced into the shunt. A compliant balloon is then advanced into the shunt and inflated to occlude the shunt. Contrast is injected to assess the anatomy, number and size of the draining veins and complete occlusion of the shunt. If small collateral venous channels are noted then each one of them are

embolized using coils/gelfoam slurry. Once the compliant balloon occludes the vein adequately and contrast is seen going towards the gastric varices then the sclerosant mixture/sclerosant foam using sodium tetradecyl sulphate or polidocanol is injected within the varices to completely fill it. Ethanolamine oleate was associated with renal complications due to haemolysis hence rarely used nowadays. Sodium tetradecyl sulphate has emerged and a safe and efficacious sclerosant and is now being widely used. The filling of shunt and the varices up to the afferent vein is considered the endpoint of the sclerosant injection. The balloon is left inflated for at least 4–6 hours and then slowly deflated after confirming the thrombosis and obliteration of shunt and varices and the balloon catheter is removed. A postprocedure CT may be done to look for complete obliteration of shunt and may be compared with the pre BRTO CT (Fig. 9.26.7).

FIG. 9.26.7 Contrast-enhanced venous phase coronal CT (A) image showing a large gastrorenal shunt (white arrows). Post BRTO noncontrast coronal CT image (B) showing lipiodol cast within the gastrorenal shunt completely obliterating it. Complications Procedure-related complications • Haematuria (related to ethanolamine oleate use as a sclerosant) • Pulmonary embolism • Anaphylaxis

• Fulminant hepatic failure (due to hemodynamic changes after shunt occlusion) • Exacerbation of ascites or pleural effusion • Exacerbation of oesophagal varices • Portal venous thrombosis • Gastropathy Discussion BRTO is used for treatment of bleeding gastric varices with associated large splenorenal or gastrorenal shunts. These large shunts are used as an access to retrogradely occlude the outflow of the gastric varices and sclerosant can be injected to obliterate these shunt and varices. BRTO leads to increase in portal flow by obliterating the portosystemic shunt and hence may aggravate the PH and its complications like formation of ascites and enlargement of oesophageal varices. So oesophageal varices should be treated before performing a BRTO procedure. However, occlusion of varices not only controls gastric variceal bleed but also improves hepatic encephalopathy arising secondary to portosystemic shunt. Portosystemic shunting may lead to high arterial ammonia levels and cause hepatic encephalopathy. Occlusion of portosystemic shunt reduces the mixing of portal and systemic blood and redirects the mesenteric blood flow towards the liver which aids in detoxification. This may result in increased hepatopetal portal flow and is associated with improved liver synthetic functions. Advances Modifications of BRTO are also being used. These modifications are Plug assisted retrograde transvenous obliteration (PARTO) in which a vascular plug is used to occlude a shunt in place of balloon, coil-assisted retrograde transvenous obliteration (CARTO) which uses coils with gelfoam. PARTO has the advantage of being a fast procedure without the risk of balloon rupture and complications due to sclerosant flowing into the systemic circulation. In PARTO a long sheath is advanced with in the shunt and a vascular plug is deployed while a catheter is placed above the plug (Fig. 9.26.8). Once the desired position of plug is confirmed, gelfoam slurry mixed with contrast is injected to completely fill the varices (Fig 9.26.8). The sheath and catheter are removed after complete obliteration of shunt and varices is confirmed. CARTO too offers similar advantages over BRTO but mostly suitable for small shunts. The disadvantage of PARTO includes loss of access to the shunt after plug deployment, which may be important in cases of recanalization or enlargement of previously existing small shunt. Also, PARTO may be difficult to perform in patients having tortuous venous shunts not suitable for advancement of long sheath for plug deployment.

FIG. 9.26.8 (A) Venogram showing catheter deep within the lienorenal shunt. (B) Fluoroscopic image showing long sheath reaching the shunt with plug deployed within the shunt (white arrows) and column of gelfoam slurry mixed with contrast above the plug obliterating the shunt (black arrows).

Partial splenic embolization Patients with PH have hypersplenism, leading to platelet sequestration and thrombocytopenia. Partial splenic embolization (PSE) has been used as an alternative to other interventional techniques in a few subset of patients with PH. It involves occluding some of the branches of the splenic artery using various embolic materials like polyvinyl alcohol particles, gelfoam and glue. The rationale behind PSE is that reducing splenic artery flow reduces splenic venous pressure and its contribution to the portal pressure. There is reduction in sequestration and increase in platelet and leucocyte counts after PSE. It has an additional benefit of preservation of partial splenic function. Earlier splenectomy was used to prevent complications of hypersplenism but due to complete loss of the splenic function there are increased chances of infection in addition to the disadvantages of surgery like increased hospital stay, portal vein thrombosis and more blood loss. Technique The procedure is done conscious sedation. After cannulation of the splenic artery, some of the distal branches are selectively embolized preserving other branches (Fig. 9.26.9). Nonselective embolization is another technique in which embolization is performed from the main artery distal to the origin of the pancreatic branches till the

blush within the parenchyma is reduced. Pre and postprocedural antibiotic are important to prevent or control infection.

FIG. 9.26.9 (A) Coeliac angiogram. (B) Superselective cannulation of splenic artery branches supplying the lower pole. (C) Post glue embolization digital subtraction angiography image shows devascularized lower pole of spleen (white arrows). Complications The pulmonary complications are left-sided pleural effusion and atelectasis, commonly associated with upper pole embolization. Splenic abscess and sepsis can occur secondary to a large area of embolization or inadvertent asepsis during the procedure. Aggressive antibiotics and drainage of abscess is recommended. Portal vein thrombosis can result in over-embolization and increased platelet count which creates a hypercoagulable state. Anticoagulation therapy should be initiated in case of portal vein thrombosis. Pancreatitis can occur due to embolization of pancreatic branches of the splenic artery. Portal vein recanalization Portal vein obstruction accounts for approximately 5%–10% cases of PH with the incidence being higher in children. There is cavernous transformation of the portal vein due to chronic narrowing and PH develops as the small portal venous channels provide inadequate drainage. The causes of portal vein narrowing include: postoperative, secondary to compression by pseudopancreatic cyst, enlarged lymph nodes or malignancy. Portal vein recanalization can be done by balloon dilatation of the narrowed segment (Fig. 9.26.10). Percutaneous transhepatic or transjugular approaches are the preferred routes. Transjugular approach is technically challenging but preferred in patients with ascites or deranged coagulation. After gaining access using the

safest route, the measurement of the pressures across the narrowed segment should be performed. Following this angioplasty is done. Stenting is done if there is recoil and persistence of the stricture. Resolution of the narrowing and reduction of the pressure gradient after dilatation is considered an optimal result. If the flow after angioplasty is sluggish or the portosystemic gradient is >12 mm a TIPS procedure may be required to bring down the pressure.

FIG. 9.26.10 (A) Percutaneous puncture of the portal vein followed by a venogram shows severe stenosis (white arrows) of the portal vein. (B) Balloon angioplasty of the stenosis. (C) Postprocedural venogram shows resolution of the stenosis with no recoil or residual stricture. Portal vein thrombosis Portal vein thrombosis is one of the common complications of PH. Medical management consisting of anticoagulation is the first-line therapy in acute thrombosis, however, it is effective in approximately half the cases. There are also concerns of increased chances of bleeding in a cirrhotic patient on anticoagulation as these patients inherently have coagulation abnormalities. TIPS may be an alternative for patients not responding to oral anticoagulation or who have progression of thrombus despite anticoagulation. TIPS restore the physiologic flow and helps in resolution of the thrombus and reduces variceal bleeding. TIPS can be attempted with varying degree of success even in subacute or chronic portal vein thrombosis. Transjugular, transhepatic and transsplenic routes can be used for gaining access across the thrombosed portal vein and hepatic vein/IVC. In transhepatic/transsplenic approach the portal vein is accessed and the occluded segment of portal vein is dilated and later a snare is placed in the main/right portal vein which is targeted from hepatic vein using the TIPS set. Once the puncture needle is placed in the desired branch of portal vein it is snared out

using the snare present there. Later the hepatic track is dilated and TIPS stent is placed. TIPS has shown a better resolution of the portal venous thrombus in comparison to anticoagulation. Other treatment options for portal hypertension related ascites/pleural effusion Pleural effusion and ascites are common in PH. Medical management is initiated for the management of pleural and ascitic fluid initially. Single time aspiration can be done to diagnose the cause of pleural effusion/ascites and to rule out infection. Recurrent or refractory ascites/pleural effusion can be managed by aspiration or placement of a drain. TIPS may be done in patients with recurrent or refractory ascites/hydrothorax. Pleurodesis using various sclerosants can be attempted. There are some preliminary studies on use of tunnelled drainage catheter in the successful management of hepatic hydrothorax/refractory ascites. Other options include pleurovenous and peritoneovenous shunts, which are again shunts placed subcutaneously to drain pleural fluid or ascites into the subclavian vein or the IJV. These shunts are not in vogue at present.

9.27: Interventional management of Budd–Chiari syndrome Chandan Jyoti Das, Abdul Razik

Introduction Budd–Chiari syndrome (BCS) is the eponym for the clinical presentation occurring from hepatic venous outflow tract obstruction (HVOTO) anywhere between the small hepatic venules and cavoatrial junction. Obstruction at the sinusoidal level and those resulting from cardiac and pericardial diseases, do not come under BCS. Interventional radiology plays an important role in the management of BCS and has largely replaced surgical shunts. This chapter provides a brief review of some important clinical aspects of BCS, followed by detailed description of the interventional management.

Predisposing factors BCS can be primary, when obstruction occurs due to intraluminal pathology (e.g. thrombosis, webs) or secondary, when compression is caused by extrinsic pathologies such as tumours or abscesses. Based on the site of obstruction, three types exist (Table 9.27.1). The following discussion deals with only types I and II of primary BCS. There is a well-recognized demographic difference in the etiology and location of venous occlusion between the western and eastern populations. In the west, most cases occur secondary to prothrombotic conditions, with long segment or multifocal hepatic venous stenosis being the most prevalent patterns. The most common predisposing condition is usually a myeloproliferative syndrome, often with JAK2 V617F, JAK2 exon 12 or calreticulin mutations. Other prothrombotic conditions include inherited thrombophilia (factor V Leiden mutation, protein C, protein S and antithrombin deficiency), obesity, neoplasms (tumour-induced thrombophilia or direct tumour thrombus within the vein), autoimmune disorders (antiphospholipid syndrome, Behcet’s disease), paroxysmal nocturnal haemoglobinuria, pregnancy, oral

contraceptive use and hyperhomocysteinemia. In 15%–20%, multiple predisposing factors may be present. TABLE 9.27.1 Types of Budd–Chiari Syndrome Based on the Site of Obstruction Type I Type II Type III

Obstruction of IVC with or without hepatic vein involvement Major hepatic vein involvement Obstruction of the centrilobular venules; also known as veno-occlusive disease

In Asia, most cases possess short segment (18) and high Child–Turcotte–Pugh (CTP C) scores. Among these, the Rotterdam and Clichy scores, tailored specifically for BCS, predict early (3-month) mortality better than the CTP or MELD scores. Interventional therapies are classified as physiological (angioplasty, with or without stenting) or derivative (transjugular intrahepatic portosystemic shunt; TIPS). These therapies relieve outflow tract obstruction and the resultant stagnation, thereby improving liver perfusion. The specific treatment depends on acuteness of presentation, as well as the location and length of the involved venous segment. In acute fulminant liver failure and end-stage liver disease, once permanent damage has occurred, orthotopic liver transplantation (OLT) is indicated. After the advent of interventional procedures, surgical portosystemic shunts have been rarely used.

FIG. 9.27.1 Flowchart demonstrating the management algorithm in Budd–Chiari syndrome.

Medical management Medical management involves anticoagulation; sodium-restricted diet and diuretics for ascites; beta-blockers for portal hypertension, as well as treatment of the predisposing factor. Anticoagulation is performed even in asymptomatic patients and those without predisposing factors as it improves long-term survival. It prevents thrombus propagation, rather than dissolution of an existing thrombus. Generally, anticoagulation is initiated with unfractionated or low-molecular-weight heparin (LMWH) till the effect of oral anticoagulants (vitamin K antagonists or direct thrombin inhibitors) takes over. Subsequently, oral anticoagulation is continued to maintain the target prothrombin time-international normalized ratio (PT-INR) in the range of 2–3. LMWH is preferred over unfractionated heparin in view of lower risk of heparininduced thrombocytopenia.

Thrombolysis Thrombolysis restores hepatic outflow in patients with recent (acute or subacute) thrombosis who do not respond to early anticoagulation. It may be performed as systemic infusion through a peripheral vein or as direct infusion through a catheter placed in the hepatic artery or vein (catheter-directed or local thrombolysis). Best outcomes are seen in the acute phase, and in patients having a low thrombus load and some residual flow within the thrombus.

Patients with higher clot load have poor outcomes since complete thrombolysis is difficult to achieve. Although no studies have compared systemic versus catheter-directed thrombolysis, the latter is preferred since it enables higher local concentration of the thrombolytic agent and better clot-to-drug contact, thereby increasing the chances of recanalization, while reducing the required dose and risk of remote bleeding. Technique Catheter-directed thrombolysis involves the placement of a multisidehole catheter across the thrombus, followed by administration of the drug directly into the thrombus. After securing venous access through the jugular or femoral route, a catheter–guidewire combination is used to negotiate the length of the thrombus. Failure to advance the soft end of the guidewire through the thrombus (guidewire traversal test) indicates chronicity and predicts failure of lysis. Once negotiated, the infusion catheter is placed across the thrombus to bath the thrombus with the thrombolytic agent. An initial thrombus lacing is performed with a bolus dose of the drug using a ‘pulse-spray’ technique to enable pharmacomechanical disruption, followed by continuous slow infusion of the drug. Recombinant tissue plasminogen activator (rtPA, alteplase) is the most commonly used agent. The typical doses used are 5–10 mg initial bolus followed by 0.5–1 mg/hour. RtPA has a short half-life of 5 minutes, and earlier reversal is possible in case of bleeding complications. Streptokinase and urokinase are uncommonly used in view of their adverse safety profile and lower efficacy. In view of the risk of potentially fatal haemorrhagic complications, thrombolysis is contraindicated in patients with active bleeding and recent history of stroke, trauma, surgery or other invasive procedures (e.g. paracentesis within the past 24 hours). Concurrent heparin infusion (under activated partial thromboplastin time monitoring) is performed to prevent rethrombosis. During the infusion, the patient is monitored in a high-dependency unit and a repeat angiogram is obtained after 4– 12 hours. The endpoints to thrombolysis are (a) complete lysis, (b) unchanged thrombus between two consecutive angiographic reviews and (c) occurrence of bleeding complications. Thrombus aspiration may be performed in conjunction with thrombolysis in acute thrombosis and when thrombolysis is contraindicated. In patients with subacute occlusive thrombus, portosystemic collaterals redirect hepatic circulation away from the hepatic veins, which results in suboptimal thrombus-drug contact and poor outcome following thrombolysis. In such cases, partial recanalization achieved using a balloon catheter improves the success of subsequent thrombolysis. In addition, partial hepatic decompression also reduces the risk of variceal bleeding during thrombolysis. In acute thrombosis, predilatation is better avoided

in view of the high risk for pulmonary embolism, although a small balloon may be used cautiously. In many cases, thrombolysis wuncovers an underlying segmental venous stenosis or membrane which initially predisposed the thrombus. In such cases, postthrombolysis angioplasty would be required to achieve optimal luminal patency.

Angioplasty and stenting Balloon angioplasty is performed in short-segment stenosis or membranous occlusion of the vein. Restoring flow in one of the three hepatic veins is sufficient to decompress the liver and relieve the symptoms. The best candidate vein is the one with a healthy proximal segment and is identified by its straight course, good calibre (7–8 mm) and echo-free lumen. Hence USG assessment is crucial for planning angioplasty. Hepatic angioplasty IVC is accessed through the transjugular approach using a 9/10-F, 40-cm long introducer sheath and half the bolus dose of intravenous heparin is administered. A cavogram is obtained to assess IVC patency and look for a residual hepatic venous stump. Any IVC stenosis resulting in impaired flow, collateral formation and significant pressure gradient requires angioplasty. However, in many cases, IVC may be compressed by a caudate lobe enlargement with normal flow across, in which case angioplasty is not required. A 5-F multipurpose angiographic catheter is used to cannulate the hepatic vein stump and wedge the stenosis. Subsequently, the stenosis is negotiated using the floppy end of a straight tip hydrophilic guidewire placed coaxially within a catheter, and exchanged for an Amplatz extra stiff guidewire. Once crossed, the completion dose of heparin is provided and angioplasty is performed using an 8–10 mm balloon catheter (5%–10% oversized compared to the lumen). In case there is difficulty in negotiating a tight fibrotic stenosis, the hard back end of the guidewire or a metallic needle (Colapinto needle or Rösch–Uchida trocar stylet) may be used. Ample caution must be taken to prevent inadvertent nontarget puncture and complications such as hemopericardium, haemothorax and pericaval haematoma. The procedure is demonstrated in Figs 9.27.2 and 9.27.3.

FIG. 9.27.2 Right hepatic vein (RHV) angioplasty and stenting in a 34-year-old woman with chronic Budd–Chiari syndrome and short-segment ostial stenosis. (A) The RHV stump was hooked using a stiffening cannula inserted coaxially through a 10-F sheath. (B) A catheter–guidewire combination was used to negotiate the stenosis and exchanged for an ultrastiff Amplatz guidewire. (C) Hepatic venogram showed ostial occlusion with opacification of veno-venous collaterals which drained into the IVC through an enlarged inferior accessory hepatic vein. (D) Stenting was done using a 10 mm × 4 cm balloon-mounted stent. (E) Poststenting run showed free drainage of contrast with nonopacification of collaterals. (F) Postprocedure Doppler showed good flow across the stent with a tetraphasic waveform.

FIG. 9.27.3 Middle hepatic vein (MHV) angioplasty and stenting in a 26-year-old man with chronic Budd–Chiari syndrome. (A) USG showed short-segment ostial occlusion of MHV ( arrow) with a good calibre, echo-free proximal lumen. The right hepatic vein ( open arrow) showed long-segment central stenosis. (B) Doppler examination revealed low-velocity monophasic flow in the proximal vein. (C) Hepatic venogram confirmed the ostial occlusion with opacification of veno-venous collaterals. (D) Stenting was done using a 10 mm × 4 cm balloon-mounted stent. (E) Poststenting run showed free drainage of contrast with nonopacification of collaterals. (F) Postprocedure Doppler showed good flow across the stent with a tetraphasic waveform. If the transjugular approach fails, percutaneous access of the selected hepatic vein may be performed using a micropuncture set. Subsequently, a 6-F vascular access sheath is placed within the hepatic vein and angiography performed to identify the stenotic segment. After negotiation, the guidewire is sent cranially into the right atrium or SVC, where it is snared via the jugular access and balloon dilatation is performed. Postangioplasty venogram is deemed successful when there is prompt flow across the hepatic

vein ostium with no significant residual stenosis and nonopacification of collaterals. Pressure gradient must be below 5 mmHg. Stent placement is indicated in failed angioplasty (residual stenosis >50% or unsatisfactory pressure gradients), long segment involvement and restenosis. Balloon-mounted stents are preferred in short-segment stenosis (7, should directly proceed to OLT rather than TIPS. Compared to conventional surgical portosystemic shunts, TIPS using covered stent grafts has lower morbidity and mortality, although there is a marginally higher risk of shunt failure from thrombosis or pseudointimal hyperplasia. TIPS is useful in IVC obstruction unlike surgical shunts (with the exception of mesoatrial shunt) since it redirects flow directly into the suprahepatic IVC. Contraindications to TIPS are listed in Table 9.27.2.

TABLE 9.27.2 Contraindications to TIPS Procedure ABSOLUTE CONTRAINDICATIONS • Severe hepatic insufficiency (bilirubin >3 mg/dL) • Severe hepatic encephalopathy • Severe right heart failure (>20 mmHg) • Pulmonary hypertension (mean pressure >45 mmHg) • Uncontrolled biliary or systemic infection/sepsis RELATIVE CONTRAINDICATIONS • Coagulopathy (INR >2) and thrombocytopenia (platelet count 3 months • Elevated BUN >20 mg/dL • Raised serum creatinine >1.2 mg/dL • Vital to exclude hydronephrosis • Reduced renal length • Reduced renal cortical thickness 3.5 g of protein in the urine per 1.73 m2 of body surface area/24 hours, oedema, hypoalbuminemia, hyperlipidemia, hyperlipiduria, hypertension and hypercoagulability. Diagnostic criteria (Fig. 10.12.3.4.1) Proteinuria greater than 3.5 g/24 hour or spot urine protein: Creatinine ratio of >300–350 mg/mmol. Serum albumin less than 10 mmol/L. Clinical peripheral oedema. Severe hyperlipidaemia (total cholesterol often >10 mmol/L). Pathophysiology: Pathophysiology of nephrotic syndrome is depicted in Fig. 10.12.3.4.2. Clinical presentation: The common clinical manifestations are enumerated in Box 10.12.3.4.1. The aetiology of nephrotic syndrome is depicted in Box 10.12.3.4.2.

FIG. 10.12.3.4.1 Diagnostic criteria for nephrotic syndrome.

FIG. 10.12.3.4.2 A flow chart demonstrating the pathophysiology of nephrotic syndrome. Box 10.12.3.4.1

C LINIC AL PR E SE NT AT IO N Common Oedema (periorbital, around the ankles and genitals) Anorexia, malaise, muscle wasting Abdominal pain and distention with ascites Breathlessness, substernal chest pain

Less Common Leukonychia Eruptive xanthomata Xanthelasma Hypotension or normal blood pressure

Pleural and pericardial effusions Frothy urine Orthostatic hypotension and shock due to hypovolaemia (children) Hypertension (adults) Acute renal failure with oliguria and breathlessness Box 10.12.3.4.2 AE T IO LO GY O F NE PHR O T IC SYND R O ME

Congenital Causes Alport’s syndrome

Congenital nephrotic syndrome of the Finnish type Pierson’s syndrome

Nail-patella syndrome

Acquired Causes Primary/Idiopathic Secondary Causes Causes Minimal-change Systemic diseases: glomerular disease Diabetes mellitus, (MCGD) systemic lupus erythematosus, amyloidosis Focal segmental Malignancies: Myeloma glomerulosclerosis and lymphoma (FSGS) Membranous glomerular disease

Drug induced: Gold, antimicrobial agents, NSAIDs, penicillamine, captopril, tamoxifen, lithium Membranoproliferative Infections: HIV, glomerular disease hepatitis B and C, (e.g. IgA nephropathy) mycoplasma, syphilis, malaria, schistosomiasis, filariasis, toxoplasmosis

Denys-Drash syndrome Complications • Thromboembolism due to hypercoagulable state: Deep vein thrombosis or renal vein thrombosis, pulmonary embolism and rarely arterial thrombosis. • Infections: Cellulitis, bacterial infections like pneumonia, bacterial peritonitis and viral infections in immunocompromised patients. • Metabolic derangements: Nutritional deficiencies, protein malnutrition, myopathy, hypocalcaemia tetany, vitamin D deficiency causing osteomalacia, hyperlipidemia. • Hypertension and atherosclerosis with cardiac and cerebral complications. • Hypovolaemia and acute renal failure. • Urinary loss of plasma proteins may result in complications like hypothyroidism and microcytic hypochromic anaemia. Diagnosis and investigations • Urine analysis: To confirm proteinuria and to rule out microscopic haematuria. Evaluation with urine

routine/microscopy and culture/sensitivity is indicated to exclude urine infection. • Blood analysis: • Complete blood count and peripheral smear to look for infection, anaemia and other basic blood parameters. • Blood coagulation profile to assess for hypercoagulable states. • Renal function tests including serum creatinine, blood urea and estimated glomerular filtration rate. • Serum electrolyte estimation and blood gas analysis to exclude complications of nephrotic syndrome. • Liver function tests including serum albumin. • Blood and serum analysis for secondary and systemic causes: C reactive protein and erythrocyte sedimentation rate, blood glucose, immunoglobulins, serum and urine electrophoresis. • Screening for autoimmune diseases: Antinuclear antibody (ANA), antidouble stranded DNA antibody (dsDNA) and complement values (C3 and C4). • Screening for infectious causes: Hepatitis B and C and HIV. Role of imaging Imaging aids in the diagnosis of nephrotic syndrome and its complications. It also helps exclude clinical mimics like obstruction, tumours and infections. X-ray: Radiographs of the kidney, ureter and bladder (KUB) provide anatomic information regarding the shape and size of the kidneys and demonstrate renal or ureteric calculi and nephrocalcinosis. Radiographs of the abdomen may reveal signs of ascites like distention, diffuse increase in density of the abdomen, poor definition of the soft tissue shadows, medial displacement of bowel and displacement of the pro-peritoneal fat stripe with bulging at the flanks and increased separation of small bowel loops. Chest X-rays may reveal pleural effusions and other complications like pneumonia. Features of extravascular volume overload like pericardial effusion and pulmonary oedema may be demonstrated. Bone radiographs and bone mineral density studies reveal osteomalacia or features of long-standing renal disease in the form of renal osteodystrophy. Ultrasonography (US): It is the initial and often the only imaging technique used in the evaluation of nephrotic syndrome and other glomerular diseases. Additional

techniques in US such as Doppler US, elastography and contrast-enhanced US have further led to an expansion of the role of US in the evaluation of the kidneys. In nephrotic syndrome, there is mild to moderate nephromegaly with normal echotexture. The kidneys show a smooth outline with relatively symmetrical bilateral involvement (Fig. 10.12.3.4.3A). An increase in echotexture and loss of corticomedullary differentiation indicates severe renal involvement and possible intrarenal fibrosis. Small contracted kidneys indicate the chronic nature of the disease. US also plays a role in excluding any obstruction of the urinary tract which may be visible as dilated pelvicalyceal system and ureters. Secondary metabolic and neoplastic causes of nephrotic syndrome like amyloidosis may show kidneys with increased echogenicity with prominent medullary pyramids, whereas renal lymphoma may demonstrate diffusely bulky kidneys with hypoechoic lesions within the renal parenchyma. In patients who need a confirmation of the diagnoses, US confirms the presence and anatomical site of bilateral kidneys and helps to plan renal biopsy. US of the abdomen is useful in the evaluation of other secondary features and complications of nephrotic syndrome like ascites or hepatosplenomegaly, which may indicate an underlying systemic disease (Fig. 10.12.3.4.3B and C). US is used in the quantification of the ascitic fluid, image-guided diagnostic fluid analysis and therapeutic drainage. US being a readily available bedside imaging modality can aid in the evaluation of the inferior vena cava (IVC) for thromboembolism as well as assess the IVC diameter to assess for complications like dehydration and hypovolaemia. Chest US is utilized for quantification of pleural effusions and image-guided diagnostic pleural fluid analysis as well as therapeutic tapping. Chest US has found importance in the detection of lung consolidations and assessment of pericardial effusions as well. US Doppler: It is useful for the detection of complications such as thromboembolism. Doppler ultrasound of leg veins is performed in suspected deep vein thrombosis (DVT). Abdominal ultrasound and renal vein Doppler help to rule out renal vein and IVC thrombosis. Patients with renal disease are also prone to atherosclerosis and rarely arterial thrombosis which may require Doppler evaluation of lower

limb and neck arteries depending upon the patient’s presentation. Contrast-enhanced US (CEUS): CEUS can help identify vascular complications such as arterial and venous thrombosis and ischaemia. These US contrast agents are excreted by pulmonary ventilation, and therefore they can be readily used in patients with very poor renal function. They act as blood pool agents and remain in the vascular system and hence provide an alternative to obtain information on organ perfusion and vascularity. Computed tomography (CT): CT scan of the abdomen may reveal ascites, bowel wall oedema and mesenteric oedema as the cause of abdomen pain. It can also aid in the evaluation of the renal site, size and surface with parenchymal thickness assessment. Recent advances in CT assist in the accurate volumetric analysis of the kidneys. Secondary causes of nephrotic syndrome like lymphoma may be detected on contrast-enhanced CT imaging (CECT). CECT may be required for the assessment of complications like renal vein or IVC thrombosis. However, CECT is generally avoided in patients with deranged renal parameters to prevent contrast-induced nephropathy. CT chest can detect pleural effusions, consolidation, pneumonia and pericardial effusion. CT pulmonary angiography is indicated in patients with suspected pulmonary thromboembolism, which may reveal filling defects within the pulmonary arterial branches due to thrombosis. Venography of the inferior vena cava aids in suspected cases of thrombosis. Magnetic resonance imaging (MRI): MRI of the abdomen is useful for suspected renal vein thrombosis. MRI with its superior soft-tissue resolution has the advantage of detecting renal vein thrombosis on noncontrast images as loss of flow void in T2-weighted images. Alternatively, diagnostic MR angiography and venography may be performed without intravenous contrast and using sequences called ‘bright-blood’ sequences. Although contrast-enhanced magnetic resonance angiography (CEMRA) remains the preferred method of vascular imaging, high-quality MRA without contrast media has regained popularity because of the risk of nephrogenic systemic fibrosis (NSF) in patients with poor renal function. MRI with its excellent soft tissue contrast demonstrates the normal renal corticomedullary differentiation well. On T1-weighted sequences, the renal cortex appears relatively more hyperintense than the medullary pyramids. On T2-weighted sequences, the renal cortex

is hypointense than the medullary pyramids. In the presence of kidney injury or acute glomerular disease, this corticomedullary differentiation is lost which is best seen on T1-weighted images. MRI also allows for the evaluation of the perinephric region and other surrounding structures. Large subcapsular fluid collections have been described in nephrotic syndrome. Nuclear medicine: V/Q nuclear medicine lung scan may be indicated in pulmonary thromboembolism. Radio-nuclide studies primarily contribute functional information and in conjunction with a number of novel radiotracers provide means for quantitative assessment of a variety of physiologic renal parameters like glomerular filtration rate (GFR), renal clearance and function. However, the role of nuclear medicine is limited in glomerular diseases with biopsy being the gold standard for diagnosis. Technetium 99m-labelled diethylenetriaminepentaacetic acid (99mTc-DTPA) is a common agent for assessing GFR and is used to demonstrate renal perfusion. In kidney injury, glomerular and tubular dysfunctions are reflected by abnormal findings on renal scintigraphy and renography. Renal uptake of technetium 99mlabelled mercaptoacetyltriglycine (99mTc- MAG3) and ethylene cysteine (99mTc- EC) is prolonged with tubular tracer stasis and little or no excretion. 99mTc-MAG3 can help in prognostication of patients with acute kidney injury (AKI) secondary to glomerular or other diseases. In CKD, renal perfusion, cortical tracer extraction and tracer excretion are diminished. Renal biopsy remains the gold standard for ascertaining the underlying cause of nephrotic syndrome. This is followed by histopathological assessment including light microscopy, immunofluorescence or immunoperoxidase and electron microscopy. US assists in guiding for renal biopsy and for assessing postbiopsy complications. The key imaging features of nephrotic syndrome is summarized in Box 10.12.3.4.3.

FIG. 10.12.3.4.3 A longitudinal ultrasound image (A) shows bilateral symmetrical moderate nephromegaly with smooth outlines, increased parenchymal echotexture and poor corticomedullary differentiation in a patient with nephrotic syndrome. Longitudinal ultrasound images in the same patient (B and C) demonstrate complications of nephrotic syndrome with ascites (star), right pleural effusion (curved white arrow) and right perinephric fluid (thin black arrow) surrounding an enlarged echogenic right kidney (thick white arrow). Box 10.12.3.4.3 KE Y IMAGING FE AT U R E S – NE PHR O T IC SYND R O ME • Bilateral symmetrical nephromegaly with smooth outline

• Acute glomerular disease: Loss of corticomedullary differentiation • Amyloidosis: Increased renal echogenicity, prominent medullary pyramids • Renal lymphoma: Diffusely bulky kidneys with hypoechoic lesions • Ascites, pleural effusions, pneumonia, pericardial effusion and pulmonary oedema • Osteomalacia or renal osteodystrophy • IVC/renal vein thromboembolism and DVT in leg veins • Pulmonary thromboembolism Nephritic syndrome Definition: Nephritic syndrome is characterized by proliferative changes and inflammation of the glomeruli with resultant haematuria, proteinuria, oedema, hypertension and oliguria. Classification of glomerulonephritis (GN) based on the findings from kidney biopsy.

Clinical features and biochemical findings in nephritic syndrome enumerated in Box 10.12.3.4.4. Pathophysiology: Nephritic syndrome is primarily an immune-mediated disease/immune complex disease. Inflammation and glomerular injury lead to glomerular capillary damage as well as mesangial/endothelial proliferation through a complement-mediated mechanism. This increases the permeability of the glomerular basement membrane causing leakage of proteins and RBCs, which present as nephritic sediment.

Acute postinfectious glomerulonephritis: The aetiopathogenesis and salient features of acute poststreptococcal glomerulonephritis is depicted in Fig. 10.12.3.4.4. Imaging: Imaging plays a limited yet essential role in the workup of acute glomerulonephritis. The most commonly employed imaging modality is renal US. USG findings (Fig. 10.12.3.4.5): 1. Mild nephromegaly or normal-sized kidneys. 2. Increased cortical echogenicity and reduced echogenicity of the renal sinus fat. 3. Corticomedullary differentiation may be maintained or accentuated. 4. Smooth contour of the kidneys. Renal US plays an important role to exclude other causes of haematuria and obstruction. US provides guidance for image-guided renal biopsy in atypical presentations. Characteristic changes are seen on light or electron microscopy with a typical ‘lumpybumpy’ appearance on immunofluorescence. Other imaging modalities like chest and abdomen US and CT scan are used for evaluation of complications like ascites, pleural effusions, lung infections and pulmonary oedema. Complete recovery is seen in almost all children and many adults with a very small minority developing rapidly progressive glomerulonephritis. Imaging, particularly sonogram, assists in follow up. Box 10.12.3.4.4 C LINIC AL FE AT U R E S AND B IO C HE MIC AL FIND INGS IN NE PHR IT IC SYND R O ME Clinical Features • Hypertension • Mild to moderate oedema • Oliguria • Azotemia

Biochemical Findings • Haematuria with acanthocytes • RBC casts in urine • Proteinuria (10 mm in depth. No involvement of pelvicalyceal system 2. Any low-grade trauma accompanying injury to vessels or active bleeding limited by anterior renal fascia 1. Renal parenchymal laceration involving pelvicalyceal system 2. Renal pelvis laceration or complete pelviureteric laceration 3. Intimal injury/thrombus of segmental renal artery or vein 4. Segmental or complete renal infarction due to renal vessel thrombosis in the absence of active bleeding 5. Active bleeding outside Gerota fascia into the retroperitoneum or peritoneum 1. Main renal artery or vein laceration or avulsion from renal hilum 2. Complete devascularization of kidney with active bleeding 3. Shattered kidney

GRAPHIC 10.12.5.2.1 AAST classification of renal injuries. Low grade renal injuries Grade I injury accounts for 22%–28% of cases. It is characterized by renal parenchymal contusions and subcapsular haematoma. Contusions may be hypoechoic, hyperechoic or heterogeneous on sonography. It is seen as an ill-defined hypoechoic area with reduced perfusion on contrast-enhanced sonography. It may appear iso-dense or sometime hyperdense to normal renal parenchyma depending on the presence of clotted blood on plain CT images. Its detection is limited on the corticomedullary phase due to suboptimal enhancement of renal pyramids. It is characterized by focal ill-defined area of decreased enhancement on nephrographic phase. Excretory phase shows delayed or striated nephrogram of increased enhancement due to retained parenchymal contrast. A contusion must be differentiated from renal infarct, which would upgrade the renal injury. Contusion is ill-defined with enhancement on delayed images while infarct is typically wedge-shaped with no enhancement on delayed images. Subcapsular haematoma is well defined haemorrhagic collection along the renal surface between the renal capsule and parenchyma. It is seen as a non-enhancing lenticular area around renal parenchyma on contrastenhanced ultrasound. Its density depends on the stage of blood. Acute haematoma typically appears hyperdense relative to renal parenchyma on plain CT images and does not show enhancement on post contrast images. As chronicity increases, its density decreases. Small haematoma is crescentic and large haematoma is biconvex. It causes mass effect on the underlying renal parenchyma, deforms the surface but does no displace the kidney. Occasionally, it causes enough pressure to decrease the renal perfusion and results in reactive hypertension, the so-called page kidney. Sometime, pseudosubcapsular haematoma may appear as hypodense collection along the renal surface. It is caused by patient movement during data acquisition. Presence of similar artifact in the other region on the same image helps to differentiate between true subcapsular haematoma and pseudosubcapsular haematoma. Pseudofracture appears as a sharp indentation of the renal contour near the renal hilum. It is seen on axial CT images at the level of hilar lobulation. Its characteristic location and absence of the perirenal fluid are clues to the correct diagnosis. Grade II injury accounts for 28%–30% of cases. It is characterized by renal parenchymal laceration ≤1 cm in depth without involvement of collecting system and perirenal haematoma limited by Gerota fascia. On

contrast-enhanced ultrasound, renal lacerations are seen as linear or branching hypoechoic bands perpendicular to the capsule and may be associated with capsular discontinuity. They appear as irregular, linear or branching hypodense clefts extending from the renal capsule in the parenchyma on CT. Lacerations generally contains clotted blood and hence do not enhance on post contrast images. They are visualized on portal venous phase. Perinephric haematoma is collection present between the renal capsule and Gerota fascia. Because it is contained in the Gerota fascia it produces tamponade effect on renal bleeding. Acute haematoma typically appears hyperdense relative to renal parenchyma on plain CT images and does not show enhancement on post contrast images. It extends over a wider area and generally displaces the kidney rather than causing focal indentation on the renal surface. Rarely, localized perinephric haematoma limited to the renal capsule and bridging septum can produce focal indentation of the renal surface and mimics like subcapsular haematoma. Perinephric haematoma can occur as an isolated injury, but it is often associated with renal and/or vascular injury. Hence presence of perinephric haematoma should make the radiologist alert to look for associated injuries. Occasionally, it crosses the midline and spreads in the pelvis while still being limited by Gerota fascia. Presence of fluid in this region may be medial extension of perinephric haematoma in grade II injury, haemorrhage from renal vascular damage in grade III injury, or extravasated urine in grade IV injury. Hence, medially present collections should be more carefully evaluated. Grade III injury (Fig. 10.12.5.2.1) accounts for 22%–26% of cases. It is characterized by renal parenchymal laceration >1 cm in depth without involvement of collecting system and any low-grade trauma with associated vascular injury or active bleeding limited by Gerota fascia. Laceration involves the renal cortex and medulla. When deep lacerations are present, it is important to check the status of pelvicalyceal system. Presence of homogeneously enhancing renal tissue around the calyx on nephrographic phase and absence of extravasation of contrast on excretory phase helps to rule out pelvicalyceal system injury. Criteria for vascular injury is newly added in the 2018 OIS revision and includes pseudoaneurysm and arteriovenous fistula. Collectively, it is referred as contained vascular lesions. Pseudoaneurysm is well-defined, oval or round collection limited to the renal parenchyma or lacerated segment showing post contrast enhancement. Arteriovenous fistula is diagnosed when there is distension and early enhancement of the renal vein during the arterial phase. These contained vascular lesions follow enhancement pattern of adjacent renal artery and aorta and on delayed images remain similar in size and morphology. In contrast, active bleeding tends to track into surrounding tissue and limited to Gerota fascia. It has linear or flamelike appearance. It has a tendency to increase in size and retained a higher density than the renal artery and aorta on delayed images.

FIG. 10.12.5.2.1 Contrast-enhanced CT axial image of a patient showing laceration (>1 cm of depth) involving right kidney with perinephric haematoma – AAST Grade III injury. High-grade renal injuries Grade IV injury accounts for 15%–19% of cases. It is characterized by renal parenchymal laceration involving collecting system, renal pelvis laceration or complete pelviureteric laceration, intimal injury/thrombus of segmental renal artery or vein, segmental or complete renal infarction due to renal vessel thrombosis in the absence of active bleeding, and active bleeding outside Gerota fascia into the retroperitoneum or peritoneum. Injury to collecting system is considered when the renal lacerations are deep and extends through the renal calyces, renal pelvis and ureteropelvic junction. Its definitive diagnosis is made when there is presence of extravasation of excreted contrast beyond the collecting system during the excretory phase. Hence delayed phase must be acquired in case of suspected renal injury Ureteropelvic injuries are often associated with renal injury. Occasionally, it can occur in isolation. Isolated renal pelvic injuries can present as medial fluid collection around the pelvis. There are two types of ureteropelvic injury. In complete ureteropelvic avulsion, majority of the lumen is disrupted. There is absence of excreted contrast in the distal ureter and presence of excreted contrast around the injured renal pelvis. In partial ureteropelvic avulsion, lumen is partially disrupted. There is presence of excreted contrast in the distal ureter and around the injured renal pelvis. Segmental or complete renal infarction occurs due to segmental or complete thrombosis of the renal artery. Thrombosis is the result of intimal tearing or dissection secondary to shearing forces. Segmental infarcts manifest as a welldefined wedge-shaped area of non-enhancing hypodensity in the renal parenchyma during the corticomedullary and pyelographic phases. It has wider base at the renal capsule and apex towards the renal hilum. Complete renal infarct manifest as non-visualization of the entire kidney with abrupt cut-off of the renal artery on contrast-enhanced scan. Active bleeding is absent when the devascularization is secondary to complete renal artery thrombosis. Active bleeding in grade IV injury extends

beyond Gerota fascia and spread into the anterior perirenal space, posterior perirenal space or peritoneum. On contrast-enhanced ultrasound, it is visualized in early stage as microbubble extravasation in perinephric area. It increases in size and density on delayed CT images. Grade V injury (Fig. 10.12.5.2.2A and B) accounts for 6%–7% of cases. It is characterized by main renal artery or vein laceration or avulsion from renal hilum, complete devascularization of kidney with active bleeding, and shattered kidney. Renal pedicle injuries are not common. Early detection and treatment of traumatic thrombosis or avulsion of renal artery is must because permanent, progressive loss of renal function starts after 2 hours of warm-ischemia time. In renal artery thrombosis, kidney perfusion is typically absent on contrast-enhanced ultrasound. Contrastenhanced CT reveals abrupt truncation of renal artery just beyond its origin, infarction of the entire kidney with or without cortical rim sign and retrograde opacification of the renal vein from the inferior vena cava. Perinephric haematoma is typically absent in main renal artery occlusion. Cortical rim sign may be absent in acute injury and is reported to occur as early as 8 hours after injury. In cortical rim sign, there is a thin capsular and subcapsular enhancement due to intact blood supply from the capsular, peri-pelvic and periureteric vessels. Renal venous thrombosis is suggested by enlarged kidney, absent opacification of the renal vein, presence of filling defect in the renal vein, a persistent nephrogram, and delayed excretion of contrast into the collecting system. Avulsion of renal artery causes complete devascularization of the kidney. It is uncommon and life-threatening injury. It is caused by tearing of tunica muscularis and adventitia. Contrast enhancement CT reveals global infarction of the kidney, large medial perinephric haematoma around the aorta and renal hilum, and active arterial extravasation of contrast from the disrupted stump. This is in contradiction to grade IV injury in which devascularization is caused by vascular thrombosis without active bleeding. Shattered kidney is severe form of renal laceration. Several lacerations result in multiple fragments and loss of detectable renal parenchyma. The differentiation between the shattered kidney and multiple lacerations of lower-grade injury is subjective. The term shattered (Fig. 10.12.5.2.3) denotes extreme grade of tissue damage that prevents any meaningful healing and is usually associated with urine leak and active bleed. Imagine finding that raise suspicion of major renal injuries are medial haematoma indicating vascular injury, medial urinary extravasation of excreted contrast indicating renal pelvis or ureteropelvic junction injury, global lack of contrast enhancement of the renal parenchyma indicating renal artery occlusion, and combination of two or more of the following: haematoma more than 3.5 cm, medial renal laceration, and vascular contrast extravasation indicating brisk active bleeding.

FIG. 10.12.5.2.2 (A and B) (CT axial) images showing splenic injury with complete devascularization of left kidney due to vascular pedicle avulsion – AAST Grade V injury.

FIG. 10.12.5.2.3 Contrast-enhanced CT Coronal image of a young female patient with history of blunt trauma to abdomen showing shattered kidney – AAST Grade V injury. Box 10.12.5.2.1 includes the essential elements of renal injury to be mentioned in the report. Box 10.12.5.2.1 E SSE NT IAL E LE ME NT S T O B E INC LU D E D WHILE R E PO R T ING R E NAL INJU R IE S O N C E C T

• Presence or absence of renal contusions and subcapsular haematoma • Depth and severity of lacerations • Extent of perinephric haematoma • Active bleeding and its extent • Status of renal vessels, pelvicalyceal system, and pelviureteric junction • Associated injuries Management Radiological assessment should give clear idea about the AAST grade of injury that helps to decide the treatment options. Important parameters that the clinician want to know are presence or absence of renal contusions and subcapsular haematoma, depth and severity of lacerations, extent of perinephric haematoma, active bleeding and its extent, status of renal vessels, pelvicalyceal system and pelviureteric junction and associated injuries (Table 10.12.5.2.2). Nonoperative management is the standard of care in hemodynamically stable patient regardless of AAST grade. Aims of conservative management are to reduce negative explorations and unnecessary repairs, avoid needless nephrectomy, increase the rate of renal salvage, and avoid long term complications like dialysis. Almost all grade I, II and few grade III renal injuries are treated conservatively with bed rest, analgesics, and hydration. More than 80% of collecting system injuries not involving the renal pelvis and ureter resolves spontaneously. Drainage procedures are indicated in patients with an enlarging urinoma, haematoma, abscess, fever, and increasing pain. Drainage should be achieved either with ureteral stent, percutaneous nephrostomy, or percutaneous catheter placement. First, ureteral stent placement or percutaneous nephrostomy is considered in case of persistent urinary extravasation. When perinephric collection persists in spite of stenting or nephrostomy, percutaneous catheter drainage should be considered. Role of angiography and embolization (Fig. 10.12.5.2.4) Nowadays, angioembolization is increasingly used in renal trauma. It is crucial adjunct for the successful conservative management of renal injuries. It increases the chances of renal salvage and preservation of renal function. Inappropriate settings, super-selective embolization is used to stop significant renal bleeding without the need for laparotomy. In selective cases, endovascular stents have been used in patients with renal artery thrombosis occurring secondary to intimal flaps. Indications of angioembolization are contained vascular injuries in hemodynamically stable patients, intravascular contrast extravasation, perinephric haematoma of more than 3.5–4 cm and medial site of injury. Operative management is reserved for hemodynamically unstable patients. Indications for laparotomy are life-threatening haemorrhage, renal pedicle injury, ureteropelvic junction avulsion, shattered kidney, rapidly expanding retroperitoneal haematoma, failed conservative treatment, and associated pancreatic or bowel injuries or significantly devascularized tissue in grade III or IV lacerations. These injuries have more risk of delayed complications like secondary haemorrhage from an arteriovenous

fistula or pseudoaneurysm, urinoma or perirenal abscess, and renal hypertension. Depending on the severity of injury, repair of the main renal artery or vein or partial or total nephrectomy are surgical options to achieve early control of bleeding. Most surgeons concur that vascular repair should be done within 4 hours of injury if optimal renal function is to be expected. Most surgeons avoid surgery and allow the devascularized kidney to atrophy if the renal ischemia exceeded 4 hours and the opposite kidney is normal. If devascularization injury involves bilateral or a solitary kidney, reconstruction surgery is attempted even if the ischemia time has exceeded 4 hours.

FIG. 10.12.5.2.4 A and B Contrast-enhanced CT axial image (A) and right renal angiography (B) image showing posttraumatic right renal pseudoaneurysm. Follow-up imaging can be safely omitted in low-grade renal trauma and grade IV renal trauma without urinary leak. Purpose of reimaging is to diagnose possible complications and to assess cause of clinical deterioration Reimaging is recommended after 2–4 days in patients who had grade IV renal injuries with urinary extravasation on baseline scan, contained vascular injury, grade V renal injuries, and patients with signs of complications like fever, increasing flank pain, and abdominal distension. This timeframe allows contained vascular injuries to develop or urinoma to clinically progress. Fluid collections present on successive imaging in renal injury are either haematoma, urinoma, or abscess. Urinoma density ranges from 0 to 20 Hounsfield units and it shows contrast pooling during excretory phase. Haematoma density is generally more than 30 Hounsfield units and it does not show enhancement on postcontrast images. Abscess density is around 20 Hounsfield units and it shows peripheral enhancement on postcontrast images. Contrast pooling during excretory phase is absent in haematoma and abscess. Complications Complications occur in 3%–10% of patients. Early complications are bleeding, infection, abscess, sepsis, urinary fistula, urinary extravasation with urinoma formation and hypertension. Most common complication is urinoma formation. Late complications are hydronephrosis, arteriovenous fistula, pseudoaneurysm, delayed hypertension, calculi and chronic pyelonephritis.

Ureter injuries Introduction Ureteral injuries are uncommon because they are present deep in the retroperitoneum and well-protected by fat and surrounding organs. They comprise less than 1% of genitourinary trauma. Only 20% injuries occur secondary to external trauma, with most due to penetrating trauma. Stab injury causes direct damage to short segment of ureter by penetrating object. Remaining 80% injuries are iatrogenic during intraabdominal surgeries. High-energy force in blunt injury results in rapid deceleration. It injures the ureters at fixed points, commonly at ureteropelvic and vesicoureteral junctions. It is often associated with injury to other organs mainly small and large bowel, kidney and urinary bladder. High energy also causes uncommon injuries like fracture of lumbar process and dorsolumbar spine dislocation. Hence, the presence of high-energy forces like fall from height or high-speed motor vehicle crash should always raise the suspicion of ureteral injury. Clinical features Patient often presents with gross or microscopic haematuria and flank pain. Ecchymosis may be present in flanks. As with renal injuries, haematuria is an unreliable indicator of ureter injury. It may be absent in one-quarter of patient. Variable clinical symptoms, rarity of ureteral injuries, and difficulty in clinical judgment often result in delay in diagnosis of ureter injury. Hence radiologists play a crucial role in identifying ureteral injuries. AAST grading system is used to guide the management (Table 10.12.5.2.2). The grading system is surgical and not well correlated with the imaging. Detection of ureteral contusions and degree of laceration are the major limitations of imaging. Distinction between grade II and III injury is almost impossible with any imaging technique. Role of radiologist is to detect partial laceration, complete transection, and its location. This distinction is important because partial lacerations are treated with stenting and complete transection require surgical repair. Acquisition of delayed images is very important to detect ureteral injury. Detection of contrast-opacified urine outside the confines of the ureter on excretory phase support the diagnosis of ureteric injury (Fig. 10.12.5.2.5). Presence or absence of contrast in the ureter distal the site of injury allows distinction between ureteral laceration and transection. Contrast will be present in the distal ureter in laceration and absent in transection. Opacification of distal ureter may be absent in transection, clearance of excreted contrast from the distal ureter by peristalsis, absence of distal passage of contrast due to poor peristalsis, or compression by nearby collection.

TABLE 10.12.5.2.2 AAST OIS Grading for Ureter Injuries Grade Type Injury I Haematoma Contusion or haematoma without devascularization II Laceration 50% transection IV Laceration Complete transection V Laceration Complete transection with devascularization

FIG. 10.12.5.2.5 Contrast-enhanced CT axial image (delayed phase) of a patient with history of blunt trauma to abdomen showing extravasation of contrast from left ureter (white arrow) suggestive of ureteric injury.

Lower urinary tract trauma Patients with injuries to the lower urinary tract (LUT) are being encountered more frequently in the radiology department as the incidence of severe trauma appears to be on the rise, mostly due to RTAs. The most common association of bladder and urethral injuries is with pelvic fractures. The LUT trauma occurs with pelvic fracture in highspeed collisions, run over of pedestrians or falls from heights. There is a high incidence of associated vascular damage, abdominal and thoracic visceral, ribcage, spinal and head injuries. Steering wheel impact may cause a distended bladder to burst from the steep rise of internal pressure. Imaging includes assessment of pelvic ring, vascular supply, urinary bladder, posterior male urethra, female urethra, anterior male urethra and the scrotum. These may each require a particular imaging modality or technique. Applied anatomy

The urinary bladder is a collapsible, muscular organ. When empty, it is protected from injury as it lies deep inside the pelvis and rests on the pelvic floor. When distended, it may reach up to the umbilicus. The bladder can be divided into a broad fundus, a body, an apex and a neck. The fundus or dome is the most mobile and weakest part of the bladder. The apex of the bladder is directed anteriorly towards the superior aspect of the pubic symphysis. The median umbilical ligament is seen extending from the apex of the bladder to the umbilicus along the anterior abdominal wall. It carries the peritoneum along with it forming the middle umbilical fold. The perivesical space lies under this peritoneal fold. The peritoneal reflection continues to form the recto-vesical (or uterovesical) pouch. The superior surface is related to intraperitoneal viscera like the intestine and the body of the uterus. The inferolateral surfaces of the bladder are related to the retro-pubic space of Retzius. Anterior to the urinary bladder and posterior to the pubic symphysis lies the retropubic space of Retzius which contains veins and a pad of fat. The transversalis fascia separates the space from anterior abdominal wall musculature. This potential space extends up to the umbilicus. The detrusor muscle is the thick muscular layer of the urinary bladder, made of smooth muscle fibres arranged in spiral, longitudinal and circular bundles. The trigone is a triangular part of its wall, between ureteral and internal urethral orifices, that forms the floor of the bladder above the urethra. It presents a smooth area of the bladder mucosa, in contrast to the rest of the irregular inner surface marked by rugae, a series of ridges, thick mucosal folds that allow for the expansion of the bladder as it fills. The trigone faces backward and downward and is related to the seminal vesicles, ductus deferens in men, and the vagina and cervix in women. The area surrounding the internal urethral orifice at the base of the trigone is described as the bladder neck. trigone A mucosal flap, ‘The Uvula of urinary bladder’ overhangs the internal urethral meatus posteriorly in the neck of the bladder. It probably plays a role in maintaining continence. Hypertrophy of the median lobe of prostate accentuates its obstructive effect and likely results in incomplete voiding or postvoid dribbling. The extraperitoneal parts of urinary bladder and the posterior urethra are fixed to the pelvic walls and thus more vulnerable to the shearing forces generated by rapid deceleration. Disruption of binding ligaments occurs with pelvic fractures, due to severe crushing/shearing forces. Intraperitoneal bladder injury occurs on a full bladder, due to rupture of the dome along with its investing layer of peritoneum. It may occur due to a direct impact on a distended bladder, even in absence of a pelvic fracture. This type of injury may occur more commonly in childhood due to the greater intraabdominal location of the bladder. The male urethra is divided into posterior and anterior parts. Posterior male urethra includes prostatic and membranous segments. The posterior urethra begins at the neck of the bladder and traverses the pelvic and urogenital diaphragms. The prostatic urethra, the most distensible part of urethra, is approximately 3.5 cm long. The verumontanum is a median ridge over the posterior wall of the urethral crest. The verumontanum or the colliculus seminalis is the summit of the urethral crest which is a median ridge over the posterior urethral wall. The prostatic utricle opens

as a diverticulum on the colliculus along with the ejaculatory duct. The proximal urethral sphincter has two components, the internal and the intrinsic. The internal sphincter continues from the detrusor muscle, surrounding the neck of the bladder and urethra till the lower end of the urethral crest. The intrinsic urethral sphincter is smooth muscle around the distal part of prostatic urethra. Both internal, as well as intrinsic sphincters, are innervated by sympathetic nervous system, primarily responsible for passive continence. Beyond the prostate, it continues as the membranous urethra. This segment is the narrowest part of the male urethra. It is approximately 1– 1.5 cm long. Sphincter urethrae, a band of striated voluntary muscle, arises from the posterior surface of pubic rami, and along with the transverse perineal, it encircles the membranous urethra, forming the external sphincter and inserts into the perineal body. The external urethral sphincter is under voluntary control, responsible for active continence. The male urethra is fixed to the pelvis at two points, the junction with the neck of the urinary bladder by puboprostatic ligaments and the membranous urethra by the perineal membrane at the floor of the pelvis. Injuries of the posterior urethra often involve these points. The anterior urethra in males is about 15–20 cm long and traverses through the corpus spongiosum. It runs over the ventral surface of the anus. It comprises of two parts, the bulbous (bulbar) and pendulous (penile) urethra. The membranous urethra enters the bulb of the penis below the floor of pelvis to join the bulbar urethra. The bulbar urethra has two components, a funnel-shaped proximal part and a distal part called the sump, which constitutes the widest part of the urethra. Both are located within the proximal part of corpus spongiosum of the penis, the bulb of the penis. The pendulous part of the urethra continues within the penis beyond the penoscrotal junction to the external urethral meatus at the tip of the glans penis. Within the expansion of the glans lies the dilatation called the navicular fossa of the urethra. The female urethra is 4 cm long, akin to the posterior urethra in the male (females lack anterior urethra). The proximal part of the urethral wall is made up of smooth muscle continuing from detrusor muscle of the bladder, the internal sphincter, responsible for continence. The lower urethra in the females is in close proximity to the anterior vaginal wall and the two are surrounded by the urethra-vaginal sphincter. This extends up to the inferior pubic ramus above the urogenital diaphragm. Injuries to the female urethra thus involve vaginal injury too. It is loosely attached to the pelvis and thus less prone to injury in pelvic fractures. The pelvic diaphragm consists of Levator ani muscles and their superior and inferior layers of investing fascia. Levator ani group of muscles comprise the pubococcygeus, the iliococcygeus and the puborectalis which converge from pelvic sidewalls to the perineal body. The coccygeus muscle and anococcygeal raphe complete the diaphragm posteriorly. It supports the viscera in the pelvic cavity, and surrounds the various structures that pass through it, namely the urethra, the rectum and the vagina in women.

Perineal Body is a wedge-shaped fibromuscular mass, containing both collagenous and elastic fibres as well as skeletal and smooth muscles. In females, it lies between anal canal and lower end (vestibule) of vagina, in males, between anal canal and root of penis. It is larger in the female than in the male and supports to the posterior wall of the vagina. It is the site of convergence of many perineal muscles, including the bulbospongiosus, superficial and deep transverse perineal muscle, sphincter urethrae, superficial and deep parts of external anal sphincter and the levator ani. Fascial membranes of the pelvic and urogenital diaphragms, as well as the Colle’s fascia of perineum, merge into it. The urogenital diaphragm consists of fat and muscles around the membranous urethra invested by superior and inferior fascial layers. The muscles of the urogenital diaphragm consist of flat sheet of striated muscle originating from the pubic bone and ischiopubic arch of the pelvis. These are placed obliquely, converging to insert in the perineal body. The anterior part of these muscles encircle the urethra and act as the voluntary sphincter. The posterior margin of the urogenital diaphragm is bounded by the superior and inferior membranes which also converge into the perineal body. The fascial layers fuse anteriorly below the pubic symphysis to form the transverse pubic ligament. The fat contained within the superior and inferior fascial layers is imaged on CT as a V-shaped lucency with one limb on either side of the apex of prostate. Superiorly, this fat plane communicates with fat contained within the ischiorectal fossa. Anteriorly, it is limited by the transverse pubic ligament. The space of Retzius between the urinary bladder and pubic bones communicates inferiorly with the subcutaneous perineal fat (superficial perineal space) anterior to the transverse pubic ligament. Superiorly, it communicates with fat in the anterior abdominal wall external to the transversalis fascia. It extends superiorly into the rectus sheath where the posterior fascial layer ends below the level of umbilicus. The superficial perineal space lies between urogenital diaphragm and Colle’s fascia, the membranous layer of superficial fascia which is continuous with the membranous layer of superficial fascia of anterior abdominal wall (Scarpa’s fascia). The deep perineal space lies between superior and inferior fascia of the urogenital diaphragm. Posteriorly both superficial and deep spaces are closed by the convergence and merging of all three fascial layers in the perineal body. Pudendal canal, also known as Alcock’s canal, is a sheath derived from the fascia of the obturator internus muscle and is found in the lower lateral wall of the ischiorectal fossa. The pudendal canal lies on the medial surface of the obturator internus muscle and the medial aspect of ischial tuberosity above the falciform ridge. It transmits the pudendal nerve with internal pudendal artery and vein from the lesser sciatic foramen posteriorly to the deep perineal pouch anteriorly. The nerve supply of the lower urinary tract is derived from three groups of nerves. The pelvic parasympathetic nerves cause urinary bladder excitation and urethral relaxation. The lumbar sympathetic nerves, on the other hand, cause excitation of the urinary bladder base and urethra while inhibiting the body of urinary bladder. The third group of nerves, that is the pudendal nerve contracts the external urethral sphincter.

Injuries of the urinary bladder The mortality (20%) and morbidity related to bladder trauma are high as a consequence of associated vascular, visceral and bony injuries and complications thereof, rather than bladder perforation itself. Urinary bladder trauma occurs in vehicular collision, fall from a height and pelvic crush injury. Rapid deceleration involves a shearing force that stretches and damages its ligamentous attachments along with the bladder walls. The seatbelt or a direct blow on a distended bladder may sometimes result in rupture without a pelvic fracture. Other causes are, penetrating injuries and iatrogenic injuries. Iatrogenic intraoperative injuries occur during endoscopic biopsy, prostatectomy, hysterectomy and emergency caesarian etc. If the patient has spina bifida or a previous spinal cord injury, there is limited awareness of bladder fullness and pelvic pain. The abdominal pain may be vague in onset and nature. A high index of suspicion in painless abdominal distension is needed in such cases. Intraperitoneal blood or urine may lead to ascites and ileus. Radiologic classification of bladder injuries is mentioned in Table 10.12.5.2.3. TABLE 10.12.5.2.3 Radiologic Classification of Bladder Injuries Type Injury 1 Bladder contusion 2 Intra Peritoneal rupture 3 Interstitial bladder injury (rare) 4 Extraperitoneal (EP) rupture 4a Simple 4b

Complex

5

Combined IP and EP

Radiographic Appearance Normal. These may involve contusion, intramural haematoma or incomplete laceration. Ill-defined contrast extravasation surrounding loops of bowel and in the paracolic gutters and pouch of Douglas. Contrast dissects into bladder wall, causing irregularity or filling defect; no contrast extravasation Contrast is limited to the perivesical space with linear streaks or a sunburst pattern The pelvic floor is breeched, and contrast may track up the retroperitoneal space and appear as an IP rupture; extravasation may extend to scrotum, penis, and anterior abdominal wall Combination of type 2 and 4

Complex injury involves ligamentous avulsion and breach of pelvic fascial planes by the severe forces that cause bone fracture and displacement. There is wide dispersal of blood, urine and inflammatory exudates into anterior abdominal wall, scrotum and perineum. The penis may swell and get discoloured due to haematoma, the ‘eggplant penis sign’.

In terms of clinical relevance, imaging investigations centre on differentiating EP from IP injury and simple from complex EP injury. Bladder injuries are classified by the AAST-OIS into five grades (mentioned in Table 10.12.5.2.4). TABLE 10.12.5.2.4 AAST OIS Grading for Urinary Bladder Injuries Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Includes contusion, intramural haematoma, and partial thickness laceration Extraperitoneal wall lacerations 2 cm and intraperitoneal lacerations 2 cm Intraperitoneal or extraperitoneal lacerations that extend into the bladder neck or trigone

Another classification system endorsed by a consensus panel of the Societe Internationale D’Urologie (International Society of Urologists). According to this system, bladder injuries are classified into four types. This system classifies bladder injury into following four types but it does not account for the extent of bladder wall laceration: Type 1: Contusion of the urinary bladder. Type 2: Intraperitoneal urinary bladder rupture. Type 3: Extraperitoneal urinary bladder rupture. Type 4: Mixed injury. Radiologic investigations are better suited for the above classification system. It is so because imaging focuses on assessing the presence of the full-thickness tear which manifests as extravasation of contrast on Contrast-enhanced CT or cystography. Contusions and incomplete lacerations, comprising type I bladder injury, present as haematuria with luminal and intramural haematomas in imaging studies. A urinary bladder may rupture into the peritoneal cavity (15%) or into the retroperitoneum (85%) or both (85%) Radiolucent

(7.2). b) Xanthine and Cystine Stones: Both are forms of radiolucent calculi, they are result of hereditary enzymatic defects, resulting in predisposing states of xanthinuria or cystinuria (an autosomal recessive trait), respectively. Rarely, patients on Allopurinol treatment may develop xanthine stones, as the drug action blocks conversion of xanthine to uric acid. c) Indinavir/Ritonavir Stones: An iatrogenic entrant to the stone family, these are protease inhibitor medications used in HIV patients, which are partly excreted in the urine. Having inherent low water solubility, they have tendency to precipitate easily. These calculi are unique in being genuinely radiolucent in that they are not visible on the unenhanced CT scan. They can become calcified on long-term, or be seen as filling defects in contrast opacified urine, and be suspected in the specific subset of patients.

FIG. 10.12.6.2 Postoperative spectrum of stone varieties. Radio-opaque calculi with descriptive nomenclature. (A) ‘Staghorn’ calculi Kidneys – Triple phosphate. (B) Spiculated bladder calculus – Calcium oxalate (black arrow); incidental finding of prostatic calcification (white arrow). (C) Laminated urethral calculus – Mixed calcium stone.

Urolithiasis – clinical challenges and imaging options Suspected urolithiasis is a common clinical condition requiring abdominal imaging in diagnostic practice. Depending on clinical presentation, treating doctor’s preferences and availability of imaging modalities, the range of investigations requisitioned for patients may vary from plain radiograph to MR Urography. Practitioners of Radiodiagnosis and

Urology, therefore, need to be aware of strengths, weaknesses and options within the spectrum of current imaging modalities. Clinical Presentations: 1. Acute: a) Renal/Ureteric colic: The typical acute presentation is patient with acute onset flank pain, commonly termed as ‘renal colic’. The calculus typically produces pain on impaction within the urinary tract, most commonly in the ureter. Pain is attributed to pelvicalyceal and/or ureteric dilatation proximal to level of impaction and smooth muscle contractions attempting to propel the calculus distally. The pain starts in the lumbar regions, with a characteristic ‘loin to groin’ radiation, and may extend further lower towards testes/labia. As these patients experience intermittent episodes of pain, they are seen to be ‘rolling around in pain’, quite unlike patients with peritonitis who avoids movement. b) Haematuria: Approximately a third of acute urolithiasis present with haematuria, with descriptions ranging from frank red to cloudy dark discolouration of urine. c) Other accompanying symptoms: May include frequency of micturition, dysuria and urgency. 2. Chronic: a) Symptomatic: Many patients only have vague or non-specific lumbar region discomfort, low backache or feeling of fullness/heaviness in flank, with intermittent aggravations. Chronic, unrecognised obstruction secondary to calculi can manifest rarely with hypertension or impaired renal function (Fig. 10.12.6.3). b) Asymptomatic: Majority of patients remain completely asymptomatic, till calculus grows in size or migrates and impacts within urinary tract to produces renal colic/haematuria. Many such ‘silent’ stones are being increasingly discovered incidentally, when lumbar spine/abdomen are radiographed or imaged on Ultrasonography (USG)/Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) for non-urological indications or during health check-ups.

FIG. 10.12.6.3 Long-standing effects of Urolithiasis. (A) KUB Radiograph showing bilateral renal calculi, with multiple calcified ‘cysts’ in the Right renal areas. (B and C) NCCT KUB Axial and Coronal images confirming bilateral renal calculi causing gross hydronephrosis and thinned calcified cortex (right kidney), with dilated upper pole calyces (left kidney). (D) DTPA Renogram confirming non-functioning right kidney. Radiological and imaging options Radiograph of kidney-ureter-bladder (KUB) regions Popularly requisitioned as ‘X-ray KUB’, this supine antero-posterior radiograph of abdomen-pelvis had been the only modality able to diagnose urolithiasis for many decades since induction of X-rays into medical practice. With 85%–90% of urinary calculi being variably radioopaque due to their calcium content, majority of them should be visible on an ideal KUB radiograph. Diagnostic finding on KUB radiograph is a welldefined radio-opaque shadow, which may be seen overlying renal area, ureteric course or pelvis (Fig. 10.12.6.4).

FIG. 10.12.6.4 Radio-opaque calculi in left renal (arrow), left ureter (arrowhead) and urinary bladder locations. Superimposition of bowel shadows over KUB regions highlights the necessity for good bowel preparation. Though economical and quick to perform, the overall sensitivity and specificity of KUB radiograph remain less than 60%, as it has multiple inherent drawbacks listed below: a) False-positive diagnoses: Due to overlap of KUB regions by other ‘high-density’ shadows i) Calcifications: Visceral (liver, spleen, pancreas, uterus etc), vascular (arterial, venous), lymph nodal (mesenteric, retroperitoneal) or within other pathologies overlying KUB. Among the vascular calcifications, phleboliths merit special mention as a common incidental finding of radio-opaque shadow in the pelvic region, which resembles distal ureteric calculus. Phleboliths are thrombosed veins which have undergone calcification, and typically have smooth rounded margins and central lucency (Fig. 10.12.6.5). ii) High-density bowel luminal contents: Foetal matter, undissolved tablets, enteroliths etc iii) Radio-opaque gallstones, overlying the Right renal area. b) False-negative diagnoses: i) Due to calculi overlying bony structures: Lower ribs, lumbar transverse processes, sacrum. ii) Due to low X-ray attenuation: Small-sized calculi; ‘radiolucent’ calculi (uric acid, struvite etc).

c) Inability to objectively demonstrate obstruction in patients with demonstrable calculus. d) Inability to identify alternative abdominal pathologies, which can mimic clinical presentation of urolithiasis, such as Acute appendicitis, diverticulitis. e) Uses ionising radiation, and preferably avoided in young adults and pregnant women.

FIG. 10.12.6.5 Typical oval-shaped radio-opaque phlebolith (red arrow) with central lucency seen in Left lower pelvis. Left ureter seen separate from the opacity. With current availability of alternative imaging modalities having better diagnostic accuracy, with comparable or superior biosafety profile, use of X-ray KUB should best be limited to: 1. Follow-up of calculus size and location in known patients of urolithiasis 2. For therapy planning purpose, to re-confirm calculus location on day of intervention 3. To check ureteric stent position and estimation of residual stone burden in patients who have undergone Extra-corporeal shock wave lithotripsy (ESWL) or Percutaneous nephrolithotomy (PCNL).

Protocol for Radiograph KUB: 1. Cassette size: Suitably large enough to cover the extent from renal areas to pubic symphysis, depending on patient size. A wellcentred 40 × 30 cm (15” × 12”) sized cassette in its long axis should cover most adult patients and a 30 × 25 cm (12” × 10”) sized cassette be suitable for children, in the Indian context. 2. Radiography: Patient lying supine on radiography table with Bucky facility, preferably using computed radiography (CR) or digital radiography (DR) technology. Central beam directed in midline at level of iliac crest. Exposure to be made with patient holding breath in expiration. 3. Radiograph pelvis (for bladder area only): Limited bladder area coverage can be done in specific instances using a 30 × 25 cm (12” × 10”) size film cassette, with tube angulated 15–25 degrees towards the feet. The cassette is positioned for central ray directed superior to pubic symphysis. 4. Bowel preparation: Superimposition by overlying bowel gas and foetal shadows can both mimic or mask calculi (Fig. 10.12.6.3). At many institutions, KUB radiograph is done after patient’s bowel preparation, with patient advised to take low residue diet and use mild oral laxative for preceding one or two days, and to report on empty stomach, preferably on the morning, for scheduled radiography. Ultrasonography (USG) Being a widely available, popular, non-invasive imaging technique based on the physical principle of reflection of high-frequency sound waves from acoustic interfaces, USG is a near-perfect modality with established biosafety to detect and localise calculi in most parts of the urinary tract, without radiation hazards. Stones cause complete reflection of incident sound waves from their surface producing the classical diagnostic imaging combination of hyperechoic (‘bright’/white) focus within urinary tract with posterior acoustic shadowing (Fig. 10.12.6.6). Additionally, USG also provides objective information about renal morphology and also detects dilatation of pelvicalyceal system and/or ureter as evidence of obstruction (Fig. 10.12.6.7). In the pelvis, the ureterovesical junction zone and moderately distended urinary bladder can easily be evaluated for calculi, wall thickening and real-time recording of ureteric ‘jet’ phenomenon. Vesical calculi are seen as mobile, echogenic intra-luminal lesions (Fig. 10.12.6.6). USG is, therefore, the investigation of choice at many centres for preliminary evaluation of all suspected/known patients of urolithiasis, including children, young adults and pregnant women.

FIG. 10.12.6.6 Calculus in the urinary bladder demonstrating diagnostic findings of echogenic focus with posterior acoustic shadow.

FIG. 10.12.6.7 USG findings in a patient with obstructing vesicoureteric junction calculus. (A) Dilated pelvicalyceal system in kidney. (B) Small echogenic calculus at the vesicoureteric junction. The limitations of USG, mostly relative to CT scans, are listed below: 1. Lower detection sensitivity rates for calculi in distal segment of ureters, as it may often be obscured by bowel gas. 2. Cannot differentiate between calculi and other intra-renal hyperechoic foci such as calcifications (arterial wall calcifications,

calcified urothelial tumours or calcified sloughed papillae) or rarely intra-renal gas. 3. Cannot differentiate chemical composition of stones, all having similar imaging findings. 4. Size estimation of calculi may not be precise. 5. Limited acoustic access leading to poor image quality in obese patients. 6. Limited value (when compared to NCCT) in identification of certain alternative abdominal pathologies, which are clinical mimics of urolithiasis. 7. Stone detection limited by stone size (low sensitivity of USG for stone less than 3 mm size), operator experience, grade of hydronephrosis and patient habitus. Protocol for USG-KUB Patient preparation: It is preferable for the patient to be having moderate urinary bladder distension. For the patient to be empty stomach also helps in optimal results by reducing interference by bowel gas. In the emergency room, patient would be examined without any specific preparation. Examination technique a) Grey-scale imaging: Patient can be examined in supine and oblique positions, conventionally with grey-scale imaging of the kidneys and urinary bladder using a convex sector transducer of 2–5 MHz, targeted at identifying calculi or backpressure changes within the KUB regions. i) Standard imaging planes of kidneys and urinary bladder are done for initial screening and image documentation. ii) Dilated ureter(s), if identified, can be traced with patient positioning and gentle probe compression to determine the cause and level of ureteral obstruction. iii) Observation of ureteral ‘jets’ during evaluation of the urinary bladder should be reported specifically. The ‘jets’ seen as streaming low-level echoes entering bladder lumen from the ureteral orifices, and are due to a combination of peristalsis induced fluid movement as well as density differences between the jet stream and urine contained within the bladder. iv) Interval re-scanning of the urinary bladder is warranted if the patient does not have an adequately distended bladder at time of preliminary scanning. b) Transvaginal/transperineal scanning with high-frequency probes may be of added value in detection of clinically suspected distal ureteric calculi, if not visualised on trans-abdominal scan. c) Doppler applications (supplementary role): i) If small renal calculi are suspected on grey-scale imaging, focused Doppler assessment using static and sweep images keeping high Pulse Repetition Frequency (PRF) values greater

than 60 cm/sec may demonstrate corroborative sonologic ‘twinkling’ artefact (Fig. 10.12.6.8) distal to calculi. ii) If ureteric calculi are suspected, scanning of the urinary bladder can be augmented to identify bilateral ureteral ‘jets’ by Colour Doppler (Fig. 10.12.6.9). Colour Doppler appearance and jet velocities can also help to assess degree of obstruction by ureteric calculi. Absence of ureteral ‘jet’ or depiction of continuous low-level jet are indicators of poor urine flow through ipsilateral ureter, implying high-grade upstream obstruction. iii) Unilaterally elevated Resistive Indices, using a thresh-hold value of more than 0.7 in renal cortical arterioles can be indicative of ureteral obstruction causing unilateral hydronephrosis.

FIG. 10.12.6.8 ‘Twinkling’ artefact distal to a small calculus on Colour Doppler.

FIG. 10.12.6.9 Colour Doppler images depicting ureteral ‘jets’. Computed tomography (CT) Unenhanced or Non-Contrast CT (NCCT) of KUB regions of abdomen is unequivocally the one-stop current imaging modality which provides the maximum clinically relevant information in patients of suspected/recurrent urolithiasis. NCCT-KUB, also called as ‘Stone-

protocol’ CT, not only overcomes all the limitations of KUB Radiography and USG, but also supports management decisions by providing additional objective inputs. The modality has excellent sensitivity and specificity of 95% and 98%, respectively, in the diagnosis of urolithiasis, and has completely replaced radiograph KUB/intravenous urography (IVU) in treatment planning protocols at many institutions. The advantages of NCCT-KUB in imaging Urolithiasis are: 1. Short duration of study for evaluation of complete KUB regions (10–15 seconds), without requirement of bowel preparation or iodinated contrast administration. 2. Excellent spatial and contrast resolution of the modern multidetector CT scanners, with a three-dimensional anatomic depiction of the entire urinary tract and near-isotropic multiplanar reconstruction (MPR) facility for definitive detection of stone along with its accurate anatomical localisation and size measurements. 3. Objective assessment of attenuation value of calculi in Hounsfield units (HU) which can help in determining stone composition. 4. Concurrent depiction of imaging features of urinary tract obstruction. 5. Detection of non-urological pathologies, such as acute abdominal inflammatory lesions and gynaecologic pathologies, which can mimic urolithiasis and present as flank pain or acute abdomen. Modifications of technique such as Low-dose NCCT protocols and technology advancements such as Dual Energy CT (DECT) have also found definite place in imaging algorithms related to urolithiasis. Low-dose NCCT-KUB protocols: As patients with urolithiasis are known to have high recurrence rates, they may undergo NCCT-KUB repeatedly during their management, where cumulative radiation dosage concerns need to be addressed. The same radiation dose concerns arise when children or young adults warrant evaluation by NCCT-KUB. Consequently, low-dose CT protocols have evolved to maintain high sensitivity to detect calculi while delivering radiation doses as low as 0.5– 1 mSv, which is equivalent to that of a KUB radiograph. The radiation dose reduction is achieved, at the cost of inevitable increase in image noise, by combination of: 1. Limited scan field size. 2. Exposure factors reduced to 80–90 kVp and 70–150 mA. 3. Application of Automatic Tube-current Modulation technology. 4. Use of Adaptive statistical iterative reconstruction algorithms to improve image resolution. Dual-Energy CT (DECT): DECT is a recent advancement in CT technology which has found definite application in renal stone imaging by its ability to determine stone composition based on attenuation differences. DECT works on the principle of simultaneous acquisition of paired CT images of the same body region at two different beam energy levels, typically at 80 and 140 kVp respectively. In the case of renal calculi with varied biochemistry, the stone composition can be predicted

depending on the difference in attenuation values which a particular stone generates at each of the two widely separated energy levels. It would thus be possible by DECT to definitively differentiate calcium-containing calculi from uric acid, cysteine and struvite stones. This information is of utility in therapy planning as specific calculi types like uric acid show excellent response to medical therapy, and avoids surgical intervention. Computer-aided colour-coded images and customised dual-energy ratio graphs can objectively show uric acid calculi separately from other varieties (Fig. 10.12.6.10).

FIG. 10.12.6.10 DECT application to differentiate stone composition. (Source: Courtesy of Dr Parang Sanghavi & Dr Bhavin Jankharia, Jankharia Imaging Centre, Mumbai, Maharashtra, India. ‘Applications of dual energy CT in clinical practice: A pictorial essay’ IJRI Sep 2019.) Relative contra-indication for NCCT-KUB: CT scans of the abdomen are preferably avoided in children, young adults and pregnant ladies due to its inherent hazard of ionizing radiation.

MRI MRI of the abdomen has inherent advantages of high soft-tissue contrast and anatomical detail, and avoidance of radiation exposure. MR Urography (MRU) can be performed using heavily T2-weighted sequences to demonstrate static fluid within a dilated urinary tract, but it offers no additional information compared to USG or NCCT-KUB in this respect. Its limitations are:

1. Time and cost-intensive technique, and also susceptible to motionrelated artefacts. 2. Low sensitivity for detection of urinary tract calculi. 3. Difficulty in differentiating low-signal intensity filling defects within the urinary tract. Excretory urography Evaluation of the urinary tract after intravenous administration of iodinated contrast and documenting its excretion into the pelvicalyceal system, ureters and bladder by IVU had been standard protocol in urology practice. In urolithiasis, IVU is useful for determining level and degree of obstruction, objective depiction of renal functional status and for identification of radiolucent calculi, which may be seen as filling defects within the contrast-opacified urinary tract lumen. However, the study has several limitations, as listed below: 1. Pre-requisites of good bowel preparation and normal renal functional parameters. 2. Administration of iodinated contrast medium, with its potential adverse effects. 3. Requirement of sequential radiographs, sometimes delayed up to 24 hours to demonstrate contrast opacification of dilated obstructed tract, and to confirm level of obstruction. 4. Limited primarily to evaluation of the urinary tract pathologies. IVU has been replaced in most urology centres by NCCT-KUB which can provide most information necessary to decide management. In the infrequent instances where contrast opacification of urinary tract to confirm calculus location or demonstrate ureteric course is deemed necessary for surgical therapy planning, the option of CT Urography (CTU) using conventional or hybrid protocols has found wide acceptance. CTU provides the required precise anatomical and functional details to the urologist, though with a relatively higher radiation dose to the patient, in comparison to IVU. Radiation exposure during investigation of urolithiasis: With the spectrum of patients needing imaging including young adults and pregnant ladies, and in patients with recurrent urinary stones requiring repeated radiographs or NCCT-KUB studies, radiation exposure and dosages during radiography and CT scanning is a matter of concern related to patient safety. Estimated radiation dose likely to be received by patient during radiological evaluation of urolithiasis is listed in Table 10.12.6.1.

TABLE 10.12.6.1 Imaging Modalities and its Effective Radiation Doses Investigation

Radiation Dose to Patient(in mSv)

1. Radiograph KUB

0.7–1

2. IVU (6–9 films)

03–06

3. NCCT-KUB

03–04

4. Low-dose CT-KUB

0.5–0.7

5. CT Urography (standard protocol)

06–18 (approx. 3–6 mSv per phase)

Considering all factors such as patients age, clinical presentation, available modalities of investigation and associated biosafety concerns, a broad-based algorithm for imaging evaluation of suspected urolithiasis and follow-up is suggested in Table 10.12.6.2.

TABLE 10.12.6.2 Imaging Algorithm for Urolithiasis

Abbreviations: USG: Ultrasonography, NCCT: Non contrast Computed Tomography, KUB: Kidney Ureter and Bladder, MRI: Magnetic Resonance Imaging, MRU: Magnetic resonance Urography, DECT: Dual Energy Computed Tomography. ~Abnormal renal morphology: Hydronephrosis, cortical thinning, renal contour abnormality

Imaging algorithm – urolithiasis Urolithiasis – radiologic and imaging findings Having familiarized with the pathogenesis and biochemistry of urinary ‘stones’, and with insight into various radiologic and imaging techniques

available to diagnose them, it is pertinent to understand the importance of diagnostic imaging findings in determining treatment decisions. Duly considering the clinical presentation, every aspect of diagnosis such as stone location, size, accessibility, composition and evidence of obstruction have impact on the timing and type of therapeutic intervention optimal for patient, which can range from medical therapy, ESWL, PCNL or Surgery which can be ureteroscopic (URS), laparoscopic or open. 1. Stone Location: After the preliminary visual confirmation of calculus within urinary tract on any imaging modality, the next vital step is to determine its location. Renal and urinary bladder calculi are the easiest to identify and localise in their expected typical locations in the lumbar regions and pelvis respectively, as imaging access to these sites is relatively unobstructed on any modality (Fig. 10.12.6.3). Calculi seen in unusual locations on KUB radiograph may need further evaluation to rule out congenital anomalies like ectopic kidney and horseshoe kidney, or a grossly dilated calyceal system (Fig. 10.12.6.11). In the kidney, it is important to identify the location within specific calyx or renal pelvis, and measure the stone-to-skin distance (SSD), influencing surgical and ESWL options. Lower calyx calculi and SSD more than 10 cm often have unfavourable responses to ESWL. Knowledge about relative location of solid organs and/or hollow viscera adjacent kidneys is also value addition to avoid potential complications during PCNL.

FIG. 10.12.6.11 Algorithmic approach to Urolithiasis: (A) Radiograph KUB showing a radioopaque calculus-(white arrow), right side, L3 level. (B) USG KUB: Right upper ureteric calculus (black arrow); with proximal dilatation. (C) USG pelvis: Showing distended urinary bladder with right ureteric ‘jet’ on Doppler. (D) NCCT KUB: Coronal curved MPR image confirming right upper ureteric calculus (white arrow) causing partial luminal obstruction. Ureteric calculi can pose challenge in their localisation especially on KUB radiographs and USG due to abdominopelvic non-linear anatomic course of ureters. NCCT- KUB is the best imaging modality to confirm location of these calculi, and provides additional information about hydroureter and periureteric soft tissues. The current trend favours URS or ESWL options in symptomatic ureteral calculi. Three common sites of ureteral luminal narrowing where calculi are prone to impact are wellrecognised at: i) Renal pelvis-ureter junction. ii) Site of common iliac vessels crossing the ureter, at bony pelvic brim. iii) Uretero-vesical junction, where the terminal part of the ureter has its minimum diameter of 1–5 mm while traversing an oblique course spanning 2–3 cm within the bladder wall. 2. Stone Size:

Stone size is to be measured and documented in its longest dimension in imaging report, having direct implications on management decisions. Spontaneous passage of calculi is well known, occurring in 90% measuring less than 4 mm, 60% between 5 and 7 mm, 50% between 7 and 9 mm and only 25% if larger than 9 mm. Stones less than 7 mm in size which do not exit spontaneously are likely to respond to non-surgical methods such as medical expulsive therapy using fluid pre-load and diuretics whereas calculi larger than 9 mm usually require urologic intervention. Broad-based treatment recommendations in respect of symptomatic intra-renal calculi are also related to stone size, as listed below: Size of renal calculus Less than 1 cm Between 1 and 2 cm More than 2 cm

Surgical recommendation ESWL or URS ESWL, URS or PCNL PCNL or surgery

3. Stone Composition: Biochemical constituents of calculi contribute to their physical attributes, which in turn influences their nomenclature, detection, treatment and prevention. As all stones reflect incident sound waves, USG can detect stones but cannot differentiate biochemical types. On the other hand, modalities such as KUB radiography and NCCT-KUB utilising property of differential X-ray attenuation by the calculi can predict their chemical composition. The terminology of radio-opaque and radiolucent calculi have originated from their visibility on KUB radiographs where the calcium content of calculi determined their radio-opacity (Fig. 10.12.6.12). NCCT-KUB has become modality of choice, with its objective ability to measure attenuation values of calculi as Hounsfield Units (HU), from which stone biochemistry can be inferred with reasonable accuracy. HU value ranges of urinary tract calculi are listed below: Stone Biochemistry Calcium oxalate Calcium phosphate Triple phosphate, Cystine Uric acid, Xanthine Pure Struvite Indinavir, Matrix

CT Attenuation Values (in HU) at 120 kVp 1700–2800 1200–1600 600–1100 150–450 40–60 15–30

FIG. 10.12.6.12 Radio-opaque calculi in unusual locations: (A) Bilateral renal calculi in a medial location indicative of horseshoe kidney. (B) Far-lateral location of left renal calculi suggestive of gross hydronephrosis. (C) Central pelvic location of calculus in ectopic left kidney anterior to the sacrum. It is indeed noteworthy that due to its inherent sensitivity to beam attenuation, NCCT can detect even noncalcium-containing calculi such as uric acid, cystine and xanthine; in fact, the only genuinely radiolucent calculi on NCCT are rare types like pure struvite, Indinavir and matrix. CT technology advancement of DECT introduced a new imaging dimension in stone composition determination, and can accurately separate calcium, uric acid, struvite and cystine contents. The importance of estimating stone biochemical composition on imaging is related to its impact on treatment choices. Uric acid calculi respond well to urine alkalinization and medications to regulate predisposing hyperuricemia; Calcium and cystine stones are relatively resistant to ESWL, while struvite calculi can be treated with ESWL only. Heterogenous stone density on CT images, implying triple phosphate or mixed biochemical constituents, are more likely to result in favourable ESWL response than homogenously dense stones. 4. Urinary tract obstruction: A key determinant of both symptomatology and timing of therapeutic intervention is obstruction of urinary tract by calculus. It is therefore important to identify diagnostic features of obstructive uropathy, with primary finding being presence of dilated tract proximal to level of the calculus. Radiograph KUB is the least useful in this respect, with the only indirect evidence being an enlarged renal shadow. USG can easily detect pelvicalyceal system dilatation, as a ‘splitting’ of the echogenic central sinus complex in early-stage and overt hydronephrosis in later stage (Fig. 10.12.6.7). Indirect signs on USG are ipsilateral completely absent or continuous low-grade ureteric jet and unilateral renal cortical resistive index more than 0.7 or being 0.08–0.1 more than the normal side. NCCT KUB is once again the modality of choice in detecting obstruction due to calculi, with its high sensitivity and specificity in diagnosing and

localising the causative stone, coupled with spectrum of secondary signs confirming tract obstruction by ureteral calculi: 1. Ipsilateral hydronephrosis and/or hydroureter proximal to obstructing calculus (Fig. 10.12.6.13), seen as pelvicalyceal system and/ureter distended with hypodense fluid (urine). 2. Effacement of pericalyceal fat plane (Fig. 10.12.6.14). 3. Perinephric fat stranding (Fig. 10.12.6.14), with thickened septae of Kunin, thought to be secondary to pyelolymphatic intravasation; this finding has a positive predictive value of over 90% for obstruction in the presence of calculus, but low specificity as it may also be seen in pyelonephritis, trauma, infarction, tumour and renal vein thrombosis. 4. Periureteric fat stranding (Fig. 10.12.6.13), perinephric fluid collection or pyelosinus extravasation, in patients with high-grade obstruction. 5. Other signs, compared to opposite side kidney (if unobstructed): (a) Relative reduction in renal cortical density (b) increase in renal size. 6. Named CT signs in urolithiasis: a) Soft tissue ‘rim’ sign: Thickened ureteric wall at site of impaction of calculus is called ‘rim’ sign (Fig. 10.12.6.15). b) ‘Comet tail’ sign: Visualisation of a curvilinear soft issue density ‘tail’ extending from a calcific focus (Fig. 10.12.6.15), usually in the pelvis, is likely to represent phlebolith which are incidentally seen venous calcifications located within pelvic and gonadal veins. Phleboliths may be difficult to differentiate from ureteric calculi on all modalities, as they often overlap the normal anatomic course of ureters, and rarely warrants excretory urography to discriminate (Fig. 10.12.6.5). As phleboliths do not exhibit any soft tissue rim, but have a trailing soft tissue ‘tail’, both ‘comet tail’ and ‘rim’ signs on NCCT are useful to differentiate ureteric calculus from phleboliths. c) Absent white pyramid sign: The medullary papillae in some patients can show uniform hyperdensity, compared to renal pelvis and cortex on NCCT termed as ‘white pyramid’. However, in the presence of acute unilateral obstruction, there is pyelotubular intravasation of urine resulting in dilated collecting tubules within the papillae, which may be seen as unilateral pyramidal hypodensity, described as the ‘absent white pyramid’ sign (Fig. 10.12.6.16). This sign though described in literature is not consistently identified or reported. d) ‘Steinstrasse’: German word meaning ‘street of stones’ is a radiologic/NCCT appearance of multiple small ureteric calculi arranged in a linear cluster within the ureter (Fig. 10.12.6.17) resembling a stone-paved path. It is usually a post-ESWL sequel representing fragmented proximal calculus, but can also occur de-novo in recurrent stone-formers.

FIG. 10.12.6.13 Coronal plane reconstructed image showing a right-sided proximal ureteric calculus causing obstruction and axial image demonstrating left periureteral fat stranding (white arrow).

FIG. 10.12.6.14 NCCT KUB Sagittal and Coronal plane reconstructed images showing right-sided proximal ureteric calculus causing obstruction with perinephric and periureteral fat stranding (white arrows). Note also loss of perisinus fat plane obliteration in the right kidney.

FIG. 10.12.6.15 Named CT signs: (A) Soft tissue ‘Rim’ sign left ureter – white arrow. (B) ‘Comet tail’ sign for pelvic phlebolith left side – black arrow; note that radio-opaque lesion has no soft tissue rim.

FIG. 10.12.6.16 ‘Absent white pyramid’ sign in obstructive hydronephrosis.

FIG. 10.12.6.17 ‘Steinstrasse’ appearance in course of right proximal ureter. Miscellaneous conditions associated with kidney stones 1. Medullary Sponge Kidney (MSK): MSK is a unique entity in that there is a congenital cystic dilatation of the distal collecting ducts within which small calcium stones form, likely due to stasis of urine. 2. Xanthogranulomatous Pyelonephritis (XGP): XGP is a chronic inflammatory process associated with renal pelvic calculi, causing destruction of renal parenchyma. Xanthomatous (lipidcontaining) focal areas within the kidney, presence of calculi and impaired renal function are hallmarks of this disease.

10.13: Bladder and urachus Priscilla Joshi, John D’Souza, Vandana Jahanvi

Introduction The urinary bladder is a part of the lower urinary tract. It is an extraperitoneal structure situated in pelvis and functions predominantly as a reservoir of urine. A variety of pathological conditions may involve the urinary bladder, which can be congenital, traumatic, infective, inflammatory and neoplastic. Most of these conditions manifest with dysuria, difficulty in micturition or haematuria. On imaging, few of these pathologies can show specific signs. But most of the lesions either present with focal or diffuse thickening of urinary bladder wall creating a diagnostic dilemma. Cystoscopy and histopathological examination in these cases help in coming to a final diagnosis. Imaging in such instances helps in assessing multiplicity of lesions, extravesical spread, the affliction of other organs and associated complications if any. Imaging modalities to assess the urinary bladder include radiography, ultrasonography, micturating cystourethrography, intravenous urography, CT and MR Urography. While USG remains the initial modality of choice, CT and MR because of their multiplanar capability are the preferred imaging modality in most of the cases, with MR providing superior soft-tissue contrast. However, conventional procedures like micturating cystourethrography and intravenous urography still have a role to play in diagnosis, particularly in patients with obstructive uropathy.

Urachal pathologies The urachus or the median umbilical ligament is developmentally the obliterated remnants of the allantois and the cloaca. It extends from the dome of the urinary bladder to the umbilicus in the midline (Fig. 10.13.1). It lies in the retropubic space of Retzius in between the transverse fascia and the parietal peritoneum and is extraperitoneal in location.

FIG. 10.13.1 Sagittal CT image showing the normal median umbilical ligament-obliterated urachus (white arrow). Failure of the urachus to obliterate may lead to four types of congenital Urachal anomalies (Graphic 10.13.1) which include: 1. Patent Urachus (most common, 47%) 2. Urachal cyst (30%) 3. Urachal sinus (18%) 4. Vesicourachal diverticulum (3%)

GRAPHIC 10.13.1 Pictorial illustration of urachal anomalies – patent urachus (black arrow in A), urachal cyst (asterisk in B), urachal sinus (black arrowhead in C) and vesicourachal diverticulum (white arrowhead in D) (Bl – bladder). Recent literature, however, suggests that the urachal cysts may be the most common urachal anomalies (69%). Urachal anomalies may remain asymptomatic and are sometimes incidentally detected. However, in a few cases, these are diagnosed when they presented with umbilical discharge, super-added infection, calculus formation or rarely when they develop neoplasms. Ultrasound remains the initial imaging investigations. Sinogram, Micturating cystourethrogram, CT and MRI are also helpful in diagnosing these anomalies and in evaluating for associated complications. Patent urachus

In this entity, the entire urachus remains patient, resulting in urinary leakage from the umbilicus. It is also known as a urachal fistula. It is generally diagnosed in the neonatal period when a persistent discharge from umbilicus, oedema around the umbilicus or delayed healing of the umbilical cord stump raises clinical suspicion. Ultrasound reveals tubular structure in midline extending from bladder dome to the umbilicus, containing anechoic fluid and with echogenic walls. Sinogram and micturating cystourethrogram show contrast-filled tubular tract between the umbilicus and the urinary bladder. Additionally, micturating cystourethrogram helps in ruling out vesicoureteric reflux which is believed to be associated with the patent urachus. CT or MR may be required if there is any doubt in diagnosis or to rule out complications. Urachal cyst The urachal cyst is formed when the superior and inferior ends of the urachus are obliterated, leaving behind a fluid-filled cystic structure. It generally involves the lower one-third of the urachus. Most of the times, the urachal cyst is incidentally diagnosed; however, imaging is warranted when there is any complication. Ultrasound reveals a well-defined cystic structure along the expected course of the urachus in the midline. CT and MR though not needed, may diagnose the cyst incidentally. Umbilical urachal sinus (Fig. 10.13.2) Urachal sinus is formed when the umbilical end of the urachus fails to obliterate, resulting in a blind outpouching of the urachus underneath the umbilicus. It is a potential space wherein cellular debris accumulates, and super-added infection may occur. Fluid stasis may also result in stone formation. Patient presents with intermittent discharge from the umbilicus.

FIG. 10.13.2 CECT axial image (A) of a patient who presented with recurrent foulsmelling discharge from umbilicus showing peripherally enhancing collection (white arrow) with air foci at the level of umbilicus in midline. CT sinogram sagittal image (B) revealed contrast lined tract (white arrowhead) communicating the collection with the external sinus confirming the diagnosis of urachal sinus with abscess formation. MIP coronal (C) and volume-rendered image (D) showing the same patient also having an incomplete duplex renal moiety on right side with ureteric calculus (asterisk) on left side. A sinogram study helps to rule out any communication with the urinary bladder.

Vesicourachal diverticulum This is formed when the vesical end of the urachus remains unobliterated resulting in an outpouching from the urinary bladder dome anteriorly in the midline. The diverticulum usually has a broad neck and therefore is not generally associated with complications as there is no urinary stasis. Imaging reveals (micturating cystourethrogram and Contrast enhanced CT) a tubular contrast-filled outpouching from the anterior bladder dome without any communication with the umbilicus. Management Symptomatic patients are usually treated surgically. Nowadays, however, symptomatic infants after birth may be treated conservatively with surgical treatment being employed only in cases with recurrent symptoms or when urachus fails to obliterate even at 1 year of age. Recommended operative treatment for urachal remnants is complete surgical excision of the remnant. Patent urachus and vesicourachal diverticulum extend up to the urinary bladder, and they thus require a bladder-cuff placement to avoid subsequent complications. Associations Urachal remnants may be associated with other genitourinary abnormalities like vesicoureteral reflux, hypospadias, meatal stenosis, crossed renal ectopia, umbilical or inguinal hernias, anal atresia, cryptorchidism, omphalocele and ureteropelvic obstruction. Complications Urachal remnants may give rise to the following complications: 1. Infection 2. Stone formation due to urinary stasis Infection is the commonest complication occurring in patients with persistent urachal remnants. Most common organism found in these cases is Staphylococcus aureus. Infection can lead to abscess or fistula formation, which can rupture, resulting in peritonitis and sepsis. Ultrasonography reveals complex echogenicities within the usually clear anechoic urachal remnant. CECT in such cases shows a peripherally enhancing heterogeneous collection or lesion. Enterography with positive oral contrast and sonography may sometimes be indicated to rule out a urachoenteric fistula. Neoplasms – These can be benign or malignant. Benign tumours are rare and can develop from any part of the

urachal tract. Benign tumours that can arise from urachal remnants include adenomas, cystadenomas, fibromas, fibromyomas, fibroadenomas and hamartomas. Malignant neoplasms that can occur in urachal remnants include adenocarcinomas, urothelial carcinoma, squamous cell carcinoma. Adenocarcinomas are less than 1% of all bladder cancers. However, 80% of cancers occurring in urachal remnants are adenocarcinoma. Urothelial, squamous and sarcomatoid neoplasms account for the remaining 20% of cases. Urachal adenocarcinomas are commoner in middle age and older men as compared to women. When they do occur they usually present with haematuria or palpable suprapubic mass. They are generally large at presentation with extravesical extension and hence have a poor prognosis. USG in such cases show a heterogeneous midline lesion. CT and MR are used for confirmation of the diagnosis and to evaluate for exact extent of the lesion, associated lymphadenopathy and metastases if any. Seventy per cent of urachal adenocarcinomas are calcified with the calcifications generally present at the periphery of the lesion. Thus, the presence of calcification in a midline mass at the expected location of urachus should raise suspicion of a urachal adenocarcinoma. On MRI, these show heterogeneous signal on T1W and T2W sequences, showing a predominantly hyperintense signal on T2W images; and show postcontrast enhancement. Imaging differentials A persistent omphalomesenteric duct may mimic patent urachus. In the omphalomesenteric duct, there is a communication of the anomalous tract with the bowel and not the urinary bladder, which can be confirmed on a fistulography study. Endometriosis in the bladder dome can mimic a urachal neoplasm. Urachal adenocarcinomas can also be mistaken as primary urinary bladder malignancy or carcinoma of the other pelvic organs. The vesicourachal diverticulum on imaging needs to be differentiated with postsurgical collections and simple urachal diverticulum. Characteristic midline location and communication with the bladder on cystography study helps in confirming this entity.

Infection and inflammatory conditions of urinary bladder Cystitis

Acute cystitis (Fig. 10.13.3) Etiopathogenesis: Acute cystitis most commonly occurs in women. It is defined as the infection of the bladder’s mucosal lining. Sexual intercourse and the use of spermicidal agents are some of the risk factors. Recent instrumentation, urinary bladder catheterization, bladder outlet obstruction, vesical calculi and neurogenic bladder facilitate the colonization of bacteria in the urinary bladder wall. Escherichia coli is the commonest cause of acute cystitis. Patients experience burning micturition, dysuria, suprapubic tenderness and even haematuria. Microscopic analysis of urine will reveal more than 1,00,000 per ml of bacteria in urine and the presence of pus cells. Imaging findings: History, clinical examination and laboratory investigations are adequate for the diagnosis of cystitis. Patients are usually referred for imaging to confirm the diagnosis and assess for predisposing conditions. Imaging may also serve as primary diagnostic modality if the patient presents with vague symptoms. Ultrasound requires an adequately distended urinary bladder to evaluate for cystitis. It shows urinary bladder wall thickening (>5 mm) and moving internal echoes. Care should be taken to look for renal, ureteric or bladder calculus and presence of any bladder diverticulum. Bladder outlet obstruction if present, may reveal thickened bladder wall with the presence of sacculations and trabeculations. Abdominal radiographs can be done to look for stones. Plain CT may also be performed for urinary calculi. The reporting radiologist should include the number, site of calculi and the CT attenuation values of the calculi in the report.

FIG. 10.13.3 Acute cystitis, prostatic abscess and right sided pyelonephritis: Contrast enhanced CT Abdomen study of a 75year-old male patient with burning micturition and fever spikes. Figure A demonstrates the irregular thickening of the urinary bladder (white arrow). Figure B and C show bulky right kidney with perinephric collection (white asterisk in B) suggestive of right pyelonephritis. Figure D shows peripherally enhancing collections within the prostate suggestive pf prostatic abscesses (white arrowhead). Eosinophilic cystitis Etiopathogenesis: Eosinophilic cystitis is an uncommon, chronic inflammatory disease involving the urinary bladder affecting both children and adults with a slight male predominance. Pathologically, it is seen as transmural inflammation of the bladder wall with the lamina propria most severely affected. Varying degree of fibrosis and necrosis is also appreciated. It can be idiopathic or can be seen in association with an adverse reaction to drugs or food, parasitic and nonparasitic bladder infection, autoimmune diseases, bladder carcinoma and eosinophilic

enteritis. Patients may present with haematuria, dysuria or urinary retention. Cystoscopy may reveal erythema, polypoidal or ulcerative lesions and bladder masses. Imaging findings: Urinary bladder wall in eosinophilic cystitis may be regular, normal or thickened. Single or multiple bladder masses can be seen which may be sessile. In the late fibrotic stage, the bladder is contracted and may be associated with hydronephrosis. On MRI, the bladder masses appear hyperintense relative to muscle on T1W and hypointense on T2W images. Enhancement is seen after intravenous gadolinium injection. A biopsy may be needed to rule out malignancy which may coexist with eosinophilic cystitis. Removal of causative agent results in a reversal of the disease process. However, transurethral resection of the bladder masses, coupled with antihistamine and steroid therapy, may be needed in a few cases. Chemotherapy- and radiation-induced cystitis Etiopathogenesis: Haemorrhagic cystitis may ensue after chemotherapy or radiotherapy. Chemotherapy-induced cystitis results from systemic or local therapy. Radiationinduced cystitis, on the other hand, results from external or intracavitary therapy for bladder or other pelvic malignancies. There is a breakdown of the urothelium resulting in haemorrhagic cystitis. The urothelium may then be covered with fibrinous exudates. When the bladder is severely affected, there may be bladder wall necrosis, incontinence, and fistula formation. Imaging findings: On imaging, radiation or chemotherapyinduced cystitis manifests as diffuse irregular thickening of the bladder wall. In haemorrhagic cystitis, a blood clot may be seen within the bladder lumen and may be easily differentiated from a bladder mass on ultrasound because it is generally mobile. On CT, the clot appears hyperdense. If a bladder neoplasm cannot be ruled out, a limited scan covering the bladder may be performed in a prone position when the clot occupies the dependent part confirming its mobile nature. On MRI, the bladder wall is oedematous and appears hyperintense on T2W images. In chronic severe therapy-induced cystitis, the urinary bladder is contracted, because of fibrosis. Calcifications may be uncommonly seen. This may result in hydronephrosis. Chronic changes in pelvic irradiation include fatty infiltration of pelvic organs and enlargement of presacral space. Gas within the bladder lumen is suggestive of fistula formation, and a fluoroscopic or CT cystogram study may be required to demonstrate the fistulous tract. In CT cystography, diluted water-soluble iodinated contrast is instilled into the urinary bladder

retrogradely. The contiguous axial sections at the level of the urinary bladder are then acquired, which may reveal contrast-filled curvilinear tract. Emphysematous cystitis (Fig. 10.13.4) Etiopathogenesis: Emphysematous cystitis is a rare acute inflammatory condition affecting the urinary bladder characterized by the presence of intraluminal and intramural air. Diabetes mellitus is the most important risk factor, and E. coli and Enterobacter aerogenes are the most common aetiological agents. Imaging findings: Conventional radiographs reveal mottled lucencies in the region of the urinary bladder, separate from the rectal gas. Ultrasonography may reveal abnormal thickening of the bladder wall with high echogenic areas that give dirty postacoustic shadows. The sensitivity of CT to detect emphysematous cystitis is very high. Both intraluminal and intramural gas are easily seen. Imaging differentials: Differentials of emphysematous cystitis include the causes of intravesical air, i.e. recent instrumentation, bladder catheterization, vesicovaginal and enterovesical fistulas. A CT cystogram study may be required to depict the fistulous tract.

FIG. 10.13.4 Emphysematous cystitis and left sided emphysematous pyelonephritis: NCCT abdomen study of a 64-year-old diabetic male with burning micturition and deranged renal function tests. Axial image (A) shows air within urinary bladder wall (white arrow) whereas coronal image (B) showing streaks of air (white arrowheads) within the left renal calyces. Schistosomiasis Etiopathogenesis Schistosomiasis or bilharziasis is caused by Schistosoma haematobium, a species of flukes which is believed to be endemic in Africa and the Middle East. It is the only species of flukes that affect the genitourinary system. Schistosoma may affect any organ of the genitourinary system, including the bladder, ureters, kidneys, seminal vesicles, testes, prostate and fallopian tubes, although bladder and ureters are most affected. Humans, the definitive hosts acquire this infection by coming in contact with freshwater contaminated with the cercarial stage of the fluke, which is excreted by the Bulinus snails (the intermediate hosts). The cercariae attach themselves to the skin and enter the human body by penetration. After going through various stages in the heart, lungs and hepatic portal system, the adult flukes finally lodge in vesicular venous plexuses surrounding the bladder base and prostate, and they there lay eggs. These eggs can stimulate a powerful immune response, can migrate through the host bladder and are excreted through urine or faeces. Thus, the first clinical sign of established genitourinary infection, that is haematuria generally occurs approximately 10–12 weeks after the initial infection.

Imaging findings: A spectrum of imaging findings (Table 10.13.1) can be seen in genitourinary schistostomiasis, which include the following: • Ureters and bladder: The deposition of eggs in the bladder and ureter induces a chronic granulomatous reaction. One of the earliest radiographic changes on IVU appears to be striations in the ureters and renal pelvis. A persistent ureteral filling is also initially seen on IVU followed by ureteral dilatation. The early stage of ureteral dilatation occurs predominantly due to functional abnormality rather than fibrotic obstruction. In later stages, strictures develop due to ureteral wall calcification and fibrosis. Schistosomiasis most commonly involves distal ureter below the iliac vessels crossing. The commonest site of stricture formation is vesicoureteric junction followed by distal ureter 2–5 cm above the VUJ. Due to urinary bladder involvement and calcifications, vesicoureteric reflux may be seen. On plain radiographs, parallel lines of calcification may be seen. Sometimes on IVU, polypoidal filling defects in bladder and ureter are seen. Ureteritis cystica and pyelitis cystica, which show air bubble-like filling defects in the ureter and renal pelvis, respectively, also may be seen at intravenous urography. Hydronephrosis demonstrated on IVU can be of three patterns: segmental (cylindric or fusiform), tonic and atonic. The segmental pattern of involvement is seen in 25% of cases with distal ureter being most commonly involved. Dilatation occurs proximal to areas of fibrosis which arises due to concentric replacement of ureteral muscle by fibrosis. Significant dilatation is not seen in segmental involvement. Around one-third of cases of hydronephrosis occur due to tonic hydroureter. Tortuous and thick-walled ureters characterize this pattern of involvement along with marked muscular hypertrophy. Generally, the whole length of ureter proximal to obstruction is involved with resultant functional stenosis and significant hydronephrosis.

TABLE 10.13.1 Imaging Findings in Genitourinary Schistostomiasis Organ Imaging Findings Involved Ureter Radiograph: Parallel calcifications IVU Findings: 1. Striations 2. Persistent filling 3. Stricture 4. Hydroureter (segmental, hypertonic, atonic) 5. Ureteritis cystica CT: Circular ureteric wall calcification with dilatation of involved segment. VCUG: VUR. Bladder

Radiograph: Bladder wall calcifications (‘foetal head in pelvis’, ‘egg-shell calcification’). IVU: Hazy outline, filling defect, pyelitic cystica, reduced capacity. CT: Bladder wall thickening and calcifications, reduced capacity, transformation into squamous cell carcinoma (sessile bladder wall lesion).

Kidney Prostate

Hydronephrosis, poor renal function and renal atrophy in long-standing cases. USG, CT: Prostatic calcifications, Dilatation of ejaculatory ducts. MR: Low signal intensity of prostatic parenchyma on T1W and T2W images.

Seminal vesicles Testes

Fallopian tubes

USG, CT: Calcifications. USG: Testicular oedema, testicular mass with heterogenous echotexture and intralesional colour flow (mimicking malignancy). CT: Tubal occlusion, abscess formation.

This hydronephrosis is reversible if the obstruction is relieved. The atonic pattern of ureteric involvement shows grossly dilated

and thin-walled ureters which lack peristalsis and have atrophic, fibrotic ureteral muscle. Schistosomal hydroureter usually precedes hydronephrosis. CT shows circular calcification of the ureteral wall, which is considered pathognomonic of this entity. Ureteral calcification is typically intramural and is associated with dilatation of the involved segment. This is therefore different from ureteral involvement in tuberculosis where calcifications are associated with nondilated ureters. If left untreated, hydronephrosis leads to deterioration of renal function. Voiding cystourethrography demonstrates VUR well. Initial stages of vesical involvement manifest as hazy and illdefined bladder outline on intravenous urography due to submucosal oedema and pseudotubercles. The bladder wall is thickened and ulcerated with multiple small flat papillomas. Schistosomiasis is believed to be the most common cause of bladder wall calcification in regions where S. haematobium is endemic. Bladder wall calcification occurs because of calcified dead eggs in the submucosa. The classic finding of a calcified bladder resembling a foetal head in the pelvis is considered pathognomonic of chronic urinary tract schistosomiasis. A shelllike rim of calcification can also be seen. The degree of calcification is proportional to the number of calcified eggs but not proportional to the number of eggs discharged in urine, which depends on the activity of the parasite. Bladder calcifications are first evident in the base of the bladder. In the late stages of infection, the bladder wall becomes fibrotic and contracted, resulting in a reduced capacity. The chronic schistosomal infection causes squamous metaplasia which may transform into malignancy. Schistosomiasis is strongly associated with squamous cell carcinoma. It is generally sessile, and not papillary like urothelial cell carcinoma. Purely intraluminal growth is not seen. Bladder wall thickening and calcification are seen due to a coexistent chronic S. haematobium infection and may pose difficulty in diagnosis. These tumours are most commonly found in the trigone and lateral wall of the bladder. • Kidneys: Renal involvement occurs late in schistosomal infection and is predominantly due to hydronephrosis, hydroureter and VUR. Long-standing cases may result in poorly functioning kidneys. • Prostate and seminal vesicles: Schistosomal involvement of prostate gland and seminal vesicles should be considered when they show calcification on ultrasonography or CT. Dilation of ejaculatory ducts may be seen and occurs due to distal fibrosis and obstruction. Chronic prostatitis occurs commonly in schistosomiasis and is often associated with seminal vesiculitis. On MR images, low signal intensity is seen in the peripheral zone of

the prostate gland on both T1- and T2- weighted images. This is usually not associated with any contour abnormalities; however, sometimes prostatic contour becomes nodular, and thus simulates malignancy. • Testes: Testicular schistosomiasis or bilharzial orchitis manifests as testicular oedema. But sometimes it may manifest as a testicular mass with heterogeneous echotexture and intralesional colour flow on Doppler, mimicking a malignancy. Similarly, epididymal lesions may look like neoplasms, infarcts or inflammatory lesions. • Fallopian tubes and female genitalia: Female genitalia is less commonly affected than male genitalia. Fallopian tubes if infected by S. haematobium, may develop tubal occlusion with subsequent abscess formation. Tubal calcifications are uncommon. Cervical oedema occurring due to schistosomiasis may simulate cervical carcinoma at the US. Schistosomiasis may also cause a vesicovaginal fistula, but it is believed to emerge as a complication rather than a cause; schistosome-induced fibrosis causing delayed fistula healing. Malakoplakia Etiopathogenesis: Malakoplakia is a rare granulomatous inflammatory condition characterized by the presence of von Hansemann histiocytes and Michaelis–Gutmann bodies on histopathological examination. It is highly associated with E. coli infection. But infection alone is not believed to be the cause. This condition is believed to arise due to defective macrophage function, but the exact aetiology is unknown. It is predominantly seen in individuals with diabetes mellitus and other immune-compromised patients. Von Hansemann cells, the pathological hallmark of this entity is histiocytes which contain intracytoplasmic bodies, the Michaelis–Gutmann bodies. These intracytoplasmic bodies have specific staining characteristics on histological examination. Demographics: The disease is more commonly seen in women. Although the genitourinary system is the most commonly involved organ system, this condition can involve almost any organ of the body. Bladder, ureter, prostate, kidney, female genital tract and retroperitoneal tissues are amongst the most commonly affected sites. Imaging findings: Malakoplakia presents with a myriad of imaging features. There can be multiple intravesical polypoidal enhancing lesions, or it can present with diffuse circumferential bladder wall thickening associated with vesicoureteral reflux and hydroureter. Sometimes it can be aggressive and extend into the perivesical spaces, even

causing osseous erosion. Ring-shaped calcifications which represent adherent calculi are known to occur in treated cases. Predominantly retrovesical mass involving the uterus and extravesical anterior mass are other uncommon findings. Because of its imaging features being similar to malignancy, diagnosis of Malakoplakia is primarily a histopathological one. Cystitis cystica and cystitis glandularis Etiopathogenesis: Cystitis cystica and cystitis glandularis are chronic reactive inflammatory conditions which develop due to long-standing irritation – irritants including infection, calculi and even tumour results in metaplasia of urothelium. The urothelium proliferates to form buds known as nests of von Brunn. These grow down into the subepithelial connective tissue and differentiate into cystic deposits (causing cystitis cystica) or develop into mucinsecreting glands (causing cystitis glandularis). The florid proliferation of these nests results in the formation of nodular masses in lamina propria. These differ from malignancy in lacking any cellular atypia or muscular invasion. Histopathological examination is required to differentiate this entity from malignancy. Follow-up is generally required because of rare association with adenocarcinoma. Imaging findings: They present as filling defects on cystography. Hypervascular polypoidal lesions may be seen on CT or MR. On T1-weighted images, these lesions are hypointense. On T2-weighted images they predominantly appear hypointense with a central branching high signal area which enhances on postcontrast images and represents the vascular stalk. Nephrogenic adenoma Etiopathogenesis: Nephrogenic adenomas are benign lesion which are believed to arise in response to chronic irritation due to infection, calculi or injury. The irritant induces urothelial metaplasia and results in the development of solitary or multifocal masses. Demographics: They are seen in older adults and are more commonly seen in men. They may, however, also occur in the paediatric age group. Bladder, ureter or urethra can be involved. These lesions can appear as sessile or intraluminal polypoidal growths that may grow to a significant enough size to cause obstruction or stricture. Imaging findings: On imaging, these lesions mimic malignancy. They appear as sessile or polypoidal masses or

manifest as irregular masses. Though they resemble malignancy, they differ from carcinoma in that there is no muscular invasion, and diagnosis can only be confirmed on histopathological examination. Genitourinary complications of Crohn’s disease Etiopathogenesis and demographics: About 4%–23% of patients with Crohn’s disease develop genitourinary complications. These complications generally occur in cases with chronic or severe disease. Although fistula formation is the most common genitourinary complication, patients may also develop other complications like obstructive uropathy and nephrolithiasis. Enteric fistulas are common in patients with Crohn’s disease; however, fistulas between the gastrointestinal tract and urinary system are far less common and occur in approximately 2%–3.5% of cases. Colovesical fistula is the commonest type of fistula to develop in the disease process. The occurrence of fistulas in males is found to be more and is attributed to the lack of protective effect of uterus and adnexa between the bowel and urinary system. Most commonly, fistulas arise from the sigmoid colon or terminal ileum and communicate with the bladder. Less commonly, rectovesical, rectourethral, anourethral, colovaginal, urethrocutaneous, vesicocutaneous and enteroadnexal fistulas may also occur. Other complications arising from Crohn’s disease include obstructive uropathy and nephrolithiasis. Fistula formation: Cystography and fluoroscopic barium studies were once routinely used for detection of enterourinary fistulas. But due to the advent of crosssectional imaging, Computed Tomography has now become the imaging modality of choice. CT provides an adequate assessment of the entire collecting system and gastrointestinal tract. On examination, findings to suggest enterourinary fistula include the presence of intravesical gas, adherence between thickened bowel and bladder wall and leakage of enteric contrast into the bladder lumen. Nowadays, MR (Fig. 10.13.5) is also being used for detection for enterourinary fistulas and is particularly useful in the detection of enterogenital fistulas because of its excellent soft-tissue contrast. Obstructive uropathy develops due to transmural enteric inflammation and ureteric compression and fibrosis. It may also occur due to ureteric encasement and usually affects the right ureter. Long-standing upstream hydronephrosis may eventually result in deranged renal function.

Nephrolithiasis is another urinary complication arising from Crohn’s disease and occurs due to abnormal intestinal hyperabsorption of oxalates resulting in the formation of calcium oxalate stone formation. Uric acid stones may also be formed and occur due to increased intestinal fluid and bicarbonate loss, causing acidic urine. Radiographs, Ultrasound and CT all depict nephrolithiasis, with CT being the imaging modality of choice.

FIG. 10.13.5 T2W coronal image (A) of a patient with multiple perineal sinuses and chronic abdominal pain showing communication (black arrow) between the superior wall of urinary bladder and bowel. T1W postcontrast image (B) showed enhancing thickened wall with the fistulous tract (white arrow) and bladder showing enhancement. T2W axial image (C) showed hypointense air foci (black arrowhead) within the bladder lumen in nondependent position. T2W axial image (D) at the level of perineum revealed multiple sinuses (white arrowhead). Neoplasms Bladder neoplasms account for 2%–6% of all neoplasms with cancer of the bladder being one of the more frequently occurring malignancies. The majority arise from the epithelium, the most common being from the urothelium which accounts for more than

90% followed by squamous cell carcinoma around 10% and adenocarcinoma being the rarest with an incidence of less than 2%. Other rare tumours include leiomyosarcoma, rhabdomyosarcoma, lymphomas and paragangliomas. The age incidence is 50–70 years, with men being more affected than women in a ratio of 3–4:1. Cigarette smoking, dye industry workers, specific geographic areas like North Africa and Egypt where bilharzia is prevalent, chronic bladder infection and bladder irritation by long-standing indwelling catheters are causative factors. Papillary tumours arise from the urothelium and are the most frequent. These lesions have a good prognosis; invasive papillary tumours are less common and have a poorer prognosis. Bladder infection and irritation show a higher incidence of squamous cell carcinoma and adenocarcinoma. The bladder is a four-layered structure, the innermost lining being the urothelium having flattened cells called transitional epithelium, next is the lamina propria, muscular layer and outer adventitia. Neoplasms can occur from any of the layers and are classified into epithelial and nonepithelial tumours. Epithelial tumours 1. Papilloma 2. Urothelial carcinoma 3. Squamous cell carcinoma 4. Adenocarcinoma Nonepithelial tumours 1. Benign – Leiomyoma, paraganglioma, plasmacytoma, fibroma, neurofibroma, plexiform neurofibroma 2. Malignant – Rhabdomyosarcoma, leiomyosarcoma, lymphoma Clinical presentation is by painless haematuria or at times by microscopic haematuria while being routinely investigated. Other symptoms include frequency of urination. dysuria and pelvic fullness. The pathogenesis of urothelial neoplasms is direct contact of the urothelium with the excreted toxic products of cigarette smoking, environmental chemicals in industrial exposure, chronic urothelial irritation by chronic infection, calculi, bilharzia infection and drugs like phenacetin, cyclophosphamide. Urothelial carcinoma

The bladder base is the most common location of urothelial tumours. They can be sessile, papillary or nodular. Sessile lesions tend to be invasive. Often the neoplasms are multicentric with synchronous upper tract tumours. Superficial bladder cancer is confined to the epithelium and lamina propria. Once it extends into the muscular layer and beyond it is termed as invasive with the further spread being to local nodes, bone and thereafter distant metastasis. Radiological imaging started with excretory urography, and cystography then moved onto cross-sectional modalities like Ultrasound, CT and MRI. Although cystoscopy and biopsy are the standards for bladder evaluation, imaging is essential for accurate staging and treatment planning especially invasive tumours where detection of involvement of the pelvic sidewall and lymphadenopathy are critical for management. Conventional excretory urography and cystography will show a filling defect in the affected area. Ultrasound will show a hypoechoic lesion in the bladder wall projecting into the lumen (Fig. 10.13.6) with adjacent wall thickening. Colour Doppler will show flow in the mass, which helps to differentiate it from a blood clot. CT will show an intraluminal mass which can be papillary or nodular, 5% will show calcification which is on the surface. Enhancement of the tumour on Contrast enhanced CT is early, and wall involvement will also show enhancement (Fig. 10.13.7). Perivesical fat involvement is manifest by fat stranding.

FIG. 10.13.6 Transvaginal ultrasound showing a hypoechoic bladder mass with faint flow on colour Doppler.

FIG. 10.13.7 Plain and contrast-enhanced CT showing an enhancing calcified mass at the bladder’s lateral wall. MRI – On T1-weighted images, the tumour shows intermediate intensity like the bladder wall with urine appearing dark. On T2weighted sequences, the tumour is of intermediate intensity contrasting with the high intensity of urine in the bladder lumen and low intensity of muscle thus determining the tumour depth invasion (Fig. 10.13.8).

FIG. 10.13.8 T1W (A) and T2W (B) images of a large bladder mass. With dynamic contrast scan, the tumour enhances avidly and faster than other tissues. Metastatic nodes also enhance early. The usefulness of PET FDG is of limited value on account of the excretion of the radioisotope into the bladder. Squamous cell carcinoma

Squamous cell carcinoma accounts for less than 5% of bladder tumours. However, where schistosomiasis is prevalent, the incidence can be as high as 50%. Other risk factors are chronic irritation from indwelling catheters, bladder calculi and prolonged infection. They present with haematuria and imaging shows as an enhancing sessile bladder mass with or without wall thickening. Adenocarcinoma Adenocarcinoma comprises less than 2% of bladder tumours and can be either primary or metastatic. Primary may be urachal or nonurachal (Fig. 10.13.9).

FIG. 10.13.9 Adenocarcinoma in a urinary bladder diverticulum: Axial images of a CT abdomen study in plain (Fig. A) and excretory phases (Fig. B) showing hypodense polypoidal lesion within a urinary bladder diverticulum (asterisk in Fig. A). The lesion is much better appreciated on excretory phase (white arrow in Fig. B). (Source: Courtesy of Dr. Mukund Rahalkar.) Patients present with haematuria. Imaging shows an enhancing mass with or without the involvement of the wall and perivesical fat. The urachal variety is typically located at the fundus of the bladder in the midline and presents as an infraumbilical mass. Miscellaneous

Tumours like rhabdomyosarcomas have a low T1 intensity and high T2 intensity with heterogeneous enhancement and grape-like surface. Plexiform neurofibromas have a low signal intensity on T1 and a target sign appearance on T2-weighted images due to highintensity myxoid stroma surrounding low-intensity fibrosis. Lymphangiomas, lymphomas, haemangiomas, paragangliomas, leiomyomas (Fig. 10.13.10) and neurofibromas are tumours completing the spectrum of bladder neoplasms.

FIG 10.13.10 CT and MRI of a 22-year-old female patient who presented with difficulty in micturition. CECT axial (A) and coronal images revealed large enhancing intramural lesion within the left lateral wall of urinary bladder extending to involve the neck. T2W fat saturated axial (C) and T2W coronal (D) images showed a large, heterogenous but predominantly hypointense intramural mass projecting into the bladder lumen without any extravesical spread. The lesion was later diagnosed as leiomyoma on histopathogical examination.

Miscellaneous bladder pathologies Postoperative bladder

Various types of surgery can be performed for bladder lesions like transurethral resection (TUR), cystectomy either partial or radical; neobladder reconstruction with a new bladder reconstructed from intestine, bladder suspension surgery for stress incontinence. Imaging may be required for the bladder to determine its mucosa; whether normal or hypertrophied, configuration postoperatively, its capacity, recurrence of tumours, leaks, fistulae, diverticula, the appearance of the bladder neck, stenosis and status of the pelvic floor. Conventional cystography/MCU, Ultrasound, CT and MRI have significant roles depending on the type of surgery done and for detection of any complication. Often multiple modalities are required to arrive at a definitive management plan. Bladder diverticula It is defined as an outpouching from the bladder wall whereby the mucosa herniates through the wall forming a cavity or a pouch connected to the bladder cavity through a neck which may be either narrow or broad. They may be congenital or primary or secondary which are acquired. Secondary diverticula are more frequent and are the result of chronic obstruction to the bladder outlet. Causes • Primary – Hutch diverticulum occurring in the para ureteral area. 1. Secondary or acquired – Bladder outlet obstruction due to bladder neck stricture, neurogenic bladder, urethral valves, prostatic enlargement, urethral stricture. 2. As part of specific syndromes like Ehlers–Danlos, Prune Belly and Williams’ syndrome. 3. Postoperative following surgery around the bladder neck. Clinically may be asymptomatic and detected while imaging the bladder for other causes when symptomatic present with dysuria and fever. Imaging MCU is the most frequent modality used. The diverticulum is seen as an outpouching at the affected area of the bladder with a neck (Fig. 10.13.11).

FIG. 10.13.11 Micturating cystourethrogram showing a diverticulum at the fundus of the bladder. Ultrasound will show the outpouching as an anechoic cavity with a neck communicating with the bladder cavity. They are seen as incidental findings on CT and MRI, which show the outpouching connected to the bladder cavity through the neck. Complications 1. Infection 2. Calculi formation 3. Dysplasia and cancer 4. Reflux and obstruction are rare Bladder endometriosis Etiopathogenesis and clinical features: Urinary tract is rarely involved in endometriosis. When it is involved, the urinary bladder is the commonest site. In about 1%–15% of women with endometriosis, the urinary bladder is affected. It manifests as an infiltrating mass involving the muscular and submucosal layer which forms an obtuse angle with the bladder wall. Sometimes, the mucosa may also get affected, resulting in a polypoidal intraluminal mass.

Patients generally present with cyclical pain, dysuria and urgency. The classical symptom of cyclical haematuria is seen only in 20% of cases. Imaging findings: Bladder endometriotic lesions are commonly located in the posterior wall near the vesicouterine pouch. These masses sometimes cannot be separated from the anterior uterine adenomyotic lesions. Ultrasound and CT show nonspecific bladder lesions. MRI may, however, show haemorrhagic foci within the lesions which appear hyperintense on both T1W and T1W fatsaturated images. Associated areas of fibrosis appear hypointense on both T1W and T2W images. Postcontrast image may show homogeneous or heterogeneous enhancement. Concurrent adenomyosis, and ovarian endometriomas along with typical clinical history, help to clinch the diagnosis.

Conclusion The urinary bladder can be involved by several congenital, inflammatory and neoplastic diseases. Radiological investigations not only help in diagnosing these conditions but also aid in guiding proper management. Ultrasonography remains the initial investigation of choice due to its easy availability. Intravenous urogram and micturating cystourethrography are predominantly useful in patients with obstructive uropathy. CT, because of its multiplanar capability, is the investigation of choice in most of the cases. However, because of better soft-tissue contrast, MR urography provides better characterization of the urinary bladder lesions. Moreover, it is preferred in children as there is no risk of radiation exposure. Also, in patients with deranged renal function tests where contrastenhanced CT cannot be performed, MR is a safer alternative.

10.14: Ureter Priscilla Joshi, Anand Mukund Rahalkar, Vandana Jahanvi

Introduction The ureter is a tubular structure measuring up to 3 mm in diameter and 25 cm in length. It carries urine to the urinary bladder from the kidney and is entirely retroperitoneal in its course. It arises from the renal pelvis at the pelviureteric junction emptying distally into the urinary bladder at the vesicoureteric junction (VUJ) The inner cell layer of urothelium is surrounded by an outer smooth muscle layer which allows coordinated contraction and peristalsis hence the excreted contrast agent may not opacify the entire ureter. In the past, plain radiographs of the abdomen and ultrasound were used for indirectly evaluating and imaging the ureters, in addition to visualizing and evaluating the kidneys and bladder. Recently, computed tomographic (CT) urography has emerged as the imaging modality of choice for evaluating the ureters, as well as the kidneys, bladder. The urethra can also be evaluated. A CT urography comprehensively evaluates the urinary tract, allows detailed assessment, as well as helps visualize the surrounding structures in the abdomen and pelvis. It is now the gold standard in evaluating patients with haematuria when a screening ultrasound is negative or shows equivocal results. It is also used in the initial staging and follow-up of patients with urothelial tumours. The entire ureter may not be opacified on a single acquisition. Various methods to overcome this include good hydration prior to contrast administration, administration of a diuretic and imaging in the prone position. Of these, good hydration prior to contrast administration probably gives the best results. Dual-energy CT urography allows a single contrast-enhanced acquisition phase. Virtual nonenhanced images are created thus reducing the radiation dose. The technique is limited by decreased sensitivity for small stones, noisy images and inaccurate attenuation values. Ultrasound though easily available, cheap and having no radiation risk has the inherent problem of nonvisualization of

ureters when normal in calibre. Also air-distended bowel loops interfere with visualization and assessment of ureters which are mild or moderately dilated. Noncontrast MR urography can help visualize normal ureters though dilated ureters are better visualized and evaluated. Administration of a diuretic helps better ureteric visualization. A contrast MR urography with or without diuresis since it is threedimensional, aids delineation of the ureters, their course and calibre and helps delineate or rule out intrinsic ureteric lesions as well as extrinsic causes of ureteric obstruction. Periureteric fat stranding if seen on CT or MR could be secondary to inflammation or infection.

Inflammatory and hyperplastic conditions of ureter These are uncommon lesions of the ureter. They manifest as single or multiple filling defects. On CT urography they cannot be reliably distinguished from other causes of filling defects like tumours or blood clots, hence ureteroscopic evaluation is required. Ureteritis Infection or inflammation of the ureter results in ureteral thickening with associated enhancement and periureteral fat stranding. Ureteritis can be seen in the setting of cystitis, pyelonephritis or pyonephrosis. A few infections, such as tuberculosis, fungus and schistosomes may cause discrete filling defects. In tuberculosis, the kidneys are involved before the ureter. Findings in the kidneys include papillary necrosis, parenchymal destruction and calcification. The ureteric wall maybe thickened with focal nodular areas appearing as filling defects on CT. Figs. 10.14.1 and 10.14.2 depict imaging appearance of ureteritis in 2 different patients.

FIG. 10.14.1 A case of left-sided ureteritis. CECT axial images at the level of proximal (A) and distal ureter (B) showing ureteric wall thickening on the left side (white arrow in A and black arrow in B). The patient also had leftsided pyelonephritis with thickening of left pararenal fascia and fluid along left paracolic gutter (asterisk).

FIG. 10.14.2 Ureteritis: Coronal postcontrast (A and B) and axial post- contrast (C) images in a 30-year-old patient with right flank pain, burning micturition and pus cells on routine Urine examination: Left pelvi-ureteric junction calculus (white arrow in A) is seen causing mild hydronephrosis. There was enhancing thickening of proximal ureteric wall on left side (white arrowhead in B and black arrow in C) with prominence of ureteric lumen without any distal filling defect.

Debris or sloughed papillae may also cause filling defects if associated papillary necrosis is present. Strictures can occur at multiple levels, the common sites include the infundibula, renal pelvis, pelviureteric junction and the ureter. Ureteric strictures have a typical beaded appearance. Fungal infections like candida and aspergillosis are common in immunocompromised patients. These can result in fungal balls or mycetomas which are seen as filling defects within the collecting system. These may contain air or calcifications. Rarely a urobezoar can be formed if the fungal ball extends into the ureter. This can cause obstruction. Schistosoma haematobium is a parasite endemic in Africa and the Middle East. It lays its eggs in the wall of the urinary tract. Oedema and inflammation surrounding the eggs can create a nodular filling defect. Over time the eggs calcify causing mural calcifications seen on CT. Ureter tuberculosis (discussed in genitourinary tuberculosis) Uretritis cystica (Fig. 10.14.3) Ureteritis cystica results in multiple filling defects which may also be seen in a multifocal UCC. The ureter is not obstructed hence not dilated.

FIG. 10.14.3 IVP image showing pyeloureteritis cystica: Multiple smooth oval to round lucent filling defects are seen in both ureters (white arrow and arrowhead) and in left renal pelvis (black arrow). (Source: Courtesy of Dr. Mukund Rahalkar.) In polyureteritis cystica, multiple small cysts are seen in the ureteric wall. These are seen as multiple small filling defects in the proximal ureter; however, the fluid containing cysts are too small to sample and obtain density measurements. The filling defects are more numerous than those in multifocal urothelial carcinoma. Amyloidosis Amyloidosis comprises a variety of protein-folding disorders. Extracellular deposition of amyloid/protein aggregates in the tissues is seen in amyloidosis. Amyloidosis can be either: 1. Localized: This comprises 10%–20% of cases of amyloidosis. Organs involved include skin, tongue, larynx, trachea and lungs. The nervous system, gastrointestinal tract and genitourinary tract may also be involved. Urothelial carcinoma is mimicked by localized amyloidosis affecting the urinary tract.

2. Systemic: It can be (a) Primary systemic disease or, (b) Secondary systemic disease. Primary disease can be seen in association with: I. Immune dyscrasias II. Multiple myeloma III. Waldenström’s macroglobulinemia Secondary disease can be seen in association with: I. Chronic inflammatory pathologies (e.g. rheumatoid arthritis, Crohn’s disease) II. Tuberculosis Clinical presentation: Patients may have: I. Dysuria II. Haematuria which is painless III. Urinary colic and retention Aetiology: The exact aetiology of this condition is not known. Local synthesis of amyloid and infiltration of monoclonal plasma cells are possible causes. Common sites of involvement: Prostate and seminal vesicles are commonly affected. Bladder, renal pelvis, ureter and urethra can also be involved. Primary amyloidosis of the ureter is very rare as compared to involvement of the prostate, seminal vesicles and urinary bladder. It is commoner in females and presents in the late sixth decade. It is typically unilateral and commonly affects the distal third of the ureter resulting in ureteral stricture and hydronephrosis. Localized amyloidosis of the ureter usually is benign and carries a good prognosis. Systemic amyloidosis must be ruled out prior to treatment. Imaging findings: Ultrasound is used as an initial imaging modality followed by CT and MRI. Both ultrasound and intravenous urography (IVU) can reveal hydronephrosis. Computed tomography reveals nonspecific diffuse thickening of ureteral walls with calcification. Differential diagnosis would include: I. Urothelial carcinoma II. Tuberculosis

III. Schistosomiasis IV. Haematoma On MRI localized ureteric involvement is seen as a hypointense lesion on T2-weighted images without mass effect. This helps differentiate it from a carcinoma. Urine cytology does not differentiate amyloidosis from urothelial carcinoma, because many of the amyloid deposits are subendothelial in location. Hence, cytology has a limited value (50% sensitivity for urothelial carcinoma). Biopsy is diagnostic as Congo-red staining of the amyloid produces the classical appearance of apple-green birefringence under light microscopy with polarized light. The type of amyloid protein may be determined with the help of treatment of the amyloid sample with potassium permanganate. Further information about the protein components of the amyloid may be provided by immunohistochemistry or mass spectroscopy. Treatment: Systemic amyloidosis must be ruled out prior to treatment. This maybe a result of multiple myeloma, Hodgkin lymphoma and renal cell carcinoma. Serum and urine electrophoresis, chest radiography and if appropriate, rectal biopsy or fine needle aspiration of subcutaneous fat can help exclude systemic amyloidosis. Ureteral stricture Ureteral stricture is diagnosed when there is a fixed obstruction with proximal dilatation. A physiological narrowing should be excluded before diagnosing a stricture. Physiological narrowing manifests as focal narrowing or abrupt kink and characteristically does not have any proximal dilatation. Common sites for physiological narrowing include pelviureteric junction, pelvic brim and vesicoureteric junction. The length of the stricture and its location should be described in any radiological report for guiding appropriate management. While IVU is adequate for initial diagnosis of stricture, cross-sectional imaging maybe required to determine the underlying cause. Strictures may manifest as pure ureteral narrowing without any ureteral wall thickening or periureteral abnormalities. Secondary narrowing of ureter due to extrinsic compression (either due to local inflammatory pathology or any adjacent neoplasm) is readily diagnosed on CT or MR and should be ruled out before planning any urological intervention. Causes of ureteral stricture are enlisted in Box 10.14.1. BOX 10.14.1

C AU SE S O F U R E T E R AL ST R IC T U R E Causes of Ureteral Stricture A. Intrinsic Causes (Fig. 10.14.4) 1. Iatrogenic (surgery, ureteroscopy) 2. Inflammation from a passed calculus 3. Neoplasm (Fig. 10.14.6) 4. Infection (tuberculosis, schistosomiasis) B. Extrinsic Causes 1. Adjacent inflammation: diverticulitis, inflammatory bowel disease, infection, retroperitoneal fibrosis 2. Encasement by an adjacent tumour (e.g. cervix, colon, lymphoma, retroperitoneal metastasis)

FIG. 10.14.4 Benign ureteric stricture: CT Urography study of a 36-year-old female who complained of right lumbar pain. Axial image in excretory phase (A) shows inflammatory thickening of the proximal right ureter (white arrowhead). Coronal MIP image (B) shows inflammatory thickening and kinking of proximal right ureter (white arrow) causing moderate hydronephrosis. Malakoplakia (discussed in infections) This is seen on imaging as multiple nodules or polypoid lesions which are indistinguishable from multifocal urothelial carcinoma.

Periureteral diseases Retroperitoneal pathologies may affect the ureter secondarily, compressing or encasing the ureter resulting in complications like hydronephrosis, obstructive uropathy and urinary tract infection. Periureteric haematoma or urinoma Periureteric and perirenal haematoma Introduction Haemorrhage around the kidney and ureter is common in posttraumatic cases similar to urinoma. Postoperative procedures can also result in haemorrhage. Spontaneous haemorrhage can occur, though uncommon. It can be a life-threatening condition. It can be subcapsular, perirenal haematoma or extend across the midline in the retroperitoneum. Aetiology Posttraumatic and postoperative causes are similar to that of urinoma. Postbiopsy renal pseudo aneurysms and bleed are known causes. Spontaneous haemorrhage can be due to tumours (angiomyolipoma more common than renal cell carcinoma), vascular causes, infection and unknown causes. Metastasis and antiplatelet agents are also described as cause for spontaneous retroperitoneal haemorrhage around the ureter. Clinical features are usually related to trauma. Imaging Plain films and IVU are now rarely used for the diagnosis of haematoma. Plain films are useful in diagnosing bony fractures, in cases of traumatic haemorrhage. Ultrasound shows cystic collection with internal echoes in it. However, it can mistake a haematoma for a solid mass due to the presence of echoes in it. In cases of angiomyolipoma, it can show an echogenic renal lesion as a cause for haemorrhage. However, it is very useful for follow-up of cases with haematoma. CT with contrast and delayed images is the mainstay for diagnosis in majority of cases. In cases of trauma, it shows associated renal injury signs. The density of the collection on CT suggests it as haematoma. It can also tell about the cause for haemorrhage-like presence of fat in angiomyolipoma or a renal tumour causing haematoma. CT may not find a cause in cases of vascular causes and anticoagulation bleeds.

Angiography is necessary in diagnosis of vascular causes like polyarteritis nodosa (PAN). Findings in PAN can be vascular aneurysms and stenosis of nodules. Urinoma Introduction A urinoma is loculated collection of urine outside the pelvicalyceal system. It can be traumatic, postoperative or spontaneous in the presence of obstruction. IVU was used to diagnose this condition in the past. However, after the advent of ultrasound and CT, they form the mainstay in diagnosis and location of the leak. CT with delayed images is the most important imaging technique used to diagnose and locate the site of leak. Rarely antegrade and retrograde pyelography or scintigraphy maybe required in the diagnosis of the site of leak. The extravasated urine causes inflammatory response. Deposition of fibrin and collagen tissue causes loculation resulting in urinoma formation. The leaked urine usually lies in subcapsular or perirenal space. The collection can extend across midline in the retroperitoneum. Rarely, it can cross the diaphragm and extend into the mediastinum and pleural space. Extension in the thigh, pelvis, scrotum and perineum is also described. Intraperitoneal leak is usually secondary to trauma. Rarely bilateral urinomas are also described in literature. Aetiology Traumatic leaks are usually associated with renal or other retroperitoneal trauma. Causes of obstruction include posterior urethral valves in neonates, calculi, prostatic hypertrophy and tumours in adults. Bladder or ureteric cancers, metastasis or ovarian carcinomas can also rarely result in urinoma formation. Unlike renal causes, ureteral causes for urinoma formation are mostly iatrogenic, following postsurgical antegrade or retrograde pyelography in patients who have undergone procedures like urinary diversion, renal transplantation. Clinical features include increasing abdominal girth following trauma and postoperative fever due to infection. Imaging

Plain films will show soft tissue mass like opacity in the renal region obliterating the fat planes. A calculus maybe seen in the ureter as a cause for the urinoma. IVU was earlier used as a modality to demonstrate and diagnose the leak. Signs on IVU include absent excretion of contrast, hydronephrosis, amputation of lower calyces, renal displacement and leak of contrast into the collection. However, actual leak of contrast was seen in only 30% of cases in one study. Dilution of contrast was probably cited as one of the causes of nonvisualization of the site of leak. Ultrasound is the commonest modality used in diagnosis. The urinoma is seen as an anechoic collection on ultrasound surrounded by a thin wall. Presence of echoes in the collection would suggest infection. Ultrasound can also be used for guided drainage of a urinoma. CT with delayed images demonstrates the site of leak of the contrast material into the urinoma. Increase in density of the collection in postcontrast images is diagnostic. Reformations in the coronal and sagittal plane also assist in locating the site of leak. CT may also be used for guiding drainages in areas not well demonstrated on ultrasound. Lymphomatous involvement of ureters It is a very rare condition with less than 20 cases reported in world literature. More common is diffuse retroperitoneal lymphoma displacing the ureter or causing hydronephrosis. Clinical features are related to the hydronephrosis and presence of lymphoma at other sites in the abdomen. Lymphoma involving the ureteral wall causes rind of enhancing soft tissue around the ureter causing stenosis of the lumen. Hydronephrosis is seen on CT scan. MRI showed the mass to be isointense on T1 and hyperintense on T2WI. Retroperitoneal fibrosis (RPF) Aetiopathogenesis: Retroperitoneal fibrosis includes a range of diseases characterized by proliferation of abnormal fibroinflammatory tissue. It is usually seen around the infrarenal aorta, inferior vena cava and iliac vessels. The disease process may ultimately surround the retroperitoneal structures, encasing and obstructing the ureters finally resulting in renal failure. Retroperitoneal fibrosis can be idiopathic or secondary. Idiopathic form known as Ormond disease accounts for two-thirds of cases of RPF. Secondary

form can be due to variety of causes which are listed in Box 10.14.2: Idiopathic RPF may be considered as a part of spectrum of chronic periaortitis, along with inflammatory abdominal aortic aneurysms and perianeurysmal RPF. Histopathologically, RPF has an early active inflammatory stage and a chronic inactive fibrotic stage. Early stage is characterized by immature fibrotic process, occurring predominantly in paraaortic location. There is associated capillary proliferation and presence of perivascular infiltrate of inflammatory cells. In this stage, the tissue is oedematous and highly vascular. The fibrotic stage is characterized by the presence of relatively acellular and avascular hyalinized collagen and scattered calcifications. Muscular and osseous erosions are not usually seen and if present suggest secondary RPF due to malignancy or infection. Clinical features: RPF manifests as an insidious process with initial symptoms being nonspecific and include low grade-fever, myalgia, abdominal pain, anorexia and weight loss. As disease progresses, there is compression of retroperitoneal structures by the fibroinflammatory tissue. Ureters are most commonly affected with chronic obstruction sometimes resulting in renal failure. Extrinsic compression of iliac veins and lymphatics may cause lower extremity oedema and sometimes deep vein thrombosis. Renal vessels affection may result in renovascular hypertension, and hydrocele or varicocele may occur due to gonadal vessels compression. Involvement of mesentery and bowel loops may rarely occur resulting in constipation or even intestinal ischemia. Imaging features: Ultrasound: Although sensitivity of ultrasound for retroperitoneal fibrosis is low, advanced cases may demonstrate hypoechoic or isoechoic retroperitoneal mass with irregular margin and well-demarcated contours anterior to lower lumbar vertebrae and sacral promontory. Associated hydroureter is seen which is usually bilateral. Caudal extension beyond sacral promontory and absence of lobulations suggest a benign cause. If associated sclerosing cholangitis or sclerosing pancreatitis is present, they are seen as dilated common bile duct (CBD and pancreatic ducts. Intravenous urography: IVU usually shows the classical triad of medially deviated ureters (middle third), smooth narrowing of one or both the ureters in the lower lumbar spine or upper sacral region, and

upstream hydroureteronephrosis with delayed contrast excretion. However, similar findings may also be seen in periureteral lymph nodes or inflammatory strictures. Contrast enhanced CT (Fig. 10.14.5): CT shows a welldefined but irregular periaortic infrarenal soft tissue mass. This mass envelops the aorta anteriorly and laterally. It is usually not present posterior to the aorta and hence anterior aortic displacement is not seen. On plain scan, the attenuation of the mass is similar to the psoas muscles. The postcontrast enhancement characteristics depend on the stage of the disease. The appearance and extension of RPF may be variable with the inflammatory mass showing inferior extension into the pelvis and superiorly it may extend to the renal hila. Other retroperitoneal structures such as the duodenum, renal pelvis or kidney may also be involved. Presence of hydronephrosis, deep vein thrombosis and renal vessel involvement are adequately assessed on CT when present. Additionally, paraaortic localized lymphadenopathy may be seen in RPF wherein the lymph nodes are generally discrete and subcentimetric, and probably occur due to retroperitoneal reaction. Avid enhancement is seen in active stage whereas enhancement is little or absent in late chronic stages. This imaging characteristic can be used to determine response to therapy, decrease in enhancement representing good response. Similarly, interval change in the size of the fibroinflammatory mass on follow-up can be used to assess therapy response. Associated sclerosing cholangitis and autoimmune pancreatitis can also be seen on CT. Additionally, thoracic CT may be performed to assess extraabdominal associations including mediastinal fibrosis, pericardial effusion and signs of asbestos exposure (pleural plaques or pleural thickening). MRI: Superior contrast resolution provides MRI an a dvantage over CT. RPF is typically hypointense on T1weighted images. Signal intensity on T2-weighted images is variable depending on the stage of the disease. Hyperintensity is seen in active inflammatory stage whereas in chronic fibrotic stage RPF exhibits predominantly low signal on T2-weighted images. Similarly, postgadolinium imaging can differentiate between the two stages in that the active stage shows early avid enhancement whereas little or no enhancement is seen in chronic stage. These typical features are usually seen in idiopathic RPF; however,

malignant and other secondary types of RPF may show variable appearance. FDG-PET: Positron emission tomography with 18-FDG can be used to determine metabolic activity in RPF. Additionally, it has a role to play in detecting associated conditions such as underlying malignancy, infection and autoimmune mediated inflammatory process. Quantification of metabolic activity by FDG-PET can also be used as a marker for active inflammation and hence posttreatment prognosis. Benign versus malignant RPF: Anterior displacement of aorta is seen in malignant RPF owing to the associated lymphadenopathy. Benign RPF on the other hand usually spares the posterior aspect of aorta therefore, it does not show anterior vascular displacement. Also, malignant RPF shows high signal on T2-weighted images whereas in benign RPF low signal is seen in its chronic stages. However, active inflammatory stage of benign RPF is difficult to differentiate form malignant counterpart since it also shows T2 hyperintensity. Differential diagnosis: 1. Lymphoma (Table 10.14.1) – Retroperitoneal lymph nodal mass in lymphoma generally has a lobulated appearance, causes anterior aortic displacement, and very frequently shows cranial extension above the renal hila unlike RPF which is generally infrarenal in location. Additionally, on MRI, lymphomas demonstrate significantly lower ADC values than RPF owing to their high cellularity. 2. Perianeurysmal fibrosis – Perianeurysmal fibrosis has morphological characteristics like RPF, the difference being that the aorta is pathologically dilated in perianeurysmal fibrosis. 3. Retroperitoneal haematoma – High attenuation on plain CT images helps to recognize retroperitoneal haematoma. On MRI, retroperitoneal haematoma unlike RPF shows high signal on T1-weighted images without any postcontrast enhancement. BOX 10.14.2 SE C O ND AR Y C AU SE S O F R PF 1. Malignant neoplasms 2. Infections 3. Trauma 4. Radiotherapy

5. Surgery 6. Drugs 7. Inflammation 8. Retroperitoneal haemorrhage or haematoma 9. Proliferative diseases (Erdheim–Chester disease and other histiocytosis) 10. Environmental and occupational agents: asbestos exposure

FIG. 10.14.5 Case of Retroperitoneal Fibrosis (RPF) showing retroperitoneal irregular soft tissue anterior and lateral to aorta causing mild vascular compression and significant right hydrouretero-nephrosis. The soft tissue is not causing any anterior aortic displacement.

FIG. 10.14.6 Malignant stricture: Retrograde ureterogram study in an adult male patient showing cup shaped dilatation of right ureter just distal to complete stricture, i.e., the Champagne- glass sign or Goblet sign (white arrow). The distal ureter also appears irregular with few filling defects - synchronous lesions (black arrow). Ureteroscopic biopsy revealed that the patient had Transitional cell carcinoma of ureter. (Source: Courtesy of Dr. Mukund Rahalkar.)

TABLE 10.14.1 Lymphoma Versus RPF Serial Lymphoma No. 1. Confluent soft tissue in perirenal location 2. Anterior displacement of aorta is seen 3. Ureters are not commonly involved 4. Associated discrete lymph nodal enlargement is seen 5. Splenomegaly may be seen 6. Low ADC value due to high cellularity

RPF Located below the level of infrarenal aorta, opposite sacral promontory and lower lumbar spine Soft tissue is anterior and lateral to aorta without anterior aortic displacement Ureters are commonly involved with medial ureteric bowing Lymph nodes if present are subcentimetric and reactive in nature Not associated with splenomegaly ADC values are not that low

Extramedullary haematopoiesis Introduction Formation of blood cells outside the bone marrow itself is EMH. The normal marrow is incapable of sufficient blood cell formation. It is a kind of physiologic mechanism of the body to correct inability of bone marrow to produce blood cells. Thoracic involvement is more common than abdominal involvement. Etiology Common causes of EMH are myelofibrosis, metastasis involving bone marrow, sickle cell anemia, thalassemia; and rare causes include polycythemia vera and ataxia telangiectasia. Idiopathic cases are uncommon. The sites involved are according to sites of hematopoiesis during fetal life. In the abdomen, liver and spleen are more commonly involved with or without nodule formation. Perirenal retroperitoneal involvement is a common site due to the fact that this is also a site of fetal hematopoiesis. Clinical features are related to the primary illness and presentation depends on the area involved. Abdominal hepatosplenomegaly is a common finding. Imaging Appearance

Ultrasound may show perirenal space involvement as hyperechoic focal lesions. CT scan shows perirenal and/or paraspinal mass with enhancement on contrast. Fat content in the lesions, if any is typical for the diagnosis of EMH. If this is not seen, then differential diagnosis is lymphoma or Erdheim Chester disease. Enhancing soft tissue can also involve the renal fascia in post-operative cases. On MRI, the soft tissue can vary considerably and is usually isointense on T1 and T2- weighted images. Contrast enhancement is also variable. Intraspinal extension and cord compression by these lesions is seen as epidural lesions. It is then difficult to differentiate from lymphoma or other causes. If a peripheral hyperintense rim is seen on T1W images, it is easy to differentiate from other causes. Erdheim–Chester disease Aetiopathogenesis: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytic proliferative disorder with multisystem involvement. It is believed to be an immune-mediated phenomenon characterized by increased proliferation of helper T-cells with release of proinflammatory cytokines. Histopathologically, there is tissue infiltration by lipid-laden histiocytes, with these xanthogranulomatous histiocytic infiltrates exhibiting CD68 positivity. Demographics: ECD shows a peak incidence in fifth to seventh decade of life with a male predominance. Clinical features: ECD is a multisystem disease (Flowchart 10.14.1) with the patient initially presenting with constitutional symptoms including fever, weight loss and night sweats. Skeletal system is most affected with patient presenting with multiple bone pains. Central nervous system involvement generally presents as diabetes insipidus; however, extraaxial masses and intraaxial abnormalities may also be seen. Orbital involvement presents as bilateral exophthalmos. Abdominal involvement causes retroperitoneal soft tissue which may cause ureteric obstruction resulting in renal failure. Cardiovascular system and respiratory system may also be involved in ECD. Abdominal manifestation of ECD: ECD may show plaque-like soft tissue encasing the aorta and retroperitoneal structures, and even causing extrinsic compression. This appears as hypoattenuating soft tissue encircling the ureters and renal hila. Spiculated soft tissue is also seen in perinephric fat giving ‘hairy-kidney’ appearance. It circumferentially encases the aorta giving ‘coated-aorta’ appearance. This soft tissue is hypointense

on T1W and T2W images on MRI. Although it may be associated with RPF, ECD shows a perinephric and renal hilar predominance unlike RPF, which shows distal ureteric involvement. Typical multisystem involvement of ECD helps to differentiate it from RPF.

FLOWCHART. 10.14.1 Systemic manifestations of Retroperitoneal fibrosis. Waldernstrom macroglobulinemia and extramedullary plasmacytoma Waldenstrom macroglobulinemia Introduction It is type of non-Hodgkin Lymphoma in which the cells show large amount of protein called M protein. This M protein is macroglobulin. Hence, the term Waldenstrom Macroglobulinemia. It’s a very rare type

of retroperitoneal perirenal neoplasm. It presents as systemic amyloidosis. Clinical features are nonspecific and may be due to the primary illness. Imaging features CT and MRI show perirenal soft tissue. It may show calcification. On MRI, the soft tissue is isointense on T1 and hypointense on T2WI. Hypointense on T2WI is a feature of amyloidosis. Calcification, however, can also occur in chronic renal failure, sclerosing mesenteritis, retroperitoneal fibrosis and malignancies and is nonspecific by itself. A biopsy is usually necessary for the final diagnosis. Extramedullary plasmacytoma (EMP) Introduction It is a tumour arising from plasma cells. It can arise in the skin, nodes or in the viscera. Most of the tumours arise in head and neck or in the gastrointestinal tract. It is an uncommon retroperitoneal tumour causing renal or ureteral displacement. EMP is defined when there is a solitary tumour not arising from the bone marrow or without breach in the cortex. The prognosis is better than the more common multiple myeloma arising from plasma cells. Retroperitoneal involvement is usually seen in association with multiple myeloma. Clinical features again depend on the area of involvement. In the abdomen, it can present as fever, nausea, vomiting or abdominal distension. Aetiology, diagnosis and clinical features Plasmacytoma arises from monoclonal plasma cells. It has four types: multiple myeloma, solitary plasmacytoma of bone, plasma cell leukaemia and EMP. Plasmacytoma can progress to multiple myeloma in 10%–30% of cases. The diagnosis of EMP is made by following certain criteria, which include less than 5% plasma cell in a bone marrow biopsy, normal skeletal survey, no Bence Jones protein in urine and a biopsy of an extramedullary site. Immunohistochemistry is generally necessary for the final diagnosis. The clinical features of retroperitoneal involvement are usually a lump or nonspecific features like nausea and vomiting. Depending on the location of involvement

and organs involved, patients may also present with enlarged lymph nodes or jaundice. Imaging features Ultrasound may show a solid hyperechoic mass adjacent to the kidney or in paraspinal region. It is useful for guided biopsy of the mass. CT with contrast usually shows a solid mass displacing kidney or ureter depending on the size. It is difficult to diagnose it separately from other lesions like lymphoma, sarcoma or schwannoma. Enhancement of the soft tissue is variable. Anterior displacement of aorta similar to lymphoma is also described. Small areas of calcification are described in the mass. The tumour is radiosensitive and radiotherapy is primary modality of choice after diagnosis.

Ureteric neoplasms Ureteric neoplasms are rare. When they do occur, they may present with haematuria or flank pain. Imaging is required prior to ureteroscopy to assess the site of ureteric involvement, laterality and multiplicity. Ureteric neoplasms on imaging appear as filling defects on IVU and cross-sectional imaging. Urothelial malignancy Primary ureteral neoplasms are rare tumours. They are commonly malignant, with 91% being transitional cell carcinoma (Fig. 10.14.7). Any filling defect in the ureter that shows soft tissue attenuation should be considered as malignant unless proven otherwise with ureteroscopy and biopsy.

FIG. 10.14.7 Transitional cell carcinoma of urinary bladder with synchronous lesion in left renal pelvis: Axial images of a CECT abdomen study in excretory phase showing polypoidal lesion arising from posterior urinary bladder wall (Fig. A). Another lesion was present in left kidney arising from renal pelvis (Fig. B and C)- typical of synchronous lesions in Transitional cell carcinoma. (Source: Courtesy of Dr. Mukund Rahalkar) Differential diagnosis of a urothelial malignancy includes squamous cell carcinoma, metastasis, papilloma, fibroepithelial polyp and a blood clot. Pyelonephritis, tuberculosis and inflammation due to a recently passed stone will cause ureteric wall thickening. Metastasis True haematogenous and lymphatic metastases to ureter are uncommon. When they do occur, they are commonly from the carcinomas of the breast, gastrointestinal system, prostate and uterus with metastases from carcinomas of the breast and gastrointestinal system comprising almost half of the cases. As the periureteral adventitia is richest in vascularity, it is the first affected layer in metastases. Ureteric metastases may show transmural involvement or pure mucosal infiltration without muscle layer involvement. These may uncommonly cause ureteric obstruction. It is difficult to differentiate the ureteric involvement by the periureteral malignancies from true metastases. Moreover, metastases may mimic primary urothelial malignancy. Primary urothelial malignancy usually shows long segment involvement and multiplicity. On the other hand, short segment involvement is usually seen in ureteral metastases. Imaging reveals ureteral wall thickening, stricture formation and filling defects within the ureter. As these findings may be seen in a variety of neoplastic and nonneoplastic pathologies, final diagnosis can only be made after ureteroscopy and biopsy. Fibroepithelial polyp

Ureteral fibroepithelial polyps are the most common benign tumours of the ureter though rarely seen. These are seen in adults in the third to fourth decades. They have a slight male preponderance and may also be seen in children. They clinically mimic other ureteral diseases and may present with ureteric colic, haematuria due to torsion of the polyp or intussusception causing intermittent obstruction. Aetiology: Congenital factors in children and chronic inflammation in adults are postulated as causes. The imaging findings of a vermiform and mobile solid ureteral mass would suggest the diagnosis. Pathology: These are benign lesions and can vary in size up to 12 cm in largest dimension. They are the most commonly seen in the left proximal ureter. They are of mesodermal origin and are characterized by a loose vascular fibrous stroma with an overlying benign transitional epithelium. They often mimic a urothelial malignancy and are discovered at nephroureterectomy. Coexisting transitional cell carcinomas have been reported. Differential diagnosis: 1. Malignant lesions: transitional cell carcinoma 2. Benign lesions: mesenchymal tumours 3. Nonneoplastic aetiologies: i. Blood clots ii. Sloughed papillae iii. Fungal balls iv. Rarely parasitic infections Imaging: IVU was the means of assessing ureteric lesions in the past. Ultrasound: If located within the proximal or distal ureter these may be seen as echogenic lesions within the ureter projecting into the renal pelvis or the bladder. This appears as a vermiform and mobile solid ureteral mass on ultrasound and colour Doppler. On CT urography, obtained in noncontrast and postcontrast early nephrographic phase, delayed excretory phase it is seen as an elongated ureteral lesion with a corkscrew appearance. It is enhancing in the nephrographic phase and surrounded by contrast within the ureter on the excretory phase. CT can detect the polyp as a filling defect even within an undilated ureter. Transverse images on CT help depict the relationship of the fibroepithelial wall to the ureteral wall and to confirm the absence of periureteral invasion. Virtual CT ureteroscopy can visualize the

unique 3D morphology of ureteral FEP better than conventional CT urography. On MRI without contrast, including MR urography, which is a heavily T2-weighted sequence, a polyp is well seen within a dilated system as a filling defect which appears hypointense as compared to the urine surrounding it which is hyperintense on the heavily T2weighted images. The attachment of the polyp to the ureteric wall and increased length of the ureteric mass along with lack of local invasion, absence of regional lymphadenopathy and distant metastases favour the diagnosis of a benign ureteric lesion like a polyp. Management: The treatment of choice for a fibroepithelial polyp is complete excision. Symptomatic and obstructive polyps can be treated with local resection either by open surgery or ureteroscopic removal. Accurate assessment preoperatively is important because it will direct the treatment towards endoscopic resection which is less invasive than radical surgery such as nephroureterectomy.

Miscellaneous ureteric lesions Ureterectasis of pregnancy (Fig. 10.14.8) Pregnancy results in hormonal and mechanical changes which cause hydroureteronephrosis resulting in altered renal function. Hormonal changes include increase in oestrogens, progesterone and prostaglandin-like agents which cause ureterectasis. Dextrorotation of the uterus occurs which explains the hydronephrosis which is more on the right due to the mechanical effect.

FIG. 10.14.8 Ureterectasis of pregnancy: Sagittal MRI image in an 18-week-old pregnant woman showing dilated proximal ureter (white arrow). MRI was done to rule out fetal anomalies. During pregnancy, both renal plasma flow (RPF) and Glomerular Filtration rate (GFR) are increased due to increase in cardiac output, increase in hormonal levels (progesterone, aldosterone, deoxycorticosterone, placental lactogen and chorionic gonadotropin) and decrease in renal vascular resistance. Increase in RPF and GFR results in increased urinary excretion of glucose, amino acids, proteins and vitamins. Painful hydronephrosis can occur in pregnancy. Placing the patient in the left lateral decubitus position can reduce the pressure on the right ureter and kidney. When this does not help ureteral stenting or a percutaneous drainage can help in pain relief and prevent spontaneous renal rupture in extreme cases due to the hydronephrosis. Ultrasound is the imaging modality of choice, but its field of view is limited due to the gravid uterus. Also, the pelvicalyceal and ureteric dilatation which is present due to the pregnancy maybe difficult to differentiate from that caused by obstructive uropathy. In the first trimester, pelvic radiation can increase the chances of teratogenicity. A 1 rad of radiation exposure of the foetus can result

in a 2.4-fold increase in the incidence of all childhood malignancies. MR urography (static/noncontrast) can help in evaluating the presence and level of obstruction; however, it may be limited in the detection of urinary calculi which would appear as small hypointense lesions in the static urography. It would also help in detecting other pathologies which can simulate urinary calculi.

Causes of deviated ureter The ureter begins as continuation of renal pelvis. At upper lumbar levels, it courses parallel to the outer margin of psoas muscles. At L3 vertebral level, it passes anterior to the muscles. In its upper course, the ureter courses along the lateral margins of the upper lumbar vertebrae. It enters the pelvis after crossing the iliac vessels, this vascular crossover is higher on right side. When, in the pelvis, the ureter passes parallel to the inner margin of the iliac bone, until in enters the urinary bladder at the vesicoureteric junction. Medial deviation (Box 10.14.4A and Fig. 10.14.9): Ureter is diagnosed to be deviated medially when it lies across the pedicles of lumbar vertebrae or medial to them. Medial deviation can also be diagnosed when interureteric distance is less than 5 cm. Lateral deviation (Box 10.14.4B): The ureter is deviated laterally when it lies more than 1 cm lateral to the lumbar transverse processes. BOX 10.14.4A C AU SE S O F ME D IAL D E V IAT IO N O F U R E T E R 1. Retroperitoneal fibrosis – ‘Maiden waist’ ureter 2. Retrocaval ureter – The right ureter passes behind the IVC at L4 vertebral level with the distal ureter coursing medially giving rise to ‘J- shaped’ ureter on IVP 3. Pelvic lipomatosis – Associated findings include elongation and elevation of urinary bladder, anterior displacement and elevation of rectum with increased presacral space, pelvic lucencies on radiographs 4. After abdominoperineal resection 5. Iliac lymphadenopathy 6. Iliac artery aneurysm

FIG. 10.14.9 Intravenous urography of a patient with left psoas abscess. IVU images showing soft tissue swelling on left side (white arrow) obliterating the psoas shadow causing medial deviation of ureter. BOX 10.14.4B C AU SE S O F LAT E R AL D E V IAT IO N O F U R E T E R 1. Hypertrophy of psoas muscles 2. Paraaortic lymphadenopathy 3. Neurogenic tumours 4. Aortic aneurysm 5. Pelvis mass (uterine fibroid, ovarian tumours) 6. Fluid collections (haematoma, urinoma, abscesses, lymphoceles) Ureteral deviations should always be diagnosed after comparison with the contralateral side. Any sudden change in ureteric course calls for an explanation and underlying causes should be looked for.

Causes of ureteral filling defects (Table 10.14.2) Filling defects in ureter can be single or multiple. The causes can be divided as filling defects that are inseparable from the wall and those that are within the lumen.

TABLE 10.14.2 Filling Defects in Ureter Filling Defects Inseparable from the Wall 1. Papilloma 2. Ureteritis cystica 3. Transitional cell carcinoma 4. Squamous cell carcinoma 5. Renal cell carcinoma 6. Squamous metaplasia

Within the Lumen 1. Blood clot 2. Stone 3. Sloughed papilla 4. Air

Causes of dilated ureter (Table 10.14.3) Ureter is said to be dilated when the diameter is more than 8 mm. However, asymmetrical prominence of ureter can be considered as clinically relevant ureteral dilatation. Causes of dilated ureter in listed in Table 10.14.3.

TABLE 10.14.3 Causes of Ureter Dilatation CAUSES OF URETER DILATATION A. Obstruction

1. Intraluminal: stone, blood clot, sloughed papilla, fungal ball 2. Intramural: stricture, tumour, infection (tuberculosis, schistosomiasis), postsurgical, congenital (ureterocoele, megaureter ≥7 mm, ectopic ureter, Prune– Belly syndrome) 3. Extramural: retroperitoneal fibrosis, pelvic malignancy (cervix, bladder, prostate), retrocaval ureter, aortic aneurysm

B. Without ureteric obstruction (generally bilateral)

1. Postpartum 2. Bladder outlet obstruction 3. Neurogenic bladder 4. Polyuria, diuresis

C. Vesicoureteric reflux

Conclusion A plethora of inflammatory and neoplastic pathologies may involve the ureters. Moreover, the ureters may be secondarily involved by a variety of periureteral pathologies. Imaging is indispensable in diagnosing ureteral diseases as it helps in evaluating the site and length of ureteral involvement and associated urological complications. Sometimes, radiological investigations are alone sufficient for diagnosis. However, a few pathological conditions warrant ureteroscopy and biopsy to come to a final diagnosis. Imaging in such conditions help in planning appropriate treatment. Fluoroscopy- or ultrasound-guided procedures such as percutaneous nephrostomy (PCN) catheter drainage and

urinoma/abscess aspiration are sometimes essential for patient management.

10.15: Urethra Aniruddha Joshi 1 0.1 5 .1

URETHRAL DIVERTICULUM (URETHROCELES) Introduction Urethroceles are focal outpoching of urethra. Ultrasonography (US) and MRI have improved our diagnostic ability and understanding of the disease.

Epidemiology Women especially those with stress incontinence are affected more frequently than men. Most of the women are between the ages of 30 and 50 years.

Clinical features These patients commonly present with nonspecific clinical symptoms – dysuria, postvoid dribbling, dyspareunia, frequency/urgency, recurrent haematuria, stress incontinence. Some of the patients may develop stones within the diverticulum. Repeated infection and irritation predispose to malignant transformation of the lining urothelium.

Pathogenesis Urethral diverticulum is an epithelized outpouchings of the urethral lumen into the surrounding periurethral connective tissue. Aetiology of the urethral diverticulum is unknown. Current hypothesis states that repeated infection and obstruction of the periurethral and paraurethral glands (Skene’s gland) results in formation of cyst/abscess.

At some point these rupture into the urethral lumen and connect to urethra via a neck or ostia. These outpouchings may be simple in nature, may partially encircle the urethra (saddlebag), or may completely envelop the urethra. Sometimes, they extend proximally beneath the bladder neck and trigonal area. Complicated anatomical patterns, however, may exist with multiple ostia. Iatrogenic damage to the urethra may also play a role in formation of the diverticulum.

Imaging Urethrography Voiding cystourethrography and double-balloon catheter urethrography (DBU) were used to be considered investigations of choice (Fig. 10.15.1.1).

FIG. 10.15.1.1 Urethrography reveals outpouching on either side at posterior urethra. Ultrasound Transabdominal, transvaginal, transperineal or transluminal USG techniques have been described with the patient in the dorsal lithotomy or supine position. These techniques are operatordependent leading to drawback in diagnosing of urethral.

USG provided particular benefit in differentiating a septated urethral diverticulum from multiple urethral diverticula compared with MRI. CT Poor soft tissue contrast causes limitation to the conventional contrast-enhanced CT. Urethral diverticulum may be visualized at as a hypodense mass with wall thickening and enhancement at the level of the pubic symphysis. However, urethral calculi in the dependent portion of diverticula can be reliably shown. MRI Recently MRI has become the imaging study of and is strongly advocated before performing any surgery. Diverticuli appear T1 hypointense and T2 hyperintense. IV gadolinium can be administered for detection of inflammation, infection or malignancy (Fig. 10.15.1.2).

FIG. 10.15.1.2 MRI pelvis at the level of urethra reveals focal outpouching on T2W images at posterior urethra. Differential diagnosis The differential diagnosis of urethral diverticulum includes: vaginal wall cysts, leiomyoma, Skene’s gland abnormalities, Gartner’s duct abnormalities, urethral prolapse, ectopic ureterocele urethral diverticular adenocarcinoma and urethral caruncle. 1 0.1 5 .2

URETHRAL TRAUMA Urethral traumatic injuries may be of blunt, penetrating or iatrogenic types. Other uncommon causes of injuries are penile fracture and injuries resulting from pancreas transplantation. Diagnosis and extent of the urethral injuries require high-quality imaging for effective treatment planning.

Epidemiology Male urethral injuries are much more common than female urethra.

Clinical features In clinical setting of trauma, blood at the external urethral meatus, vaginal introitus and haematuria may be seen, but these are unreliable signs. Complete urethral disruption, there may be overdistended bladder with inability to void, perineal ecchymosis and on DRE impalpable/high riding prostate. Dysuria, urinary urgency and suprapubic discomfort can ensue in the chronic stages of incomplete urethral injury due to complicating strictures.

Aetiology Urethral trauma is associated with blunt trauma, penetrating or iatrogenic types. Most commonly associated with motor vehicle accidents. Other less common causes are penile fracture, urinary extravasation in pancreas transplantation, instrumental childbirth.

Pathology Urethral traumatic injuries occur commonly associated with motor vehicle accidents. Depending on location, these can be anterior or posterior urethral injury. Anterior urethral injuries are associated with direct blow to perineum, straddle injury, penetrating traumas, penile fracture and iatrogenic. Bulbous urethra is most commonly injured in this. Posterior urethral injury is far more common. These are associated with road traffic accident and fall from a height. Posterior urethra is in close relation to the pubic bones and the puboprostatic ligaments. Urethra is also susceptible to injury by the

displaced fracture fragments. The distal membranous urethra is especially at risk. Female urethral injury is rare due to short length, internal location and less rigid attachment of the urethra to the adjacent pubic bone. And in severe pelvic trauma during road traffic accidents, there can be bladder neck injuries extending into the urethra. Iatrogenic traumas may result in injury at any level of the urethra and are seen as a consequence of urological interventions, surgery or radiotherapy.

Imaging In acute traumatic setting, any visceral/vascular injury should be managed to achieve haemodynamic stability. Patients with clinical signs indicative of urethral injury should be considered for immediate urethrography. On imaging if urethra appears intact, catheter may be inserted. If there is urethral or bladder injury, a suprapubic catheter should be inserted and later to be posted for surgery. Patients without clinical signs of urethral injury do not require immediate urethral imaging. If inadvertently blind catherization is done, it may complicate haemorrhage or increase the degree of urethral tear. Plain film radiography On plain radiography, presence of pelvic fractures with disalignment should raise suspicion for urethral injury. Fractures of ischiopubic rami or separation of the symphysis pubis is more indicative of urethral injury. Urethrography It is the standard diagnostic investigation for evaluation of a male urethral injury. Ideally ascending (or retrograde) and descending (or antegrade) urethrohraphic studies should be performed for evaluation of anterior and posterior urethra. And on follow-up imaging retrograde imaging is required. In traumatic setting, patient mobility and proper imaging techniques are not always possible. In these cases, foam cushions may be placed underneath the patient to help maintain that position, the tube may be rotated to a 30-degree left anterior oblique angulation or the table may be elevated to a 45-degree angle during voiding with a footrest.

Urethrogram allows identification of the site of injury and extent of any injury. Any extravasation outside the urethra is pathognomonic for urethral injury. Posterior urethral injuries Prostatomembranous urethra is commonly injured just above the urogenital diaphragm. On excretory urography, high-riding urinary bladder is seen due to disruption of puboprostatic ligaments and haematoma in the pelvis. Extravasation of contrast extravasation can be seen adjacent to the posterior urethra and sometimes into the pelvic extraperitoneal space (Fig. 10.15.2.1).

FIG. 10.15.2.1 Uretrography reveals posterior urethral injury with extravasation of contrast. Anterior urethral injury Anterior urethral injuries are commonly iatrogenic. In case of trauma, bulbous urethra is commonly injured. Contrast extravasation is seen in the adjacent penile soft tissues (Fig. 10.15.2.2).

FIG. 10.15.2.2 Uretrography reveals anterior urethral injury with extravasation of contrast. Distinction between a complete and partial rupture is not always clear. Typically incomplete rupture shows extravasation from the urethra which occurs while the bladder is still filling. In complete rupture, there is massive extravasation of contrast without bladder filling. In complete transection, it is important to know the length of the defect accurately, as a long defect requires more extensive urethroplasty. This length of the defect can be determined by performing simultaneous ascending and descending studies. On ascending urethrography, after contrast distension of anterior urethra, the catheter is blocked and taped to the side of the thigh. Next, descending study is performed by instillation of contrast via a suprapubic bladder catheter. Two commonly followed classification systems of urethral injury are by the American Association for the Surgery of Trauma (AAST), another one proposed by Colapinto and McCallum and subsequently revised by Goldman. In the AAST, classification depends more on the degree of disruption, urethral separation and treatment required. And the later classification system is based on anatomic location of an injury. Goldman’s system for classification of urethral injuries at urethrography Type I. It is stretching injury to the prostatic urethra, but no discontinuity. No extravasation of contrast is seen. There is rupture of puboprostatic ligaments due to which prostate is detached from the urogenital diaphragm. Elevation of urinary bladder cystography may be seen due to retropubic haematoma.

Type II. Disruption of urethra is noted of the membranoprostatic junction above the urogenital diaphragm. Contrast extravasation is seen in the pelvic extraperitoneal space above the urogenital diaphragm but not in the perineum. Type III. Disruption of membranous urethra and urogenital diaphragm with contrast extravasation above and below urogenital diaphragm, that is into pelvis and diaphragm. Type IV. There is bladder neck injury with extension into the posterior urethra. Contrast extravasation is seen in the pelvic extraperitoneal space with disruption of bladder neck. Type IVa. Bladder base rupture is noted but not involving bladder neck. Radiologically it is indistinguishable from type IV injury. Type V. Anterior urethra is injured commonly involving bulbous urethra. It is associated with straddle injury. Contrast extravasation is seen into the penile soft tissues. CECT Now a days, CT may precede retrograde urethrography for visceral and bony injuries. Presence of following findings are frequently associated with posterior urethral injuries – alteration or obstruction of the urogenital diaphragm fat plane, (haematoma) of the ischiocavernosus muscle, the bulbocavernosus muscle, obturator internus muscle and distortion or obscuration of the prostatic contour are common in patients with pelvic fractures associated with urethral injuries (Fig. 10.15.2.3).

FIG. 10.15.2.3 CT scan coronal images reveal posterior urethral injury with extravasation of contrast in pelvis. MRI and ultrasound There is no role of MRI in acute setting for evaluation of urethra. Posttraumatic imaging provides information about the pelvic anatomy, position of the prostate, pelvic fibrosis and estimation of the prostato-membraneous defect length. On USG, anterior urethral injuries can be evaluated by ultrasound. Common findings include subcutaneous or intraspongiosal haematoma and complete or incomplete mucosal interruption. However, role of ultrasound in evaluating posterior urethral injuries is limited (Fig. 10.15.2.4).

FIG. 10.15.2.4 USG reveals posttraumatic collection/hematoma in anterior urethra.

Treatment Accurate classification of urethral traumatic injury is important for further management. Most of the surgeons prefer suprapubic catheterization and delayed urethral repair. Goldman type I injury can be managed conservatively with placement of a urethral or suprapubic catheter. If immediate surgery is required in any associated intraperitoneal, rectal or bladder injury, then the associated urethral injury can also be dealt with. Goldman type II–V injuries result in a severe stricture and some surgeons select these cases for immediate surgery. 1 0.1 5 .3

URETHRAL TUMOURS Primary neoplastic lesions of the urethra and periurethral tissue are rare. Without imaging diagnosing urethral tumours is difficult due to nonspecific and overlapping clinical signs and symptoms.

Epidemiology Incidence of urethral tumours is common in females compared to the males. Urethral cancers may occur at any age but is observed more often during the seventh decade.

Clinical features Malignant urethral lesions in males commonly present as palpable mass in the perineum or along the length of the penile urethra. Common presenting complaints are urethral bleeding, palpable urethral mass, urethral stricture or bleeding, serosanguinous discharge, obstructive voiding symptoms, perineal pain urethral fistula or periurethral abscess.

Pathogenesis Chronic inflammation secondary to sexually transmitted infectious urethritis, urethral stricture, recurrent urinary tract infection and proliferative lesions such as caruncles, papillomas, adenomas, polyps and leukoplakia of the urethra are associated with the development of urethral cancers. Most of the malignant urethral tumours are epithelial in origin. Histologically, squamous cell carcinoma is the most common followed by transitional cell carcinoma and adenocarcinoma. Considering locations, transitional cell carcinoma is most common in the prostatic urethra. Urethral lymphoma, leiomyosarcoma and malignant melanoma are rare in both men and women. Common location of the urethral neoplasms in male is bulbomembranous and followed by penile and prostatic urethra. In females tumours are located commonly in the distal third of the urethra. These lesions commonly spread by direct extension to adjacent structures. Stage I urethral tumour is confined to the subepithelial connective tissue. Stage II tumour invades the corpus spongiosum, prostate or periurethral muscle. Stage III tumour invades the corpus cavernosum and bladder neck or beyond the prostatic capsule. Stage IV tumour invades other adjacent organs. Metastasis to regional lymph nodes is also identified. Lymphatic drainage of the penile urethra in male and the distal urethra in female are in the superficial and deep inguinal lymph nodes. Drainage of the bulbous, membranous and prostatic urethra in male and the proximal urethra in female are in pelvic lymphodes at obturator, external iliac and internal iliac locations. Benign mesenchymal tumours like fibrous polyp, leiomyoma and haemangioma are very rare.

Imaging Urethrography Retrograde urethrography and voiding cystourethrography have very limited role in the detection and evaluation of complications in urethral malignancy. RGU is ideal for evaluating anterior urethral masses in male patients, whereas VCU is good for posterior urethral tumour in male patients. However, urethrography is often the first imaging modality in evaluating male patients. Urethral tumours present at urethrography as irregular narrowing of the urethral lumen. These imaging techniques only allow intraluminal features of urethral tumours. In patients with high-grade strictures, that also can’t be evaluated. It also doesn’t allow to evaluated the periurethral extent of disease and metastatic lesions. USG In retrograde sonourethrography, normal saline/anaesthetic jelly/intraluminal lubricant is introduced to distend the lumen and allows excellent evaluation of the anterior penile urethra. And the posterior urethra can be evaluated with through endorectal approach. Transvaginal and transrectal ultrasound provide the better evaluation of the female urethra. On greyscale imaging, malignant urethral lesions appear hypoechoic to isoechoic and irregularly marginated lesion. Otherwise, benign lesions appear quite well defined. USG also allows to identify the associated urethral stricture and periurethral extension. On colour imaging, increased vascularity may aid in the differentiation of benign from the malignant causes. CT scan Accuracy of urethral lesions with CT imaging is very limited due to poor contrast resolution for soft tissues. Evaluation of tumour involvement of the anterior vaginal wall and urinary bladder is a major drawback. Other indications for CT scan imaging are evaluation of nodal disease and pulmonary, cerebral, hepatic, adrenal and other abdominal metastases. MRI Voiding cystourethrography and retrograde urethrography are invasive and unable to characterize extraluminal spread or periurethral conditions. These imaging can lead to incorrect diagnosis and delayed treatment.

MRI allows for high soft tissue resolution imaging of the urethra with improved evaluation of urethral and periurethral disorders (Fig. 10.15.3.1).

FIG. 10.15.3.1 Sagittal T2-weighted MRI of the pelvis revealed a localized urethral tumour extended to vagina. Location of tumour, size and local extent are well demonstrated on MRI. Tumours are relatively hypointense at T1-weighted imaging (T1WI), hypointense at T2-weighted imaging (T2WI) to the normal corporal tissue. On postcontrast imaging, progressive enhancement of the lesion is noted. As the corpora tend to be very vascular, a mass may appear to be relatively hypoenhancing. In addition to direct extension, metastatic lymph nodes can be identified (Fig. 10.15.3.2).

FIG. 10.15.3.2 MRI of the pelvis showing the urethral tumour (arrow). Tumours of squamous cell or transitional cell origin will be relatively hypointense on T1WI and hypointense to intermediate intensity at T2WI and demonstrate heterogeneous enhancement. In contrast, adenocarcinoma tends to be relatively T2 hyperintense, with variable enhancement. Primary malignant melanoma of urethra appears hyperintense on T1-weighted images, suggesting the presence of melanin and shows strong enhancement after IV injection of gadolinium. Secondary malignant melanoma of urethra is far more common than primary. However, MR appearance of melanoma may not be specific. Primary lymphoma of urethra presents in male as multiple polypoid masses and these appear homogeneous intermediate to high signal intensity on T2-weighted images. Also shows restricted diffusion and homogeneous moderate postcontrast enhancement. Leiomyosarcoma of urethra appears isointense to muscle on T1weighted images, heterogeneously hyperintense to muscle on T2weighted images with heterogeneous postcontrast enhancement. Urethral leiomyomas are present in reproductive female. These are very well defined and appear low to intermediate signal intensity on both T1WI and T2WI with fairly homogeneous enhancement. Urethral haemangiomas appear hyperintense on T2 and shows early arterial enhancement on postcontrast imaging.

Fibroepithelial polyps of the urethra present more commonly in children. In adults polyps are located at the bladder neck and prostatic urethra, presenting as obstructive mass. On. MRI, they appear in typical polypoid shape with a stalk connected to the bladder neck. Homogeneous enhancement after intravenous gadolinium administration is characteristic for polyps. Differential diagnosis Complex cystic periurethral lesions may mimic a solid mass on imaging. Examples include inflamed/infected urethral diverticula and urethral bulking agents. An uncomplicated urethral diverticulum will be high signal on T2WI and demonstrates little, if any, enhancement. In a complex urethral diverticulum, the fluid is intermediate signal on T2WI and may enhance heterogeneously.

10.16: Adrenals 1 0. 1 6 .1

ADRENAL ANATOMY AND IMAGING TECHNIQUES Dipak Patel, Sanjay Mehta, Vishal Shah

Introduction The adrenal glands (also called suprarenal/surrenal glands) are a pair of endocrine glands, retroperitoneal in location, situated superior and ventromedial to kidney on either side. Bartolomeo Eustachi described regrading adrenal in 1563 while its importance was recognized by Thomas Addison in 1855 and Brown-Séquard in 1856. It has two distinct components, the cortex and medulla, responsible for the production, release of the multiple hormones, regulating the metabolism, salt–water equilibrium in blood stream and immune system functions; besides helping body’s response to stress.

Anatomic features Adrenal has two main parts: the cortex and the medulla. It is enclosed in complete fibrous capsule, merging with the renal capsule on either side and liver on right side. Because of lipid rich contents, cortex appears yellow. It consists of three microscopic zones. Zona glomerulosa – outer most layer, produces mineralocorticoids, largely responsible for the regulation of blood pressure; zona fasciculata – central layer, responsible for the production of glucocorticoids and zona reticularis – inner zone, thinner and darker, produces androgens. Medulla is the core of the adrenal, surrounded by the cortex and mainly found in head of the gland. It is ellipsoid in shape, grey-tan in colour and 10% negative pixel (i.e. less than 0 HU correlate with the amount of lipid content) on histogram has sensitivity of 91% to detect adenomas accurately as compared to sensitivity of 66% on unenhanced CT scan, if used alone. Dedicated multiphasic adrenal CT protocol consists of unenhanced phase, followed by venous (about 60–90 s, after intravenous injection of nonionic iodinated contrast about 1.3–1.5 mL/kg body weight at the rate of 3–4 mL/s) and delayed (at 15 min) phases. Routinely neutral oral contrast is preferred unless indicated otherwise. Acquisition of additional arterial phase images (20–25 s) may be considered for two reasons, one for understanding adrenal arterial anatomy, may provide a guide for surgical mapping, if needed, and another to see for any hypervascular lesion like pheochromocytoma. Adrenal washout ratios are obtained using venous and delayed contrast images. (Venous and delayed phase images are required for the calculation of adrenal washout ratios.) For the evaluation of HU values, ROIs have to be placed covering at least two-thirds of the lesion, excluding areas of calcification, necrosis or haemorrhage, if any. Contrast washout

Accuracy of washout calculation improves after the incorporation of unenhanced HU value (inclusion of noncontrast HU value helps in more accurate calculation of washout); therefore, whenever possible, absolute percentage wash-out (APW) should be calculated. Absolute and relative washout of about ≥60% and ≥40%, respectively, strongly suggest benign adrenal adenoma. There are certain pitfalls to washout ratios, ROI calculation may be inappropriate if it is a heterogeneous lesion with haemorrhage/necrosis and few of the lesions may show similar enhancement characteristics (hypervascular adrenal metastases, pheochromocytomas and adrenocortical carcinoma). Certain technical modifications can be applied to reduce the radiation dose and scan time, like higher pitch (should not be more than 1.5 for optimal image quality). Low-dose CT scan (LDCT) is performed with kilovoltage peak (kVp) in the range of 90–120 and mA of 40–80, particularly for lung cancer screening. According to Godoy et al., adrenal masses >2 cm (or ≥1 cm in patients with cancer history) and 60%

>52.5%

>40%

>37.5%

Pitfalls CSI on MRI is dependent on the presumption that a mass containing microscopic lipid is specific for an adenoma. Clear-cell carcinoma of the kidney and hepatocellular carcinoma is known to contain macroscopic lipid, and metastatic lesion of adrenal gland lose SI on CSI. A rare lesion, called collision tumour, where two histologically distinct tumours are seen in adrenal without the mixture of two cell types. This can occur more commonly with adenoma coexisting with myelolipoma, and occasionally adenoma, coexisting with a metastasis. Two tumours should exhibit different signal intensities and different behaviour at CSI. Characterizing the various components of the collision tumour can provide improved guidance for biopsy.

Myelolipoma Myelolipoma has haematopoietic elements and fats that are similar to bone marrow. These lesions are no active as far as hormone secretion is concerned, and are often seen as incidental finding. Myelolipomas usually are slow growing and symptoms may arise from compression of adjacent organs or rarely from haemorrhage. Average size of lesion is approximately 10 cm, but can range from 2.5 to 20 cm. The tumours more than 10 cm size are known to have increased risk of haemorrhage. However, no malignant potential has been shown with increased size. Imaging findings Diagnostic criteria are the demonstration of macroscopic fat. CT scan demonstrates macroscopic fat, (HU ≤ 30) with dense myeloid

tissue in between (Figs. 10.16.3.4 and 10.16.3.5).

FIG. 10.16.3.4 Adrenal haemorrhage. (A) Axial unenhanced CT shows well-defined hyperdense (+56 HU) mass involving both adrenal glands. (B) Axial contrast-enhanced CT shows no enhancement of both adrenal masses.

FIG. 10.16.3.5 Adrenal myelolipoma. (A) Axial unenhanced CT shows right adrenal mass containing macroscopic fat (–50 to –100 HU), diagnostic of a myelolipoma. (B) Coronal contrast-enhanced CT shows contrast enhancement in central myeloid component. MRI demonstrates hypointense signal on T1 fat-saturated images (Fig. 10.16.3.6). CT scan reveals punctate intralesional calcifications. A variable pattern – shapes of calcification may be evolved as sequelae of intralesional haemorrhage. Myeloid component of the lesion may demonstrate contrast enhancement. Myelolipomas show India ink artefact at the interface of lesion– adrenal or on opposed-phase images, similar to renal angiomyolipoma. The reasonably characteristic feature is finding the macroscopic fat in myelolipoma, not diagnostic though, in contrast with renal angiomyolipoma. For detecting fat containing

mass is adrenal in origin and not renal (angiomyolipoma) or retroperitoneal (liposarcoma) origin, a multiplanar evaluation is essential.

FIG. 10.16.3.6 Adrenal myelolipoma. (A) Axial in-phase T1-weighted MRI shows hyperintense mass in right adrenal gland. (B) Axial opposed-phase T1-weighted MRI shows decrease in signal intensity in fatty component of the myelolipoma.

Adrenal cysts Cystic lesions of adrenal gland include parasitic cyst, pseudocyst and endothelial cysts. Most common are endothelial cysts (45% of total cysts), which are also known as simple cysts. Typically, the

simple cysts show nonenhancing thin/imperceptible wall, while the cyst fluid shows reduced attenuation with density ≤20 HU on CT scan and T2 hyperintense signal on MRI. The second-most common cysts are pseudocysts which accounts for about 39% of total cysts. Most often, they are secondary to previous insult like infarct, haemorrhage or healed infection. Thus show thick fibrous wall, which appear T2 hypointense on MRI. They may have varied appearance including internal variable thickness septations and calcifications. Echinococcal infection (hydatid cyst) is the commonest cause for parasitic cysts, which accounts for the least common cystic lesion of adrenal (7% of total cysts). Hydatid cyst may have varied imaging presentation ranging from complex, multicystic to simple cyst. Axial imaging, MRI/CT scan can detect cystic lesions with higher sensitivity. The mimics of cystic lesions arising from nearby organs like kidneys, liver and pancreas, differentiation may be made by multiplanar imaging technique. Incidental detection is the commonest presentation of adrenal cysts; however, sometimes with larger size, there may be compression on adjacent structures causing minor symptoms. Moderate to severe abdominal pain may occur if the cyst becomes haemorrhagic, infected or if it ruptures. Imaging findings CT scan and MRI show cystic lesion, which are diagnostic for adrenal cyst. Due to inherent higher sensitivity to detect simple fluid, haemorrhagic content, septation and soft tissue, MRI is the modality of choice of adrenal cyst evaluation (Fig. 10.16.3.7).

FIG. 10.16.3.7 Adrenal cyst (A) Axial T1weighted MRI shows lobulated low signal intensity mass in right adrenal gland. (B) Coronal T2-weighted MRI demonstrates corresponding homogeneous high signal intensity mass with thin wall and septations. The only pitfall being smaller calcifications. CT helps in such cases, like thin wall calcification (Fig. 10.16.3.8).

FIG. 10.16.3.8 Adrenal cyst. (A) Axial and (B) coronal contrast-enhanced CT show lobulated nonenhancing right adrenal mass that is water density (HU) with internal tiny calcific foci. The wall appears smooth and thin, which measures up to 3 mm. Cysts demonstrate wall and septal enhancement without central enhancement on postcontrast MRI. If the cystic lesions are complex, showing internal soft tissue, thick septae, larger size, abnormal enhancement then, cystic malignancy, like metastases or pheochromocytoma may be thought of.

Pheochromocytoma A type of neuroendocrine neoplasm, pheochromocytoma, grows from adrenal medulla chromaffin cells. Pheochromocytoma, also known as, ‘10% tumour’, as in 10%, lesions are bilateral, extraadrenal, in children, with 10% having malignant potential. They are

known as paragangliomas when outside adrenal gland and seen from skull base to pelvis along sympathetic chain. Most (90%) of the pheochromocytomas are sporadic and rest (10%) can be seen with various syndromes. These include multiple endocrine neoplasia (MEN) syndrome, types IIa and IIb, familial nonsyndromic pheochromocytoma, von Hippel–Lindau (VHL) syndrome, NF type-1, tuberous sclerosis, Sturge–Weber syndrome and Carney triad. The definite reliable criteria about malignant disease include metastatic spread of the disease and/or local invasion. The age of presentation is mainly fourth to sixth decade. Headaches, palpitations, flushing, diaphoresis and paroxysmal hypertensions (refractory) are often presenting symptoms, which may be new or associated with recent exacerbation. Diagnosis is often clinical. Persistently raised 24-h urinary vanillylmandelic acid (VMA) and/or metanephrines is seen in more than 90% of cases. According to size criteria, pheochromocytomas come in the middle, larger than adrenal adenomas, and smaller than carcinoma. Larger sizes of the pheochromocytomas are generally seen in nonfunctioning ones than functioning ones. Imaging findings Smaller pheochromocytomas have homogeneous, soft tissue attenuation on CT scan. However, larger have heterogeneous appearance as result of internal structural variability due to myxoid changes, necrosis, haemorrhage and cystic degeneration. Calcifications may be present in 10% of cases. CT attenuation and CS change are not specific 100% for adenomas due to the above reasons. Thus, pheochromocytomas having attenuation values less than 10 HU on CT scan, might show in false-positive diagnosis as adenoma (Fig. 10.16.3.9).

FIG. 10.16.3.9 Pheochromocytoma. (A) Axial unenhanced CT shows large, well-defined soft tissue density left adrenal mass (+30 HU). (B) Axial arterial phase CT shows heterogeneous avid contrast enhancement with central necrosis. (C) Axial venous phase and (D) axial excretory phase CT show contrast retention within mass compatible with a pheochromocytoma. Pheochromocytomas may have smaller quantities of macroscopic fat; finding that is not specific for, myelolipoma. Pheochromocytomas appear hypointense T1 images on MRI with variable high signal of T2-weighted image. The term ‘light bulb’ sign has been used to describe pheochromocytoma, but is probably more appropriate for the adrenal cyst. Increased – variable T2 intensity with heterogeneous signal may be due to internal cystic/myxoid degeneration or haemorrhage. MRI may be of help in extra-adrenal pheochromocytomas as hyperintense T2 appearance would be better appreciated on fat-suppressed images. In contrast to adenoma, pheochromocytomas enhance avidly and in delayed contrast-enhanced scans show contrast retention. Gadolinium-enhanced images can be useful in differentiating pheochromocytoma from a debris-containing adrenal cyst (debris show T2 shortening). Pheochromocytoma would mimic adrenal adenoma if APW and RPW alone is considered. Hence,

pheochromocytoma diagnosis must be based on various other imaging features and more so on clinical parameters. If MRI features highly suggest pheochromocytoma, then, fractionated free plasma metanephrines – a more sensitive bio-chemical test, may be utilized. If MRI findings are indeterminate but suggest a diagnosis other than pheochromocytoma, use of a more specific biochemical test may reduce false-positive diagnoses includes 24-h urinary VMA, metanephrine and/or other catecholamines. Chemical analogue of guanethidine and norepinephrine is metaiodobenzylguanidine (MIBG), which is abundantly found in adrenergic tissues. Adrenergic tumours like pheochromocytoma, paragangliomas and neuroblastomas may be detected by Iodine-123 (I-123)–labelled or Iodine-131 (I-131)–labelled MIBG scintigraphy. I-123 results in a lower radiation dose, whereas I-131 allows for delayed imaging and greater washout of background activity. When lesions could not be localized with MRI or CT imaging, then MIBG scintigraphy may be performed. Larger pheochromocytomas and paragangliomas are shown to show higher risk of metastases. These lesions are better identified/detected with scintigraphy. MIBG shows 82% of sensitivity and 95% of specificity for pheochromocytomas. Second, in scintigraphy, the whole body is scanned in one study, which is another advantage over imaging. Lower spatial resolution and longer study time of 1 to 3 days remains the major pitfall or disadvantages of the study. However, diagnostic certainty in equivocal patients may be increased with single-photon emission computed tomography (SPECT) – MIBG. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) shows increased tracer activity in pheochromocytomas. PET is also helpful in MIBG-negative pheochromocytomas.

Infective lesions One of the most common manifestation in inflammatory lesions of adrenal glands is bilateral involvement and symmetric appearance. It is mostly caused by granulomatous disease, due to either Koch’s or histoplasmosis. During subacute phase, the adrenal glands become enlarged and may contain cystic or necrotic masses with peripheral enhancement. Calcification occurs later in the disease. As the granulomatous process matures, the adrenal glands decrease in size and become more calcified. Granulomas show little enhancement (Figs. 10.16.3.10 and 10.16.3.11). Bacterial (pyogenic) abscesses of adrenals are uncommon; however, mostly happen in neonates following adrenal haemorrhage. Most common form of Addison’s disease is idiopathic, followed by granulomatous disease. In patients evaluated for Addison’s disease, presence of both

adrenal enlargement should raise differential possibility of granulomatous infection.

FIG. 10.16.3.10 Adrenal tuberculosis. (A) Axial unenhanced CT shows diffuse mass-like enlargement of bilateral adrenal gland. (B) Axial and (C) coronal contrast-enhanced CT shows heterogeneous enhancement with central necrosis. (D) Axial high resolution CT shows centrilobular and tree-in bud nodules in both lung fields.

FIG. 10.16.3.11 Adrenal calcification. Coronal contrast-enhanced CT shows small calcifications in left adrenal gland. Patient has history of tuberculosis infection.

Adrenal hyperplasia Congenital adrenal hyperplasia Congenital adrenal hyperplasia comprises a group of disorders (autosomal recessive), each involves a deficiency of enzyme involved in synthesis of cortisol (steroidogenesis). Adrenal hypertrophy is the end result of raised ACTH secretion due to low cortisol level. Altered (increased or decreased) levels of androgens and mineralocorticoids are part of the syndrome. Congenital adrenal hyperplasia shows increase in frequency of adenomas. Macronodular adrenal hyperplasia Adrenal glands may develop hyperplasia due to primary or secondary causes. Secondary causes (due to elevated levels of ACTH) are more common and usually secondary to an ACTHproducing pituitary adenoma (Cushing’s disease). In Cushing’s disease, adrenal glands increase in size and may take on a multinodular configuration. Prolonged exposure to ACTH may result in development of autonomous adrenal adenomas. The adrenal cortex shows hyperplastic tissue between the nodules. Hyperplastic tissue secretes excessive cortisol for the same amount of ACTH stimulation. This may finally lead to low levels of ACTH, despite the fact that this is an ACTH-dependent cause of Cushing’s syndrome. Due to subtle hyperplasia in normal size, adrenal glands diagnosis of Cushing’s syndrome could not be excluded. ACTH-independent macronodular adrenal hyperplasia has been rarely reported cause of Cushing’s syndrome with markedly enlarged adrenals compared to ACTH-dependent hyperplasia and

displays numerous variable-sized nodules ranging from 0.1 to 5.5 cm in size. On MRI, they show T1 hypointense and T2 hyperintense signal. Diagnosis can be suggested prospectively, as the imaging findings are characteristic, while the patients usually only have mild Cushing’s syndrome. Choice of treatment is bilateral adrenalectomy. Primary pigmented nodular adrenocortical disease Primary pigmented nodular adrenocortical disease (PPNAD) is a rarest cause of ACTH-independent Cushing’’s syndrome, which is believed to be due to mutation of a regulator of protein kinase A and leads to abnormal intracellular signalling and cellular proliferation. Inheritance of PPNAD is autosomal–dominant, which is a familiar heritable form of Cushing’s syndrome. Adrenal glands contain numerous pigmented nodules measuring about 2 to 4 mm in diameter, but as large as 3 cm, with variable lipid content. The nodules paradoxically secrete cortisol upon dexamethasone administration. Imaging found unilateral or bilateral adrenal nodularity. Choice of treatment is bilateral adrenalectomy. Approximately one-quarter of patients with PPNAD also have findings of the Carney complex, a multiple endocrine neoplasia consisting of PPNAD, myxomas of the heart, skin, breast, spotty mucocutaneous pigmentation, mucosa and calcified Sertoli cell testicular tumours. McCune–Albright syndrome McCune–Albright syndrome reveals café-au-lait skin lesions, polyostotic fibrous dysplasia and polyendocrine abnormalities. The adrenals, ovaries, thyroid, parathyroid and pituitary may involve in syndrome. It is caused by a G-protein mutation resulting in an ‘always on’ state. At the level of the adrenal gland, this simulates constant stimulation by ACTH and can cause adrenal hyperplasia, sometimes with a nodular configuration. Cushing’s syndrome occurs in 5% of cases.

Adrenal insufficiency Adrenal insufficiency occurred directly due to adrenal abnormality (primary) or indirectly due to abnormality in hypothalamus or pituitary gland (secondary). Primary adrenal insufficiency or Addison’s disease indicates an abnormality of the adrenal glands themselves. Secondary causes arise from abnormal function of the hypothalamus or pituitary gland. Primary adrenal insufficiency occurs as a result of extensive loss of adrenal tissue. Over 90% of the adrenal glands must be destroyed for the onset of functional abnormalities. Autoimmune disease is cited as leading cause of Addison disease. Granulomatous disease, particularly due to

tuberculosis, was previously considered the most common cause, and continues to be an important aetiology of Addison’s disease worldwide. Adrenal metastases can also result in adrenal insufficiency with primary tumours in lung, lymphoma and hepatocellular carcinomas. Adrenal haemorrhage and infiltrative disorders like sarcoidosis, haematochromatosis and amyloidosis are another causes for adrenal gland destruction. Functional failure due to enzyme deficiency leads to primary adrenal insufficiency, congenital adrenal hyperplasia is an example of it. Clinical features are nonspecific symptoms with acute or chronic presentation. Hypotension, fever, vomiting and abdominal pain are acute symptoms due to Addision’s disease, chronically, symptoms of fatigue, weakness and irritability predominate. Renin–angiotensin–aldosterone system, which primarily related to mineralocorticoid, do not affect by secondary cause, so mineralocorticoid deficiency only seen in primary adrenal insufficiency. ACTH levels are high only in primary adrenal insufficiency, resulting in hyperpigmentation, if the condition persists for a longer time. Biochemical diagnosis of primary adrenal insufficiency can be accomplished with cosyntropin stimulation tests and measurements of cortisol and ACTH levels. One of the causes of adrenal insufficiency is autoimmune adrenalitis, which show autoantibodies in circulation. The diagnosis of adrenal insufficiency becomes more challenging in the acute setting (e.g. sepsis or the postoperative state), because of wide variation in cortisol and cosyntropin response during stress. No imaging is needed in clinically proven autoimmune adrenalitis. Other aetiology of adrenal failure may need imaging. Use of MRI is to characterize adrenal mass, haemorrhage and size of adrenal gland. Small, atrophic adrenal glands in the setting of primary adrenal insufficiency suggest a late stage of granulomatous disease, particularly if the glands are calcified. Enlarged glands with primary adrenal insufficiency raise the possibility of acute/subacute granulomatous disease, metastatic disease, lymphoma or haemorrhage. If a patient with adrenal insufficiency presents with unilateral adrenal gland destruction, metastatic disease to the pituitary gland as a cause of secondary adrenal insufficiency should be considered. 1 0. 1 6 .4

ROLE OF MULTIMODALITY IMAGING IN ADRENAL MALIGNANCIES Nilesh P. Sable, Aparna Katdare, Kunal Gala, Gagan Prakash, M.H. Thakur

Introduction The adrenal gland is a common site for disease, with a prevalence reported to be as much as 9% in autopsy series. Adrenal lesions are frequently found with the increasing use of CT and are diagnosed on up to 5% of CT examinations performed for various reasons. The incidence of adrenal lesions increases to about 9%–13% in patients being scanned with a known malignancy, but only 26%–36% of these adrenal lesions turn out to be metastatic. This subset of patients with incidentally found adrenal mass with a background of malignancy pose the biggest radiological challenge in adrenal imaging. Better understanding of washout patterns and advent of chemical shift MRI has greatly added to the imaging accuracy in differentiating adenoma from metastasis and second primaries. It is essential to characterize an adrenal lesion in patients with a known malignancy because many tumours can metastasize to the adrenal glands, and a metastasis might contraindicate a curative treatment of the patient and affect survival.

Anatomy The adrenal glands lie immediately superior and slightly anterior to the upper pole of each kidney. The glands are surrounded by perinephric fat enclosed within the renal fascia, and separated from the kidneys by a small amount of fibrous tissue. In adults, each adrenal gland weighs approximately 5 gm and has a volume of approximately 3–6 cm3. The right adrenal gland is pyramidal in shape and has two welldeveloped limbs. The left gland is more semilunar in shape, flattened in the anteroposterior plane and marginally larger than the right. The bulk of the right suprarenal sits on the apex of the right kidney and usually lies slightly higher than the left gland, which lies on the anteromedial aspect of the upper pole of the left kidney. The right suprarenal gland lies posterior to the inferior vena cava, separated from it by only a thin layer of fascia and connective

tissue. The left suprarenal gland is closely applied to the left crus of the diaphragm, separated from it by a thin layer of fascia. The arterial supply to the adrenal comes from superior, middle and inferior suprarenal arteries, which are branches of inferior phrenic artery, aorta and renal artery, respectively. The venous drainage of the adrenal glands is via the suprarenal veins; the right drains into the inferior vena cava and the left into left renal vein. The left suprarenal vein may be joined by inferior phrenic vein prior to draining into the left renal vein. Lymphatic channels within the capsule of the suprarenal gland communicate with subserous lymphatics that drain medially to paraaortic and paracaval nodes. As adrenals are the organs of hormone production, they have rich nerve supply. A suprarenal plexus lies between the medial aspect of each gland and the coeliac and aorticorenal ganglia. It contains predominantly preganglionic sympathetic fibres that originate in the lower thoracic spinal segments, reach the plexus via branches of the greater splanchnic nerves and synapse on clusters of large medullary chromaffin cells. The adrenal gland is made up of two distinctly functioning portions: the adrenal cortex and the adrenal medulla. The adrenal cortex is divided into three zones which synthesize steroid hormones, all of which are derived from cholesterol. The three zones are zona glomerulosa, zona fasciculata and zona reticularis. The zona glomerulosa is a major source of glucocorticoids, and the zona fasciculata and the zona reticularis play a role in the production of cortisols and androgens. The zona fasciculata contains the lipid laden cells which play an important role in the imaging characteristics of adrenal lesions. The adrenal medulla is neuroectodermal in origin and contains catecholamine-producing cells called as chromaffin cells. Norepinephrine and epinephrine are the primary catecholamines produced by the adrenal medulla. They act primarily on the α and β adrenergic receptors with their main endocrine effects seen on the cardiovascular system and glucose metabolism.

Imaging CT scan Normal adrenal glands are seen as inverted V- or Y-shaped structures. These glands lie anterosuperior to the kidneys in retroperitoneum. The two limbs are thinner as compared to the body where they join. Mean thickness of gland is 5–6 mm with maximum width of 10 mm and approximate length is 2–4 cm in one section of CT (Figs. 10.16.4.1 and 10.16.4.2).

FIG. 10.16.4.1 Contrast-enhanced CT images showing the normal adrenal glands.

FIG. 10.16.4.2 Schematic diagram and axial CT image of the adrenal gland demonstrating the measurement technique: 1 shows the maximum thickness of the body of the adrenal gland, and 2 and 3 show the maximum thickness of the lateral and medial limbs, respectively. The anterior margin of the right adrenal gland lies immediately posterior to the IVC at the level of junction of the intra and extrahepatic portions while the lateral margin lies adjacent to the posteromedial aspect of the right lobe of the liver. The separation of the gland from the liver varies depending on the amount of retroperitoneal fat and occasionally it is difficult to clearly delineate the lateral border of the right gland. The right crus of the diaphragm lies medial to the right adrenal. The medial margin of the left adrenal gland lies lateral to the left crus of the diaphragm. Its lateral margin lies posterior to the pancreatic tail and the splenic vessels. It is somewhat more anterior than the right gland. Both noncontrast CT and multiphase contrast-enhanced CT play a role in adrenal imaging. On noncontrast CT, the presence of macroscopic fat confirms diagnosis of a myelolipoma while an attenuation of less than 10 HU suggests diagnosis of an adenoma and further evaluation is not required. However, when the attenuation is more than 10 HU then an adrenal protocol CT is done to look for rapid washout and calculate percentage washout to differentiate between adenomas and nonadenomas. CT protocol and adrenal washout: Multiphase CT protocol is based on the fact that while both adenoma and malignant lesions show rapid contrast enhancement, adenomas both lipid-rich and

lipid-poor, show rapid washout of contrast as well while malignant masses for instance metastases show slower washout. Protocol: 1) Baseline noncontrast scan. 2) Venous phase at 60–70 seconds. 3) Delayed phase at 15 minutes. From these scans, absolute enhancement washout is calculated which helps in differentiating adenomas from nonadenomas. If an adrenal lesion is discovered on a contrast scan while the patient is still on the table, then a delayed scan at 15 minutes can be made and the relative enhancement washout can be calculated. For attenuation measurement the ROI should occupy at least two-thirds of the lesion to ensure a representable assessment. Absolute Percentage Washout (APW) ≥60% and Relative Percentage Washout (RPW) ≥40% is suggestive of an adenoma. Contrast washout

MRI The single most important MRI protocol for the adrenal glands is chemical shift imaging (CSI). CSI is noncontrast MRI technique which can be used for diagnosis of adenoma when either CT is contraindicated or when washout values are equivocal. It is based on the principle that fat has a lower precession resonant frequency than water in the presence of an externally applied magnetic field. Thus, during T1-weighted GRE sequence, if microscopic fat and water are present in the same voxel as seen in adenomas, the signal of lipid and water gets summated in the inphase but gets nulled out during out-phase sequence. Thus, lipid poor adenomas which contain enough microscopic fat show signal drop on out-of-phase imaging compared to in-phase imaging due to the chemical shift artefact. MRI can also be used to confirm macroscopic fat in myelolipoma which shows drop in signal in the fat-suppressed sequence. Dual-energy CT DECT allows simultaneous acquisition of CT data sets at different tube voltages (commonly, 80 and 140 kVp) during a single breathhold scan. It is based on the principle that the attenuation coefficients of substances in the human body vary with applied tube

voltage, hence images acquired with DECT scanning can be analyzed for the presence of specific substances in human tissues such as fat, water, calcium and iodine. DECT has the potential to improve the workup of adrenal masses by enabling characterization of adrenal nodules on the initial contrast-enhanced CT and thus obviating the need for additional imaging (Fig. 10.16.4.3A and B). One method subtracts iodine from contrast-enhanced DECT to generate ‘virtual’ noncontrast (VNC) images that can be used to replace true noncontrast CT images. VNC data sets can then be used for characterization of adrenal nodules with CT densitometry.

FIG. 10.16.4.3 (A) Axial unenhanced DECT image at 140 kVp shows indeterminate left adrenal nodule with attenuation value of +13 HU. (B) Axial unenhanced image of the same patient at 80 kVp shows attenuation decrease in lesion to +8.5 HU, suggesting presence of intracellular lipid. Another method uses material decomposition analysis to generate material density basis pairs, which can quantify the proportions of materials such as lipid and water within adrenal nodules and enable differentiation of adenomas from metastases. Nuclear medicine imaging Two main types of nuclear medicine examinations are used in adrenal imaging. The traditional study uses iodine-123 (123I)labelled metaiodobenzylguanidine (MIBG). MIBG is an analogue of norepinephrine, so it is used to detect tumours of the adrenal medulla, most commonly adrenal pheochromocytomas. It can also be used to localize extra adrenal paragangliomas and metastatic disease from malignant pheochromocytomas. Another type of study uses fluorine-18 fluorodeoxyglucose (18F FDG), which is a radiolabelled d-glucose analogue used with

positron emission tomography (PET). FDG PET can detect tissue with high metabolic activity and is therefore sensitive at distinguishing malignant from benign disease. FDG PET/CT has also been shown to have high sensitivity and specificity for diagnosis of metastatic disease, with diagnostic performance percentages greater than 90%. Furthermore, absence of FDG uptake in an adrenal nodule has a high negative predictive value (93%–97%) for the absence of metastatic disease. Ultrasonography The visualization of the normal adrenal glands is difficult on USG. However, it plays an important role in imaging adrenals in the paediatric population, owing to the lack of ionizing radiation; furthermore, the small body habitus of children allows for better visualization of retroperitoneal structures. Though the visualization of retroperitoneal structures like adrenals is difficult on USG in adults, it can still play a role in monitoring changes during treatment of already established pathology, enables visualization of other abdominal organs in the same setting without any risk of radiation exposure as well as incidentally detecting adrenal masses. On USG, if no mass is seen with or without visualization of normal adrenals, it is considered to be specific for the absence of malignancy. Friedrich Rust et al. have studied the efficacy of CEUS in evaluation of adrenal masses using phospholipid-stabilized microbubbles filled with sulphur hexafluoride. Arterial enhancement with rapid washout is seen in the nonadenomatous masses. The study recommended opting for CEUS for analysis of adrenal masses as initial radiological examination as it would reduce the radiation exposure occurring in multiphase computed tomography and significantly reduces the cost and time required for MRI. In general, the vast majority of the adrenal lesions are benign adrenal adenomas, even in the absence of pathological confirmation, since adrenal adenomas are rarely excised. The table 10.16.4.1 shows the malignant adrenal masses.

TABLE 10.16.4.1 Common Tumors of the Adrenal Gland ADRENAL CORTEX LESIONS • Adrenocortical carcinoma (secreting or nonsecreting) ADRENAL MEDULLA LESIONS • Pheochromocytoma (benign or malignant) • Neuroblastoma, ganglioneuroblastoma • Metastases (ling, breast, kidney, melanoma, lymphoma)

Adrenocortical carcinoma Adrenocortical Carcinoma (ACC) is the most common malignant adrenal tumour. It shows bimodal age of presentation, affecting children in the first decade and adults in the fourth and fifth decades. ACCs are more likely to be smaller in size and functioning in children thus presenting early with endocrine dysfunction. In adults, tumours tend to be larger in size and nonfunctioning and hence present late with abdominal pain and lump, local invasion and distant metastases. ACC can be associated with genetic syndromes such as Li–Fraumeni syndrome, Beckwith–Wiedemann syndrome, familial adenomatous polyposis coli and Carney’s complex, especially in children. ACCs are typically large at presentation with an average size more than 6 cm. On CT scan, they show heterogeneous enhancement with areas of necrosis and haemorrhage replacing the entire adrenal gland (Fig. 10.16.4.4). They can be well defined and less than 5 cm especially in children, thereby mimicking adenomas. However, RPW and APW are typically less than 40% and 60%, respectively, thus differentiating them from benign adenomas. Calcifications can be seen in up to 30% of these tumours. This differentiates them from adenomas which do not show calcifications and pheochromocytomas which show calcifications in only 10%.

FIG. 10.16.4.4 Adrenocortical carcinoma. Axial contrast-enhanced CT scan shows a large heterogeneously enhancing mass with central necrosis arising from the left adrenal gland. Most adrenal masses at presentation should undergo a thorough history and physical examination which can often point out towards secretory tumours and those associated with syndromes. Based on these initial findings, endocrinological laboratory evaluation and washout studies preoperative diagnosis of ACC in majority of patients. Local invasion and contiguous tumour extension into adjacent structures such as kidney, liver, pancreas and diaphragm can be seen. Similarly, IVC invasion is typical for ACC. Metastases can be seen in up to 30% of cases and occurs to regional lymph nodes, liver, lungs and bones. On MRI, ACCs show heterogeneous signal intensity on T1W and T2W sequences, with T1 hyperintensity due to haemorrhage and T2 hyperintensity due to necrosis. MRI can also better evaluate the IVC invasion and extent of tumour thrombus. Atypical imaging features of ACCs include the presence of intracellular fat resulting in signal drop on opposed phase CSI-MR images and APW and RPW of more than 60% and 40%, respectively thereby mimicking adenomas.

ACC shows high avidity on FDG PET/CT. FDG PET/CT is also useful for staging because it can detect metastases and determine tumour response to chemotherapy. For staging of ACCs, TNM classification proposed by ENS@T is used (Table 10.16.4.2). T stage: T1 – Tumour less than or equal to 5 cm. T2 – Tumour more than 5 cm. T3 – Tumour invasion into the surrounding tissue. T4 – Tumour invasion into the adjacent organs or venous tumour thrombus in the inferior vena cava or renal vein. N stage: N0 – No evidence of spread to the locoregional lymph nodes. N1 – Spread to the locoregional lymph nodes is present. M stage: M0 – No evidence of distant metastasis. M1 – Metastatic disease is present. TABLE 10.16.4.2 Staging of Adrenocortical Carcinoma Stage Stage I Stage II Stage III Stage IV

T1N0 MO T2N0 M0 T3 or T4 with N1 Any T, Any N, M1

Surgical resection, which can be either curative or debulking, is the treatment of choice for ACCs irrespective of the tumour size and local invasion. Currently, the curative approach to ACCs is complete surgical resection. Open surgical resection is the gold standard for this solid cancer and achieving R0 resection is the single most important factor governing prognosis. Concerns have been raised about the oncological safety of minimally invasive surgery in this cancer and if at all they should be performed for a select group of patients in high volume centers. Owing to the poor response of this cancer to chemotherapy and radiotherapy surgery remains the mainstay. If resectable, metastatectomy can also be considered. In certain patients with secretory tumours there can be a role of debulking surgery even in metastatic disease. Adjuvant radiotherapy has some role in larger tumours particularly those with capsular breach. For

‘unresectable/metastatic ACCs’, the therapy is palliative (radiotherapy/mitotane).

Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumour which originates from the adrenal medulla. It often manifests clinically with hypertension. Other symptoms include palpitations, headaches, sweating, tremor and anxiety. In 5%–10% of cases, it can be detected on imaging as an incidental finding. On CT, these tumours are usually well-defined solid homogeneous masses when small but can show heterogeneity with foci of calcification and cystic areas when larger (Fig. 10.16.4.5A and B). The average tumour size in sporadic cases is 5 cm while they tend to be smaller in familial cases. The noncontrast CT attenuation is almost always greater than 10 HU. With contrast CT most pheochromocytomas show slow enhancement followed by delayed washout, with an APW of less than 60% and RPW of less than 40%. However, recent reports demonstrate that approximately 30% of pheochromocytomas show greater than 60% APW or greater than 40% RPW.

FIG. 10.16.4.5 (A) Axial contrast-enhanced CT shows a 4.2 cm well-defined round left hypodense (22 HU) adrenal mass with thick enhancing wall histologically proven to be a pheochromocytoma and (B) Axial contrastenhanced CT shows a 5.7 cm well-defined round right hypodense (19 HU) adrenal mass with thick enhancing wall histologically proven to be a pheochromocytoma.

On MRI, pheochromocytomas show typically low signal on T1weighted images and demonstrate heterogeneous intermediate to high signal on T2-weighted images and at least 30% showing moderate to low T2-weighted signal intensity. They generally exhibit substantial enhancement on MRI. The treatment of choice for pheochromocytoma is surgical resection and majority of tumours are amenable to minimally invasive surgery. Adequate alpha and beta blockade (using alpha and beta adrenergic blockers and the calcium channel blockers) should be achieved before the surgery to avoid intraoperative haemodynamic instability. Symptoms and blood pressure respond dramatically to a well-done surgery.

Adrenal metastases The adrenal gland is a frequent site for metastases because of its rich sinusoidal blood supply. Tumours which commonly metastasize to the adrenals include primaries of the lung, breast, kidney, colon, oesophagus, pancreas, liver and stomach. In patients with known primary malignancy, up to 38%–50% of detected adrenal masses will represent metastatic disease. Morphologic features of metastases that differentiate them from benign adrenal tumours like adenomas include heterogeneous density, size greater than 4 cm, irregular shape or margins and bilateral lesions. However, these are nonspecific and poorly sensitive for distinguishing benign from malignant adrenal lesions. Interval increase in size of an adrenal nodule over a 6-month interval is highly suggestive of metastatic disease in patients with known primary malignancy. On noncontrast CT adrenal metastases typically have attenuation greater than 10 HU and absence of signal loss on opposed phase. On contrast-enhanced CT and MRI adrenal metastases typically show slow contrast enhancement followed by delayed washout of contrast (Fig. 10.16.4.6A–C). Most metastases can be differentiated from adenomas by demonstrating less than 60% APW and less than 40% RPW. However, a recent report found that hypervascular metastases, like those originating from HCC and RCC, may demonstrate perfusion dynamics similar to adenomas. In that study, 84% of HCC and RCC metastases demonstrated greater than 60% APW and greater than 40% RPW.

FIG. 10.16.4.6 (A) Left adrenal metastasis from lung cancer on axial contrast-enhanced CT (Note a metastatic splenic deposit along its posterior pole). (B) Right adrenal metastasis from lung cancer on axial contrast-enhanced CT. (C) Bilateral adrenal metastases from breast cancer on axial contrast-enhanced CT. The most effective treatment for adrenal metastases is to treat the primary cancer, usually with chemotherapy and/or radiation therapy. Steroid hormone replacement therapy should be given, if there is adrenal insufficiency. Surgical removal of adrenal may be considered if the primary disease is in control and the adrenal is the only site of metastasis. With the concept of curative surgery in oligometastatic setting gaining evidence in various cancers, the role of concomitant or interval adrenal metastatectomy is bound to expand. In patients with an underlying malignancy, the most common dilemma is to differentiate benign adenoma from metastatic disease. Since the presence of an adrenal metastasis will usually worsen the staging and prognosis, it is vital to differentiate between the two. Mistakenly determining an incidentally detected adrenal lesion as metastatic will deny a patient potential curative therapy. Conversely, reporting a mistaken diagnosis of adrenal adenoma will potentially subject the patient to unnecessary aggressive curative therapy. In patients with known malignancy, the risk of an adrenal mass being a metastasis is high, ranging from 45% to 73%. Of the adrenal abnormalities found in oncologic patients by Frilling et al. in their study, 70% proved to be metastases. In patients with known primary malignancy, up to 38%–50% of detected adrenal masses will represent metastatic disease. Benign adenomas are overwhelmingly the most common adrenal nodule encountered in the general population. Benign masses generally have Low HU (20 HU). In patients with malignancy, attenuation of less than 10 HU on unenhanced CT is a specific finding of adenoma.

The American College of Radiology (ACR) White Paper suggests that stability in size and appearance over a period of 12 months or longer is a reassuring feature of benignity. It also suggested that an increase of more than 20% in the diameter together with an at least 5-mm increase in this diameter were suspicious features. Pantalone et al. in their study stated that with at least two imaging studies 3– 12 months apart, a change in tumour size of 0.8 cm provided the highest combined sensitivity (60%) and specificity (84.6%) for the differentiation of benign versus malignant adrenal mass. In patients with incidentally detected adrenal lesion, a 6-month follow-up CT is recommended to ensure lesion stability to confirm benign disease. Any lesion growth is suspicious for malignant disease. Therefore, in a patient with a growing adrenal mass over 6 months, the adrenal mass should be considered malignant until proven otherwise, usually either an ACC or metastatic disease. Image-guided biopsy is used to establish the definitive tissue diagnosis in adrenal lesions which can’t be fully characterized with imaging and/or laboratory tests. Improvements in image-guidance, biopsy tools and biopsy techniques now routinely allow for safe biopsy of adrenal lesions which previously were considered difficult to reach and technically challenging. Staging of known malignancy, identifying an unknown primary malignancy, differentiating benign from malignant adrenal mass in equivocal cases are three accepted indications for adrenal biopsy. Various imaging modalities may be used for guidance such as CT, USG or fluoroscopy; though USG and CT guidance are usually preferred. A needle path that avoids diaphragm, kidney, aorta and splenic vessels is desirable and in many cases may be best depicted by these modalities (Fig. 10.16.4.7). Preprocedure platelet count and coagulation profile are absolutely necessary investigations and should be in the normal limits. Assistance of an anaesthesiology may be considered for blood pressure control. Choice of the guidance modality and position is decided as per the availability and preference of the radiologist performing the biopsy.

FIG. 10.16.4.7 CT guided biopsy of adrenal lesion. (A) Prebiopsy image showing adrenal mass. (B, C and D) Serial images showing needle path avoiding injury to the adjacent vital organs.

The risk of an adrenal mass being malignant increases with adrenal mass size, as malignancy rates of 43%–100% have been reported for masses larger than 3 cm. The incidence of metastasis increases to 71% if the adrenal lesion is larger than 4 cm. Frilling et al. reported a mean diameter for metastases to be 3.6 cm and that for adenoma to be 2.5 cm. Zeiger et al. stated that majority of tumours 6 cm in size. However, in our study majority of the lesions more than 2 cm were malignant and the percentage increases further with size >4 cm. The bilateral adrenal lesions were found to be metastatic, according to the data from retrospective study from MD Anderson Cancer Centre of patients presenting with an occult malignancy, where they found that, about 75% of metastases were bilateral. The most effective treatment for adrenal metastases is to treat the primary cancer, usually with chemotherapy and/or radiation therapy. Steroid hormone replacement therapy should be given if the patient has adrenal insufficiency. If the primary disease is well controlled and the adrenal is the only site of the metastasis, surgery can be an option.

Inflammatory lesions Bilateral adrenal involvement is most common in adrenal inflammatory lesions. It is mostly caused by granulomatous disease, due to either Koch’s disease or histoplasmosis. During subacute phase, the adrenal glands become enlarged and may contain cystic or necrotic masses with peripheral enhancement. Calcification occurs later in the disease. As the granulomatous process matures, the adrenal glands decrease in size and become more calcified. Granulomas show little enhancement. Pyogenic adrenal abscesses are rare with most cases occur in neonates following episodes of adrenal hemorrhage. Granulomatous disease of the adrenal glands is the most common cause of Addison’s disease after the idiopathic form. In patients being evaluated for Addison’s disease, the presence of bilateral adrenal enlargement should suggest a differential diagnosis that includes granulomatous infection.

10.17: Retroperitoneum 1 0. 1 7 . 1

CROSS-SECTIONAL IMAGING ANATOMY OF THE RETROPERITONEUM Tanvi Vaidya

Introduction The retroperitoneum is a complex anatomical space, bordered anteriorly by the posterior parietal peritoneum and posteriorly by the transversalis fascia; extending superiorly from the diaphragm to the pelvic brim. It is composed of two lateral compartments and a central compartment; all of which are delineated by various fascial planes. Each lateral compartment is further divided by the fasciae into three distinct spaces: (1) the anterior pararenal (APR), (2) perirenal and (3) posterior pararenal (PPR) spaces. The central or vascular compartment is situated between the perirenal spaces, posterior to the anterior pararenal space and in front of the vertebral column.

Anatomy of the lateral compartment 1) The anterior pararenal space (Figs. 10.17.1.1 and 10.17.1.2) Boundaries, communication and extent: This space is located between the posterior parietal peritoneum anteriorly, the anterior renal fascia/Gerota’s fascia posteriorly and lateroconal fascia laterally. Medially it is potentially continuous across the midline, around the pancreas. Superiorly, the anterior pararenal space extends to the dome of diaphragm, just posterior to the intraabdominal segment of the oesophagus; and hence to the mediastinum, on the left and up to the inferior layer of the coronary ligament on the right. Inferiorly, the anterior and posterior pararenal spaces merge below the cone-shaped perinephric space, to form a common infrarenal compartment which communicates with

the extraperitoneal spaces of the pelvis including the perivesical, prevesical and presacral spaces. Contents: The anterior pararenal space contains the pancreas, duodenum, ascending and descending colonic segments, root of the small bowel mesentery and the transverse mesocolon. Owing to paucity of fat, delineation of this space may be difficult, unless it is distended due to fluid accumulation. Applied anatomy: Inflammatory conditions such as pancreatitis, appendicitis and diverticulitis and resultant fluid collections such as pseudocysts and abscesses involve the anterior pararenal space (Fig. 10.17.1.3). Pancreatic pseudocysts could sometimes occur in the posterior mediastinum owing to its communication with the anterior pararenal space. Similarly, fluid collections related to appendicitis could extend into the pelvis. 2) The perirenal space Boundaries, communication and extent: located between the anterior renal fascia and the posterior renal fascia, this space mainly contains the kidneys, suprarenal glands and renal vessels on either side. Laterally, it is limited by the lateroconal fascia formed by the fusion of the anterior and posterior renal fascia, posterior to the ascending and descending colon on either side. The lateroconal facia continues anteriorly to merge with the posterior peritoneal reflection thus forming the paracolic gutter on either side. Medially the anterior renal fascia with connective tissue that surrounds the great vessels in the central compartment while the posterior renal fascia fuses with the fascia of the psoas major or quadratus lumborum muscles. The perirenal spaces communicate across the midline via the Kneeland narrow channel located immediately anterior to the central/vascular compartment. Superiorly the anterior renal fascia blends with the inferior coronary ligament on the right and with the gastrophrenic ligament on the left, while the posterior renal fascia fuses with the inferior phrenic fasciae bilaterally. Thus, the perirenal space is in continuity with the bare area of the liver on the right and the subphrenic space on the left and also communicates with mediastinum via the diaphragm hiatus and splanchnic foramina of the diaphragmatic crura. Inferiorly the anterior and posterior renal fascia begin to converge below the inferior pole of the kidney lying in close contact with periureteric connective tissue however, do not fuse. The inferior cone of the perirenal space is open towards the iliac fossa, in contact with the psoas muscles, ureter and is continuous with prevesical and presacral spaces. Contents: The perirenal space contains the kidneys, suprarenal glands, proximal ureters, perirenal fat, lymphatic

vessels and renal vessels. The perirenal fat contains numerous bridging fibrous septae, which are of three types: (1) those extending between capsule and the anterior/posterior renal fascia, (2) those attached only to the renal capsule forming a curved arch and (3) those connecting the anterior and posterior renal fascia. These septa serve as supports for the kidneys; furthermore this may limit the spread of disease or serve as conduits for disease extension between the perirenal space and the renal fasciae (Fig. 10.17.1.4). Applied anatomy: Blood from a ruptured abdominal aortic aneurysm may track into the perirenal space via the narrow channel across the midline. Haematomas or laceration involving the liver parenchyma or capsule adjacent to the bare area, can manifest with blood collection in the right pararenal space. Conversely right-sided perirenal haematomas or fluid collections could extend along the bare area of the liver. In addition, perirenal space collections may extend into the retroperitoneal space of the pelvis via the inferior communication/aperture. 3) The posterior pararenal space Boundaries, communication and extent: located between the posterior renal fascia, anteriorly and the fascia transversalis, posteriorly. The space is limited medially by fusion of the posterior renal and transversalis fasciae with the muscular fasciae, adjacent to the psoas major with no communication across the midline. In its lateral aspect, continues as the properitoneal fat of the abdominal wall outer to the lateroconal fascia. It is this properitoneal fat which is visualized as the lucent flank stripe on plain abdominal radiographs. Inferiorly the posterior pararenal space is open to the pelvis and communicates with the prevesical space, femoral sheath, the anterior pararenal and perirenal spaces via the infrarenal space. The superior extent of the posterior pararenal space is determined by fusion of the posterior perirenal fascia with the fascia of the psoas and quadratus lumborum muscles and the inferior phrenic fascia. It generally continues as a thin layer of extraperitoneal fat in the subdiaphragmatic region. Contents: The posterior pararenal space contains fat, blood vessels and lymphatics, but no major organs. Thus, involvement of this space by disease processes is usually due to extension from adjacent spaces/viscera (Fig. 10.17.1.5).

FIG. 10.17.1.1 Schematic transverse section depicting the anatomy of the retroperitoneum and fascial planes: Lateral compartment: Anterior pararenal space, perirenal space, posterior pararenal space. Central/vascular compartment containing the great vessels.

FIG. 10.17.1.2 Schematic sagittal section depicting the anatomy of the retroperitoneum and fascial planes: Anatomy of the lateral compartment, extent and relationship of the retroperitoneal spaces.

FIG. 10.17.1.3 Contrast-enhanced axial CT sections in a case of acute pancreatitis (asterisk in A); the pancreas appears diffusely bulky with peripancreatic fat stranding. Thickening of the anterior renal fascia (blue arrows in B and C) with fluid collection in the anterior pararenal space (blue arrow in D).

FIG. 10.17.1.4 Contrast-enhanced axial and sagittal CT sections in a case of acute right pyelonephritis (A and B); the right kidney appears bulky with perinephric fat stranding. Thickening of the perinephric bridging septae (blue arrows in A and B) and posterior renal fascia. Axial T1W and axial STIR images also depict the thickened perinephric bridging septae (blue arrows in C and D).

FIG. 10.17.1.5 Contrast-enhanced axial CT sections in a case of acute right pyelonephritis (A–D); the right kidney appears bulky with perinephric fat stranding (asterisk in A). Thickening of the posterior renal fascia (blue arrow in A) and perinephric bridging septae (blue arrow in B). The inflammation extends into the right iliac fossa via the inferior cone of the perirenal space, in contact with the psoas major muscle (blue arrows in C and D).

Concept of retroperitoneal interfascial planes The retroperitoneal fasciae are not composed of single-layered membranes, but are multilayered, thereby leading to the formation of potential, expansile fascial planes. These may serve as connecting channels for the spread of inflammatory or neoplastic conditions between the peritoneal, retroperitoneal and pelvic spaces. Alternatively, spread along these pathways could aid the decompression of large haematomas, fluid or gas collections in the abdomen. The four fascial planes of the retroperitoneum include the retromesenteric, retrorenal, lateral conal and combined interfascial planes (Fig. 10.17.1.6). Location: The retromesenteric plane is the fascial plane located between the anterior pararenal space and the perirenal space. The potential space between the layers of the lateroconal fascia is termed as the latero conal plane. The retrorenal plane separates the perirenal space from the posterior pararenal space, while the combined interfascial plane is formed by the inferior fusion of the

retromesenteric and retrorenal planes which continues into the pelvis. Communication and extent: The anterior interfascial retromesenteric plane is continuous across the midline, and communicates laterally with the lateroconal and retrorenal planes, at the fascial trifurcation. The combined interfascial plane extends into the pelvis, along the anterior to the psoas major and communicates with the extraperitoneal presacral and perivesical spaces. This communication can thus serve as a pathway of disease extension from the abdominal retroperitoneum into the pelvis and vice versa (Fig. 10.17.1.7). In addition, the retrorenal plane communicates with the fascia transversalis via two pathways: (1) a cleft at the lumbar triangle, located between the medial border of the posterior pararenal space and the lateral border of the quadratus lumborum fat pad and (2) another narrow passage which connects the retrorenal plane with the subfascial plane, located between the posterior pararenal space anteriorly and the fascia transversalis posteriorly. Applied anatomy: An understanding of the interfascial planes is crucial as various diseases involving the retroperitoneal organs can easily involve the interfascial planes and spread along them to involve other subsites. On CT or MRI, any fluid collection within these potential spaces tends to be sharply defined with linear or curvilinear margins. Thickening of the retroperitoneal fasciae on cross-sectional imaging is indicative of the presence of disease in the retroperitoneal organs and requires a detailed evaluation for the same. Several disease entities, both inflammatory and neoplastic can involve the interfascial planes, as follows: • Acute pancreatitis: CT imaging is commonly used to assess the severity of pancreatitis by detecting the presence and extent of pancreatic necrosis and associated peri-, extrapancreatic fluid collections in the retroperitoneum, peritoneal cavity and rarely mediastinum. Often, inflammatory fluid collection initially accumulates in the anterior pararenal space, extends posteriorly to involve the anterior interfascial retromesenteric plane (Fig. 10.17.1.3). This collection may further spread posteriorly via the fascial trifurcation to the renorenal plane and extend to the flank via the subfascial plane between the posterior pararenal space and the transversalis fascia, giving rise to the flank discoloration in patients with pancreatitis, termed as the ‘Grey Turner’s sign’. Tracking of fluid into the subfascial plane can be identified by means of the ‘Checkmark sign’, which is an indicator of severe disease. Haematomas resulting from great vessel injuries (Fig. 10.17.1.8): Haemorrhage resulting from rupture of aortic aneurysms or IVC injuries can extend to the retroperitoneum via the interfascial planes. Abdominal aortic aneurysms tend to bleed posteriorly and the

resulting haemorrhage may extend into the left renorenal plane. Aortic haemorrhage may also track into the pelvis via the combined interfascial plane and present as a groin haematoma and rarely via the retromesenteric plane leading to compression of adjacent viscera such as the duodenum or colon resulting in features of intestinal obstruction. The IVC on the other hand, usually bleeds directly into the right renorenal plane, with haemorrhage also involving the perirenal spaces. Extension of haemorrhage into the subfascial plane, is depicted by the checkmark sign on imaging, which is associated with a worse prognosis and a higher mortality rate. Perirenal haematomas: resulting from renal or adrenal injuries may extend into the retromesenteric and retrorenal planes by means of bridging septae which traverse the perirenal space. The haematoma may further extend into the pelvis via the combined interfascial plane (Fig. 10.17.1.9). Urinomas: could occur secondary to forniceal rupture due to an obstructing renal calculus. CT imaging demonstrates encapsulated collections of urine in the perinephric space with leak of contrast material into the collection. The fluid which may in turn gain access to the retromesenteric plane via the bridging septae. Duodenal perforation: resulting from blunt trauma or peptic ulcer disease could lead to leakage of fluid and air which may decompress into the retromesenteric plane. These can readily extend along the interfascial planes to distant sites (Fig. 10.17.1.10). Spread of malignancies: Involvement of the perinephric space could occur via its rich lymphatic network that drains the renal hilar lymph nodes, which in turn communicate with paraaortic and paracaval lymph nodes. Pleural and transdiaphragmatic lymphatics connect with the perinephric lymphatic network; which can potentially lead to metastases from a lung cancer into the perinephric space. Infection and inflammation: The ascending and descending mesocolon are in close proximity with the retromesenteric and lateroconal interfascial planes, thus infectious and inflammatory conditions of the ascending and descending colon, such as colitis, diverticulitis and retrocaecal appendicitis, can spread into the interfascial planes.

FIG. 10.17.1.6 Schematic transverse section depicting the anatomy of the inter-fascial planes of the retroperitoneum, their communication and extent.

FIG. 10.17.1.7 Schematic sagittal section depicting the anatomy of the interfascial planes of the retroperitoneum, their communication and extent.

FIG. 10.17.1.8 Contrast-enhanced axial (A–D) and sagittal CT (E) sections in a case of a pelvic retroperitoneal haematoma. The right kidney appears bulky with perinephric fat stranding. Active leak of contrast from the right external iliac artery is seen on the arterial phase (blue arrow in A) with a resultant large haematoma (asterisks in A–D). Superiorly, it extends along the combined interfascial plane into the perirenal space (blue arrow in E) as well as along the retromesenteric (blue arrows in C and D) and retrorenal planes (asterisk in C). Medially the haematoma tracks into the central compartment (asterisk in D) via the perirenal space.

FIG. 10.17.1.9 Contrast-enhanced axial (A, B) and sagittal CT (C) sections in a case of a perinephric haematoma (asterisks in A and B). It extends into the retromesenteric and retrorenal planes by means of bridging septae which traverse the perirenal space (blue arrow in A). Inferiorly, it extends along the combined interfascial plane into the pelvis (blue arrow in C).

FIG. 10.17.1.10 Axial CT sections (A, B) in a case of duodenal perforation diagnosed following administration of oral positive contrast. The extravasated contrast extends into the retromesenteric plane (blue arrow in B).

Pelvic extraperitoneal spaces These are situated between the transversalis fascia and the parietal peritoneum, and include the prevesical, perivesical and perirectal spaces (Figs. 10.17.1.11 and 10.17.1.12). Anterior to the peritoneal cavity and posterior to the transversalis fascia, lies the umbilicovesical fascia (UVF). It has a triangular shape with its apex at the umbilicus, extending inferiorly to surround the urinary bladder, obliterated umbilical arteries and urachus. The UVF separates the prevesical space anteriorly from the perivesical space posteriorly. The prevesical space: It is located anterior to the UVF and posterior to the transversalis fascia. It extends up to the umbilicus superiorly and inferiorly behind the pubis. Inferiorly, just

posterior to the pubis, it is designated as the space of Retzius. The prevesical space is contiguous with the rectus sheath, the presacral space as well as the femoral sheath. Thus, rectus sheath haematomas as well as femoral sheath haematomas may extend into the prevesical space and cause compression of the pelvic viscera. Prevesical space fluid/blood collections assume a ‘molar tooth’ configuration on axial CT and MRI images due to the presence of the UVF. The ‘crown’ of the tooth lies between the fascia transversalis and the UVF, displacing the bladder posteriorly; while the roots extend laterally between the UVF and the peritoneum. The perivesical space: It is a thin space, enclosed by the UVF which contains the urinary bladder, urachus, obliterated umbilical arteries and fat. The perivesical space lies in contact with the prostate, seminal vesicles in males and the cervix in females. Fluid collections within the perivesical space are generally small and may be confused with bladder wall thickening on CT images. The perivesical space communicates with the prevesical and perirectal spaces. Both, the prevesical as well as the perivesical spaces communicate with the abdominal retroperitoneum, which includes the perirenal space and the anterior/posterior pararenal spaces via the infrarenal compartment; thus accounting for pelvic extension of retroperitoneal collections. The perirectal space: It contains the rectum, perirectal adipose tissue and the haemorrhoidal vessels. It is enclosed by the rectal fascia, which in its anterior aspect extends along the posterior surface of prostate and seminal vesicles in males and along the uterus and vaginal fornix in females. In its posterior aspect, the fascia lies parallel to the sacrum. Superiorly, it attaches to the peritoneal reflection. The perirectal space communicates with the prevesical and perivesical spaces.

FIG. 10.17.1.11 Schematic sagittal section depicting the anatomy of the pelvic retroperitoneum and its fascial planes. The prevesical, perivesical and perirectal spaces are depicted. The umbilicovesical fascia separates the prevesical space anteriorly from the perivesical space posteriorly.

FIG. 10.17.1.12 Schematic axial section depicting the anatomy of the pelvic retroperitoneum and its fascial planes. The prevesical, perivesical and perirectal spaces are depicted in the axial plane. 1 0. 1 7 . 2

IMAGING TECHNIQUES AND PROTOCOLS FOR THE RETROPERITONEUM Tanvi Vaidya, Shivani Mahajan

Introduction Disorders of the retroperitoneum often have subtle, nonspecific and variable clinical signs and symptoms and hence their diagnosis is often challenging. Cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MR) allow excellent, noninvasive evaluation of the normal anatomy and pathology and so are routinely preferred techniques for assessment of suspected retroperitoneal abnormalities.

Although retroperitoneal neoplasms have overlapping imaging features, a systematic image-based approach can help narrow the differential diagnosis.

Imaging techniques and protocol Conventional radiography Conventional radiographic means do not provide an accurate evaluation of retroperitoneum. The blurring of the psoas margins may be seen in mass lesions but is nonspecific. Intravenous urography may show secondary features such as ureteral obstruction and hydronephrosis. Transvertebral retroperitoneal gas insufflation is an obsolete historical radiographic technique that involved the injection of gas into the retroperitoneal spaces through the presacral route. Ultrasonography Evaluation of clinically suspected abdominal masses often begins with a transabdominal ultrasound examination. Often asymptomatic/clinically silent retroperitoneal lesions are incidentally detected on abdominal ultrasound. USG is an excellent tool for primary screening, for differentiation of solid from cystic lesions and also to guide interventions such as image-guided percutaneous biopsies or aspiration. But USG has certain drawbacks, such as poor definition of soft tissue planes, limited reproducibility and limited evaluation due to overlying bowel gas. CT and MRI Cross-sectional imaging techniques such as CT and magnetic resonance imaging (MRI) are the most widely used techniques in retroperitoneum imaging, and play a crucial role in accurate anatomic localization, disease characterization, evaluation of extent, adjacent organ invasion, distant organ involvement and staging. Both these techniques have multiple advantages such as short study time (5–10 minutes for a CT and 20–30 minutes for an MRI), high spatial resolution, multiplanar and volumetric display of data, the capacity of whole-body imaging, and good soft tissue contrast. Computed tomography CT is the primary and most widely used imaging modality in cases of clinically suspected retroperitoneal pathology and also for in-depth evaluation and characterization of ultrasonographically encountered retroperitoneal lesions. CT provides excellent anatomic details, has high spatial resolution, and aids in accurate compartmentalization of the disease. CT is superior to MRI in detecting calcifications, ossification and gas, and is often more accessible than MRI, and can be used when MRI is contraindicated. The CT protocol depends on the type of scanner and the indication for the study. Careful attention should be paid to patient preparation and technical details of the scan. Five- millimetre thick slice with 1–2 mm detector collimation is routinely used for a survey examination on a 4–16

slice multidetector-row CT (MDCT). Thinner collimation of 0.5–0.7 mm is used for the angiographic examination of the abdominal aorta and its main branches on an MDCT. Multiplanar image reconstruction can be done at 1–2 mm intervals. CT examination of the retroperitoneum is always performed after the ingestion of oral contrast medium, except in case of emergencies such as a suspected ruptured aortic aneurysm. The patient is asked to ingest approximately 1000 mL of oral contrast material (such as dilute barium suspension or iodinated water-soluble contrast material) about 1 hour before the examination to opacify the distal small bowel and large bowel, followed by 300–500 mL of contrast 15 minutes before the study to distend the stomach and proximal small bowel. In addition, 200 mL of contrast can be administered per rectally to opacify the rectum and sigmoid colon. CT examination is performed with the patient in a supine position with axial sections extending from lung bases to pubic symphyses. Precontrast images are acquired for detection of haemorrhage, calcification, ossification, macroscopic fat, cystic or necrotic changes and as a baseline scan to assess the degree of enhancement after IV contrast injection. Intravenous contrast is administered using a power injector at a rate of 2–3 mL/sec for regular survey examination and 3–5 mL/sec for CT angiography. CT angiography images are acquired 25 seconds after injection of contrast, followed by images in the venous phase at 60–70 seconds. Delayed-phase or excretory urography phase images at 5–10 minutes are useful for visualization of the pelvicalyceal system, ureters and bladder. The data set can be reconstructed in coronal, sagittal and oblique planes, and threedimensional volume-rendered image can be created through postprocessing software. Magnetic resonance imaging MRI has certain advantages over CT such as lack of ionizing radiation, superior contrast resolution and can be used when CT contrast is contraindicated or contrast allergy is present. It is preferred over CT in pregnant and paediatric patients. Through the acquisition of various imaging sequences, MR allows a better understanding of the inherent characteristics of the disease pathology. The MRI protocol for retroperitoneum is similar to that of abdominal imaging. MR examination is performed with a torso phased array coil using breathhold sequences. Both T1-weighted imaging (T1WI) and T2weighted imaging (T2WI) aid in lesion detection and characterization. T1WI can be obtained using either SE (spin-echo sequence, TR 300–1000 msec, TE as short as possible) or GRE sequences (gradient echo sequences such as FLASH, GRASS etc.) GRE is preferred as multiple sections and can be acquired in a single breathhold and so high-quality images are obtained with no respiratory artefacts and minimal artefacts due to bowel peristalsis. Precontrast T1 GRE sequence is performed in both in phase and out of phase. T2WI (TR >1500 msec and TE >70 msec) can be conventional SE sequences or fast spin-echo (FSE)/turbo spinecho (TSE) such as HASTE. The FSE has the advantage of significantly lesser image acquisition time and hence it is preferred. Diffusionweighted imaging can be performed when necessary.

Standard MRI protocol of the retroperitoneum includes coronal SSFSE (single-shot fast spin echo) T2WI, axial FSE (fast spin echo) T2WI, axial T1WI with fat saturation, axial in-phase and out-of-phase T1WI and 3D T1-spoiled GRE breathhold sequence. Axial DWI may be acquired when necessary. Axial images are acquired with a 3-mm thickness and 2-mm interslice gap. Coronal and sagittal images help in better visualization of the aorta, IVC and the psoas. High signal intensity fat/blood products, lymph nodes and vascular invasion are best seen on noncontrast TIWI. T2 fat-saturated images provide good visualization of lymph nodes, cystic changes, central tumoural necrosis, retroperitoneal fluid collections, marrow oedema and dilatation of ureters. Precontrast and postcontrast T1WI images (both arterial and venous phases) provide insights into the etiopathology of the abnormality. However, the delayed postcontrast T1WI is the most important sequence for characterizing the nature of the disease (solid or cystic), define the disease extent, detect vascular thrombosis, evaluate vascular encasement by the tumour and for screening the abdomen and pelvis. Gadolinium-based intravenous contrast is routinely used in retroperitoneal imaging. The recommended dose is 0.1–0.2 mmol/kg of body weight given as a bolus injection at a rate of 2 mL/sec. FLASH images are acquired at 45 seconds followed by fat-saturated FLASH sequences at 90 seconds. MR angiographic (MRA) images can be acquired using GRE sequences based on time of flight (TOF) of phase-contrast (PC) techniques. The 2D TOF requires less time and is accurate, but has the disadvantage of inplane flow saturation in slow flow and tortuous vessels. The PC technique is more sensitive to flow but is time consuming and there is signal loss in turbulent flow. Three-dimensional gadolinium-enhanced GRE MRA overcomes the limitations of both these 2D angiography techniques and is based on the principle of T1 shortening by gadolinium contrast. The 3D images acquired can be reconstructed with maximum intensity projection (MIP) so that the entire arterial and venous system can be viewed in multiple projections. MRA requires a contrast dose of 0.1–0.2 mmol/kg of body weight at a rate of 2–3 mL/sec with a power injector, followed by 15 mL of normal saline. Despite the many advantages of CT and MRI, they often fail to provide a definite diagnosis or differentiate between benign or malignant lesions. In such cases accurate percutaneous-guided biopsies can be performed under USG, CT or MR guidance to arrive at a conclusive diagnosis (Tables 10.17.2.1–10.17.2.2).

Table 10.17.2.1 Computed Tomography (CT) in Retroperitoneal Imaging Advantages Shorter time High spatial resolution Multiplanar and volumetric data set Whole-body imaging possible in single scan Good soft tissue contrast Superior in detection of calcification, gas, ossification Can be used if MRI is contraindicated Preparation Oral contrast, except in emergent conditions Intravenous access Protocol Multidetector CT scan Supine position – Axial sections Coverage: Lung bases to pubic symphysis Precontrast – for haemorrhage, calcification, cystic changes, baseline HU of lesion IV contrast – 2–3 mL/sec for regular examination, 3–5 mL/sec for CT angiography Arterial, venous and delayed phases acquired Postprocessing software – multiplanar reconstruction, 3D volume rendering Table 10.17.2.2 Magnetic Resonance Imaging (MRI) in Retroperitoneum Advantages

Technique

Standard Protocol

No ionizing radiation Superior contrast resolution Used in cases of CT contrast allergy Whole-body imaging possible Body coil/torso phased array coil Breathhold sequences Slice thickness 3–6 mm 2-mm interslice gap Contrast – gadolinium-based intravenous contrast, Dose: 0.1–0.2 mmol/kg Precontrast Coronal T2 SSFSE/HASTE Axial T2 FSE Axial GRE T1 Chemical shift imaging – in phase and out of phase 3D GRE volumetric interpolated fat-saturated breathhold sequence Additional sequences - DWI, SWI Noncontrast MR angiography – TOF/PC Postcontrast T1 fat saturated – Arterial, venous and delayed-phase images Contrast MR angiography

Cross-sectional imaging-based approach to primary retroperitoneal neoplasms Retroperitoneal tumours consist of a diverse group of pathologies, often with considerable overlap in imaging features. Radiological diagnosis of these lesions can be challenging and requires a stepwise image-based approach. This consists of determining the precise tumour location (within the retroperitoneal anatomical space), identifying the most probable organ of origin, and detecting certain specific imaging features which further narrow down the differentials, such as the pattern of spread, degree of tumoural vascularity and the internal components (Fig. 10.17.2.1). 1. Tumour location: A lesion located in the true retroperitoneal space will cause mass effect and resultant anterior displacement of normal retroperitoneal structures. This displacement of normal organs can be used to confirm the true retroperitoneal location of the pathology. Any lesion causing anterior displacement of the ascending or descending colon, duodenum, pancreas, adrenals or kidneys would suggest a lesion with primary retroperitoneal origin. 2. Organ of origin: Once we have confirmed the primary location of the lesion, the next step is to determine the most probable organ of origin. Before labelling a tumour as a primary retroperitoneal neoplasm, it is imperative to rule out the possibility of it arising from a retroperitoneal organ. Radiological signs which aid in deciding the organ origin include: ‘organ-embedded sign’, ‘phantom organ/invisible organ sign’, ‘beak sign’, ‘feeding artery sign’. Beak sign If a mass deforms the margin of an adjacent organ into a beak shape, then the mass probably originates from that organ – this is the positive ‘beak sign’. On the contrary, if the mass has dull edges or fuzzy margins (no sharp beak seen) with adjacent organs, it indicates that the mass probably does not arise from the organ but just compresses it (Figs. 10.17.2.2–10.17.2.3). Organ-embedded sign If a part of the organ appears to be in close contact with the tumour or embedded in the tumour, the intervening contact surface may be sclerosed or occasionally ulcerated – this is the positive organ-embedded sign, the presence which indicates that the tumour originates from the involved organ (Figs. 10.17.2.4–10.17.2.5). If a retroperitoneal tumour compresses an adjacent plastic organ which is not the organ of origin (such as compression of the intestine or IVC) then these plastic

organs are deformed into a crescent shape – this is known as the negative embedded organ sign. Phantom (invisible) organ sign When a large mass originates from a relatively smaller organ, the primary organ of origin is often completely engulfed by the tumour and is not seen separately. This sign is seen in tumours of adrenal gland origin. Prominent feeding artery sign: Multiple prominent feeding arteries are seen on CT and MRI in the case of highly vascular tumours, and this aids in determining the origin of the tumour. 3. Patterns of spread Extension between normal structures Certain neoplasms tend to grow and spread in-between normal structures and encase vessels without causing luminal narrowing or compression. This is also known as a mantle growth pattern. Examples include lymphoma, lymphangiomas and ganglioneuromas. Lymphomas typically encase the aorta, IVC and major retroperitoneal vessels and displace the aorta anteriorly – this is known as the ‘floating aorta sign’ or the ‘CT angiogram sign’. Nonneoplastic diseases such as Erdheim–Chester disease and retroperitoneal fibrosis also present with mantle growth (Figs. 10.17.2.6–10.17.2.7). Extension along with normal structures Neoplasms of the sympathetic ganglia such as paragangliomas and ganglioneuromas appear elongated in shape and typically extend along the sympathetic chain. 4. Tumour components Certain internal components of tumours detected through CT and MRI give important clues to narrow down the differential diagnosis significantly. These include fat, myxoid stroma, necrosis, cystic contents, small round cells, vascularity, calcifications and fibrosis. Fat A lipoma appears as a homogeneous tumour consisting entirely of fat. Fat shows low attenuation on CT with characteristic T1 hyperintensity with loss of signal on T1 fat-saturated MR images. Whereas an ill-defined irregular mass with fat content often represents a liposarcoma. High-grade liposarcoma may not contain appreciable amounts of fat and may appear similar to soft tissue sarcoma. Another common fat-containing retroperitoneal tumour is teratoma, which also contains fluid, fat fluid levels and calcification. Intralesional fat is also seen in extramedullary haematopoiesis, extraadrenal myelolipoma and cystic lymphangioma (Fig. 10.17.2.8). Myxoid stroma It consists of a mucoid matrix rich in acid mucopolysaccharides and appears T2 hyperintense with typical delayed contrast

enhancement. Myxoid malignant fibrous histiocytomas, malignant liposarcoma and neurogenic tumours such as malignant peripheral nerve sheath tumour, ganglioneuroblastoma, ganglioneuromas, neurofibromas and schwannomas commonly contain myxoid stroma. Necrosis Often seen in high-grade malignant tumours such as leiomyosarcomas, undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma. Necrosis appears as nonenhancing hypodense areas on CT and T2 hyperintense areas on MRI. Paragangliomas may contain central haemorrhagic necrosis and fluid–fluid levels due to their hypervascular nature. Cystic contents Lymphangiomas and mucinous cystic tumours are completely cystic, whereas neurogenic tumours such as schwannomas and neurofibromas are mixed solid cystic lesions. Schwannomas can be completely cystic and should be considered in the differentials of purely cystic masses. Myxoid liposarcoma, cystic mesothelioma, cystadenoma, cystadenocarcinoma, Müllerian cysts, epidermoid cysts and nonpancreatic pseudocysts are few of the other less common cystic lesions (Fig. 10.17.2.9). Hyperattenuating cysts are usually posttraumatic haematomas or urinomas. Low-attenuation cysts with recent operative history of lymphadenectomy or renal transplant are lymphoceles. Small round cells Small round cell tumours such as lymphoma appear homogeneous on CT with minimal contrast enhancement and appear characteristically homogeneously hypointense on T2WI, due to densely packed cellular components. Vascularity Hypovascular tumours include low-grade liposarcoma, lymphomas and many benign tumours. Moderately vascular tumours are myxoid malignant fibrous histiocytomas, leiomyosarcomas and many other sarcomas. Tumours such as paragangliomas and haemangiopericytomas are extremely vascular and show intense contrast enhancement. Progressive enhancement Cystic masses with slow progressive enhancement include urinoma, due to gradual delayed contrast excretion into the urine, and lymphangioleiomyoma, due to slow lymphatic flow. Calcifications Solid retroperitoneal tumours with calcifications include dedifferentiated liposarcoma, neurogenic tumours, teratoma, extra gastrointestinal stromal tumour, undifferentiated pleomorphic sarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing sarcoma and synovial sarcoma. Fibrosis Lesions with dense fibrosis appear hypointense on T2WI, such as desmoid tumour and nonneoplastic conditions such as

retroperitoneal fibrosis and Erdheim–Chester disease.

FIG. 10.17.2.1 Positive beak sign – Drawing (A) shows beak-shaped interface (arrows) of lesion with organ. Axial CT (B) shows sharp beak like interface (white arrow) between the retroperitoneal enhancing mass (asterisk) and the kidney (black arrow) which implies the lesion arises from the organ.

FIG. 10.17.2.2 Negative beak sign – Drawing (B) shows dull rounded interface of lesion with organ. Axial CT (D) shows blunt interface (white arrow) between the retroperitoneal mass (asterisk) and the kidney (black arrow) which indicates the lesion does not arise from the organ. Source: Authors own

FIG. 10.17.2.3 Negative organ-embedded sign – Drawing (A) shows lesion compressing the organ, and the organ becomes crescent shaped. Axial contrastenhanced CT scan (C) shows adrenal lesion (asterisk) and crescent-shaped kidney (white arrow) with smooth interface between lesion and kidney. Source: Authors own

FIG. 10.17.2.4 Positive organ-embedded sign – Drawing (B) shows lesion which appears to be embedded in organ at the contact surface. Axial CT (D) shows irregular contact surface between the renal mass (asterisk) and the kidney (white arrow). Source: Authors own

FIG. 10.17.2.5 Mantle growth pattern – Axial CT angiogram in a 64-year-old male with DLBCL (diffuse large B cell lymphoma) shows the lymphomatous mass encases aorta and major retroperitoneal vessels (black arrows) by extending in between normal structures. Source: Authors own

FIG. 10.17.2.6 Axial CT scan (arterial phase) in a 70-year-old male with lymphoma shows the ‘floating aorta sign’ caused by anterior displacement of the aorta (black arrow) by the large hypodense retroperitoneal mass (asterisk). Source: Authors own

FIG. 10.17.2.7 Well-differentiated liposarcoma. (Source: Courtesy of Ajit H. Goenka, Shetal N. Shah, Erick M. Remer. Imaging of the retroperitoneum. Radiol Clin N Am 50 (2012) 333–355. doi:10.1016/j.rcl.2012.02.004 0033-8389/12/$.)

FIG. 10.17.2.8 Lymphangioma. (Source: Courtesy of Ajit H. Goenka, Shetal N. Shah, Erick M. Remer. Imaging of the retroperitoneum. Radiol Clin N Am 50 (2012) 333–355. doi:10.1016/j.rcl.2012.02.004 00338389/12/$.)

FIG. 10.17.2.9 Diagnostic algorithm for evaluation of retroperitoneal masses. (Source: Courtesy of Mota MMS, Bezerra ROF, Garcia MRT. Practical approach to primary retroperitoneal masses in adults. Radiol Bras. 2018 Nov/Dez;51(6):391–400. Radiol Bras. 2018 Nov/Dez;51(6):391–400)

Conclusion Lesions of the retroperitoneum include a diverse group of neoplastic and nonneoplastic diseases, including some rare conditions. Cross-sectional imaging techniques such as CT and MRI play an indispensable role in the detection and characterization of these lesions, and also in disease staging and hence are the modalities of choice for retroperitoneal imaging. A definite diagnosis may not always be possible based on cross-sectional images alone due to many similar and overlapping imaging features of these retroperitoneal tumours, but identifying specific characteristic imaging features along with clinical presentation helps to narrow the differential diagnosis. 1 0. 1 7 . 3

SOLID NONNEOPLASTIC LESIONS Tanvi Vaidya, Shivani Mahajan

Nonneoplastic conditions Retroperitoneal fibrosis Incidence Retroperitoneal fibrosis (RPF) includes a range of diseases that are characterized by an excessive and aberrant proliferation of fibroinflammatory tissue, which surrounds the abdominal aorta, inferior vena cava and extends laterally to encase the ureters. RPF may be idiopathic (also known as Ormond’s disease) or secondary to malignancy, drugs such as methysergide, and bromocriptine and other aetiologies. RPF is a rare disorder with an incidence of 1 per 200,000 populations. It commonly occurs in adults between the ages of 40 and 60 years and has a male predilection. There is no known familial or ethnic predisposition. Aetiology The precise aetiology of RPF is unclear but one of the proposed mechanisms is an immune reaction to a lipoprotein polymer called ceroid which is a component of ruptured atherosclerotic plaque. Another theory is the presence of an underlying systemic autoimmune process. RPF is associated with other fibrosing conditions such as fibrosing mediastinitis, sclerosing mesenteritis, orbital pseudotumour, primary sclerosing cholangitis and Riedel’s thyroiditis in up to 15% of cases. RPF is also associated with other autoimmune and inflammatory disorders such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis and asbestos exposure. Perianeurysmal fibrosis is seen in up to 25% cases of abdominal aortic aneurysm (known as inflammatory abdominal aortic aneurysm [IAAA]) and this is believed to be an early or mild form of RPF. A fibrotic desmoplastic response is initiated by

metastatic foci to the retroperitoneum, commonly from lymphoma, retroperitoneal sarcoma, carcinoid tumours, carcinoma breast, lung, thyroid, stomach, colon, kidney, bladder, prostate and cervix, and this leads to malignant RPF. RPF can also occur secondary to infections (such as tuberculosis, syphilis, actinomycosis, fungi) or due to gastrointestinal inflammation (appendicitis, Crohn’s disease, diverticulitis). retroperitoneal haemorrhage or previous irradiation or surgery. Histopathology Gross pathological specimen examination reveals an ill-defined, greyish white, hard, plaque-like soft tissue mass usually at the level of the lumbar vertebrae, encasing the abdominal aorta, IVC, iliac vessels and the ureters. Rarely there is an anterior extension to the root of mesentery. Histologically the abnormal soft tissue is seen in two phases – early active inflammatory phase followed by the late chronic fibrotic phase. The process of maturation of the plaque progresses in a centrifugal manner from the midline so the central part is in the fibrotic phase and the lateral peripheral areas are inactive inflammatory phase. The early active cellular phase has immature periaortic fibrosis which is rich in perivascular inflammatory lymphocytes in a loose collagen matrix, and which is oedematous and high in vascularity. This is followed by the late inactive fibrotic phase where the collagen is gradually hyalinized and the cellularity decreases, to form the mature plaque which contains relatively avascular hyaline, is acellular, and contains scattered calcifications. Most of the inflammatory cells seen are positive for Ig G4 and HLA – DR on immunohistochemical analysis. RPF characteristically starts below the aortic bifurcation at the level of lower lumbar vertebrae, and progresses superiorly up to the kidneys in a periaortic and pericaval distribution, encasing one or both ureters. It may also extend inferiorly into the pelvis. Clinical features Signs and symptoms occur as a result of encasement and compression of retroperitoneal structures such as the aorta, IVC, ureters and gonadal vessels. Symptoms of idiopathic and secondary RPF often overlap and these are indistinguishable clinically. Initial symptoms are nonspecific with patients complaining of malaise, anorexia, weight loss, low-grade fever, vague abdominal pain or discomfort. As the soft tissue mass increases in size and extent, gradually specific symptoms are manifested according to organ involvement such as severe abdominal or flank pain, lower limb oedema, renal failure due to ureteric obstruction, testicular swelling in males and ovarian endometriosis in females. Almost 56%– 100% of patients develop ureteric obstruction and eventual obstructive renal failure due to entrapment by the soft tissue. Renal vascular involvement may cause renovascular hypertension. IVC compression causes lower limb oedema and compression of aorta and its branches can cause lower limb claudication. Due to a lack of early specific clinical symptoms and often due to associated clinical disorders, the diagnosis is often delayed. Laboratory findings include altered renal function tests, elevated ESR and CRP. Imaging features

Conventional abdominal radiographs are often unremarkable. Later stages may show a central abdominal soft tissue shadow with obscured normal psoas shadow, but these findings are variable. Complications of RPF may be seen such as dilated bowel in case of obstruction, pneumatosis in bowel infarction, nephrogenic pulmonary oedema, pulmonary fibrosis secondary to SLE, and ankylosing spondylitis, widening of mediastinum due to fibrosis. Features of Pott’s spine, ankylosing spondylitis and osseous metastases may also be seen. Intravenous urography and retrograde pyelography have been obviated due to limited sensitivity and specificity and due to recent advances in cross-sectional imaging. The classic triad seen in IVU includes medial deviation of the middle third of the ureters, luminal tapering of ureters and a bilateral variable degree of hydroureteronephrosis with delayed contrast excretion. The sensitivity of ultrasound in detecting RPF is low, and only 25% of cases detected on CT show a corresponding abnormality on USG. A welldefined irregularly marginated hypoechoic to anechoic plaque is seen in the prevertebral and paravertebral region, often with secondary hydroureteronephrosis. Abdominal ultrasound may aid in the diagnosis of associated conditions such as primary biliary cirrhosis, biliary strictures, portal hypertension, and sclerosing pancreatitis (Fig. 10.17.3.1).

FIG. 10.17.3.1 Urography of RPF. (Source: Courtesy of Rafael Oliveira Caiafa, Ana Sierra Vinuesa, Rafael Salvador Izquierdo, Blanca Paño Brufau, Juan Ramón Ayuso Colella, Carlos Nicolau Molina. Retroperitoneal fibrosis: Role of imaging in diagnosis and follow up. RadioGraphics 2013; 33:535–55.) Multidetector CT is the preferred modality for a comprehensive evaluation of the location, disease extent, adjacent organ invasion and vascular involvement by the disease. Most commonly it appears as a welldefined, irregularly demarcated, paraspinal soft tissue mass which is isodense to paraspinal muscles. There is a direct correlation between the degree of enhancement and the level of disease activity. Acute phase is characterized by intense homogeneous contrast enhancement of the soft tissue with an increase in HU by up to 20–60 on CT, with no to minimal enhancement in the late chronic fibrotic inactive stage. MRI plays an important role in characterizing the disease activity. Low to intermediate signal intensity is seen in T1WI in RPF. But the T2 signal intensity changes according to the degree of maturity of the fibrotic plaque. A mature fibrotic plaque in benign RPF shows low T2 signal intensity. An immature fibrotic plaque in benign and malignant RPF shows higher T2 signal intensity due to hypervascularity, oedema and inflammation. Variable contrast enhancement is seen depending on disease activity, and an immature fibrotic plaque enhances more due to higher vascularity. After treatment with corticosteroids, the inflammation decreases and so does the T2 signal and degree of enhancement. Imaging features such as retroperitoneal lymphadenopathy, adjacent osseous destruction, heterogeneous soft tissue mass with poorly defined margins and T2 hyperintense signal in the adjacent psoas muscle are all

suggestive of malignant RPF. Sometimes confluent malignant retroperitoneal lymph nodes can mimic RPF. However, metastatic nodes have more lobulated margins and are seen in paraaortic and paracaval regions. Moreover, lymphadenopathy due to lymphoma causes anterior displacement of the aorta and lateral displacement of ureters, both of which are not seen in RPF (Fig. 10.17.3.2).

FIG. 10.17.3.2 CT and MRI in retroperitoneal fibrosis. (Source: Courtesy of Ajit H. Goenka, Shetal N. Shah, Erick M. Remer. Imaging of the retroperitoneum. Radiol Clin N Am 50 (2012) 333– 355 doi:10.1016/j.rcl.2012.02.004 0033-8389/12/$. Elsevier.) Treatment and prognosis Spontaneous regression of disease is seen rarely, and RPF requires some medical intervention. Treatment depends on the aetiology. Discontinuation of drugs is recommended in drug-induced RPF. A biopsy may be obtained to exclude malignant or infectious causes of RPF before starting therapy. Infections are treated with appropriate antimicrobial therapy. In early idiopathic RPF, medical therapy with corticosteroids is used to shrink the soft tissue and relieve symptoms. Nonmalignant RPF has been treated successfully with tamoxifen. If medical therapy fails to relieve symptoms of ureteric obstruction, surgical intervention is attempted with ureteric stenting or ureterolysis. Malignant RPF has a poor prognosis with a mean survival of 3–6 months after diagnosis. Idiopathic RPF has a favourable prognosis. Successful prevention of recurrent urinary obstruction through medical treatment and ureterolysis is obtained in more than 90% of cases. Concurrent atherosclerotic disease and related complications lead to a reduced 10-year survival rate of less than 70%. Lipomatosis

It is a benign metaplastic pseudotumoural condition characterized by the overgrowth of mature encapsulated white fat and it presents as a solid nonneoplastic mass. The mass consists of homogeneous, unencapsulated, mature, adult white fat cells separated by fibrous stroma. It might be idiopathic or associated with pelvic lipomatosis, obesity, corticosteroid administration, Cushings syndrome, lipoblastic lymphadenopathy. Lipomatosis has a male predilection (18:1), is seen more in African Americans, and has a mean age of presentation of 48 years. Patients may be asymptomatic or present with nonspecific abdominal pain and gastrointestinal or urinary symptoms. The abnormal excessive fat deposition in lipomatosis is more often seen in the pelvis, surrounding the rectum and the urinary bladder, and less frequently seen in the abdominal retroperitoneum. CT or MRI of the abdomen and pelvis shows excessive amounts of fatty tissue in the pelvic cavity surrounding the normal pelvic organs, and which distorts and compresses the rectum and bladder. Few thin linear fibrous strands might be seen within, but there are no abnormal soft tissue components and typically no contrast enhancement. A typical pear-shaped urinary bladder is seen due to compression by the excess pelvic fat and there may be medial deviation and narrowing of the distal pelvic ureters, leading to proximal hydroureteronephrosis. Ureteral stenting, urinary diversion, and surgical fat excision may be required in case of a worsening of urinary obstruction. Extramedullary haematopoiesis EMH is rarely seen in the retroperitoneum and more commonly involves the liver, spleen and lymph nodes. EMH is a compensatory mechanism as a result of reduced normal bone marrow haematopoiesis in conditions such as haemoglobinopathies, myelofibrosis, lymphoma, leukaemia and carcinomas. Multiple abnormal deposits of haematopoietic tissue are seen at certain characteristic sites due to the presence of erythroid precursors in extramedullary sites. Hepatosplenomegaly, vague abdominal pain, anorexia are few of the common clinical presentations. Complications include urinary tract obstruction, bowel obstruction, portal hypertension and ascites, spinal cord compression and embolization of haematopoietic tissue leading to occlusion of pulmonary and myocardial vessels. CT typically shows multiple bilateral paravertebral soft tissue masses with lobulated margins, which are isodense or hypodense to skeletal muscles. They may or may not contain fat. MR features are variable due to the varying contents of the masses. It may appear intermediate on T1WI and intermediate to bright on T2WI. Red marrow or hemosiderin content appears hypointense on T1 and T2WI. Fatty tissue appears bright on T1 and T2WI. Mild enhancement may be seen. No bone erosion or tumoural calcifications are noted. Concurrent imaging features of chronic anaemia or myelofibrosis seen in the skeletal system and history of haemoglobinopathy provide important diagnostic clues. These paraspinal masses may decrease in size after treatment with blood transfusions. Posttreatment massive iron deposition in these leads to an increase in CT attenuation (more than skeletal muscles), low signal intensity on T1 and T2WI, and lack of enhancement.

Desmoid tumours/deep fibromatosis The term fibromatosis encompasses a group of disease conditions arising in the musculoaponeurotic tissue and characterized by fibrous tissue proliferation, with disruption of soft tissue planes. Fibromatosis may be of two types – superficial (fascial) or deep (desmoid tumour). Deep fibromatosis is further subdivided into the extraabdominal, abdominal wall and intraabdominal (mesenteric, mesocolic, omental and retroperitoneal). Desmoid tumour is a type of deep fibromatosis consisting histologically of uniform elongated spindle cells and collagen. These are rare neoplastic lesions that account for less than 1% of retroperitoneal tumours. They can occur sporadically or in association with familial adenomatous polyposis (FAP). Sporadic tumours are often solitary and large (mean diameter 13.8 cm) whereas tumours associated with FAP are multiple and smaller (mean diameter 4.8 cm). Desmoid tumours are oestrogen-dependent hormonally responsive tumours and are more common in females between puberty and 40 years of age. They are aggressive rapidly growing tumours with a postsurgical recurrence rate of 50%. The exact aetiology is unknown, with various proposed mechanism including idiopathic, genetic, traumatic and hormonal. On histology desmoids show slender highly differentiated fibroblasts in abundant collagen matrix, with variable cellularity. Large tumours show central necrosis or cystic degeneration. CT features are nonspecific and show a well-defined or ill-defined high-attenuation infiltrative mass which typically crosses fascial boundaries. Their MR signal intensity depends on tissue composition and degree of vascularity, which helps in assessing disease activity and monitoring response to therapy. T2 hyperintense signal is seen in early active cellular phase which gradually changes to T2 hypointense signal in the later phases due to decrease in cellularity and increase in the collagen content of the tumour. Moderate contrast enhancement is frequently seen. Some tumours may cause encasement of the bowel, mesenteric vessels or ureters. Despite the high local rate of recurrence of up to 90%, surgical excision with wide margins remains the primary treatment option. Postoperative radiation therapy may reduce the risk of local recurrence. Recurrent lesions have imaging features similar to original tumours and often occur at the margins of the original lesion. Other treatment options include cytotoxic drugs, radiation therapy, noncytotoxic drugs and observation – however, none of these have proved to be effective consistently (Fig. 10.17.3.3).

FIG. 10.17.3.3 Desmoid tumour. (Source: Courtesy of Prabhakar Rajiah, Rakesh Sinha, Carlos Cuevas, Theodore J. Dubinsky, William H. Bush, Jr, Orpheus Kolokythas. Imaging of uncommon retroperitoneal masses. RadioGraphics 2011; 31:949–976.) Certain imaging features in intraabdominal desmoids can be used as indicators of poor prognosis and these include mesenteric mass > 10 cm, multiple masses, small bowel involvement, bilateral hydronephrosis. Intraabdominal desmoids have a mean survival rate of 5 years after diagnosis. Lymphadenopathy Retroperitoneal lymph nodes are seen as ovoid soft tissue attenuation structures around the aorta and IVC. They show T1 intermediate and T2 hyperintense signal (as compared to skeletal muscle). The CT attenuation and MR signal on conventional imaging sequences do not accurately differentiate between benign and malignant nodes. In cases of primary carcinoma with retroperitoneal lymphadenopathy, a short-axis diameter of lymph node measuring less than 10 mm is considered benign and a diameter of more than 10 mm is suspicious for malignancy. However, malignant nodes can sometimes be less than 10 mm in short-axis diameter and benign nodes can be more than 10 mm in diameter in cases of benign reactive lymphoid hyperplasia. Ultrasmall superparamagnetic iron oxide particles (USPIO) can be used to differentiate benign from malignant nodes, and this increases the specificity and sensitivity for detecting micrometastases in normal-sized nodes. Normal benign lymph nodes accumulate iron particles in macrophages and so appear dark on T2* images. But malignant lymph nodes are unable to do so and show intermediate to high T2* signal. Malignant nodes are round in shape, whereas benign reactive nodes have an oval shape. Central necrosis in nodes is seen as low-attenuation areas on CT and T2 hyperintense signal on MR with no central enhancement. Necrosis in

nodes is seen in malignant lymphadenopathy from metastatic squamous cell carcinoma, lymphoma, testicular carcinoma and also in benign infective and inflammatory conditions such as mycobacterial infections, Whipple’s disease, histoplasmosis and SLE. Short-axis diameter is used to differentiate benign from malignant nodes. Almost all intraabdominal and pelvic neoplasms can cause retroperitoneal lymph nodal metastases. This is because pelvic lymph nodes directly drain into the retroperitoneal nodal system and almost all the celiac and mesenteric nodes have interconnections with retroperitoneal lymph nodes. However, the most common malignant neoplasms causing metastatic retroperitoneal lymph nodes are lymphoma, cervical carcinoma, testicular carcinoma, prostatic carcinoma and renal cell carcinoma. Malignant lymph nodes may displace the aorta anteriorly and the ureters laterally (Fig. 10.17.3.4).

FIG. 10.17.3.4 Metastatic lymphadenopathy. (Source: Courtesy of Ajit H. Goenka, Shetal N. Shah, Erick M. Remer. Imaging of the retroperitoneum. Radiol Clin N Am 50 (2012) 333–355. doi:10.1016/j.rcl.2012.02.004 0033-8389/12/$.) The abdomen is the most common site of extrapulmonary tuberculosis and lymphadenopathy is the most common finding. Pericaval and paraaortic nodes may be seen due to lymphatic drainage from the small bowel and right colon. Histologically the lymph nodes may be seen in various stages such as granuloma formation, caseation necrosis, perilymphadenitis, rupture and abscess formation and finally healing by fibrosis and calcification. CT and MRI in tuberculosis typically show multiple enlarged nodes with a mean size of 2–3 cm, with low attenuation on CT. Active nodes have a low to intermediate T1, and central high T2 signal intensity due to caseation necrosis. In the late stage of the disease, due to fibrosis and calcification, these nodes show low T2 signal intensity.

Nonnecrotic nodes show homogeneous enhancement. Central nonenhancing areas are seen in 40% of cases due to necrosis. Castleman’s disease is also known as angiofollicular lymph node hyperplasia and is a lymphoproliferative disorder of unknown aetiology. It is seen either as stable unicentric localized lymphadenopathy or as a multicentric disseminated disease. The multicentric form of the disease presents in the sixth decade, is more common in males and is frequently associated with POEMS syndrome. Retroperitoneal involvement is seen in multicentric disease in 7%–12% cases. The multicentric disease has a median survival of 24–33 months and has a poor prognosis. Three histologic subtypes of Castleman’s disease exist namely hyaline vascular, plasma cell and mixed subtype. CT and MRI show soft tissue attenuation masses (HU similar to muscle), with low to intermediate T1 signal and high T2 signal. These lesions show mild to marked arterial enhancement with slow washout. Sometimes a peripheral hyperenhancement is seen due to greater vascularity along with dilated feeding arteries. Central stellate or irregular nonenhancing areas may be seen due to fibrosis. Calcifications with lumpy, irregular or peripherally radiating arborizing patterns may be seen in one-third cases of Castleman’s disease. A single large dominant mass is seen in unicentric disease and multiple smaller variable-sized nodal lesions associated with hepatosplenomegaly, ascites, and fascial thickening are seen in multicentric disease. The unicentric disease is treated with surgery (sometimes with preoperative embolization to reduce the vascularity of lesion) and radiation therapy. Combination chemotherapy, corticosteroids and interferon therapy are the treatment options for the multicentric disease. Other less common causes of retroperitoneal lymphadenopathy include leukaemia, bacterial or fungal infections, AIDS, sarcoidosis, Whipple’s disease and amyloidosis. Histiocytosis – rosai–dorfman, Erdheim–Chester disease sinus histiocytosis/rosai dorfman disease It is a rare, benign, self-limiting, idiopathic disease affecting nodal and extranodal tissues and with a mean age of presentation of 21 years. Histologically the nodal tissues show large histocytes with round nuclei and pale cytoplasm, and presence of lymphocytophagocytosis. Clinical features include fever, massive bilateral cervical lymphadenopathy with elevated leukocyte count ESR and hypergammaglobulinemia. Large nodal lesions are infrequently seen in retroperitoneum and the pelvis. CT and MRI show nonspecific retroperitoneal lymphadenopathy, which often requires tissue diagnosis. Surgical resection may be done for symptomatic cases. However, the majority of cases are treated conservatively due to the self-limiting nature of this disease. Erdheim–Chester disease/Xanthogranulomatosis (Fig. 10.17.3.5)

FIG. 10.17.3.5 Erdheim–Chester disease. (Source: Courtesy of Ajit H. Goenka, Shetal N. Shah, Erick M. Remer. Imaging of the retroperitoneum. Radiol Clin N Am 50 (2012) 333–355. doi:10.1016/j.rcl.2012.02.004 0033-8389/12/$.) Xanthogranulomatosis is a rare, multicentric, idiopathic, nonLangerhans form of histiocytosis of unknown origin with a variable clinical course and a predisposition for the retroperitoneum. It is also known as lipoid granulomatosis or polyostotic sclerosing histiocytosis. It is called Erdheim–Chester disease when multiorgan involvement is present. ECD is more common in men and affects the middle-aged and elderly population. Clinical features and clinical outcomes are variable. Retroperitoneal involvement occurs in one-third of cases and characteristically produces a thick soft tissue rind around bilateral kidneys and ureters secondary to fibrous peri nephritis, which can lead to renal failure. CT shows infiltrative soft tissue with attenuation similar to or less than that of skeletal muscle. MRI shows T1/T2 intermediate signal similar to skeletal muscle with mild enhancement. Sometime macroscopic fat and adjacent organ infiltration are also identified. Typically there is circumferential periaortic involvement with bilateral symmetrical perirenal space infiltration and sparing of IVC and pelvic ureters, which is extremely important in differentiating retroperitoneal xanthogranulomatosis from RPF. Associated findings such as periostitis, partial epiphyseal involvement and medullary infarcts are seen. On MRI the normal fatty marrow in metadiaphyses of long bones is replaced by bilaterally symmetrical heterogeneously hypointense signal on T1WI and intermediate signal on T2WI. CT shows osteosclerosis in corresponding bones. Chemotherapy, radiation therapy, steroids and immunotherapy are the various treatment options available. Gossypiboma Gossypiboma or textiloma or cottonoid occurs due to accidental retention of surgical sponge in the body, most commonly in the abdominal cavity after emergency surgeries, prolonged surgical procedures or excessive bleeding during surgery. A gossypiboma can produce two types of foreign-body reactions in the body, either an aseptic fibrinous response causing adhesions, encapsulation and granuloma formation or it can

cause exudation leading to formation of an abscess or fistula. Clinical presentation is variable and patients may present in the early postoperative period up to many decades later. About 40% of these are detected within the first year of surgery, and 5% are detected after 5 or more years. The mortality may be as high as 11%–35% with morbidity of nearly 50%. Radiologically they have a variable presentation and often mimic tumours. Imaging features may depend on the type of material, type of foreign-body reaction and the time after surgery. Ultrasound may show a cystic mass with thick echogenic wavy components or a solid mass with mixed echogenicity. Acoustic shadowing is often seen within the lesion and can be either due to the retained abnormal surgical material/sponge or due to calcifications or air foci. On CT it appears as a heterogeneously hypodense soft tissue mass with whorled pattern and multiple trapped air foci within the fibres of the sponge. Abscess formation will be seen as a low-attenuation collection thick enhancing wall. A towel might be seen as a linear density with a typical whorled or infolding appearance. Peripheral wall calcifications may be seen in chronic cases. On MRI, a variable signal intensity mass will be seen on T1 and T2WI, with central fluid signal intensity, wavy nonenhancing hypointense structures on T1WI and whorled appearance on T2WI due to the sponge. Surgical clips may be seen adjacent to the mass. Surgical exploration with the removal of sponge, drainage of inflammatory collection and treatment of associated complications is required. IG G4 (immunoglobulin G4)-related diseases They are a group of recently recognized chronic inflammatory disorders, whose pathogenesis are unclear, but are believed to be probably autoimmune and allergic in nature. They are characterized by the presence of fibroinflammatory lesions rich in IgG4 positive plasma cells and often with increased serum IgG4 levels. It is important to recognize these conditions early since they show a marked response to steroid therapy. Clinical symptoms are often mild and nonspecific. Retroperitoneal involvement occurs in the form of Ig G4-related RPF and Ig G4-related periaortitis. In RPF, CT shows soft tissue attenuation masses that encase and entrap the aorta and ureters, with resultant hydronephrosis and hydroureter. Multiple irregular soft tissue lesions with delayed contrast enhancement are seen around the aorta in IgG4related periaortitis, which do not cause vascular stenosis and may be associated with vascular dilatation. Amyloidosis Amyloidosis consists of a heterogeneous group of disorders caused by the extracellular deposition of the amyloid protein in organs and tissues. The retroperitoneum is infrequently involved, with no specific imaging features or clinical symptoms. Systemic amyloidosis includes primary, familial and secondary forms. Amyloid light (AL) amyloidosis is seen in multiple myeloma, plasma cell dyscrasias or primary systemic amyloidosis and is associated with monoclonal immunoglobulin light chains. Amyloid A (AA) (secondary amyloidosis) is due to the accumulation of serum amyloid A protein (an acute phase reactant) which

is produced in many chronic inflammatory conditions. Retroperitoneal amyloidosis is a form of system amyloidosis which causes abnormal extracellular amyloid protein deposits in the soft tissues of the retroperitoneum and the pelvis. On CT or MRI, nonspecific diffusely infiltrative soft tissue is seen in the retroperitoneum which encases the aorta, IVC, kidneys and ureters. The normal fat in the retroperitoneum is gradually replaced by soft tissue attenuation amyloid deposits. It typically appears hypointense on T2WI and intermediate on T1WI. The amyloid tissue can undergo gradual coarse calcification and may show avid enhancement. Focal amyloid mass (known as amyloidoma) may also be seen. A biopsy is necessary for diagnosis since myeloma and lymphoma have a similar imaging appearance. Diagnosis is confirmed by histologic examination with Congo red stain and the presence of apple-green birefringence under polarized light. Treatment depends on the type of amyloidosis and the underlying condition, such as plasma cell dyscrasias or chronic inflammatory disorders such as rheumatoid arthritis. Inflammatory myofibroblastic tumour It is a rare benign idiopathic disorder that mainly affects the lung and the orbits in young individuals and the retroperitoneum is rarely affected. These tumours rarely metastasize. Patients present with constitutional symptoms, abdominal lump and elevated ESR. Histologically there is myofibroblastic proliferation, with myxoid, vascular and inflammatory areas, compact spindle cells and dense plaque-like collagen. On CT and infiltrative, well-defined mass with soft tissue attenuation is seen in retroperitoneum, with a density similar or less than that of the skeletal muscle. MRI shows low T1 and T2 signal as compared to skeletal muscle, with variable enhancement. High-dose steroids, radiation therapy and chemotherapy can be administered, but the treatment of choice is surgical resection. These lesions have a favourable prognosis despite the high propensity for local recurrence (Table 10.17.3.1).

Table 10.17.3.1 Non-neoplastic Conditions Retroperitoneal fibrosis 40–60 years, M>F

Metastatic retroperitoneal lymphadenopathy

Extramedullary haematopoiesis

• Periaortic and paraspinal soft tissue plaque • Starts below level of aortic bifurcation and progresses upwards • Encases and compresses aorta, IVC, ureters, gonadal vessels • Medial deviation of middle third ureters • Early active inflammatory phase • Intense enhancement on CT • Bright T2 signal on MR (oedema, inflammation, vascularity) • Late chronic fibrotic phase • Minimal enhancement on CT • Low T2 signal on MRI (fibrosis) • Most common causes: lymphoma, cervical carcinoma, testicular carcinoma, prostatic carcinoma and renal cell carcinoma • Soft tissue masses with lobulated margins • Paraaortic and paracaval location • May have central necrosis • May displace the aorta anteriorly and ureters laterally • More commonly involves liver, spleen, lymph nodes; rarely involves retroperitoneum • Multiple bilateral paravertebral soft tissue masses • Isodense to skeletal muscle • Posttreatment (blood transfusion) – Decrease in size, increased attenuation • Imaging features of chronic anaemia, myelofibrosis may give clue to diagnosis

Desmoid tumours/Deep fibromatosis F>M, Puberty to 40 years

Erdheim–Chester disease/Xanthogranulomatosis M>F, middle aged – elderly

Amyloidosis

• Well-defined or ill-defined highattenuation infiltrative mass • Typically crosses fascial boundaries • T2 signal depends on disease activity – T2 bright signal in active cellular phase and T2 low signal in collagen phase • High propensity for local recurrence • May encase bowel, ureters, mesenteric vessels • Indicators of poor prognosis: Size >10 cm, multiple lesions, small bowel involvement and bilateral hydronephrosis • Thick soft tissue rind around kidneys and ureters • Circumferential periaortic involvement with bilateral symmetrical perirenal space infiltration and sparing of IVC and pelvic ureters (important to differentiate from RPF) • Periostitis, medullary infarcts, osteosclerosis in skeleton • Nonspecific diffusely infiltrative soft tissue which encases the aorta, IVC, kidneys and ureters • May show avid enhancement and coarse calcifications

1 0. 1 7 . 4

IMAGE-GUIDED INTERVENTIONS OF RETROPERITONEAL MASSES AND IMAGING OF POSTPROCEDURAL COMPLICATIONS Tanvi Vaidya, Shivani Mahajan

Retroperitoneal biopsies Introduction Retroperitoneal lesions demonstrate overlapping imaging features and a definite diagnosis based solely on imaging is often challenging. Tissue sampling and histopathological diagnosis are required for final diagnosis, disease staging, planning treatment and determining disease prognosis. Retroperitoneal biopsies can be of three types: open, laparoscopic or percutaneous image-guided. Surgical biopsies are invasive and have a high rate of morbidity. Minimally invasive image-guided percutaneous biopsies are safe, effective and have high diagnostic yields and hence are the preferred technique for tissue sampling in retroperitoneal lesions. Image-guided biopsies can be performed under ultrasound or CT guidance. Ultrasound has many advantages such as ease of accessibility, real-time evaluation of the needle course, evaluation of vascularity with Doppler and is free from ionizing radiation. USG-guided biopsy can be freehand or using specially designed needle guides which can be attached to the transducer. CT-guided biopsy is preferred in small and deep-seated lesions that are difficult to access through USG. Multiplanar reconstruction (MPR) in CT plays a vital role in planning difficult procedures. Kariniemi et al. performed MRI-guided biopsies of the liver, spleen, lymph nodes and retroperitoneum on a low-field MRI in 31 consecutive patients in whom USG-guided biopsy was not feasible, and they found high sensitivity and specificity for MRI-guided biopsies ranging from 71% to 100%. Optical tracking and specialized MR compatible nonferromagnetic needles were used in these procedures. FDG PET CT can be used to target functional viable tissue and avoid areas of necrosis or fibrosis. In large tumours or post-treatment cases, FDG PET CT can help identify the region of active disease which can be targeted for tissue sampling. In a retrospective study conducted by Shao et al to assess the technique, diagnostic yield and clinical value of retroperitoneal lymph node biopsy, it was found that percutaneous needle biopsy has an overall sensitivity of 91.5%, a specificity of 100%, and an accuracy of 92.8%, with a technical success rate of 99.7%. Percutaneous needle biopsy (PNB) can be of two types: Core needle biopsy (CNB) and fine needle aspiration biopsy (FNAB). Both these techniques can be used to obtain sufficient tissue samples for cytopathological examination, molecular and genetic studies, polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH), flow cytometry and microbiological studies. FNAB is less time consuming, more cost-effective and does not require anaesthesia. Due to small gauge needles, there is minimal patient discomfort, less trauma to tissues and hence a lower rate of complications. But it has certain limitations, such as insufficient tissue fragments with poor architectural characteristics and inadequate sample for molecular testing and immunohistochemistry (IHC).

CNB overcomes the disadvantages of FNAB by providing better tissue samples, preserved architecture and suitability for performing further molecular studies and IHC. However, due to the larger needle gauge and cutting edge of the needle, there is an increased risk of haemorrhage, infection and pneumothorax. Indications A biopsy is indicated when: a. The imaging features of the retroperitoneal lesion are not characteristic for a definite diagnosis. b. Histopathological analysis with IHC and genetic markers is required for targeted therapy. c. In posttreatment cases to differentiate between viable residual disease versus local tumour recurrence versus posttreatment fibrosis/granulation tissue. Common absolute contraindications include uncorrected coagulopathy and severe thrombocytopenia. Relative contraindications include compromised haemodynamic function, lack of patient cooperation, the inability of the patient to be positioned appropriately for the procedure, lack of safe needle pathway and pregnancy when the procedure requires exposure to ionizing radiation.

Image-based approach Preparation Patients should have normal coagulation parameters. Retroperitoneal biopsies (except renal biopsy) have been labelled as Category 3 procedures with a moderate risk of bleeding by the Society of Vascular and Interventional Radiology Standards of Practice Committee. A preprocedure INR 50,000/microlitre is recommended. A written and informed consent should be acquired (including a copy in local language) with details about the procedure, the technique, the risks and complications involved, and the remote possibility of a need for rebiopsy. History of contrast reaction and drug allergies should be elicited and documented. The recent use of aspirin or clopidogrel is related to a minor increase in postprocedural bleeding. This increased risk of bleeding must be carefully contrasted to the risks of stopping aspirin or clopidogrel – such as major coronary or cerebrovascular events and peripheral limb ischaemia. In the majority of cases, a percutaneous biopsy can be performed in patients who are on aspirin or clopidogrel. The patient is asked to stay nil by mouth for 6–8 hours (overnight fasting). Vitals such as blood pressure, heart rate and oxygen saturation are recorded before the procedure. Peripheral venous access with a 20gauge cannula is obtained for injection of contrast and emergency IV drug administration.

A contrast-enhanced CT scan is acquired before the procedure to confirm the presence and anatomical location of the mass, to assess the degree of vascularity, assess the necrotic areas, to evaluate the relationship with major retroperitoneal arteries and veins, ureters and bowel, and to determine the safest and most ideal puncture site and needle path. Multiplanar reconstructions can be obtained for planning the safest needle path in challenging cases. Technique Although patient position depends on the site of the lesion, most retroperitoneal lesions are accessed with the patient in a prone or lateral decubitus position. The preferred route for retroperitoneal biopsy should be the retroperitoneal/lumbar approach, because of the reduced risk of intraperitoneal organ rupture and intraperitoneal tumour seeding. A metallic marker is placed on the skin and axial scans are acquired to decide the site of entry and ideal needle trajectory. The safest and most effective technique is to form a straight needle trajectory from the skin to the target lesion in a single axial plane. The biopsy path should avoid vessels, pleura, viscera, ureters and nerves. Also, viable areas of the tumour should be targeted and necrotic areas should be avoided. Tumour viability can be indicated by soft tissue attenuation more than muscle and enhancement on postcontrast studies. The procedure is routinely performed with local anaesthesia. Light sedation or general anaesthesia may be required in children and uncooperative patients. Continuous haemodynamic monitoring is recommended during and after the procedure. The coaxial technique is used with a 16-gauge coaxial needle guide and an inner trocar. The trocar is used for needle positioning. It is then removed and replaced with a 16-gauge core biopsy cutting needle to get tissue cores and a 22-gauge Chiba needle to obtain fine-needle aspiration samples. A repeat axial CT scan is performed to confirm the position of the needle tip in the lesion (cutting edge should be in the lesion to be sampled). The specimen can be placed in formalin or normal saline. Immediate on-site cytopathological examination increases the chances of complete and correct diagnosis and increases the diagnostic accuracy to more than 95%, and thus prevents the need for rebiopsy. Once the required samples have been obtained, the needle is removed and a repeat CECT is performed to exclude any immediate procedure-related complications. Post procedure patient is kept under clinical observation for 4 hours to exclude major complications. The above-mentioned standard biopsy techniques can be applied in most cases. But sometimes biopsies can be difficult due to unfavourable anatomy, imaging limitations or inappropriate patient position. Additional techniques used in such challenging cases include hydrodissection, blunt needle technique, transvenous biopsy and alternate approaches such as transgluteal, transosseous and anterior extraperitoneal approach through the iliopsoas (Fig. 10.17.4.1).

FIG. 10.17.4.1 CT-guided percutaneous biopsy. (Source: Courtesy of Schiavon LHO, Tyng CJ, Travesso DJ, Rocha RD, Schiavon ACSA, Bitencourt AGV. Computed tomography-guided percutaneous biopsy of abdominal lesions: Indications, techniques, results, and complications. Radiol Bras. 2018 Mai/Jun;51(3):141–146.) Hydrodissection-assisted image-guided percutaneous biopsy for retroperitoneal lesions can be used to create a safe pathway to the target lesion. The advantages of this organ displacement technique are the lack of need for special equipment and no increase in overall procedure time. Using 0.9% normal saline or 5% dextrose is an effective technique to displace organs, and create a safe window to biopsy lesions that would otherwise be inaccessible due to intervening/overlying vital organs. A 20gauge Chiba needle is inserted into the retroperitoneum with a tip adjacent to the organ or structure which is to be displaced. A check CT scan is taken to check the needle tip position and then a test injection of 10 mL of 0.9% normal saline is injected. A repeat CT is acquired to check the displacement of the organ in retroperitoneum, and the needle tip is repositioned if required. Once the ideal tip position is achieved, more fluid is injected until adequate displacement of the adjacent organ is obtained to provide a safe passage of the biopsy needle into the target tumour without injuring vital structures. Small mesenteric vessels can be displaced by a coaxial technique using a blunt tip needle and a blunt needle access system. Transvenous biopsy can be performed in infrarenal or perivascular lesions (Fig. 10.17.4.2).

FIG. 10.17.4.2 CT-guided transcaval biopsy. (Source: Courtesy of Haibo Shao, Colin McCarthy, Eric Wehrenberg-Klee, Ashraf Thabet, Raul Uppot, Steven Dawson, Ronald S. Arellano. CT-guided percutaneous needle biopsy of retroperitoneal and pelvic lymphadenopathy: Assessment of technique, diagnostic yield, and clinical value. Vasc Interv Radiol 2018; 29(10), 1429–1436.) Lesions and nodes along the internal or external iliac vessels can be approached via the transmuscular route through the iliopsoas muscle, to prevent trauma to the external iliac vessels and pelvic bowel loops. Presacral and pararectal lesions can be targeted through the transgluteal route while avoiding the sciatic nerve. Rarely, in difficult to access lesions, a transosseous biopsy can be performed through the iliac bone. After the procedure, patient monitoring and management along with tracking the outcome are important to maintain the safety and efficacy of the procedure (Table 10.17.4.1).

Table 10.17.4.1 Image-Guided Percutaneous Biopsy Advantages

USG-Guided Biopsy • Real-time needle course visualized • Assess vascularity through Doppler • Ease of accessibility • No ionizing radiation

Advantages

• Minimally invasive • Safer than open/laparoscopic biopsy • Effective • High diagnostic yield CT-Guided Biopsy

• Small, deep seated lesions can be accessed • Multiplanar reconstruction used in challenging cases

FNAB

CNB

Fine Needle Aspiration Biopsy

Core Needle Biopsy

Less time

Better tissue sample

More cost effective

Preserved tissue architecture

No anaesthesia

Adequacy of sample for IHC and molecular testing

Minimal patient discomfort Less tissue trauma Fewer complications Disadvantages

Insufficient sample

More tissue trauma

Poor tissue architecture

Local anaesthesia required

Inadequate sample for IHC, molecular testing

Higher incidence of complications such as infection and bleeding

Sample Checklist for Image-Guided Biopsy Preprocedure

Normal coagulation profile (INR 50,000/microlitre) Written and informed consent – Explain procedure, complications Elicit history of contrast allergy History of drug reactions Anticoagulant therapy Intravenous access Nil by mouth for 6–8 hours Confirm site of biopsy/laterality

Procedure

Monitor vitals

Postprocedure

Observation for 30 min to 2 hours Monitor vitals

Complications Postprocedural complications can be defined as absent, minor or major complications based on the recommendations of Society of Interventional Radiology Standards of Practice Committee classification. Complications after a percutaneous needle biopsy can be either generic or organ-specific. Generic complications include bleeding, infection, organ perforation and target organ injury. The overall risk of significant haemorrhage following image-guided biopsy is low (1% or less). Although clinically significant haemorrhage is not seen frequently, the relative risk of bleeding increases with an increase in needle size, cutting needles and high vascularity of the target organ or tissue. There is a low (2 mm is the adopted criteria by most clinicians. It is important to note that likelihood of patency of AVF and survival increases with diameter of artery used to create AVF. • Wall thickness and calcification: Presence of wall thickening, wall irregularities and wall calcifications should be assessed with its extent of involvement. Presence of these factors affects distensibility of arteries and thereby outcome of AVF. • Vascular depth: Depth of the artery from skin should be recorded especially in difficult situation like obese patients or anatomical variant. This is to be done in specially for brachial and radial arteries as these are common sites for AVF. • High brachial artery bifurcation is a normal variation in 12% population and is a predictor for autologous brachio-cephalic fistula failure; therefore, it can affect preoperative planning substantially. • Pulse-wave Doppler (PWD): Arterial spectral waveform must be recorded in upper limb arteries. The normal waveform is triphasic, high resistance flow with no evidence of dampening. Presence of low-resistance spectral pattern may suggest significant proximal stenosis/obstruction in arterial system. Usually peak systolic velocity (PSV) > 50 cm/s in artery shows good postoperative results. Patency of entire arterial system is essential in construction of AVF and should be carefully looked for any stenosis or obstruction. Significant arterial stenosis causes increase in PSV at the level of stenosis and low-resistance blood flow distal to stenosis. • Reative hyperaemia: Reactive hyperaemia refers to the increase in blood flow through an artery after a period of ischaemia. It is induced by clenching a fist for 2 minutes and then releasing it. The changes in arterial waveform, PSV and RI are recorded. Normally in response to ischaemia, the artery dilates with increase in the diastolic flow, the wave form changes from triphasic high-resistance flow to monophasic low-resistance flow, with increase in PSV and decrease in RI (Fig. 10.18.3.2). Intensity of reactive hyperaemia is inversely proportional to RI values; therefore, high intensity of the test causes RI to decrease. The RI value of 6 weeks) of surgically created AVF. 2. Inadequate blood flow through vascular access during haemodialysis. 3. Persistent ipsilateral oedema or pain of extremity after vascular access placement or haemodialysis. 4. Decreased or absent thrill over the AVF. 5. Suspected pseudoaneurysm (PSA), stenosis, perigraft infection or fluid collection. 6. Sign and symptoms of hand/digit ischaemia. 7. Access collapse during haemodialysis. 8. Repeated difficult cannulations. Normal doppler findings in AVF

Normally, inflow artery shows low-resistance high-velocity blood flow with arterial phasicity and spectral broadening (Fig. 10.18.3.3). PSV increases as probe moves towards anastomosis. Anastomosis shows highly turbulent flow with broadening of spectrum extending above and below the baseline with high PSV values. In outflow vein, arterial phasicity is observed due to ‘arterialized’ venous structure with spectral broadening (Fig. 10.18.3.4). As distance from anastomosis increases, arterial phasicity is lost with decrease in PSV and spectrum eventually takes form of continuous venous flow.

FIG. 10.18.3.4 Colour and spectral Doppler images of brachial artery (A) and cephalic vein (B) in case of patent brachio-cephalic arteriovenous fistula. Note the spectral broadening and diastolic flow in brachial artery proximal to fistula. Cephalic vein shows pulsatile high-velocity flow. Maturation of AVF Artery and vein undergo physiological changes after creation of AVF. This includes increase in diameter of vessels, increase in blood flow and thickening of wall. The process is called as maturation of AVF. Practically, AVF is matured when it is suitable for recurrent cannulation with large gauge needles. DUS helps in deciding maturation of AVF and also mapping of outflow vein facilitates cannulation during dialysis. DUS should be performed 4–6 weeks after creation of AVF. ‘The rule of six’ has been incorporated in the guidelines of K-DOQI, where DUS findings confirm that AVF has matured and is ready to use. US findings include flow volume more than 600 mL/min, outflow vein diameter ≥6 mm and depth ≤6 mm below skin surface. D is the diameter of vessel, preferably measured on B-mode US. Mean velocity is calculated from PWS tracing in cm/s and 60 is number of seconds in a minute. Accurate measurement of vessel diameter is the first step on appropriately enlarged B-mode image of vessel in longitudinal or transverse axis. PRF should be adjusted with PW Doppler scan and mean velocity is calculated from time/velocity curve (Fig. 10.18.3.5). Tips for accurate and optimum calculation of flow volume are listed in Table 10.18.3.1. Many modern US machines allow automatic calculation of flow volumes with well-incorporated algorithms; however, manual check should be performed on automatic calculations (Box 10.18.3.1).

FIG. 10.18.3.5 Patent arteriovenous fistula (AVF) demonstrating turbulent flow on colour Doppler and high velocity flow on spectral tracing. Volume flow in AVF is 947 mL/min. TABLE 10.18.3.1 Tips for Volume Flow Quantification on DUS TIPS FOR VOLUME FLOW QUANTIFICATION 1 Longitudinal view of the vessel 2 Accurate determination of vessel diameter 3 Avoid significant turbulence (which can be analyzed as circular motion on colour Doppler) 4 Angle of Doppler insonation should be ≤60° 5 Sample volume marker should be perpendicular to vessel wall 6 Sample volume should cover at least 70% lumen 7 A sequence of 3–5 cardiac cycles should be obtained to allow calculation of timeaveraged velocity 8 Average of three separate measurements should be reported BOX 10.18.3.1 FO R MU LA FO R C ALC U LAT IO N O F AV F FLO W V O LU ME O N DUS Flow volume (mL/min) = Cross-sectional area × Mean velocity (cm/s) × 60 Crosssectional area of vessel = 3.14 × D2/4 Failure to mature (FTM) fistula or early failure fistula is defined as a fistula which has never matured to be useful or difficult to cannulate or cannot generate enough flow volume necessary for haemodialysis. Most common cause was found to be juxtaanastomosis stenosis at venous end followed by arterial inflow stenosis. Other causes can be venous outflow stenosis or presence of prominent accessory vein. Large collateral vein should be searched near to the fistula site (within 5 cm) which can be the cause of FTM. DUS is an excellent modality in diagnosis of FTM fistula and detection of its cause. Main causes are discussed in Complications section. Recommended proforma for AVF maturity assessment is provided in Appendix II. Complications Most common complication of AVF includes thrombosis, stenosis, congestive heart failure, ischaemic neuropathy, steal syndrome, aneurysm and infection. Most of these complications are detected early with help of DUS.

Thrombosis and Stenosis: Significant stenosis or occlusion at the level of inflow artery, anastomosis or outflow stenosis can result in vascular access dysfunction (Figs. 10.18.3.610.18.3.8). Therefore, it is important to look for stenosis or obstructive lesions in the entire AVF loop. Usual causes of stenosis/obstruction are atherosclerosis of inflow artery, turbulence and thrombosis at the level of anastomosis or graft and intimal hyperplasia and puncture-induced dissection at the outflow vein level. Stenosis of >50% is considered as significant stenosis on DUS and should be treated with intervention like angioplasty. B-mode US allows evaluation of intimal hyperplasia, presence of thrombus and narrowing of lumen with quantification of narrowing or stenosis. Colour Doppler shows aliasing at the level of stenosis and PWD demonstrates increased PSV at the level of stenosis. PSV of ≥500 cm/s are generally reliable in predicting stenosis of ≥50%. However, it is difficult to interpret degree of stenosis based on PSV alone. On the other hand, peak systolic velocity ratio (SVR) is used to predict the haemodynamic significance of stenosis. SVR is calculated as maximum PSV at the level of stenosis divided by PSV, 2 cm proximal to stenosis with preferably similar Doppler settings. SVR >2 at arterial inflow or venous outflow stenosis and SVR>3 at the level of anastomosis are considered to be significant corresponding to ≥50% stenosis. There are few indirect signs suggesting stenosis based on Doppler indices at the level of anastomosis. RI >0.7 at the level of anastomosis may represent inflow arterial stenosis. Tardus parvus flow pattern in inflow artery suggests more proximal significant stenosis. Aneurysm/pseudoaneurysm (PSA): True aneurysms occur due to weakening of vessel wall with subsequent wall protrusion and aneurysm formation. These are common in outflow veins due to remodelling after AVF or downstream stenosis. Stenosis in outflow veins can be due to repeated punctures and subsequent fibrosis. B-mode US findings of aneurysm refer to the diffuse or segmental dilatation of vessel with or without layered thrombus (Fig. 10.18.3.6A). Colour Doppler shows turbulent flow in the dilated vessel. PSAs refer to false aneurysm which is not lined by vessel wall and they are usually caused by repeated venous punctures. PSA can be cause of haematoma formation surrounding the vessel. PSA shows ‘yin-yang sign’ on CD images and ‘to and fro pattern’ on PWD images. PSAs are usually associated with thrombus formation. Intervention/surgery is needed in larger PSA or PSA with partial thrombus in the sac. Adjacent soft tissue haematoma, fluid collections and abscess are also diagnosed using B-mode US. Steal syndrome: Steal phenomenon refers to the reversal of flow in arterial segment distal to the AVF. Due to the low-resistance circuit in AVF, fistula not only attracts blood flow from feeding artery but also steals blood from distal arteries through palmar arch. Steal phenomenon is usually clinically silent and occurs in many (75%–90%) cases after the AVF creation. Reversal of flow is detected on DUS in arteries distal to AVF. Some patients experience symptoms of hand or digit ischaemia, especially during dialysis due to decreased perfusion of hand as a result of failure of compensatory mechanisms of maintaining distal perfusion. Symptoms of ischaemia include pain at rest or during haemodialysis, ulceration, necrosis or gangrene of digits. Steal phenomenon associated with ischaemia symptoms is called as ‘steal syndrome’. Risk factors for steal syndrome include female gender, age >60 years and diabetes mellitus. DUS assessment prior to AVF creation can predict possibility of steal syndrome, especially, poor response to reactive hyperaemia test increases chances of steal syndrome. Other imaging modalities like DSA, CT or magnetic resonance imaging (MRI) are recommended in preoperative and postoperative assessment of AVF when USG is not able to provide sufficient information. Main indication of these modalities is suspected central venous stenosis or obstruction.

FIG. 10.18.3.6 Colour Doppler of arterio-venous fistula showing thrombosis and occlusion of fistula (arrow) with absent flow on colour Doppler.

FIG. 10.18.3.7 Case of AVF with significant cephalic vein stenosis (thin arrows) in Figure 6A. Colour Doppler shows significant aliasing at the site of stenosis with high velocities (>500 cm/s) on spectral waveforms. Also note prestenotic dilatation of cephalic vein (star).

FIG. 10.18.3.8 Case of patent arteriovenous fistula where outflow cephalic vein filled with isoechoic thrombus (arrow) causing total occlusion (A). Colour Doppler shows absent flow in cephalic vein (B). Digital subtraction angiography Preoperative venography is able to identify the clinically occult veins which can be used for AVF creation. Venography is recommended in suspected cases of central venous thrombosis. It is gold standard investigation for assessment of central veins. Preoperative venography should be performed in patients with history of central venous catheters. DSA is also considered as gold standard for evaluation of poor maturation of fistula allowing greater vessel visualization. DSA also can offer treatment in the same session for FTM fistulas. Complete angiographic evaluation of AVF can be performed with retrograde puncture of brachial artery and injection of contrast. Puncture of outflow vein

with proper compression of distal vein, AVF and inflow artery are visualized with reflux of contrast medium. Main limitation of DSA is use of iodinated contrast medium (ICM) as it is not recommended in severe renal disease and patients who are not on haemodialysis. In patients on haemodialysis, dialysis can be performed after the DSA. Dilute ICM also can be used to decrease the risk of renal dysfunction. Diluted ICM, gadolinium and CO2 can be used as alternatives to ICM during DSA. Diluted ICM with volume of about 10 cc is safe and sufficient for diagnostic evaluation of AVF. Use of gadolinium is good alternative; however, its use is discouraged due to its association with NSF in patients with renal disease. CO2 angiography is a good alternative to conventional DSA and is useful in diagnosis and intervention of AVF failures. Despite all the benefits, use of DSA only for diagnostic purpose is not recommended due to its invasiveness and radiation. Computed tomography Computed tomography angiography (CTA) is an excellent technique and a good alternative to the conventional DSA as it is noninvasive and more economical. CTA, however, requires radiation exposure and ICM administration. Therefore, CTA is recommended only if DUS findings are inconclusive or inconsistent. Technique. Upper extremity should be placed in overhead abduction to reduce artefacts from body and radiation dose. Palm should face ventrally with all fingers straightened if possible. Intravenous access should be in contralateral upper limb with 18–20 G needles. Standard CT protocols for angiography should be used with bolus tracking method or test bolus method. In bolus tracking method, scan should be triggered at the maximum enhancement of aortic arch at threshold of 180–200 HU. Contrast should be administrated in 100–120 cc in volume at 4–5 mL/s followed by 40 cc saline chase at the same rate. Saline chase reduces streak artefacts of neat contrast. Arterial as well as venous phases should be obtained. Entire chest should be covered especially in venous phase to assess central veins. Applications: CTA is helpful in evaluating vascular stenosis in terms of location, degree and length of stenosis involved. Three-dimensional (3D) maximum intensity projection (MIP) and volume rendering (VR) techniques are excellent in demonstrating vascular tree and planning of appropriate surgical intervention (Figs. 10.18.3.9A and B and 10.18.3.10A and B). It can also detect proximal arterial stenosis where DUS cannot be performed like proximal subclavian artery or brachiocephalic trunk.

FIG. 10.18.3.9 Maximum intensity projection (A) and volumerendering (B) reconstructions showing patent radio-cephalic arteriovenous fistula (arrow) and severe narrowing of cephalic vein (arrowhead) cranial to fistula.

FIG. 10.18.3.10 MIP images demonstrating patent brachiocephalic fistula (arrows) and cephalic vein showing multiple fusiform aneurysmal dilatations (arrowheads). CTA is an excellent modality for evaluation of central veins. It is useful in assessing cause of central venous obstruction, like thrombotic occlusion, stenosis or narrowing due to external compression (Fig. 10.18.3.11A–D). It is even superior to DSA assessing external compression of central veins due to its greater soft tissue visualization. Distinction between luminal stenosis and external compression is essential to guide further intervention in central venous obstruction.

FIG. 10.18.3.11 Cases of central venous thrombosis (A and B) and central venous compression by mass lesion (C and D). Thrombosis is shown as hypodense filling defects in the right internal jugular vein and SVC (white arrow). (C and D) SVC (black arrows) compression by enhancing mass lesion (star). Aneurysmal dilatations and PSA are very well demonstrated on CT with the help of MIP and VR postprocessing techniques (Fig. 10.18.3.12A and B). Preoperative CTA also can be helpful in assessing atherosclerosis changes in upper limb arteries and presence of arterial stenosis.

FIG. 10.18.3.12 MIP images of CT angiography in first (A) and second (B) run showing brachio-cephalic fistula with large pseudoaneurysm (arrow) arising from brachial artery just proximal to fistula. Magnetic resonance imaging Magnetic resonance angiography (MRA) is a noninvasive and radiation-free investigation. Noncontrast MRA techniques include time-of-flight (ToF), phase contrast (PC) and 3D multiecho data image combination (MEDIC). ToF refers to the bright blood imaging and the effect is produced when plane of image is perpendicular to the direction of blood flow. Therefore, there can be signal loss at the vessel where blood flow is not perpendicular to image slice and this is the limitation of ToF MRA. On the other hand, preoperative vessel diameter measurements using PC-MRA and MEDIC sequences are comparable to the US data. Contrast-enhanced MRA (CE-MRA) is an excellent technique for better vessel visualization and assessment of AVF. CE-MRA is based on administration of gadolinium-based contrast medium and success of the examination depends on presence of contrast medium in the vessel at the time of data acquisition. However, use of gadolinium is not recommended in patients with severe renal disease. MR venography also can be performed when there is suspicion of central vein stenosis, limb oedema and in patients with multiple previous attempts for vascular access. MRI is more suitable than CTA or DSA in predialysis patients having minimal renal function because of the risk of acute renal failure with iodinated contrast media in the later.

Appendix I AVF mapping (bilateral upper limb) Findings: Right:

Arterial: Diameter (mm)

Velocity (cm/sec)

Phasicity

Brachial artery at cubital fossa Distal radial artery Distal ulnar artery Venous: The basilic and cephalic veins are normal in course and calibre. The diameters of basilic and cephalic veins in arm and forearm are as follows: Basilic Vein (mm)

Cephalic Vein (mm)

At mid arm At cubital fossa At mid forearm At distal forearm Left: Arterial: Diameter (mm)

Velocity (cm/s)

Phasicity

Brachial artery at cubital fossa Distal radial artery Distal ulnar artery Venous: The basilic and cephalic veins are normal in course and calibre. The diameters of basilic and cephalic veins in arm and forearm are as follows: Basilic Vein (mm)

Cephalic Vein (mm)

At mid arm At cubital fossa At mid forearm At distal forearm *Marking done for cephalic/basilic vein.

Appendix II Proforma for colour doppler evaluation of AVF maturity Findings: a. Feeding Artery Diameter:…. mm. Flow pattern: monophasic/biphasic/triphasic. PSV at anastomosis….. cm/s. PSV 2 cm cranially….. cm/s. PSV ratio:…. b. Draining Vein Diameter…. mm Flow: present/absent Depth form skin surface….. mm PSV at the site of stenosis: (if any)….. cm/s. PSV 2 cm caudally….. cm/s. PSV ratio:…. c. AVF Fistula at the Anastomosis Depth form skin surface….. mm Flow volume:….. mL/min. d. Accessory Findings:

Accessory vein: present/absent. IJV/subclavian vein: Patent/thrombosed. Arterial steal: Present/absent. Asymptomatic/symptomatic. Impression: • Mature AVF fistula (Please specify type of fistula).

10.19: Imaging in urological complications after renal transplantations Rohan S. Valsangkar, Bhalchandra Kashyapi

Surgical anatomy In renal recipient surgery, donor kidney is generally placed in the right iliac fossa extraperitoneally in adults and intraperitoneally in paediatric transplants if extraperitoneal space is small. Ureter of the donor kidney (living related or deceased donor) is anastomosed to anterolateral wall of recipient bladder by modified Lich Gregoir technique extraperitoneally (Fig. 10.19.1), while in young children or in some cases of robotic/laparoscopic renal recipient surgery, the ureter is anastomosed to the dome of bladder intraperitoneally. Care is taken to avoid redundancy of donor ureter so as to avoid subsequent kinking. The ureterovesical anastomosis is generally stented (Double J stent). Healing of anastomosis and good ureteric vascularity depends on the preservation of ureteric vascular supply by saving periureteric adventitial tissue, preservation of tissue between lower pole and ureter (golden triangle) and patency of lower polar arterial supply (if separate artery).

FIG. 10.19.1 Ureterovesical reimplantation (anterolateral bladder wall) an in right iliac fossa extraperitonially by creating submucosal tunnel for ureter to create non refluxing anastomosis. Always seek following intraoperative details from the transplant team regarding ureteroceveisal anaestomosis: stented or not, accessory renal arteries in donor, lower polar artery anastomosis status, presence of extrarenal pelvis, borderline pelviureteric junction obstruction in the donor kidney in CT IVU (which can cause hydronephrosis post-transplant) or pre-existing small renal stones in donor kidney. Sometimes native ureter is used for anastomosis to donor ureter in inadvertent ureteric injury during retrieval. Ureteral problems in early postoperative period (first 3 months) Urinary leaks occur at ureterovesical anastomotic site (technical reason/ureteral ischaemia), at proximal ureter or pelvis (inadvertent proximal ureteric or pelvis injury during donor/bench

surgery). Very rarely leak can occur due to anastomosis of ureter to peritoneum, it being mistaken as bladder. Ureteric obstruction is much less common than leak and occurs in nonstented anastomosis. It is caused by oedema/clot at anastomosis. Rare causes are kinking of redundant ureter, small stone in donor kidney slipping in ureter due to diuresis. Investigations 1. Sonography/Doppler can show a. Collection due to urine leak or haematoma and its location (extraperitoneal/intraperitoneal). Urinomas are nonechoic collections while haematomas have echogenic, complex and septate appearance. b. Transplant kidney hydronephrosis and hydroureter in obstruction, whether stent is in situ or migrated. Lower pole vascularity is assessed by Doppler. c. Bladder: bladder clot, urinary retention due to block in Foleys or high post void residue (PVR) due to bladder outlet obstruction or hypotonic bladder. d. USG-guided tapping and fluid creatinine level analysis for diagnosis of urinoma. e. USG and C-arm-guided percutaneous nephrostomy insertion (Fig. 10.19.2) and antegrade stenting. 2. CT IVU study (if normal creatinine)/CT cystogram (if raised creatinine) a. Diagnosis of leak and anatomical site of leak (distal or rarely proximal ureter/pelvis/bladder). b. Hydronephrosis and hydroureter level in case of obstruction in nonstented anastomosis. A small ureteric stone/stent migration (rare causes) can be ruled out. c. Collection (lymphocele/haematoma/abscess) with ureteric compression. 3. 99mTc -mercaptoacetyl triglycine(MAG3) or 99mTcdiethylenetriamine pentacetic acid (DTPA) nuclear scans for demonstrating leak/obstruction if creatinine raised.

FIG. 10.19.2 Nephrostogram showing leak urinoma. ( Source: https://symbiosisonlinepublishing.com/urology -nephrology/images/urology-nephrology41g001.gif) Ureteral problems in late postoperative period (after 3 months) Hydroureteronephrosis may be nonobstructive (due to reflux) or it may be obstructive (anaestomotic or ureteric stricture, compression by lymphocele, kinking of ureter, viral infections or rarely due to a new stone formation or blood clot). Obstruction typically develops after DJ stent removal. 1. USG is the first investigation to be done a. Degree of hydroureteronephrosis can be measured in full and empty bladder (can indicate reflux as cause). b. For serial follow-up of hydronephrosis as minimal to mild hydronephrosis is common post-transplant without obstruction (due to diuresis). c. Collection (lymphocele causing ureteric compression). d. USG-guided nephrostomy placement for obstructive HN/HU with raised creatinine. 2. Voiding cystourethrogram a. For reflux diagnosis as cause of hydronephrosis and hydroureter (Fig. 10.19.3).

b. Bladder abnormalities detection (trabeculation, large capacity bladder, PVR, etc.) as cause of hydronephrosis. 3. CT IVU (with normal creatinine) or plain CT KUB Anatomical details of ureteric narrowing (proximal vs distal/anastomotic and short vs long segment), lymphocele causing compression, very rarely new stone in formation recipient kidney or even rarer bladder mass causing ureteric compression (Figs 10.19.4 and 10.19.5). 4. MAG3/DTPA nuclear medicine scans for demonstration of obstruction with raised creatinine. 5. Antegrade contrast study (nephrostogram) after doing nephrostomy for location and length of stricture. If required, for short segment stricture, balloon dilatation of stricture and antegrade stenting can be done at same time. A case of ureteric stricture post-transplant with typical ultrasound findings and balloon dilatation of stricture is illustrated (Figs 10.19.6 and 10.19.7).

FIG. 10.19.3 VCUG showing low grade reflux in left iliac fossa transplant.

FIG. 10.19.4 Lymphocele causing mild hydronephrosis by compression.

FIG. 10.19.5 Transplant kidney hydronephrosis due to thickened bladder which turned out to be bladder malignancy causing ureteric block.

FIG. 10.19.6 (A and B) worsening HNdue to ureteric stricture post transplant. ( Source: A. Hakim www.myESR.org)

FIG. 10.19.7 (A–D) In same case, nephrostogram showing ureteric stricture (arrow) with balloon dilatation and antegrde stenting. Source: (A. Hakim www.myESR.org)

10.20: Endovascular management of renal artery stenosis Vikash Jain

Introduction Renal artery stenosis (RAS) may result in refractory hypertension, progressive renal insufficiency and cardiovascular complications such as refractory heart failure, flash pulmonary edema and acute coronary syndrome. There is overwhelming evidence that hypertension associated with a haemodynamically significant atherosclerotic RAS is better controlled with fewer medicines following renal revascularization. A meta-analysis of small series indicated that renal function is improved in about 30% and stabilized in 38% with an overall favourable response of 68% following percutaneous transluminal renal angioplasty (PTRA) in atherosclerotic renal artery stenosis (ARAS). Several randomized controlled trials have shown no difference in outcomes with optimal medical therapy (OMT) and PTRA compared with OMT alone in terms of BP control, preservation of renal function or major cardiovascular events. However, each of these trials had significant design flaws that ranged from variability in inclusion and exclusion criteria, inconsistent definitions of improvement that limit their applicability in day to day practice, making the selection of patients for renal artery stenting a controversial topic. These trials excluded patients with resistant hypertension, accelerated hypertension, advanced kidney disease, history of refractory heart failure or a recent acute coronary syndrome. This patient group who was most likely to be benefitted by PTRA was excluded in the trials. Atherosclerosis is the most common cause (90%) of RAS in adults, with fibromuscular dysplasia (FMD) being more common in younger female patients. ARAS is the most common cause of secondary hypertension affecting 25%–35% of the patients with secondary hypertension. Approximately 25% of elderly patients with chronic kidney disease (CKD) were found to have unsuspected

ARAS. In elderly population referred for coronary angiography and having coexistent hypertension, haemodynamically significant RAS (>70%) was found in more than 20% of patients. FMD is a nonatherosclerotic, noninflammatory, congenital condition that leads to dissection, aneurysm or stenosis of mediumsized artery predominantly affecting renal, carotid and femoral. It usually involves mid to distal portion of the renal artery. On angiography, FMD shows characteristic ‘string of pearls’ appearance or less commonly concentric smooth stenosis (Fig. 10.20.1). Renal FMD has a female preponderance, and can lead to HTN, which is preferentially treated with balloon angioplasty.

FIG. 10.20.1 A 35-year-old female patient with beaded right renal artery secondary to fibromyscular dysplasia.

Clinical manifestation of RAS Hypertension: In patients with haemodynamically significant ARAS, the renin–angiotensin–aldosterone system is activated, leading to hypertension. In unilateral RAS, the ischaemic kidney secretes renin, causing increased angiotensin formation and increased blood pressure while

bilateral or solitary kidney RAS results in hypertension with sodium retention and volume overload. Resistant or refractory hypertension due to RAS is defined as blood pressure above goal on three different classes of antihypertensive medications, ideally including a diuretic drug. Cardiac destabilization syndrome: ARAS causing uncontrolled hypertension and volume retention may destabilize patients with flash pulmonary edema, heart failure or acute coronary syndromes. In a study of 207 patients with decompensated heart failure, 19% of patients had severe ARAS for which PTRA was done. It resulted in a decreased frequency of congestive heart failure admissions, flash pulmonary edema and improved NYHA Class symptoms and tolerance to angiotensin-converting enzyme (ACE) inhibitors. Ischemic nephropathy: ARAS is a potentially a reversible cause of renal dysfunction. Favourable predictors of improvement following revascularization include a recent rapid decline in renal function, intolerance to ACE inhibitors, kidney pole-to-pole length >8.0 cm, absent glomerular or interstitial fibrosis on kidney biopsy and the absence of proteinuria. C LINIC AL FIND INGS ASSO C IAT E D WIT H R E NO V ASC U LAR D ISE ASE 1. Onset of hypertension before age of 30 years 2. New onset of hypertension after 55 years of age (suggestive of ARAS) 3. Accelerated, resistant, malignant hypertension 4. Acute renal failure precipitated by ACE inhibitors or angiotensin-receptor blocker 5. Asymmetric kidneys with more than 1.5 cm of difference in the size and otherwise unexplained loss of kidney function 6. Flash pulmonary edema 7. Unstable angina in setting of suspected RAS Diagnostic evaluation of RAS Noninvasive assessment: Duplex imaging: Renal Doppler ultrasound is screening investigation for the diagnosis of RAS. A peak systolic velocity (PSV) of >200 cm/s is associated with 95% sensitivity and 90% specificity for >50% stenosis. A ratio of renal artery PSV to the PSV of the aorta of >3.5 has 92% sensitivity for >60% diameter stenosis.

Computed tomographic angiography (CTA) and magnetic resonance angiography can provide high-resolution cross-sectional imaging of ARAS and 3D volumerendered and maximum intensity projection angiographic images of the aorta and renal arteries providing estimation of stenosis, localization and enumeration of the renal arteries, including accessory branches. Both have >90% sensitivity for diagnosis of RAS. Invasive assessment: Digital subtraction angiography is still the gold standard angiographic technique for evaluation of degree of renal arteries. Severe stenosis causing >70% diameter stenosis (>90% area stenosis) is almost certainly haemodynamically significant. Stenosis between 50%– 70% is of uncertain haemodynamic significance. Moreover, it is not possible to obtain orthogonal views of renal artery and stenosis may be located in tortuous and overlapping segment. So, confirmation of haemodynamic significance is recommended in cases of ≥50%–70% stenosis. Haemodynamic assessment: A resting or hyperemic mean translesional gradient of ≥10 mm of Hg, a resting or hyperemic translesional systolic gradient of ≥20 mm of Hg or a renal fractional flow reserve of ≤0.8 suggest haemodynamically significant stenosis. A 0.014-inch pressure wire or a nonobstructive catheter (4F) should be used for translesional pressure gradient measurement. Intrarenal bolus of papaverine at a dose of 40 mg or an intrarenal bolus of 50 µg/kg of dopamine may be used to induce hyperemia. Treatment Medical management of RAS: OMT of ARAS involves blood pressure control, lipid-lowering therapy, antiplatelet agents and lifestyle modification which includes dietary counselling, smoking cessation and physical activity. The ACC/AHA guideline and SCAI PAD Appropriate Use Criteria recommends that first-line therapy for patients with newly discovered RAS and hypertension is a trial of OMT. For those who fail OMT (resistant hypertension), PTRA remains an appropriate strategy. Indications for renal revascularization:

Patients most likely to benefit from PTRA have haemodynamically significant stenosis (>70% stenosis or 50%–70% any one of the following stenosis with significant translesional gradient) and 1) resistant, uncontrolled hypertension or refractory hypertension or hypertension with intolerance to medication, 2) ischaemic nephropathy and 3) cardiac destabilization syndromes. Technical aspects of revascularization: Atherosclerotic stenosis is often due to bulky aorto-ostial plaque for which balloon angioplasty alone is mostly ineffective due to recoil associated with these plaques. Renal artery stenting with bare metal stent is the preferred method of treatment. Most paediatric and FMD cases as well as truncal atherosclerotic stenosis can be treated by plain old balloon angioplasty. There are several important technical considerations for a successful PTRA. Adequate prehydration with crystalloids and limiting the contrast dose are helpful to prevent contrast-induced nephropathy. Selective renal angiography should be preceded by nonselective abdominal aortography or noninvasive imaging with CTA or MRA. Vascular access can be planned on the basis of configuration of renal artery; strong consideration should be given for radial access over femoral (Fig. 10.20.2). An ipsilateral oblique projection (right anterior oblique 15–30 degrees for right renal artery) may be required to profile renal artery ostium. It is advantageous to use a guide catheter (renal double curve catheter for femoral approach) than guide sheath. Currently, majority of devices meant for PTRA are 0.014-inch wire compatible, balloon expandable, rapid exchange (monorail) system. Catheter-in-catheter and no-touch technique are useful techniques to minimize contact with the aortic wall and injury to the renal ostium during guiding catheter engagement and thus avoiding atheroembolism. In notouch technique, a 0.035-inch J-wire is placed cephalad from the guide catheter tip aligned along the wall of the aorta. This J-wire prevents the tip of the guide catheter from scraping the aortic wall during maneuvering. Once renal artery is engaged, a 0.014-inch angioplasty guidewire is introduced across the stenosis before the safety J wire is removed (Fig. 10.20.3). In catheter-incatheter approach, a 4- or 5-F diagnostic catheter is placed inside a guiding catheter that is 2-F larger. Cannulation of the renal artery is done with a diagnostic catheter and a 0.014-inch wire is used to

cross the stenosis, following which the guide catheter is then advanced over the diagnostic catheter. When the guide is in correct position, the diagnostic catheter is removed. Some operators prefer to advance guiding catheter across the stenosis, thereby ‘dottering’ the lesion and then placing the stent for deployment. The guiding catheter is then pulled back similar to unsheathing and stent is deployed (Fig. 10.20.4). If lesion is >75%, it is predilated with 4- or 5-mm angioplasty balloon. Pressure measurements are required across the stenosis in cases of narrowing of luminal diameter between 50% and 70%. When treating ostial atherosclerotic lesion, the stent should protrude at least 2 mm in aorta. Flaring of aortic end of the stent is advantageous when recatherization is required. Complication: Major complications are atheroembolism, renal artery occlusion by thrombus or dissection, stent malposition and renal artery perforation. Atheroembolism has been associated with higher morbidity and significant decrease in 5-year survival in comparison with patients with no evidence of periprocedural atheroembolism (54% versus 85%, P = 0.011). Role of embolic protection devices (EPD) has been explored to prevent atheroembolism and optimize outcomes after renal intervention. Early renal artery bifurcation makes distal protection complex, requiring 2 EPD devices with its associated new set of complications. EPD may be selectively considered in patients with impaired renal function and is not routinely recommended currently. Occlusion of main renal artery by thrombus or dissection is usually secondary to inadequate anticoagulation or flow-limiting dissection. Acute thrombosis may require intraarterial administration of thrombolytics (t-PA) or a glycoprotein IIb/IIIa receptor antagonist (abciximab). Flow-limiting dissection may require stenting to seal off the flap. Haemorrhage secondary to main renal artery rupture is a life-threatening event. Balloon tamponade, reversal of anticoagulation and, if required, a covered stent should be used to seal the site of rupture. Appropriate stent sizing is important to avoid complications. Oversizing stents leads to increased procedural complications like dissection and rupture, and undersizing leads to increase in restenosis rate. Intravascular ultrasound, if available, allows more

precise measurement of vessel luminal diameter than two-dimensional angiography, which improves the operator’s confidence to safely maximize stent size. Patient with PTRA should be regularly followed up for blood pressure control, renal function and surveillance duplex imaging. Duplex is the recommended imaging technique for screening of in-stent restenosis (ISR). ISR of >70% can be confirmed with PSV of 395 cm/s. Renal stents have an excellent long-term patency rates, demonstrating a 5-year primary patency rate of >80% and a secondary patency rate of >90%. Repeat stenting is preferred over balloon angioplasty as it had shown 58% reduction in repeat ISR.

FIG. 10.20.2 A 70-year-old patient with refractory hypertension and worsening renal function. (A) Extensively calcified right renal artery stenosis. (B) Angioplasty done with 4 × 10 mm balloon. (C) Renal artery stenting done with 6 × 15 mm balloon expandable bare metal stent through radial approach.

FIG. 10.20.3 No-touch technique: It prevents the guide catheter from scraping the aortic wall, thereby minimizing the risk of atheroembolization. (A) A 0.035-inch J tip guide wire is positioned through the guide catheter distally during initial engagement. It prevents the guide catheter from scrapping aortic wall. (B) When the renal artery is engaged, a 0.014-inch wire is inserted alongside the 0.035-inch J wire and advanced into the target vessel. (C) Once the 0.014-inch wire is placed across the target lesion, the 0.035-inch wire is removed and angioplasty is done as per conventional method.

FIG. 10.20.4 A 60-year-old patient with flash pulmonary edema and refractory hypertension presents for renal angiogram and stenting; Catheter in catheter technique: (A) Angiogram demonstrates 90% left renal artery stenosis. (B) Lesion crossed with hydrophilic wire and diagnostic catheter placed across the stenosis. (C) Guide catheter dottered over diagnostic catheter. (D) 6 × 18 mm balloon expandable bare metal stent is positioned across the stenosis.

Conclusion Renal artery stenting is beneficial for patients with resistant or refractory hypertension despite OMT, ischemic nephropathy and

cardiac destabilization syndrome who have haemodynamically significant atherosclerotic RAS. Screening with noninvasive imaging modalities is initially recommended. Trans-stenotic gradients are useful guide to assess the haemodynamic severity of renal hypoperfusion in 50%–70% stenosis and therefore help in patient selection for renal artery revascularization. Overall, the technical success rate and primary patency rate are acceptable.

10.21: Other renal vascular interventions 1 0.21 . 1

NONVASCULAR RENAL INTERVENTION Amitha Vikrama

Introduction Nonvascular renal interventions have come a long way and have significantly reduced the surgical mortality and morbidity. It also paves way for short hospital stay and thus reducing the chances of nosocomial infection. They are usually pinhole or keyhole procedures with less distortion of the anatomy and physiology. They vary from image-guided aspiration/biopsy to percutaneous nephrostomy to complex procedures like ureteric stenting, strictureplasty, percutaneous nephrolithotomy etc. Renal biopsy Iversen and Brun were the first to perform percutaneous renal biopsy of native kidneys in 1951. Over the years, newer imaging and biopsy techniques have evolved which have increased the biopsy yield to >95% and significantly reduced the complications of renal biopsy, resulting in decreased mortality rates from 0.12% to 0.02% during the last 50 years Indications • Medical renal disease. • Renal neoplastic mass lesions with local spread or metastases. NOTE: Solitary renal mass lesions suspicious for malignancy should not be subjected to percutaneous biopsy, as there are

chances of tumour seeding along the biopsy track. Excision biopsy is preferred for those lesions as it can be curative. Contraindications • Bleeding diathesis. • Severe hypertension. • Active renal or perirenal infection. • Skin infection at biopsy site. Relative contraindications • Restless or Uncooperative patient. • Renal anatomic abnormalities which may increase risk of bleeding. • Small sized kidneys. • Solitary kidney. Techniques USG-guided renal biopsy is the preferred method over blind biopsies. It avoids nontarget biopsies and reduces bleeding risks. Usually the lower pole of the kidneys is preferred site in native renal biopsy. The needle has to be directed into the lower cortex and care taken to avoid renal medulla and collecting system. 18G trucut biopsy needles are usually used in adults. In paediatric population, 20G can be used. Rarely, Coaxial technique is used in very obese patients and in those who are unable to lie prone. It is usually done as an inpatient procedure. Four hours of fasting is required to prevent aspiration of gastric contents during the procedure. Antiplatelets and anticoagulants are stopped at least 3– 5 days prior. Informed written consent has to be taken after explaining the risks and benefits of the procedure. Patient is to be positioned in prone and USG-guided marking of the site of biopsy done prior to cleaning and draping. The depth of the renal cortex from the skin surface has to be noted. If the ribs are coming in line with the lower pole cortex, then a cranially angulated path is preferred. After infiltration of 2% lignocaine, the biopsy needle is advanced up to and not into the lower pole cortex. As the kidney keeps moving with respiration, the biopsy should be properly timed to avoid hitting the collecting system and medulla. This method is real-time ultrasound guided renal biopsy (Fig. 10.21.1.1). There is another method practiced in few of the institutes where the location of lower pole of the kidney is marked on the skin after ultrasound screening. The marking corresponds to the lower most renal cortex at the end of normal inspiration and the biopsy path will be perpendicular to the

bed without any craniocaudal or mediolateral angulation. The distance between the skin and the renal cortex is measured. The patient will be instructed strictly not to change his position. Then the biopsy will be done blindly without any real time USG guidance. With this method, more number of patients can be biopsied in a short interval time.

FIG. 10.21.1.1 Real-time USG-guided renal biopsy. Arrows pointing to the needle targeting the lower pole cortex. Biopsy of renal transplants In a transplanted kidney, which is usually grafted in the iliac fossa, biopsy can be obtained from upper or lower pole. Points to remember: • Avoid inferior epigastric vessels. Use high frequency linear ultrasound probe to visualize the superficial vessels. • Avoid the renovascular pedicle and ureter. • Avoid adjacent bowel loops especially when the graft is intraperitoneal. Cortical tangential and cortical non tangential approaches have been described (Fig. 10.21.1.2). Cortical tangential approach is described to have better diagnostic yield with lesser complications. In this approach, the needle track will be almost parallel to the capsule so that only the cortical tissue is targeted (Fig. 10.21.1.3A– C).

FIG. 10.21.1.2 Illustration showing cortical nontangential and tangential biopsy.

FIG. 10.21.1.3 (A) USG screening of a graft kidney before the biopsy. (B) USG-guided trucut biopsy with cortical tangential approach. Arrows pointing to the needle trajectory. (C) Track embolization of the needle track by using gelfoam. Arrow shows gel foam along the needle track within the cortex. Arrow head shows gelfoam just outside the capsule with reverberation artefacts. (D–F) Transjugular renal biopsy. (D) Multipurpose catheter (arrow) within the renal vein to get a renal venogram. Arrow head points to the renal vein. (E) 10F sheath and metallic cannula (arrow) with the biopsy needle within. (F) Plunging of the biopsy needle (arrow) into the renal parenchyma. Renal biopsy can also be done with coaxial technique. In this method, a coaxial needle, one size bigger than the biopsy needle, usually 17G, is inserted up to the renal capsule. The stylet is then removed and the 18G biopsy needle is inserted through the coaxial needle and the required number of biopsy specimens obtained. After this, the rent in the capsule can be sealed off with gelatine plugs before removing the coaxial needle. This helps in preventing bleeding complications. In patients with high risk of bleeding due to coagulation abnormalities, transjugular renal biopsy can be done in which renal vein is cannulated and biopsy done from within (Fig. 10.21.1.3D– F).

In obese patients who cannot lie prone, biopsies are done in lateral or oblique lateral positions under CT or USG guidance. CT guidance is especially helpful when the visualization of the kidney is difficult on ultrasound. In these cases, coaxial technique is always helpful. Guidelines In 2019, KHA-CARI guidelines were first published for renal biopsy. A few of the salient recommendations are given below: • Not to stop aspirin in patients at high risk for a cardiovascular event. • Stop aspirin for 3–7 days prior to the renal biopsy for patients at low risk for a cardiovascular event. • Start anticoagulation in patients at highest risk for thromboembolic event, for example, patients with prosthetic cardiac valves, additional stroke risk factors, antiphospholipid syndrome etc.

Percutaneous nephrostomy It is an image-guided procedure in which the renal pelvicalyceal system is accessed percutaneously which is predominantly used for decompressing an obstructed system and also for various other therapeutic procedures. Indications • To decompress an obstructed pelvicalyceal system due to stones, malignancy or stricture. • Acute urosepsis due to obstruction, emphysematous pyelonephritis. • As an access to various endourological procedures like stone removal, ureteric stenting, endopyelotomy, delivery of chemotherapy or antibiotics etc. • For urinary diversion in case of urine leak. • For diagnostic tests like whitakers test, pyelography, ureteroscopy and biopsy. Contraindications • Bleeding diathesis • Severe hyperkalaemia • Uncooperative patient Technical aspects It is usually done under local anaesthesia and IV sedation. Major procedures might require general anaesthesia. All routine

preprocedural blood tests and coagulation profile should be done. Appropriate antibiotics are administered intravenously prior to the procedure. Materials 21G needle, 018 and 035 wires, appropriate dilators, sheath and pigtail drainage catheter. Ultrasound and fluoroscopy is required for guidance. Patient is usually positioned prone on the table. Under special circumstances, lateral or oblique positions are also used. After instillation of local anaesthesia, a 21G needle is used to access the renal calyx under USG guidance. Once the urine flow is seen, nonionic contrast is injected to delineate the renal collecting system. A 018 wire is passed through the needle into the pelvicalyceal system and later exchanged for a 035 wire. Appropriate tissue dilators are used to dilate the track before placing a pigtail drainage catheter. The drain is secured by stay sutures and connected to a urobag. The initial urine sample is to be sent for culture and sensitivity (Figs. 10.21.1.4–10.21.1.6).

FIG. 10.21.1.4 Illustration showing the steps of the PCN procedure. (A) Puncture of the lower calyx with a needle. (B) A guidewire passed through the needle into the pelvicalyceal system. (C) A pigtail catheter that has been passed over the guidewire, with the holes within the collecting system.

FIG. 10.21.1.5 (A and B) CECT images with bilateral hydronephrosis. (C) Fluoroscopic image with bilateral PCN drainage tubes within the dilated collecting system.

FIG. 10.21.1.6 (A) The patient draped in prone position for PCN, USG probe in a sterile covering. (B) The materials required for the postoperative changes are noted in the anterior abdominal wall and in the sternum. (C) Local anaesthesia being injected. (D) USG-guided puncture of the renal collecting system. (E and F) Wire inserted through the needle into the collecting system. (G and H) Fasical dilators

over the guidewire. (I and J) Drainage catheter with stay sutures. Complications • Bleeding complications leading to perinephric haematoma or haematuria. • Pneumothorax can occur in case of transpleural puncture. • Injury to adjacent organs like liver, spleen and bowel. • Urinoma.

Percutaneous antegrade ureteric DJ stenting Ureteric stenting was first described by Zimskind et al endotracheal tube al in 1967. It is one of the commonest procedure done in urology practice Indications • Ureteric obstruction due to benign or malignant causes. • As an adjunct to treatment of renal/ureteric calculi. • Ureteric tear with urine leak and urinoma. • Perioperative insertion. • Infection – pyelonephritis. Contraindications • When ureteric tear is more than two-thirds circumference. • Bladder outlet obstruction. • Bladder fistula. • Spastic or noncompliant bladder. Technique It is usually done after doing a percutaneous nephrostomy. The percutaneous nephrostomy (PCN) drain is replaced with a 6F or 8F sheath over a guidewire and ureterogram is obtained to assess the site of stricture or obstruction. Using a catheter and guide wire combination, the stricture is negotiated and the exchange length hydrophilic wire is parked in the bladder. The ureteric length is measured and appropriate-sized double J (DJ) stent is inserted over the wire. Care is taken to get the loops formed at both ends of the DJ stent so that stent migration is prevented (Fig. 10.21.1.7).

FIG. 10.21.1.7 (A) DJ stent insertion within the graft kidney in the right iliac fossa. Urterogram done through the PCN drain showing leakage in the mid ureter with contrast extravasation (arrowhead). (B) Arrow shows insertion of 8F malecots drain. A variety of delivery systems are available for the deployment of the ureteric stent exist: pusher mechanism, string release and sheath (similar to an inferior vena cava (IVC) filter). Post stent insertion, the nephrostomy drain can be retained for a couple of days. The drain is closed externally and USG screening is done the next day to confirm antegrade flow after which the drain can be removed. Tips for complex cases • Use hydrophilic 0.035 or 0.014 inch wires for crossing the strictures. • Balloon plasty of the tight strictures will help pass the stent easily. • Use preattached thread or an indigenous thread to the upper end of the ureteric stent to from the proximal loop in the pelvis. • In case of difficulty in negotiating the acute bend in the ureters, reattempt after few days of decompression of the system. Complications • Pelvic or loin pain • Haematuria and infection

• Stent fracture • Ureteral erosion • Stent migration/malposition • Sepsis • Stent block • Encrustation/calcification • Incontinence

Ablation of renal tumours Ablation of renal cell carcinoma is a minimally invasive, treatment modality to treat renal malignancies in their early stages. For smaller tumours, the thermal ablations are better than partial nephrectomy as it minimizes the nephron loss (thermal ablation 11% versus partial nephrectomy 35%). It also avoids intraoperative ischemia, thus preventing the associated parenchymal injury. Radiofrequency ablation (RFA), microwave ablation (MWA) and Cryoablation are the most common ablative procedures being practiced. Basic physics of radio frequency ablation It is essentially a thermal injury to the tissues by using electromagnetic energy. The term radio frequency ablation is generally used to denote coagulation induced by electromagnetic waves with frequency less than 90 kHz. Most of the currently available devices operate in the range of 375–500 kHz. The term radiofrequency (RF) actually refers to the alternating current that oscillates in this frequency. In monopolar RF ablation, a closed circuit is formed between the RF generator, RF probe, patient and the grounding pads. The alternating current generated by the RF generator is transmitted to the tissues around the RF probe, which will make the ions to agitate due to the high resistance offered by the tissues for the passage of the current. This in turn leads to generation of heat. The gross discrepancy between surface area of the RF probe and the grounding pads will cause the heat to get focussed and concentrated around the RF probe. Studies have shown that thermal energy in the range of 50–55°C for 4–6 minutes will cause irreversible cellular damage; 60–100°C will cause coagulation of proteins and irreversible damage to mitochondria, cytoplasmic enzymes and nucleic acid – histone protein complexes; 110°C causes vaporization and carbonization of the tissues. In ablation of larger tumours requiring more time, excessive charring happens at the tip of the RF probe, which will break the electrical circuit. This can be prevented by injecting saline into the tissues or by passing cold saline through the needle.

Another shortcoming is the presence of large vessels close to the tumour, which will take away the excess heat leading to suboptimal ablation. This is called as heat sink effect. In these thermal ablative procedures, an electrode is inserted into the tumour substance under image guidance, usually ultrasound or CT, and high frequency alternate current or microwaves are passed through the electrode to generate local heat to induce coagulative necrosis of the cancer cells. Cryoablation is another thermal ablative procedure which is still not widely used in India. In this procedure, a cryoprobe is inserted into the target tissue and the tissue is frozen to –40 to –60° C by using helium or argon. Indications • Small renal neoplasms, less than 4 cm, especially in those with a single kidney or impaired renal function. • Patients who are unfit for surgery due to comorbid conditions. • Hereditary diseases (von Hippel-Lindau syndrome, tuberous sclerosis, Birt-Hogg-Dubé syndrome) in which both kidneys are involved. • Patients who refuse to consent to surgery. Contraindications • Severe coagulation abnormalities • Excessive primary tumour burden • Untreatable extrahepatic metastases • Child’s class C cirrhosis and • Infection • Close abutment of adjacent normal viscera is a relative contra indication • Hip prosthesis – a relative contraindication as it may act as an electrical conduit leading to skin burns • Pacemaker or defibrillator – as the RF energy can interfere with their proper functioning Planning and procedure Proper history and physical examination is important as in any other surgery. Laboratory studies namely complete blood count, coagulation profile (INR and platelet count) and renal function tests are done routinely. If the patient is on antiplatelets, it should be stopped 5 days before the procedure. Low molecular weight heparin should be stopped 12 hours prior and unfractionated heparin, 6 hours. If these medications could not be stopped in view of recent coronary

intervention, then proceed with high-risk consent after proper explanation to the patient. Preanaesthetic evaluation is done in all cases requiring general anaesthesia or intravenous sedation. Review of the cross-sectional images, planning of the procedure including patient positioning, site of needle entry, adequate window, depth from the skin, need for hydrodissection etc. will help in reducing the procedure time and complications. Procedure is usually done under local anaesthesia and IV sedation in the CT room. Semiprone position or lateral decubitus position is the preferred one, as it will push the bowel away from the perinephric region. Initial planning CT scan sections are obtained and the needle path determined. Local anaesthesia (2% lidocaine) is injected along the planned needle track. Whenever colon or any other visceral organ is closely abutting the tumour, hydro dissection can be done by injecting 5% dextrose in between the kidney and the adjacent organ. Any saline solution cannot be used for hydrodissection It is accomplished by using a 20G needle. Once the path is clear of any other organs, the Ablation needle is inserted into the lesion and ablated. Sometimes transpleural approach will be inevitable to properly target the lesion. The power (watts) and time for ablation depends upon the size of the lesion. Postablation check CT is done with contrast to look at any residual areas of nonablation which can be immediately addressed (Fig. 10.21.1.8). Any complications like bleeding/pneumothorax also can be evaluated and managed accordingly.

FIG. 10.21.1.8 Radio frequency ablation of the right renal exophytic renal cell carcinoma. (A) Enhancing exophytic cortical tumour. (B) The RFA probe within the lesion. (C) Postablation CT with completely ablated nonenhancing lesion.

Complications • Bleeding requiring embolization • Clots in the collecting system requiring ureteric stenting • Abscess formation • Tumour seeding • Urine leak, acute renal injury/infarct • Adjacent organ injury like colonic perforation, pneumothorax • Acute hypertensive crisis due to adrenal injury/ablation • Injury to genitofemoral/ilioinguinal nerves • Pulmonary embolism • Skin burn • Infection • Nontarget ablation American urological association guidelines • Thermal ablation is an alternate treatment modality for management of cT1a renal masses 200 mg/dL immediately before injection, repeat measurements can be performed at 20–30 minutes. If the glucose level decreases 200 mg/dL, then FDG can be injected. If the blood glucose levels are consistently >200 mg/dL, the study can be rescheduled. Administration of shortacting intravenous regular insulin is also recommended to reduce serum glucose, but the administration of 18F-FDG should be delayed for 60–90 minutes and frequent blood sugar monitoring to be done to identify and correct potential hypoglycaemia. If PET study is scheduled in the early morning, all insulin and oral medications should be withheld. Several published studies have proven that metformin significantly increases FDG uptake in the colon and the small intestine to a lesser extent and some

recommend to discontinue the drug for 2 days before the study if this study is intended for evaluation of gastrointestinal tumours (Fig. 11.1.12.1).

FIG. 11.1.12.1 Maximum intensity projection (MIP) image showing diffusely increased 18FFDG uptake in colon in a patient on Tab. metformin. In patients with suspected urinary bladder wall/uterine malignancies, an intravenous diuretic is administered to minimise overlap between the FDG activity of the tumour and nonspecific radioactivity in the urine. 1 mg/kg body weight of furosemide (to a maximum of 40 mg) is slowly injected 30 minutes before the scan and patients are encouraged to void 2–3 times and then hold urine to maximum bladder distension. Some studies recommend administration of diuretics after routine PET-CT and acquisition of delayed images after 1–2 hours to achieve higher diagnostic value in cases of muscle-invasive urinary bladder cancer. However, care should be taken to avoid furosemide in patients with medical contraindications, including allergies (e.g. Sulpha allergy). For 68Ga PSMA PET-CT study, the patients need not fast and are allowed to take all prescribed medications. Patients are encouraged to take water before the study and advised to void immediately before acquisition. Intravenous Furosemide administration shortly

before or after 68Ga-PSMA injection may be useful to avoid falsepositive findings due to activity in the ureters. PET-CT acquisition protocol Basic protocol for 18F- FDG and 68Ga-PSMA PET-CT are given in Table 11.1.12.3.

TABLE 11.1.12.3 18F-FDG

and 68Ga-PSMA PET-CT Acquisition Protocol

Parameters Activity

18F-FDG

PET-CT

185–740 MBq

68Ga

PSMA PET-CT ~1.8 × 2.2 MBq/kg of body weight

Remarks

Minimum recommended administered FDG activity, and optimal PET acquisition duration is preferred to achieve ALARA. Administration Intravenous Intravenous Administered through an indwelling intravenous device. Uptake time 60 minutes 60 minutes Consistency of SUV (55–75 (50–100 measurements minutes) minutes) depends on uptake time. When treatment response assessment scan is done for the same patient, the same uptake time should be applied. Patient Arms Arms To avoid beam position elevated elevated hardening artefacts in above the above the abdomen and pelvis. head head FOV Skull base Skull Base The extended wholeto midto midthigh body study can be thigh performed if there is high suspicion for metastasis in the skull and lower extremities. Intravenous 1.5 mL/kg 1.5 mL/kg, Contraindications for contrast portal intravenous contrast venous should be excluded. phase Positive or negative oral contrast regions may be used if necessary.

Parameters PET protocol

18F-FDG

PET-CT

Scanning time per bed adjusted depending on the dosage of activity

68Ga

PSMA PET-CT 3–4 min per bed position

Remarks

Pitfalls With an ever-increasing demand for PET-CT in the management of urology and gynaecologic tumours it is essential to have precise knowledge about potential pitfalls to ensure a safe and accurate image interpretation. Physiological FDG uptake may be seen in the brain, heart, kidneys, urinary tract, gastrointestinal tract, Waldeyer’s ring, lymphoid tissue of terminal ileum and caecum, thymus and brown fat. Physiological 68Ga PSMA uptake may be seen in kidneys, renal pelvis, ureters, salivary and lacrimal glands, vocal cords and ganglion of sympathetic chain (Fig. 11.1.12.2).

FIG. 11.1.12.2 Maximum intensity projection (MIP) images of 18F-FDG (A) and 68Ga PSMA PET (B) showing physiological uptake. The following are the common pitfalls encountered in abdominopelvic PET-CT studies. Technical pitfalls i. Artefacts due to attenuation correction at high-attenuation structures such as metallic prosthesis, pacemakers, surgical clips and barium within the bowel ii. Miss registration of PET and CT datasets due to patient movement, respiratory motion, bowel motility and the difference in bladder distension iii. Respiratory motion artefact may obscure small subdiaphragmatic peritoneal nodules Physiological uptake mimicking disease i. Physiological FDG uptake in normal endometrium during ovulatory and menstrual phases ii. Physiological FDG uptake in normal ovaries in follicular and luteal phases iii. Physiological focal FDG uptake in the ureter may mimic metastatic lymph nodes (Fig. 11.1.12.3)

iv. Physiological FDG uptake in brown adipose tissue in the paraspinal region may mimic paraaortic lymphadenopathy/paraganglioma Physiological uptake obscuring disease i. Increased physiological uptake within the bowel may mask adjacent small serosal/peritoneal nodules ii. Physiological uptake within the renal pelvis, ureter and bladder may obscure underlying tumour iii. Increased tracer uptake within the urinary bladder may mask adjacent disease Benign disease showing increased tracer uptake i. Benign uterine leiomyoma may show increased FDG uptake ii. Benign endometriotic cysts may issue variable FDG activity iii. Inflammatory and infective pathology may demonstrate increased FDG uptake (e.g. acute pyelonephritis, renal abscess, prostatic abscess) iv. Paget’s disease in the pelvic bone may show increased PSMA uptake v. Meningioma, follicular adenoma of thyroid, haemangioma, sarcoidosis, pancreatic serous cystadenoma, desmoid tumour, myxoma, peripheral nerve sheath tumour, gynecomastia, fibrous dysplasia and vertebral fracture may show increased 68Ga PSMA uptake Malignant tumours showing less/absent FDG uptake i. Renal cell carcinoma (Fig. 11.1.12.4) ii. Primary mucinous ovarian tumours iii. Lymph nodal and peritoneal metastases from mucinous carcinomas iv. Metastatic necrotic lymph nodes v. Mature differentiated teratoma vi. Cancer prostate

FIG. 11.1.12.3 Tracer ( 68Ga PSMA) excreted in left ureter (arrow) mimicking as a lymph node in a case of cancer prostate.

FIG. 11.1.12.4 Renal cell carcinoma of left kidney. Exophytic mass (asterisk) with heterogeneous enhancement in lower pole of the left kidney (A) showing mild FDG uptake. It is a good practice to note the patient’s menstrual history routinely to aid interpretation of endometrial and ovarian FDG uptake. Increased endometrial or ovarian FDG uptake in a postmenopausal woman should raise the concern for malignancy, and further evaluation should be done with clinical history, transvaginal US/MRI. Ovarian uptake in premenopausal women positive for BRCA1 and BRCA 2 should be interpreted with caution since the high risk for developing ovarian cancer. PET-MRI in pelvic tumours Due to the low soft tissue contrast nature of CT, tumour extension in pelvic tumours cannot be done accurately in almost all pelvic tumours with PET-CT. Integrated PET-MRI, a recently developed imaging modality, overcomes this disadvantage with its superior soft tissue contrast by MRI and also eliminates the ionizing radiation by CT. PET-MR has the advantage of precise assessment

of T staging with MRI component and N and M staging with PET component. Multiple recent meta-analyses revealed high diagnostic confidence of PET-MRI in the evaluation of gynaecological malignancies, especially for tumour invasion into the adjacent anatomical structure such as pelvic sidewall, bladder and rectum. PET-MRI has a high diagnostic performance for assessment of locoregional extension and nodal metastasis of cervical cancer and thus provides specific gross tumour volume (GTV) for the planning of chemotherapy. One of the studies proved that combined PETMRI markedly increases the diagnostic accuracy for the radiologist. However, longer scanning time and assessment of pulmonary nodules are some of the challenges in PET-MRI. Diagnostic pearls • PET-CT is an excellent tool for staging, treatment response assessment, restaging, and follow-up of almost all of the urologic and gynaecologic tumours. • Selection of radiotracer is based on type of tumour and sometimes differentiation. • PET-CT has a limitation in precise T staging of pelvic tumours due to the inherent low soft-tissue contrast by CT. Addition of MRI can be considered as an integrated or standalone technique. • Knowledge about the various pitfalls will be helpful to improve diagnostic accuracy. • Additional techniques such as forced diuresis can be used with consideration of patients’ medical background.

11.2: Anatomy and normal variants 1 1 .2.1

IMAGING ANATOMY OF MALE REPRODUCTIVE SYSTEM Ganesh Rajagopal

Introduction The male reproductive system is formed by testes, ejaculatory ducts, seminal vesicles (SVs), prostate and penis. Various diagnostic imaging modalities like ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) are helpful in the diagnostic evaluation of male reproductive system. Various indications for imaging may include acute scrotum (testicular torsion, trauma and epididymo-orchitis), scrotal swelling (hydrocele, spermatocele, idiopathic scrotal wall oedema and scrotal abscess) and infertility. US and MRI are the commonly used imaging modalities in male reproductive system which complement each other. CT is not very useful due to poor contrast resolution.

Imaging anatomy of male genital system Ultrasound imaging (US) with a high-frequency linear (7.5–10 MHz) transducer probe has become the imaging modality of choice for scrotal evaluation. Scrotal US is an excellent imaging modality as it can demonstrate abnormalities in testis as well as in paratesticular structures. Scrotal wall is formed by the skin, superficial fascia, dartos muscle, the external spermatic fascia, cremasteric fascia and the internal spermatic fascia. The scrotum is divided into two cavities by a median raphe. This multilayered scrotal wall is poorly delineated in US and MRI, it is typically hypointense on both T1- and T2-weighted images. Testes are paired organs, located normally in scrotal sac, suspended by the spermatic cords. Each testis is examined in orthogonal transverse and longitudinal planes, with both grey scale and colour Doppler modes, to assess its volume and blood flow. Volume of testis is calculated by length × height × width × 0.71. A total volume (both testes) of >30 mL and a single testicular volume of 12–15 mL is generally considered normal for adults. Testes are supplied by the testicular arteries, which arise from the aorta and enter the spermatic cord at deep inguinal ring to reach the upper pole of testis. Pampiniform plexus of veins surrounds the testis and appears as a

serpiginous tubular structure posterior to it, measuring >2–3 mm in diameter. Testes are oval shaped, with homogeneous echotexture on grey scale US. Along with the epididymis, they are surrounded by an echogenic capsule, known as the tunica albuginea. Tunica albuginea is covered by tunica vaginalis, which is a remnant of the processus vaginalis and both represent closed sac of peritoneum with two layers. This tunica albuginea is seen extending into posteromedial testis and form the mediastinum testis (Fig. 11.2.1.1), which consists of ducts, nerves and blood vessels. The mediastinum testis is seen as a thin echogenic band. Rete testis is formed by the convergence of seminiferous tubules, seen as a hypoechoic area adjacent to mediastinum testes.

FIG. 11.2.1.1 Ultrasound image of normal testis with hyperechoic mediastinum testis (M). The epididymis is a comma-shaped, elongated structure placed at the posterior border of the testis, which drains the efferent ductules (Fig. 11.2.1.2). It has head, body and tail. The head overlies the superior pole of the testis and is isoechoic or slightly hyperechoic whereas, the body and tail are located behind and along the inferior pole and are usually isoechoic. The tail of the epididymis continues into vas deferens (VD), which along with the nerves, lymphatic and vascular structures, forms the spermatic cord (Fig. 11.2.1.3). The spermatic cord appears as an echogenic band in the inguinal canal.

FIG. 11.2.1.2 (A and B) Ultrasound image of head (H), body (B) and tail (Ta) regions of epididymis.

FIG. 11.2.1.3 Ultrasound image of cord structures (C) at the level of inguinal canal. The normal adult testis is a homogeneous oval structure that appears hyperintense on T2-weighted sequences and hypointense–isointense on T1weighted images (Fig. 11.2.1.4). The tunica which surrounds the testis is hypointense T1- and T2-weighted sequences. Epididymis is isointense on T1weighted images but hypointense on T2-weighted images compared to testis (Fig. 11.2.1.5). Both testicles and epididymis enhance after intravenous administration of gadolinium (Gd) MR contrast agents.

FIG. 11.2.1.4 (A) MR T2 and (B) T1 images of testis (T), showing the homogeneous hyperintense signals of testis in T2 and hypointense in T1-weighted sequences.

FIG. 11.2.1.5 MR images of epididymis (E). (A) T1weighted image and (B) T2-weighted image. Prostate, though visualized by transabdominal scan is better assessed by transrectal high frequency (7.5–10 MHz) ultrasound transducer (TRUS) with patient in left lateral decubitus position. The prostate gland is divided into the anterior fibromuscular stroma (devoid of glandular tissue), transition zone, central zone, periurethral zone and peripheral zone. The base of the prostate is located superiorly and contiguous with the bladder neck whereas, the apex of the prostate is located at the inferior aspect continuous with the striated muscles of the urethral sphincter. The neurovascular bundle is seen to course near the posterolateral aspect of prostate, which is a preferential route of tumour spread. The prostate appears as a cone-shaped organ and shows uniform low echogenicity (Fig. 11.2.1.6). The outer gland (central and peripheral zones) is generally more echogenic than the inner gland.

FIG. 11.2.1.6 Ultrasound prostate. (A) Transabdominal and (B) TRUS images. The transition and central zones of the prostate have similar MR signal intensity and cannot be differentiated, hence, are collectively referred as the central gland. On T2-weighted MR images, the normal peripheral zone is homogeneously hyperintense, whereas the central gland tissue is typically hypointense or isointense compared to the skeletal muscle (Fig. 11.2.1.7). The capsule and the anterior fibromuscular stroma appear hypointense on T2weighted MR images.

FIG. 11.2.1.7 T2-weighted MR image of prostate showing peripheral (P) and central (C) glands with hypointense capsule (Ca – arrow). The SVs are seen as septate tubular cystic structures, appearing uniformly anechoic in US, above the prostate with distal portion of VD is seen medial to it. The duct of SV and VD joins to form the ejaculatory duct, which drains into the prostatic urethra via verumontanum. SVs show ‘bow-tie’ appearance in transversal scans, and a club or tennisracket shape in longitudinal scans (Fig. 11.2.1.8). On MR, SVs are seen as elongated fluid-containing structures with thin septa, which is hypointense on T1 and hyperintense on T2-weighted MR images (Fig. 11.2.1.9). The VD is seen as a tubular structure with low signal intensity in both T1- and T2weighted images, on either side. The dilated distal portion of VD (ampulla), appears hyperintense on T2-weighted images, similar to that of the SV due to the fluid content (Fig. 11.2.1.10).

FIG. 11.2.1.8 TRUS image showing bow tie appearance of seminal vesicle (SV).

FIG. 11.2.1.9 MR images of SVs. (A) T1-weighted image and (B) T2-weighted image.

FIG. 11.2.1.10 T2-weighted MR image of vas deferans (VD) and ampulla of vas (A). The penis, being a superficial organ, is usually examined with US, although MRI is reserved as problem solving modality. The penile body contains two paired muscles – corpora cavernosa and a corpus spongiosum. The former performs as a main erectile body while the latter contains the penile urethra (Fig. 11.2.1.11). Dartos fascia forms the outer layer and the Buck fascia forms the inner layer, which contain the deep dorsal vein (DDV) and a paired dorsal neurovascular bundle.

FIG. 11.2.1.11 US image of penis showing paired corpora cavernosa (Cc) and corpora spongiosum (Cs). The corpus spongiosum and corpora cavernosa are of high signal intensities on T2-weighted MR images and intermediate-low signals on T1weighted MR images. The tunica albuginea being a fibrous sheath, surrounds all the three muscles, is hypointense on all sequences (Fig. 11.2.1.12).

FIG. 11.2.1.12 T2-weighted MR images of penis showing paired corpora cavernosa (Cc) and corpora spongiosum (Cs). 1 1 .2.2

IMAGING ANATOMY OF FEMALE REPRODUCTIVE SYSTEM Saranya

The female reproductive system comprises of uterus, cervix, fallopian tubes, ovaries, vagina and vulva. Ultrasonography (transabdominal and transvaginal) is the primary imaging modality of choice for imaging the female pelvis. Computed tomography (CT) is less often used for pelvic imaging. It provides a quick and systematic overview with coverage of the abdomen in the same session. Hence, CT is well suited for staging pelvic cancers and for imaging gynaecologic and nongynaecologic diseases presenting with acute abdominal pain. Pelvic anatomy is well demonstrated by magnetic resonance imaging (MRI). The contrast resolution of T2weighted images form the basis for superb tissue characterization of MRI.

Uterus Uterus is a thick-walled fibromuscular organ composed of myometrium and endometrium. It has two major divisions, namely, the body (corpus) and cervix. The fundus lies above the ostia of fallopian tubes. The normal uterus measures between 5 and 9 cm in length and is in an anteverted position, in relation to the urinary bladder. The myometrium shows three layers on USG, a compacted thin, hypoechoic inner layer forms subendometrial halo, a thicker, homogenously echogenic middle layer and a thinner, hypoechoic outer layer (peripheral to arcuate vessels). The appearance of the endometrium varies with the phase of the menstrual cycle. It appears as a thin echogenic line early in the proliferative phase and shows hypoechoic thickening (4–8 mm) as proliferative phase progresses. It shows a triple layer (sandwich or trilaminar) appearance in the mid cycle and may measure up to 12–16 mm. During secretory phase after ovulation, the layers are seen hyperechoic due to the increasing complexity of glandular structure and secretions (Fig. 11.2.2.1).

FIG. 11.2.2.1 (A) Sagittal and (B) axial ultrasound images of female pelvis shows uterus and cervix with thick echogenic endometrium (arrow). Postmenopausally, the endometrium decreases in thickness. Endometrial thickness of 5 mm is taken as cut-off. Women on hormonal therapy acceptable endometrial thickness is up to 8 mm. Three-dimensional US permits multiple views to be reconstructed from a single sweep through the uterus. Sonohysterogram is the study of choice for detailed evaluation of the endometrial cavity pathologies.

The cervix begins at the inferior narrowing of the uterus (isthmus) at the internal os, which is identified by the entrance of uterine vessels. It has supravaginal and vaginal portions. It is 3–4 cm long and shortens after childbirth. In premenarche women, cervix is larger than corpus, forming approximately 2/3 of the uterine mass. During menarche, there is preferential growth of the corpus and in nulliparous women, corpus and cervix are roughly equal, whereas in parous woman, corpus forms approximately 2/3 of the uterine mass. Uterus is an extraperitoneal organ. The peritoneum extends over urinary bladder dome to anterior uterus, forming anterior cul-de-sac (vesicouterine pouch) and posteriorly, the peritoneum extends more inferiorly to the upper portion of vagina, forming the posterior cul-de-sac (pouch of Douglas, rectouterine pouch), which forms the most dependent portion of the female pelvis. Supporting ligaments of the uterus comprise mainly of broad ligaments, which extend laterally to the pelvic wall and round ligaments, which arise from uterine cornu near fallopian tubes to course anteriorly, pass through the inguinal canal to insert on the labia majora. Connective tissue thickening at the base of the broad ligament forms the uterosacral ligaments posteriorly, cardinal ligaments laterally and vesicouterine ligaments anteriorly. CT examination displays the uterus as a triangular or ovoid soft tissue structure behind the urinary bladder (Fig. 11.2.2.2). Following the administration of intravenous contrast, there is enhancement of myometrium that helps to delineate the endometrium. The vagina, cervix and corpus can be differentiated by morphological characteristics and enhancement pattern. The uterine corpus is typically triangular, whereas cervix is more rounded. The vagina has an appearance of flat rectangle at the level of fornix. The broad ligament and round ligaments are seen coursing laterally and anteriorly, respectively.

FIG. 11.2.2.2 Normal uterus and ovaries. (A) Axial CT image showing normal uterus ( white arrow) and bilateral ovaries ( yellow arrows). (B) Sagittal CT image showing normal uterus ( red arrow). (C) Coronal CT images showing normal uterus ( red arrow) and bilateral ovaries ( yellow arrows). The main source of vascular supply to uterus is from the uterine arteries. The uterine arteries pass within the broad ligament to enter the uterus, adjacent to the lateral fornices. The uterine artery passes over the ureter at the level of the cervix. Then it courses superiorly, along the lateral margin of the uterus and anastomoses with the ovarian artery. Uterine arteries give rise to arcuate arteries, which run in the outer third of myometrium. Radial

arteries extend through the myometrium, which terminate as spiral arteries in the endometrium. The venous system parallels the arterial system, forms a complex venous network in the parametrium and drains to the iliac veins. Middle and lower thirds of the uterus are drained by obturator, parametrial and paracervical lymph nodes. Lymphatic drainage from the upper corpus and fundus goes to the common iliac and paraaortic lymph nodes. MRI provides a more comprehensive view of the uterine anatomy. On MRI, the uterus and cervix show uniform low to intermediate signal on T1weighted images. On T2-weighted images, uterus shows three distinct zones, namely high signal endometrium, low signal junctional zone and intermediate signal myometrium (Fig. 11.2.2.3). The normal thickness of the junctional zone varies from 2 to 8 mm. A thickness of 9 to 12 mm is equivocal and greater than 12 mm is abnormal. Both endometrium and junctional zone become thin with oral contraceptive intake. Endometrial atrophies and the junctional zone is absent in postmenopausal women.

FIG. 11.2.2.3 Normal uterus and ovaries. (A) Axial T2-weighted MR image showing normal uterus ( red arrow) and bilateral ovaries ( yellow arrows). (B) Sagittal T2-weighted image showing normal uterus ( yellow arrow) and ovary. The endocervical canal shows high signal on T2-weighted images, whereas cervical stroma shows low signal, contiguous with the junctional zone. An outer layer of intermediate signal smooth muscle is present. Nabothian cysts representing obstructed, mucous secreting glands are commonly seen as low signal on T1-weighted images and high signal on T2-weighted images. Parametrium shows low to intermediate signal intensity on T1-weighted images and variable signal intensity on T2-weighted images. The round ligaments and uterosacral ligaments show low signal intensity, cardinal ligaments and associated venous plexuses show high signal intensity on T2weighted images.

Ovaries Ovaries are located posterolateral to the body of the uterus between the uterus and the pelvic sidewall. The internal iliac vessels lie immediately posterior to the ovary. Exact position is variable due to the laxity in the ligaments, parity, uterine size and position. On USG, medulla of the ovaries is mildly hyperechoic compared to the hypoechoic cortex. Developing follicles appear anechoic (Fig. 11.2.2.4). Corpus luteum may have a thick, echogenic ring and haemorrhage is common.

FIG. 11.2.2.4 Ultrasound image showing normal ovary with anechoic follicles and echogenic stroma. A normal ovary measures 30 mm in any two dimensions, but may measure 50 mm or more in one plane. The volume of the ovary can be estimated from the formula of an ellipsoid (0.5 × length × width × breadth) and is usually less than 10 cm cube. The appearance of normal ovaries depends on age, hormonal influence and phase of the menstrual cycle in women of reproductive age. On CT, ovaries are identified in premenopausal women by small cystic regions representing follicles, which punctuate the uniform soft tissue density. On MRI, ovaries show uniform intermediate signal with low signal follicles on T1-weighted images. On T2-weighted images, multiple high signal follicles of varying sizes are seen with a low signal intensity capsule (Fig. 11.2.2.5). The medulla shows higher signal intensity than the cortex. Haemorrhagic and corpus luteal cysts display high to intermediate signal on T1-weighted images and intermediate to high signal on T2-weighted images. Postmenopausal ovaries show homogenous low signal on T1- and T2-weighted images. Suspensory ligament of the ovary attaches ovary to the pelvic wall. Proper ovarian ligament (uteroovarian ligament) extends from ovary to uterine cornu.

FIG. 11.2.2.5 Sagittal T2-weighted MR image shows normal ovary with hyperintense follicles and hypointense capsule. Fallopian tubes The normal fallopian tubes are not routinely seen because of their small size and tortuous course. They are seen only when dilated and fluid filled. The fallopian tubes are approximately 6–10 cm long, with a variable degree of tortuosity. They comprise four segments. Interstitial or intramural portion, approximately 1 cm in length, is that portion of the tube, which traverses the uterine wall. Isthmus is the narrow portion of the tube, immediately adjacent to the uterus. Ampulla is the tortuous, ectatic portion contiguous with isthmus. Fertilization usually occurs in this portion of the tube. Infundibulum is the funnel-shaped opening, ringed by finger-like fimbriae. It is seen adjacent to the posterior surface of the ovary, allowing it to capture ovum after ovulation. Hysterosalpingography (HSG) is an imaging test whereby radioopaque contrast medium is instilled into the uterus and fallopian tubes. It is mainly used to evaluate infertility (e.g. tubal obstruction). Please see Fig. 11.1.7.1 in the chapter on Hysterosaliphingography.

Vagina The vagina is 7–9 cm long and is divided into three parts. The urethra defines the lower third, the urinary bladder base and the middle third and the fornices, the upper third. On transaxial scans, normal vagina has an ‘H’ shape. On T2-weighted images, the outer fibromuscular wall is of low signal intensity and it encompasses a central high signal intense area, consisting of mucosa and intraluminal secretions.

Vulva The vulva includes the mons pubis, labia majora and minora, prepuce, frenulum, clitoris and vestibule. The vagina, orifices of various glands including Bartholin’s glands, and the urethral meatus open into the vestibule. 1 1 .2.3

IMAGING ANATOMY OF THE PERITONEAL SPACES Mohideen Ashraf A. ‘Imagination is more important than knowledge’. Albert Einstein

Embryology During embryologic development, the intraembryonic coelom (coelomic cavity) is partitioned to give rise to the three major body cavities (pleural, pericardial and peritoneal cavities). The coelomic cavity is lined by a serous membrane. The area subjacent to the serous membrane is called the subserous space. This subserous space which is referred to as the subperitoneal or extraperitoneal space in the abdomen and the subpleural or extrapleural space in the thorax is made up of loose areolar tissue. Let us imagine the peritoneal cavity as an inflated balloon that fills the abdomen and is lined by peritoneum. There are no organs within the peritoneal cavity per se and it is not normally visualized during axial imaging. All the organs lie within the subperitoneal/extraperitoneal space in the posterior abdomen and with continued growth, some of the organs push into the peritoneal cavity from behind, without actually entering it. In the process, these organs become wrapped with peritoneum that is now referred to as visceral peritoneum. The visceral peritoneum is continuous with the parietal peritoneum lining the abdominal wall. The parietal peritoneum dips inferiorly to cover the bladder dome and upper third of the rectum, in addition to the uterus in females. The peritoneum is not normally visualized on imaging, unless it is thickened due to various pathologies. During development, the primitive gut is suspended within the coelomic cavity by means of ventral and dorsal mesenteries that serve to divide the cavity into right and left cavities (Fig. 11.2.3.1). The mesenteries are essentially double-layered folds of visceral peritoneum with intervening

subareolar tissue and serve as conduits for blood vessels and lymphatics from the posterior abdominal wall.

FIG. 11.2.3.1 Diagrammatic representation of axial section through foetal abdomen. Parietal peritoneum is shown in blue, visceral peritoneum in green and body wall in brown. LIV: liver develops in ventral mesogastrium; S: spleen develops in dorsal mesogastrium; G: gut; RP: retroperitoneum. In the upper abdomen, while the spleen develops within the dorsal mesentery, the liver bud develops within the ventral mesentery. The area of liver at the coronary ligament is devoid of peritoneum. This is called the bare area. The liver is covered by peritoneum in most of its surface except the bare area where the peritoneum is reflected onto the diaphragm and retroperitoneum. Ascites cannot extend into the space between the bare area and the diaphragm – bare area sign. The visceral peritoneum invaginates into the liver parenchyma along named fissures on its visceral surface (Table 11.2.3.1).

TABLE 11.2.3.1 Fissures in Liver Visceral Surface

Embryology

Relevant Radiologic Anatomy

Fissure for ligamentum venosum

Obliterated ductus venosus

Separates caudate lobe from left lobe

Fissure for ligamentum teres

Obliterated umbilical vein

Divides left hepatic lobe into medial and lateral segments

Gallbladder fissure

Shallow fissure divides liver into right and left lobes

Divides liver into right and left lobes

Invagination of the hepatic pedicle into liver hilum

Contains horizontal portion of right and left portal veins

Hilar fissure

Becomes widened in cirrhosis

Fissure for ligamentum venosum + fissure for ligamentum teres = umbilical fissure. As always fissure is lined by two layers of peritoneum. These fissures are continuous with the peritoneal cavity. The space between the two leaves is continuous with the subperitoneal space. The subperitoneal fat of the gastrohepatic ligament continues into the liver as Glisson capsule. The liver and spleen along with the attached peritoneal folds, rotate in a counterclockwise direction to occupy the right and left hypochondria. The primitive gut along with its mesentery also undergoes varying degrees of rotation. This creates double-layered folds of peritoneum variably referred to as omentum, ligament and mesentery (Fig. 11.2.3.2) (Table 11.2.3.2). Ligaments – holds the organs in place and are named according to the two structures they serve to connect. Omentum – folds associated with the stomach. Mesentery – in the fully formed foetus, specifically refer to the folds that suspend the small intestines from the posterior body wall.

FIG. 11.2.3.2 Axial contrast-enhanced CT (CECT) abdomen in a woman with tuberculous peritonitis. Visceral peritoneum is shown in green and parietal peritoneum in blue colour. Greater omentum is outlined in yellow and shows nodular infiltration.

TABLE 11.2.3.2 Various Ligaments in Abdomen Name of Embryology Attachments Peritoneal Fold SUSPENSORY LIGAMENTS OF LIVER Falciform ligament (Fig. 11.2.3.3)

Ventral part of ventral mesentery

Triangular ligaments (right and left)

Formed by convergence of superior and inferior reflections of coronary ligaments on both sides

Imaging Significance Umbilical vein collateral along its free edge separates the right and left subphrenic spaces

Right ligament is long and is attached posteriorly to diaphragm Left ligament extends from superior surface of left lobe to diaphragm

Right triangular ligament divides right perihepatic space into right subphrenic and right subhepatic spaces

LIGAMENTS OF STOMACH Gastrohepatic ligament (lesser omentum) (Figs 11.2.3.4 and 11.2.3.5)

Dorsal part of ventral mesentery

From the lesser curvature of stomach to the fissure for LV

Easily visualized on USG. In portal hypertension, left gastric collaterals can be visualized within this ligament.

Hepatoduodenal ligament (lesser omentum)

Dorsal part of ventral mesentery

From the first part of duodenum to the transverse fissure

Free edge contains portal vein, hepatic artery and common bile duct

Name of Peritoneal Fold

Embryology

Attachments

Imaging Significance

Gastrocolic ligament (greater omentum)

Dorsal mesentery below the level of spleen. Due to folding, it is made of four layers of visceral peritoneum.

From greater curvature of stomach to transverse colon

Strip of curvilinear fatty tissue just beneath the anterior abdominal wall

Phrenicocolic ligament

Supports the inferior pole of spleen

From splenic flexure to diaphragm

Separates supramesocolic space from left paracolic gutter

Transverse mesocolon

Dorsal mesentery

From the retroperitoneum along anterior surface of pancreas to transverse colon

Pancreatic processes can involve transverse colon (Fig. 11.2.3.6). For example, colon cut-off sign in acute pancreatitis

Small bowel mesentery

Dorsal mesentery

Extends obliquely from ligament of Treitz in left upper quadrant to ileocecal valve in right lower quadrant

Divides inframesocolic space – larger left inframesocolic space opens into pelvis Smaller right space is limited inferiorly by junction of mesentery with ascending colon

Name of Peritoneal Fold Sigmoid mesocolon

Embryology

Attachments

Sigmoid colon to posterior abdominal and pelvic walls

Left ureter courses underneath

Imaging Significance There is holdup of ascitic fluid at the level of sigmoid mesocolon on left side, before overflowing into the pelvis

FIG. 11.2.3.3 Longitudinal sonogram through liver in a patient with portal hypertension shows recanalized umbilical vein (UMBV.) running along the free edge of falciform ligament (FL).

FIG. 11.2.3.4 Transverse section through upper abdomen in patient with ascites shows gastrohepatic ligament (GHL) outlines above and below by fluid in the greater and lesser sacs, respectively.

FIG. 11.2.3.5 Transverse USG image through upper abdomen shows gastrohepatic ligament (GHL) extending from stomach (STO) to insert into fissure for ligamentum venosum (FLV). Fissure for ligamentum teres (FLT).

FIG. 11.2.3.6 Axial section plain CT through the epigastrium shows inflamed pancreas within the anterior pararenal space (APS). Inflammation also is seen tracking into through transverse mesocolon (TMC) into transverse colon (TC).

FIG. 11.2.3.7 Coronal MPR in a woman with ascites. Observe that the right perihepatic spaces (RPHS) are continuous inferiorly with the right paracolic space (RPCS) and communicate with the pelvis. On the left side, the sigmoid mesocolon (SMC) separates the left paracolic space from the pelvis. At the level of spleen, the ventral part of the dorsal mesentery becomes the gastrosplenic ligament and the dorsal part of the dorsal mesentery becomes the splenorenal ligament. Above the level of spleen, the dorsal mesentery gives rise to gastrophrenic ligament and below the level of spleen, it gives rise to gastrocolic ligament. Peritoneal cavity is divided by the transverse mesocolon into supramesocolic and infracolic compartments (Tables 11.2.3.3–11.2.3.4). Rest of the peritoneal folds serve to further compartmentalize the peritoneal cavity, albeit incompletely. The peritoneal reflections also form blind alleys where disease processes tend to lodge.

TABLE 11.2.3.3 Supramesocolic Spaces Name of the Space Boundaries

Radiologic Significance

RIGHT PERIHEPATIC SPACE ( FIG. 11.2.3.7) Right subphrenic space (anteriorly located)

Between diaphragmatic surface of liver and diaphragm; limited superiorly by superior leaf of right coronary ligament

Right subhepatic space (posteriorly located)

Between visceral surface and the right kidney; limited superiorly by inferior leaf of right coronary ligament

Pelvic collections tend to ascend along right paracolic gutter to reach right subhepatic space

LEFT PERIHEPATIC SPACES – SURROUND LEFT LOBE OF LIVER ( FIG. 11.2.3.7) Left subphrenic space

Between gastric fundus and diaphragm

Left subhepatic space

Between visceral surface of left lobe of liver and stomach

Left perisplenic space Lesser sac – relatively secluded space that communicates with rest of peritoneal cavity through epiploic foramen

Perforated gastric ulcers

Splenic abscess, haematoma Bounded anteriorly by the lesser omentum and stomach and posteriorly by the pancreas. On the left side, it is bounded by the gastrosplenic and lienorenal ligaments. Superior recess surrounds the caudate lobe

Collections localized to this space result from pancreatitis, perforated gastric ulcers

TABLE 11.2.3.4 Inframesocolic Spaces Right infracolic space

Smaller and to the right of mesentery

Limited inferiorly by the attachment of mesentery to ascending mesocolon

Left infracolic space

Larger and to the left of mesentery

Limited by sigmoid mesocolon

Right paracolic gutter (Fig. 11.2.3.7)

Lateral to ascending colon and is wide

Communicates freely with pelvic spaces below and with right subhepatic space above

Left paracolic gutter (Fig. 11.2.3.7)

Lateral to descending colon and is shallow

Limited superiorly by phrenicocolic ligament. So does not communicate with supramesocolic space.

Posterior pelvic spaces

Rectouterine pouch is the most dependent area of peritoneal cavity in both supine and erect postures

Pelvic spaces – communicate freely with one another. Rectovesical pouch (males) Rectouterine pouch and uterovesical pouch (females) Paravesical spaces

Lateral pelvic spaces

Due to the differential growth of the small bowel, the colon is pushed to the periphery. This causes the ventral mesentery to regress below the level of transverse colon. There is a dynamic flow of fluid in the peritoneal cavity that is determined primarily by the peritoneal attachments, under the influence of gravity. Adhesions resulting from inflammatory processes, however tend to cause localized collections. Loculated ascites in the hepatic fissures may be mistaken for liver cysts/abscess. Similarly, peritoneal seeding of metastasis along with the fissures (considered stage 3 disease) should not be mistaken for parenchymal metastasis (qualifies for stage 4 disease).

The normal flow of fluid within the peritoneal cavity determines the intraperitoneal seeding of neoplasms. The sites mostly involved by peritoneal seeding are the pouch of Douglas, the right paracolic gutter and the right lower quadrant at the inferior junction of the small bowel mesentery. Negative subdiaphragmatic pressures during respiration cause pelvic collections to ascend along the paracolic gutters and reach the perihepatic spaces. 1 1 .2.4

NORMAL VARIANTS OF PROSTRATE Akash Kumar B.Y.

Prostate agenesis, hypoplasia and ectopia Prostate agenesis is frequently associated with deficiency of 5-alphareductase and testicular feminization (Fig. 11.2.4.1).

FIG. 11.2.4.1 Agenesis of prostate. (A) Axial T2weighted MR image shows an empty prostate fossa. (B and C) Coronal and sagittal T2-weighted MR images show the absence of prostate around the prostatic urethral segment. Prostatic hypoplasia is seen in Prune belly syndrome with dilated prostatic urethra. Ectopic prostate can be located in bladder, urethra, seminal vesicle, epididymis or testis.

Prostatic utricle cyst Prostatic utricle cysts represent embryologic remnant of Müllerian duct system. They communicate with the urethra and result in postvoid dribbling. They may become infected and contain pus or haemorrhage. On transrectal ultrasound, they are seen as anechoic cystic cavity in the midline, posterior to the urethra. Magnetic resonance imaging (MRI) shows hyperintense signal on T2-weighted images and hypointensity on T1-

weighted images (Fig. 11.2.4.2). If associated with infection or haemorrhage, may show hyperintensity on T1-weighted images.

FIG. 11.2.4.2 Prostatic utricle cyst. (A) Axial T2weighted MR image shows a hyperintense midline cyst in the prostate. (B) Sagittal T2-weighted MRI shows the cyst not extending above the base of prostate. (Source: Courtesy of Dr. Reginald Wesley.)

Müllerian duct cyst Müllerian duct cyst is the result of focal dilatation of mesonephric duct due to the failure of regression. They may be associated with renal agenesis. They are usually asymptomatic, but may sometimes cause urinary infection, impairment of ejaculation, etc. On imaging, they are seen as anechoic cystic cavity in the midline on transrectal ultrasound posterior to the urethra and extend above the base of prostate. MRI appearance is similar to prostatic utricle cyst. They do not show communication with the urethra unlike prostatic utricle cysts (Fig. 11.2.4.3) (Table 11.2.4.1).

FIG. 11.2.4.3 Müllerian duct cyst. (A) Axial STIR MR image shows a hyperintense midline cyst in the prostate. (B and C) Coronal and sagittal STIR MRI shows the cyst extending above the base of prostate.

TABLE 11.2.4.1 Differentiating Features Between Prostatic Utricle Cyst and Müllerian Duct Cyst Prostatic Utricle Cyst Embryologic remnant of Müllerian duct system Communicate with the urethra Does not extend above the base of prostate Spermatozoa present

Müllerian Duct Cyst Failure of regression and focal saccular dilatation of Müllerian duct Does not communicate with urethra Extend above the base of prostate Spermatozoa absent

Seminal vesicle agenesis Seminal vesicle agenesis is a rare anomaly with an incidence of about 0.08%. It can be either unilateral or bilateral. Bilateral agenesis is most commonly associated with cystic fibrosis due to thick secretions obstructing the lumen. Unilateral agenesis is commonly associated with ipsilateral renal agenesis. It is asymptomatic in most of the cases, but may cause infertility. On imaging, there will be nonvisualization of the seminal vesicle posterior to prostate. It ponders to look for associated renal anomalies.

Congenital seminal vesicle cyst It can be either congenital or acquired. Its incidence is about 0.005%. It is also most commonly associated with ipsilateral renal agenesis. Zinner syndrome is a rare entity characterized by renal agenesis, ipsilateral seminal vesicle cysts and ejaculatory duct obstruction. It is attributed to the common embryologic origin of mesonephric duct and ureteral bud. Cysts 12 mm) may cause symptoms like dysuria, frequency, recurrent infection, painful ejaculation and infertility. MRI is the imaging modality of choice, which shows hypointensity on T1weighted images and hyperintensity on T2-weighted images (Fig. 11.2.4.4). If there is bleeding or infection of the cyst, it shows hyperintensity on T1weighted images.

FIG. 11.2.4.4 Seminal vesicle cyst. (A to C) Axial, coronal and sagittal T2-weighted MR images show a hyperintense cyst in the left seminal vesicle. Differential diagnosis includes prostatic utricle cyst, Müllerian duct cyst, abscess, ureterocele or lymph nodes. The differentiation feature of seminal

vesicle cyst is its paramedian location (Fig. 11.2.4.5) and association with renal anomalies. Symptomatic cases may be treated with aspiration or surgical excision.

FIG. 11.2.4.5 Various Cysts in prostate and seminal vesicle. 1 1 .2.5

NORMAL VARIANTS OF SCROTUM Akash Kumar B.Y.

Cryptorchidism Cryptorchidism is defined as absence of testis in the scrotum. It may be present anywhere along the path of testicular descent from the level of kidney to the scrotal sac. The testicular migration is usually completed by 30 weeks of gestation. It is associated with syndromes like Prader–Willi syndrome, Noonan syndrome and Prune belly syndrome. Ultrasound is the imaging modality of choice for localization of testis. It shows a homogeneous hypoechoic ovoid structure with echogenic mediastinum, but ultrasound is limited in intraabdominal, pelvic or retroperitoneal locations. Magnetic resonance imaging (MRI) has higher sensitivity than ultrasound in the localization of testis. They show low signal on T1-weighted images and high signal on T2-weighted images. It is treated by orchiopexy after the age of 1 year, because the descent may occur anytime up to 1 year of age. Untreated cases have a higher risk of

developing germ cell tumour.

Polyorchidism, monorchidism and anorchia Polyorchidism, also known as supernumerary testis is defined as presence of more than two testis. The extra testicle is more commonly seen on the left side. It is a risk factor for torsion and malignancy of testis. It is managed by yearly ultrasound and orchidectomy is done if malignancy is suspected during the course of the follow-up. Monorchidism is the presence of a single testis. It is more often seen on the left. Anorchia also known as ‘vanishing testis syndrome’. It refers to the absent testicular tissue.

Congenital absence of vas deferens Congenital absence of vas deferens is encountered in around 1.3% of infertile men. It is most commonly seen in association with cystic fibrosis due to mutation in cystic fibrosis transmembrane conductance regulator gene. The embryological origin of vas deferens, seminal vesicles and epididymis are the same; therefore, agenesis of vas deferens is most commonly associated with anomalies of seminal vesicles and epididymis. It may also be associated with ipsilateral agenesis of kidney. Ultrasound can be used to identify agenesis of vas deferens. MRI is better to evaluate for other associated anomalies of seminal vesicles, epididymis and kidney. 1 1 .2.6

NORMAL VARIANTS OF URETHRA Akash Kumar B.Y.

Posterior urethral valve It is the most common cause of bladder outlet obstruction in a child. They are of three types (Fig. 11.2.6.1): Type 1: It is the most common variant. It is characterized by the presence of two mucosal folds that extend from the verumontanum and fuse anteroinferiorly at a lower level. Type 2: It is characterized by the presence of mucosal folds that extend posterolaterally along the urethral wall from urethral orifice to verumontanum. Type 3: It is characterized by the presence of circular diaphragm with an opening centrally in the membranous urethra. It is located below the verumontanum and is the result of abnormal canalization of urogenital membrane.

FIG. 11.2.6.1 Posterior urethral valve types. Diagnosis is made on voiding cystourethrography (VCUG), which shows dilated posterior urethra with bladder neck hypertrophy and trabeculation/sacculation of the bladder. It is now termed as ‘congenital obstructive posterior urethral membrane’. Antenatal ultrasound may show keyhole sign due to distension of bladder and posterior urethra proximal to the valve. Severe cases may be associated with oligohydramnios and renal dysplasia. Treatment consists of transurethral ablation of the valve. Prune belly syndrome Prune belly syndrome, which is additionally referred to as ‘Eagle–Barrett syndrome’, is characterized by the deficiency/underdevelopment of abdominal wall muscles, bilateral cryptorchidism and dilatation of ureter and pelvicalyceal system. Antenatal ultrasound shows disproportionately distended abdomen with gross dilatation of urinary bladder and ureters. Posterior urethra is not dilated, and presence of this finding rules out the diagnosis of Prune belly syndrome. There may be associated cystic renal dysplasia and oligohydramnios. This condition has to be differentiated from posterior urethral valve, which shows dilatation of posterior urethra. The other differential is megacystismicrocolon-intestinal hypoperistalsis syndrome, which shows polyhydramnios. Urethral duplication Urethral duplication is a rare congenital anomaly. It is characterized by two urethras, with either partial or complete duplication. It is classified into three types in males (Fig. 11.2.6.2): Type I: Incomplete urethral duplication with accessory urethra ending blindly. Type II: Accessory urethra is completely patent.

Type III: Duplicated or septated bladders giving rise to accessory urethra.

FIG. 11.2.6.2 Effman classification of urethral duplication. The accessory urethra may be either dorsal or ventral to the normal urethra. Rarely they communicate with the seminal vesicles and prostatic ducts. In females, it is classified into five types: Type 1: Double urethra with double bladder. Type 2: Double urethra with single bladder. Type 3: Accessory urethra posterior to the normal urethra. Type 4: Double proximal urethra with single distal urethra. Type 5: Single proximal urethra with distal urethral duplication. They can be diagnosed by VCUG or magnetic resonance imaging (MRI). Megalourethra Congenital megalourethra is a rare anomaly resulting from faulty development of corpora cavernosa and spongiosum. It is characterized by diffuse anterior urethral dilatation. They are of two types (Fig. 11.2.6.3):

FIG. 11.2.6.3 Megalourethra types. Scaphoid megalourethra, which occurs due to deficiency of corpus spongiosum. Fusiform megalourethra is the more severe form with deficiency of corpora cavernosa and corpus spongiosum. Anterior urethral valve and diverticulum Anterior urethral valve is characterized by the presence of a semilunar fold that arises from the floor of anterior urethra and directed posteriorly. Anterior urethral diverticulum is characterized by a saccular outpouching, which is seen arising from the ventral surface of anterior urethra. It most commonly arises from the bulbar urethra. Anterior urethral diverticulum can be differentiated from valve by the presence of posterior lip in diverticulum which is absent in valve. Hypospadias Hypospadias is the most common urethral anomaly. It is characterized by the opening of the meatus on the ventral surface of the urethra (Fig. 11.2.6.4). It is commonly associated with dorsal chordee.

FIG. 11.2.6.4 Hypospadias and epispadias. Epispadias

Epispadias is characterized by the opening of meatus on the dorsal surface of urethra (Fig. 11.2.6.4). It can be seen as a part of exstrophy–epispadias complex. It is classified into three types in males: Glandular, penile and complete. In females, it is classified into three types: Clitoric, subsymphyseal and complete. Congenital urethral polyp Congenital urethral polyps are usually seen to arise from verumontanum near the bladder base as an elongated pedunculated polypoid lesion. It may cause recurrent urinary obstruction. VCUG shows a lucent filling defect which moves downward during micturition. Congenital rectourethral fistula It is characterized by fistulous communication between the anterior wall of rectum and the posterior urethra. There is narrowing and stenosis of urethra distal to the fistula causing poor stream of urine.

11.3: Nomogram (which plane, where, in tables) P. Reginald Wesley

Nomograms in female reproductive system The imaging appearance of the uterus and ovaries depend on age and sexual maturation of the individual as they are under hormonal influence. Furthermore, the endometrium and ovaries vary their appearance depending on the time of imaging during the menstrual cycle. Uterus and cervix How to measure the uterus? Fig. 11.3.1 shows the technique of measuring the uterus. Uterine length is more accurately measured with transabdominal ultrasound compared to transvaginal scan where the cervix may not be included within the field of view. Table 11.3.1 shows the normal uterine length and size ratio between the uterus and cervix in various age groups.

FIG. 11.3.1 First, the sagittal image of the uterus is taken. Length is measured from the outer margin of the fundus up to the external os of the cervix. Depth (anteroposterior diameter) is measured from the most anterior to the posterior margin of the uterine walls perpendicular to the length. The probe is then rotated 90 degrees to the sagittal plane. In transverse image, the maximum width of the uterus is measured. TABLE 11.3.1 Normal Uterine Length and Size Ratio Between the Uterine Body and Cervix Uterine Length (cm)

Uterine Body to Cervix Ratio

Neonatal

3.5

2:1

Paediatric

1–3

1:1

3–4.5

1–1.5:1

Pubertal

5–8

1.5–2:1

Reproductive

8–9

2:1

3.5–7.5

1–1.5:1

Stage

Prepubertal

Postmenopausal

How to measure the endometrium? Optimally assessed by transvaginal ultrasound. It represents the sum of the thickness of the two endometrial layers. To measure the

endometrium, first the midline longitudinal image of the uterus is taken. Then place the cursor at the interface between the endometrium and the myometrium at the anterior and posterior walls of the uterus. Fig. 11.3.2 shows the appearance of the endometrium in various stages of menstrual cycle. The measurement is preferably taken at the fundal region with widest endometrium (Fig. 11.3.3).

FIG. 11.3.2 Transvaginal ultrasound images showing the endometrium in various stages of menstrual cycle. (A) Menstrual phase, (B) proliferative phase, (C) LH and ovulatory phase, (D) secretary phase and (E) postmenopausal endometrium.

FIG. 11.3.3 Transvaginal ultrasound showing the technique of measuring the endometrium.

The echogenic line at the centre denotes the interface where the anterior endometrial layer opposes the posterior endometrial layer. The hypoechoic layer peripheral to the endometrium represents the inner layer of myometrium and should not be included while measuring the endometrial thickness. Table 11.3.2 shows the endometrial thickness and appearance in different stages of menstrual cycle. TABLE 11.3.2 Endometrial Thickness and Appearance Endometrial Stage Thickness Appearance (mm) Menstrual phase (days 4.6 Mildly echogenic 1–4) Proliferative phase 4.6–12.4 Mildly echogenic (days 5–13) Luteinizing hormone 12.4 Striated with an inner (LH) surge (12–48 h hypoehoic and a before ovulation) peripheral more hyperechoic layer Ovulatory phase (days Decreases Striated with an inner 13–16) slightly hypoehoic and a peripheral more hyperechoic layer Secretary phase (days Increases by 2 Thick and hyperechoic 16–28) mm Postmenopausal 1–2 Thin hyperechoic line or band

Ovaries Technique of scanning Ideally, transvaginal ultrasound is better because of its higher resolution especially in the assessment of polycystic ovaries. However, transabdominal scan has its use in adolescent girls and virginal women. It is also useful in cases of displaced ovaries. Fig. 11.3.4 shows the technique of measuring the ovarian volume.

FIG. 11.3.4 Ovarian volume measurement is performed using the simplified formula for a prolate ellipsoid: Ovarian volume = length × width × thickness × 0.5. While measuring the volume in transabdominal scan, urinary bladder should be adequately distended. However, care should be taken not to over distend the bladder as it may compress the ovaries leading to incorrect measurement of the size. Bladder distension is not required for transvaginal ultrasound. Table 11.3.3 shows the appearance and size of ovaries in various age groups. TABLE 11.3.3 Normal Ovarian Volume and Appearance Stage

Ovarian Volume (cc)

Neonatal

1–3.5

Paediatric

0.5–1.5

Appearance Follicles and cyst common

Prepubertal

1–4

Fewer than six follicles, cysts uncommon Follicles and cysts common

Pubertal

2–6

Follicles and cysts common

Reproductive

4–16

Follicles and cysts common

1.2–5.8

Follicles and cysts in about 15%–20%

Postmenopausal

Polycystic ovarian syndrome According to the technical recommendation for the assessment of polycystic ovaries as per 2003 Rotterdam PCOS consensus: Time of performing ultrasound:

Women who have regular menstrual cycles – early follicular phase between days 3 and 5. Women who are oligomenorrheic or amenorrheic – random or between 3 and 5 days after inducing withdrawal bleeding following progestin administration. Estimation of the number of follicles – done in both longitudinal and anteroposterior planes of the ovaries. The follicles which measure less than 10 mm, their size should be given as the average of the two diameters measured in each plane. Criteria for diagnosis of PCOS Presence of 12 or more follicles in each ovary measuring 2–9 mm in size and/or ovarian volume of more than 10 mL. Ovarian volume is a surrogate measurement for stromal hypertrophy. The presence of a single polycystic ovary is sufficient for the diagnosis of polycystic ovary syndrome (PCOS). How to measure antral follicle count and size? Measurement of the number of follicles (antral follicle count) should be done in longitudinal plane. Measurement of the size and distribution of the antral follicles should be done in orthogonal plane. Average of two orthogonal measurements is used for antral follicle diameter. Ovarian and stromal areas In PCOS, there is ovarian androgenic dysfunction, which leads to stromal hypertrophy. This is called hyperthecosis where there is enlarged ovaries with increased stromal thickness and echogenicity without mature follicles. This is indicated by the stromal area. How to measure the stromal and ovarian areas? To measure the areas, first the stroma is identified which is represented by the central echogenic area of the ovary. Using the callipers, this central area is measured along with its outer margin. Then the total area of the ovary is measured by placing the callipers along with the outer margin of the ovary (Fig. 11.3.5).

FIG. 11.3.5 Ultrasound image showing the technique of measuring the (A) ovarian area and (B) stromal area. The ratio of stromal area to the ovarian area is calculated by taking the mean value of the stromal and ovarian areas of both ovaries (S/A ratio). A ratio of 0.34 or more had the highest correlation with PCOS. Multifollicular ovary Ovary with six or more follicles of 4–10 mm size with normal stroma. It is seen in early follicular phase, puberty, hyperprolactinaemia, hypothyroidism and hypothalamic amenorrhoea (Fig. 11.3.6).

FIG. 11.3.6 Transabdominal ultrasound image showing enlarged multifollicular ovary with normal stroma.

Pelvic congestion syndrome Normal diameter of the pelvic veins on ultrasound is less than 4 mm. In pelvic congestion syndrome, the diameter of the veins is greater than 6 mm in diameter. Velocity is less than 3 cm/s or has reversed flow (Fig. 11.3.7).

FIG. 11.3.7 Transabdominal ultrasound image showing dilated periuterine and paraovarian veins measuring 6 mm in maximum diameter. Fallopian tubes The fallopian tubes extend from the ovaries to the uterus along the superior edge of the broad ligament (Fig. 11.3.8).

FIG. 11.3.8 Transabdominal ultrasound image showing the left fallopian tube.

Normal size Length – 10–15 cm. Diameter – 1–4 mm. Parts of the fallopian tube From the uterus to the lateral aspect Interstitial or intramural segment Isthmus Ampulla Infundibulum Fimbriae Congenital uterine anomalies How to differentiate septate and bicornuate uterus? In ultrasound A line is drawn between the two tubal ostia. Then the distance between this line and the apex of the fundal contour is measured as shown in Fig. 11.3.9A and B.

FIG. 11.3.9 Schematic representation showing distinction between septate and bicornutate uterus. The technique can be used in 3D ultrasound and MRI. When the distance is more than 5 mm, it is septate uterus. When the fundal contour is below this line or the distance is less than 5 mm, it is bicornuate uterus. In hysterosalpingogram Here the intercornual distance and angle and the fundal cleft are measured (Fig. 11.3.10).

FIG. 11.3.10 Schematic representation showing distinction between septate and bicornutate uterus based on intercornual angle. In bicornuate uterus: Intercornual distance >4 cm Intercornual angle >105° Fundal cleft >1 cm

Nomograms in male reproductive system How to measure the testis?

Patient is in the supine position with the thighs and scrotum exposed. The penis is supported over the patient’s abdomen. Thighs can be adducted to support the scrotum. The examination should be done gently without using undue pressure on the probe while measuring the testicular size as compression may underestimate the size (Fig. 11.3.11).

FIG. 11.3.11 Technique to measure the volume of the testis. Volume of the testis is calculated using the formula: Testicular volume = length × width × height × 0.71 Normal volume Total volume (both testes) – 30 mL. Single testicular volume – 12–15 mL. Testicular atrophy Volume of the affected testis is 50% less than the volume of the unaffected testis as shown in Fig. 11.3.12.

FIG. 11.3.12 Longitudinal and transverse images of the testes showing atrophy. Testicular volume in obstructive azoospermia – 11.6 mL (7.7– 25.8 mL). Testicular volume in nonobstructive azoospermia – 8.3 mL (1.2– 16.4 mL). Testicular microlithiasis Identified on ultrasound by the presence of multiple tiny echogenic foci in testes without posterior acoustic shadowing (Fig. 11.3.13).

FIG. 11.3.13 B-mode scrotal ultrasound image of the testis in transverse and longitudinal sections showing few echogenic foci of 1–2 mm size without posterior acoustic shadowing suggestive of limited type of testicular microlithiasis. Classic type Presence of five or more microliths in one ultrasound image. Limited type Presence of fewer than five microliths in all the images. Epididymis Consists of head, body and tail. The epididymis measures 6–7 cm in length. Epididymal head measures 5–12 mm. Body measures 2–4 mm. Tail measures 2–5 mm. Prostate How to measure the prostate? Can be measured in transabdominal ultrasound and transrectal ultrasound (TRUS). Technique of measuring prostate volume is shown in Fig.11.3.14.

FIG. 11.3.14 The transverse diameter is measured in the axial plane and the anteroposterior and longitudinal diameters are measured in sagittal plane. Grading of prostate enlargement based on volume Normal: 80 mL Intravesical prostatic protrusion It denotes the extent to which the enlarged prostate has protruded into the bladder lumen. It is measured in midsagittal image of prostate (Fig. 11.3.15).

FIG. 11.3.15 Midsagittal image of the prostate showing the technique to measure the intravesical prostatic protrusion. How to measure it? Take the midsagittal image of the prostate. Draw a line connecting the most anterior and posterior points in the base of the prostate. Draw another parallel line along the protruded prostate and measure the distance between the lines. It denotes the intravesical prostatic protrusion. Grading 10 mm

Grade I Grade II Grade III

Penis Thickness of the tunica albuginea: 0.8 mm in thickness at 5 o’clock position and 7 o’clock position just lateral to the corpus spongiosa to 2.2 mm in thickness at 1 o’clock position and 11 o’clock position.

During erection, the thickness is reduced to 0.5 mm. Table 11.3.5 shows the normal length and circumference of penis in flaccid and erect states. TABLE 11.3.4 Doppler Parameters of Cavernosal Artery Parameter Peak systolic velocity (PSV) End-diastolic velocity (EDV) Resistive index (RI)

Normal Borderline Abnormal >35 cm/s 25–35 cm/s 0.9

0.75–0.9

15 mm Ejaculatory duct diameter >2.3 mm Vas deferens diameter >5 mm Fig. 11.3.21 shows dilated ejaculatory duct and Fig. 11.3.22 shows dilated seminal vesicles with thickened walls due to seminal vesiculitis.

FIG. 11.3.21 TRUS parasagittal image showing dilatation of the right ejaculatory duct up to the verumontanum, which developed as a sequelae of seminal vesiculitis.

FIG. 11.3.22 TRUS image at the level of seminal vesicles showing bilateral dilated seminal vesicles with wall thickening (⇐) and fluid of increased echogenicity (⇓) within the dilated seminal vesicles. Seminal vesicle hypoplasia Width or = 4 defined as varicocele Grade 1 (Fig. 11.11.4.10)

0–9

FIG. 11.11.4.10 Grade 1. (A) At rest: no varicosities on standard USG. (B) During Valsalva: reflux in vessels noted during Valsalva. Grade 2 (Fig. 11.11.4.11)

FIG. 11.11.4.11 Grade 2. (A) At rest: small varicosities extending to superior pole of testis. (B) During Valsalva: small varicosities exhibiting reflux only Valsalva. Grade 3 (Fig. 11.11.4.12)

FIG. 11.11.4.12 Grade 3. (A) At rest: venous reflux evident in basal condition. (B) During Valsalva: venous diameter increases during Valsalva. Grade 4 (Fig. 11.11.4.13)

FIG. 11.11.4.13 Grade 4. (A) Venous reflux evident in basal condition. (B) Venous diameter does not increase during Valsalva. Greyscale ultrasonography will give a rough estimation of echotexture, calculate testicular volume, and establish parenchymal calcifications or tumours. Doppler ultrasound will give information concerning parenchymal flow on a macrovascular level. However, the amount of detail afforded by these studies is inadequate to find varicocele-induced damage to the testicular parenchyma. More modern advances together with real-time elastography and

contrast-enhanced ultrasonography have incontestable potential to correlate the presence of varicoceles to sonographic findings of testicular parenchymal injury and microvascular perfusion defects. Elastography involves postprocessing techniques to quantify testicular tissue stiffness supported measured strain. Findings such as increased tissue stiffness or loss of microvessel density might recommend early signs of testicular pathology. Though still investigational, these technologies may prove to be clinically useful in determining patients that may benefit from varicocele repair based on imaging findings. However, USG is not the modality of choice, CT may show a dilated cluster of enhancing serpiginous veins. Venography, which is often performed during endovascular treatment, might show dilatation of testicular vein, retrograde contrast flow towards the scrotum and the dilatation of pampiniform plexus must not be imaged directly, as the testes must be kept out of radiation. MRI show dilated enhancing serpiginous veins with signal intensity depending on the velocity of flow. Low-flow varicocele exhibit intermediate T1 and high T2 signals and high-flow varicocele exhibit flow voids. Varicocele show enhancement following gadolinium enhancement. Imaging Modalities Used to Diagnose Varicoceles Methods Sonography

Diagnostic Criteria Tortuous, tubular, and anechoic structures located adjacent to the testis corresponding to dilated veins of the pampiniform plexus with calibres of 2–3 mm during the Valsalva manoeuvre Colour Reflux into the spermatic vein that increases Doppler during the Valsalva manoeuvre; classified as sonography static (grade I), intermittent (grade II), or continuous (grade III) Phelobography Increase in the calibre of the internal spermatic vein with reflux into the abdominal, inguinal, scrotal or pelvic portions of the spermatic vein, and the presence of collateral circulation Magnetic Dilatation of the vessels of the pampiniform resonance plexus with signal intensity that varies depending imaging on the flow rate and enhancement after injection of contrast medium Scintigraphy Intrascrotal accumulation of technetium-99labelled red cells with reflux observed during dynamic manoeuvres

Treatment Subclinical varicocele is not an indication for treatment as it has not proven to be affecting fertility. Patients with (a) palpable varicocele, (b) abnormal parameters of semen, (c) infertility, (d) female partner with normal fertility serve as candidates for treatment. Treatment options include (a) ligation of dilated internal spermatic cord veins, (b) embolization that guided radiographically, (c) microsurgical techniques sparing lymphatic system and internal spermatic cord veins This repair improves quality of sperm, serum follicle-stimulating hormone and testosterone levels and sperm penetration. It modifies the determination of oxidant level and DNA fragmentation.

Intratesticular varicocele They are rare and reported in less than 2% male. They can occur alone or along with extratesticular varicoceles. The US appearance is dilated tubular intratesticular veins more than 2 mm in close proximity to the mediastinum of testes. On performing Valsalva manoeuvre with colour Doppler US, they show increased flow in intratesticular veins (Fig. 11.11.4.14). Stretching of tunica albuginea postactive or passive venous dilatation leads to pain, which is the presenting complaint. Extra- and intratesticular varicoceles have similar pathogenesis thus affecting spermatogenesis causing infertility.

FIG. 11.11.4.14 Intratesticular varicocele – Longitudinal colour Doppler US images of the left testis at rest and during the Valsalva manoeuvre show tubular structures with flow adjacent to the mediastinum testis at rest but increased dilatation and flow during the Valsalva manoeuvre.

11.12: Prostate Karthik Ganesan, Disha Lokhandwala, Ujjwal Bhure, Jay Mehta

Prostate gland embryology Morphogenesis of the male genitourinary system is governed by the coherent interaction of three units, namely the Wolffian duct, urogenital sinus and foetal gonads. The Wolffian ducts are the embryonic precursors of the male internal genitalia, arising in the anterior intermediate mesoderm at 4 weeks of gestation. They elongate as a cord of cells that caudally extend to the urogenital sinus. Between 5 and 8 weeks of gestation, the urorectal septum divides the cloaca into a ventral compartment, which forms the urogenital sinus, and a dorsal compartment, which forms the rectum. The gonads form as epithelial thickenings on the ventromedial surface of the mesonephros and produce testosterone at 8 weeks of gestation, reaching a peak at 10–15 weeks. Under the effect of testosterone produced by the foetal testis, the prostate anlage forms at the tenth week of gestation. Precursor of the anlage begins with proliferation of solid epithelial buds from the epithelium of the urogenital septum into the adjoining mesenchyme in response to interaction of 5α-dihydrotestosterone with mesenchymal androgen receptors. As growth progresses, solid cords of epithelial cells are formed, growing into the mesenchyme in a specific three-dimensional arrangement (establishes the lobar divisions of the prostate gland). These solid cords develop a central lumen at birth and are lined by a layer of flat basal epithelium and a luminal layer of tall columnar secretory epithelium. Mesenchymal component forms the stroma, which has a large proportion of smooth muscle. Postnatally, the epithelial cords continue to arborize till puberty without any change in volume or glandular architecture. Although the foetal prostate has been described to have a histologically distinct peripheral zone (PZ) as early as 12 weeks of gestation, the mature zonal anatomy develops in concordance with the androgen surge at puberty.

Ultrasonography of prostate The most commonly utilized ultrasonographic technique for the evaluation of the prostate is via a suprapubic approach. The abdominal transducers used in this approach are relatively low frequency and while it offers the advantage of greater depth of penetration without intracavitary probe insertion; however, it does not depict the zonal anatomy and its chief application lies in volume estimation. Hence, transrectal ultrasonography (TRUS) completely outweighs the transabdominal approach in terms of depicting zonal anatomy, visualizing and localizing small lesions, demonstrating vascularity and performing biopsies. TRUS is performed using high frequency transducers (5–7.5 MHz) to optimize soft tissue resolution. An enema is administered 1 h prior to the examination to clear the field of insonation. Patient is positioned in left lateral decubitus, with knees bent toward the chest and ideally a digital rectal examination (DRE) is conducted prior to probe insertion. The transducer is first draped with a sterile barrier and lubricated, After insertion, the barrier is filled with 40–50 cc of water, making sure that no air enters. On completion, water is aspirated and the probe is withdrawn. The gland is initially scanned in the axial plane from the base to the apex, beginning at the level of the seminal vesicles, and the probe is gradually withdrawn to view the entire glandular parenchyma in axial sections up to its caudal aspect. This approach allows a cursory evaluation of glandular symmetry as both halves of

the prostate can be evaluated simultaneously. Subsequently, sagittal views are acquired by rotating the probe across the transverse span of the gland, demonstrating the seminal vesicles, midline gland (visualizing both the apex and the base), with sequential scanning up to the contralateral margin of the gland. Sonographically, the prostatic capsule is seen as a smooth well-delineated, hyperechoic structure. With the newer ultrasound systems, the zonal anatomy can be delineated by TRUS; PZ appears echogenic relative to the central zone (CZ) and the transition zone (TZ), which are hypoechoic in juxtaposition (Fig. 11.12.1). Anterolaterally, the preprostatic venous plexuses are seen as anechoic tubular structures with intervening echogenic preprostatic fatty tissue. Glandular volume is estimated using an ellipsoid formula by obtaining the maximum anteroposterior, superoinferior and transverse dimensions and multiplying their product by π/6.

FIG. 11.12.1 Normal anatomy of prostate on TRUS. Transverse section of the prostate gland shows a hypertrophied TZ and periurethral glandular tissue compressing the normal appearing echogenic PZ. TZ appears hypoechoic relative to the PZ. Colour Doppler imaging is utilized to illustrate vascularity, as majority of the normal prostatic tissue (excluding the neurovascular bundles [NVBs] and pericapsular and periurethral regions) has symmetrical but sparse flow and an increased microvessel density raises the suspicion of prostatic carcinoma. However, the appearances of prostatic carcinoma can be variable on colour Doppler imaging, ranging from focal increase in vascularity around a nodule to an asymmetric increase in size and number of vessels on

the affected side and conventional Doppler has found to elevate specificity by about 5%–10%. Additionally, Doppler imaging has also demonstrated some utility in distinguishing fibrotic tissue from local recurrence. However, vessels supplying cancerous tissue are of the order of 10–50 μm, which is well below the 1-mm resolution limit of conventional Doppler techniques. Contrast-enhanced colour Doppler imaging overcomes this limitation and facilitates imaging of microvessels, using intravenously administered microbubbles (less than 10 μm diameter) of an inert gas (sulphur hexafluoride) with a lipid or galactose shell, allowing quantification of blood flow in the cancerous microvessels. Additionally, these microbubbles act as vascular tracers and by monitoring the passage of a bolus injection through the tissue of interest, time–intensity curves are created. This permits the formulation of functional indices, including bolus arrival time, time to peak intensity, area under the curve and washin/wash-out curves. These indices can further extrapolate functional images, on a pixel-by-pixel basis, overlaid on grey-scale images. Quantitative methods to demonstrate perfusion are based on the destruction of microbubbles by high-power ultrasound pulses, and then observing the rate of microbubble replenishment in the field of interest to calculate flow rate. Halpern et al. utilized contrastenhanced ultrasound and intermittent harmonic imaging with power Doppler, and exhibited an increment in sensitivity from 38% to 65% with a specificity of 80% in prostate cancer detection. Cadence contrast pulse sequencing (CPS) is a low-power multipulse imaging technique utilizing pulses with variable amplitudes and phases followed by a summation of the resulting echoes, permitting tissue suppression, allowing detection of even a small amount of contrast agents retained in the tissues. Real time elastosonography evaluates and quantifies tissue stiffness (Young’s modulus) by measuring strain under an applied stress (transducer compression) and maps areas of variable stiffness in colour-coded and grey-scale images simultaneously and shows potential in improving prostatic carcinoma detection. In a study comparing elastography and T2-weighted (T2-w) endorectal magnetic resonance imaging (MRI), similar sensitivity rates and negative predictive values (NPVs) were attained in the detection of prostatic carcinoma.

MR anatomy of prostate gland and periprostatic structures Prostate gland is an inverted cone-shaped subperitoneal retropubic gland, with its base located rostrally and apex located caudally. The base is attached to the bladder neck and the apex sits on the urogenital diaphragm and abuts the medial surface of the levator

ani muscles, namely the pubourethralis portion, which is separated from the inferolateral surfaces of the gland on either side by the prostatic venous plexus. Normal prostate gland measures approximately 4 × 3 × 3 cm, 15–20 g in weight, with a median volume of 11.5 mL (range, 1.6–20.6) in patients between 21 and 25 years and a median volume of 39.6 mL (range, 13–169.8) in patients between 38 and 83 years. The first comprehensive publication describing the anatomical subdivision of the prostate gland was in 1912 by Lowsley, based entirely on the embryonic glandular morphology at a series of gestational age groups. The budding prostatic ducts were seen to proliferate in five distinct clusters from the primitive urogenital sinus, which formed the basis of its lobar subdivision. It was divided into a ventral lobe (anterior to the urethra), two lateral lobes (lateral to the ejaculatory ducts), a posterior lobe (between the ejaculatory ducts) and a middle lobe (above the ejaculatory ducts). This classification had several shortcomings, the foremost being inclusion of only the embryonic prostate during its conception. Frank highlighted these aspects in 1953 and stated that no definite lobar boundaries exist in the adult prostate and further criticized the exclusion of periurethral glands (inner gland), identifying them as the sole site of origin of benign prostatic hyperplasia (BPH). The chief drawback of all research prior to 1968 was the lack of a concrete histological basis to support the seemingly arbitrary subdivision. McNeal was the first to ascertain histological heterogeneity within the glandular tissue and used it as the basis of his well-acclaimed prostatic zonal classification. The zonal anatomy of the prostate gland conceived by McNeal divided the gland into four distinct zones, namely the TZ, PZ, anterior fibromuscular zone (AFMZ) and the CZ (Fig. 11.12.2). McNeal used the plane of the distal urethra to describe the zonal relationships and divide the gland broadly into three parts, namely the base, midgland and the apex (Fig. 11.12.3). The improved understanding of the prostate anatomy coincided with the development of MRI in the late 1980s, which could depict the zonal anatomy, unlike ultrasonography (USG) or computed tomography (CT).

FIG. 11.12.2 Normal anatomy of prostate on MRI: (A) Sagittal, (B) axial and (C) coronal T2-w images reveal the classic zonal anatomy of the prostate gland, comprising of the paired TZ, PZ and CZ, and the midline AFMZ.

FIG. 11.12.3 Normal anatomy of prostate on serial axial sections from base to apex. At the (A) base, all four zones of the gland are visible including the midline AFMZ, TZ (dominant), CZ (surrounding the ejaculatory ducts) and the compressed PZ. At the (B) migland, the gland comprises of the TZ and the PZ. At the (C) apex, the gland only comprises of the PZ, which surrounds the prostatic urethra. Prostate gland zonal anatomy

Patterns of ductal growth and radiation from the prostatic urethra form the basis of the zonal anatomy of the gland. Ducts arising from the proximal urethral segment grow towards the urinary bladder. Tiny ducts which are confined by the preprostatic sphincter form the small periurethral gland, whereas ducts which develop distal to the lower border of the preprostatic sphincter extend laterally and then anteromedially to form the TZ. Ducts arising from the verumontanum in the vicinity of the ejaculatory duct orifices and are directed towards the base along the course of the ejaculatory ducts form the CZ, whereas ducts which arise from the lateral recess of the posterior urethral wall of the verumontanum and distal urethra radiate laterally to form the PZ and rostrally posterior to the CZ at the base of the gland. Peripheral zone PZ is the dominant glandular component of the prostate gland comprising approximately 70% of the glandular tissue. On T2-w images, the normal PZ has a high T2 signal intensity (SI), owing to the abundant ductal and acinar elements with sparsely interwoven smooth muscle, and can broadly divided into three sections as per the sector map in Prostate Imaging Reporting and Data System Version 2.1 (PI-RADS v2.1), namely posterior medial, posterior lateral and anterior sections (Fig. 11.12.4). At the apex, the anterior sections have a horn-like morphology, curving anteromedially, to nearly encircle the urethra and abut the AFMZ. At the midgland level, the PZ comprises the posterior, both lateral and the anterolateral parts of the gland. At the base, the PZ is located posterior and superior to the CZ and TZ.

FIG. 11.12.4 Normal anatomy of PZ at the midgland: Axial T2-w images reveal a homogeneously hyperintense PZ extending between the 1-o’clock and 11-o’clock positions at the midland level. PZ comprises of the anterior horn, posterolateral (PL–PZ) and posteromedial (PM–PZ) regions based on the sectoral maps. Central zone CZ is an ovoid-shaped structure at the base of the gland, comprising approximately 25% of the glandular tissue, with its apex located at the verumontanum, surrounding the ejaculatory ducts. Beyond age 35, volume of the CZ starts to gradually diminish, as well as the CZ is compressed by the enlarged TZ. In the initial MR studies of prostate, the CZ could not be easily delineated from the TZ. Vargas et al. demonstrated in a population with a mean age of 60 years undergoing MR for prostate cancer assessment, the CZ was visible in 81%–84% of patients. Hansford et al. identified the CZ in 92%– 93% of patients on T2-w images and 78%–88% of patients on apparent diffusion coefficient (ADC) maps. Histologically, substantial differences exist between the CZ and PZ, which reflect in the differential appearance on T2-w imaging. These differences are probably attributable to the differential origin, as the CZ is derived from the Wolffian duct, and the PZ and TZ are derived from the urogenital sinus. In the CZ, the acini appear larger and more irregular, with numerous epithelial covered ridges or septa project from the walls of the acini into the lumen, forming a characteristic

Roman bridge architecture and intraglandular lacuna, with a prominent basal layer, crowded epithelial cells with granular eosinophilic cytoplasm, decreased luminal fluid and compact stroma. PI-RADS v2 has discouraged the use of the term central gland, as it is not reflective of zonal anatomy or reported on pathologic specimens. CZ demonstrates homogeneously low signal on the T2-w images and ADC maps and can, therefore, mimic prostate cancers. CZ is best identified on the coronal plane T2-w images paralleling the plane of the distal urethra, and appears as a symmetric paramedic paired structures surrounding the ejaculatory ducts from the base of the gland to the verumontanum (Fig. 11.12.5).

FIG. 11.12.5 Normal anatomy of CZ: (A) Axial T2-w and (B) coronal T2-w images reveal discrete paired T2 hypointense structures (CZ) at the base of the gland, surrounding the ejaculatory ducts. Transition zone TZ comprises approximately 5% of the glandular tissue of the prostate. On T2-w images, the TZ normally appears as a homogeneously hypointense structure surrounding the proximal urethra at the base and the midgland level; however, it can also demonstrate inconsistent SI, depending on the relative proportion of glandular and stromal elements (Fig. 11.12.6). Glandular hyperplasia produces higher SI (dominance of acinar elements and secretions), while stromal hyperplasia exhibits lower SI (dominance of muscular and fibrous elements). The TZ is easily demarcated from the PZ by a thick homogeneously low T2 signal surgical capsule, which becomes pronounced in BPH. With increasing age, the TZ demonstrates variegated signal on the T2-w images and ADC

maps, due to differential growth of the stromal and glandular elements.

FIG. 11.12.6 Normal anatomy of TZ: (A) Sagittal, (B) axial and (C) coronal T2-w images reveal a hypertrophied TZ and periurethral glandular tissue, stretching the prostatic urethra and protruding into and distorting the bladder neck. Hypertrophied TZ comprises of numerous, well-circumscribed, encapsulated nodules demonstrating variable T2 signal, representing a combination of stromal and glandular hyperplasia. Anterior fibromuscular zone AFMZ is a nonglandular muscular tissue that drapes the anterior surface of the gland, superiorly blending into the smooth muscles of the bladder neck and inferiorly extending to the prostatic urethra at the glandular apex. AFMZ is comprised of smooth muscles, which blends with the smooth muscle fibres surrounding the urethra, and rostrally merges with the bladder neck and preprostatic sphincter. High smooth muscle content of the AFMZ is responsible for the MR signature, where in it appears markedly hypointense on the T2-w images and ADC maps, and hypoenhances on the multiphase contrast series (Fig. 11.12.7). With the advancing age, temporal reduction in the size of the AFMZ is noted due to the compressive effects of the BPH.

FIG. 11.12.7 Normal anatomy of AFMZ: (A) Sagittal T2-w and (B) postcontrast T1-w FS sagittal images reveal a markedly T2 hypointense and hypoenhancing structure in the anterior aspect of the gland, at the base and midgland, rostrally becoming contiguous with the bladder wall and laterally merging with the prostatic fascia. Prostate capsule Capsule surrounds the prostate gland, anteriorly merging with the AFMZ anteriorly. Two discrete defects are identified in the prostate capsule, at the base of gland where the ejaculatory ducts enter the prostate and at the apex where in the stroma blends with the sphincter. The capsule is perforated along the anterolateral aspect by multiple vessels and nerves. The capsule appears as a thin dark rim surrounding the gland on the T2-w images and may reveal delayed enhancement on the postcontrast images (Fig. 11.12.8).

FIG. 11.12.8 Normal prostate capsule: (A–C) Serial axial sections of the prostate gland at the midland level, reveal a concentric thick condensation of compressed fascial tissue (white arrows) surrounding the gland, separating the gland from the periprostatic fat and rectoprostatic shelf. Periprostatic fascia and neuroanatomy of prostate Primary goal of radical prostatectomy (RP) is to achieve oncologic efficacy, both in terms of short-term and long-term clinical outcomes. However, as the majority of prostate cancers have an indolent clinical course, preservation of function in terms of continence and potency is equally important, and the key to this is a keen understanding of the fascial anatomy and neuroanatomy of the prostate gland. Fascial anatomy of the prostate gland is anatomically complex and poorly understood, and a thorough understanding of the interfacial planes is crucial to avoid mechanical or thermal injury to the NVBs. Periprostatic fascia comprises of a condensation of layers of connective tissue that encapsulate the gland and suspend it from anterior pelvic wall via puboprostatic ligaments. Laterally, the visceral and parietal endopelvic fascial layers fuse to form the fascial tendinous arch. Periprostatic fascia covers the prostate gland and capsule, comprises of two fascial layers, including an inner layer (prostatic fascia) and an outer layer (levator ani fascia), with thin interfascial planes separating these fascia from one another and the prostate capsule. Posteriorly, a continuous fascial layer known as Denonvilliers’ fascia covers the prostate and seminal vesicles. Distribution of periprostatic nerves is highly variable, with growing evidence of nerves both along the dorsolateral and ventrolateral surfaces of the prostate gland. Most of the periprostatic nerves are

found posterolaterally; however, a significant portion of the nerves are located ventrally as seen by Eichelberg et al. (21.5%–28.5%) and Lee et al. (19.9%–22.8%). Although anatomic studies have confirmed the presence of ventrolateral periprostatic nerves, the exact clinical importance and functionality of these nerve fibres has not been proven. The cavernous nerves are situated posterolaterally and are the basis of nerve-sparing RP procedure proposed by Walsh and Donker. Unlike the initial theory of Walsh and Donker, few papers have proposed that the nerves are diffusely scattered along the surface of the gland in the form of a curtain or spray-like arrangement without clear bundle formation. Kourambas et al. assessed the precise relationship of the NVBs and cavernous nerves to Denonvilliers’ fascia and proposed that the nerves were not restricted posterolaterally, but were rather diffusely scattered within the fascia extending up to the midline (Lunacek et al., Takenaka et al.). On the basis of more diffuse arrangement of the periprostatic nerves, surgical techniques have been modified, resulting in a more anterior dissection called the ‘curtain dissection technique’ or alternatively a ‘superveil’ technique to preserve the NVBs within the lateral prostatic fascia. The NVB lies within areolar connective tissue surrounding the gland, which separates the capsule from the periprostatic fascia and provides a plane of dissection during nervesparing prostatectomy. Periprostatic vasculature and lymphatic drainage Prostate gland is supplied and drained by periprostatic vessels, which also supply and drain the penis. Arterial supply of the gland is highly variable and is typically from branches of the internal pudendal artery, which course inferior to the gland prior to supplying the penile cavernosal tissue. Off late, these vessels have gained prominence in radiation-induced erectile dysfunction (ED) (potential vasculopathy), which have led to the development of newer vessel-sparing radiotherapy techniques. Further, with the advent of prostate arterial embolization in benign prostatic hypertrophy (BPH), the vascular supply of the gland is becoming increasingly vital to understand. Gland drains into the obturator, internal iliac, external iliac, common iliac and presacral lymph nodes. Dorsal venous complex is identified immediately ventral to the gland and also drains the penis. Periprostatic nodes are uncommon, are usually discovered near the base of the gland, and are only occasionally seen on MRI. Prostatic urethra Urethra is the principal anatomic reference point in the prostate gland. Urethra can be divided into a proximal segment and a distal segment, the point of differentiation being located at the verumontanum wherein the urethra makes an approximately 35degree angulation. The angulation is highly variable and is further

affected by the growth of the TZ. On MRI, the distal segment is more conspicuous vis-à-vis the proximal segment and appears a hyperintense core surrounded by a low signal rim on T2-w images. Preprostatic sphincter encases the proximal urethra from the base of the gland to the base of the verumontanum and merges with the AFMZ anteriorly. Verumontanum appears hyperintense on the T2w images, lies within the distal urethral segment, beyond which the distal urethral segment is partially encircled by striated muscles which blend with the external sphincter beyond the apex of the gland. External sphincter is located distal to the apex is incomplete posteriorly and is anchored into the PZ and surrounds the membranous urethra. Damage to the external sphincter during RP or transurethral resection of the prostate (TURP) may lead to urinary incontinence. Seminal vesicles, vas deferens and ejaculatory ducts Seminal vesicles are paired structures identified posterosuperior to the base of the prostate gland, which appear as convoluted fluidfilled structures. Due to the high fluid content within the normal seminal vesicles, these structures appear as paired structures with intermediate signal walls surrounding a hyperintense core on T2-w images (Fig. 11.12.9). Vas deferens are paired structures located rostral to the base of the gland and anteromedial to the seminal vesicles and appear as cord-like structures with variable signal on the T2-w images. Duct of the seminal vesicle and vas deferens unite in the posterior aspect of the base of the gland to form the ejaculatory duct, which courses caudally to the verumontanum along the plane of the distal urethra, and drain into the orifices in the midconvexity of the verumontanum.

FIG. 11.12.9 Normal seminal vesicles: (A) Axial T2-w fat-suppressed and (B) coronal T2-w images reveal paired near symmetric polylobulated structure comprising of multiple fluid-filled convolutions representing the seminal vesicles (SV). Loss of the normal T2 hyperintense of the vesicles may be observed in prostate cancer invading the vesicles or chronic seminal vesiculitis or may represent posttreatment sequelae. Cord-like structures observed superomedial to the vesicle represent the vas deferens (VD).

Prostate-specific antigen Prostate-specific antigen (PSA) is a serine protease, secreted by epithelial cells of the prostate gland and has been found in normal, benign and malignant prostatic tissues. Traces of PSA have also been isolated from endometrial tissue, breast tissue, adrenal neoplasms and renal cell carcinomas; however, for all clinical purposes, PSA is considered as an organ-specific biomarker. Papsidero first demonstrated and quantified serum PSA, which steered the epoch of prostate cancer screening and early detection of prostatic carcinoma. Subsequent studies showed that PSA screening often led to overdiagnosis of low-grade prostate cancers, with no survival difference between the PSA screened and nonscreened groups. Additionally, PSA levels were found to be elevated in a spectrum of prostatic pathologies apart from carcinoma, including prostatitis and benign hyperplasia. The likelihood of overdiagnosis coupled with the lack of specificity set grounds for the longstanding

PSA controversy. Did the benefits of screening outweigh the risks of overtreatment? To elevate the specificity of serum PSA testing, a plethora of indices were devised, including free PSA and total PSA, free-to-total PSA (f/t PSA) ratio, age-specific PSA, PSA velocity (PSA-V) and PSA density (PSAD). Serum PSA exists in three forms; the major form (approximately 75%) is bound to alpha-1-antichymotrypsin, followed by free PSA (constituting 5%–50% of serum PSA). The third form (PSA bound to alpha-2-macroglobulin) is not clinically relevant and cannot be detected by any commercial test. A study by Stenman et al. established that a higher proportion of bound PSA and hence a lower ratio of f/t PSA is associated with prostate cancer. Conversely, free PSA can be utilized during follow-up for men with an initial negative biopsy result, wherein declining free PSA with a persistently elevated total PSA would raise suspicion of a neoplastic aetiology.

*Alpha-1-antichymotrypsin (ACT), alpha-2macroglobulin (A2M), alpha-1-trypsin inhibitor (API). As per the ACS guidelines (Table 11.12.1) for early detection of prostate cancer, men with a 10-year life expectancy or higher should have the opportunity to make an informed (regarding benefits, risks and uncertainties associated with PSA screening) decision for serum PSA testing, with or without DRE. For those who choose to undergo PSA screening, subsequent screening interval is determined on the basis of baseline PSA value. For values below 2.5 ng/mL, screening interval can be extended to 2 years and for PSA between 2.5 ng/mL and 4 ng/mL, an individualized approach is adopted following risk assessment to recommend either further referral or screening on a yearly basis. A PSA level of 4 ng/mL or higher warrants referral for further evaluation or biopsy, for men at average risk for prostate cancer. Although age-specific PSA (Table 11.12.2) is not a component of the ACS guidelines, it is considered as a beneficial parameter in determining the need for biopsy. As there is an

expected rise in PSA values with age, setting a lower cut-off value for younger men would increase the sensitivity of detecting organ confined cancers and a higher value in older men would increase specificity. TABLE 11.12.1 ACS Guidelines for Prostate Cancer Screening PSA (ng/mL) 4 PSA density PSA velocity aThere

value.

Recommendations Screen every 2 years Individual risk assessment and yearly screening Referral for further evaluation or biopsy 0.75 ng/mL/year raises suspicion of cancera

is no proven rationale for using a single PSA-V threshold

TABLE 11.12.2 Age-Specific PSA Values AGE-SPECIFIC PSA FOR WESTERN POPULATION Age Group (Years) PSA Range (ng/mL) 40–49

0–2.5

50–59

0–3.5

60–69

0–4.5

>70 0–6.5 AGE-SPECIFIC PSA FOR INDIAN POPULATION Age Group (Years) Mean PSA (ng/mL)

SD

40–49

1.22

1.19

50–59

1.97

3.17

60–70

2.08

2.63

PSA screening guidelines for treated localized prostate cancers are variable and the definition of biochemical (PSA) recurrence remains debatable. Due to this inconsistency, the Prostate Cancer Guidelines Update Panel recommended a standard definition for biochemical recurrence (BCR) after RP and set a cut-off serum PSA (acquired between 6 weeks and 3 months of surgery) of 0.2 ng/mL or greater, along with a second confirmatory PSA. While there is a significant fall in PSA values after RP and a single raised PSA is

sufficient to raise suspicion of recurrence, postradiotherapy recurrence requires a rising trend rather than a single cut-off value. The ASTRO Consensus Panel defined postradiotherapy prostate cancer recurrence as three consecutive raises in PSA values after a baseline has been reached. A hiatus in this definition was that no specific time interval between consecutive increases in PSA was determined. In addition to its utility as a screening tool, PSA is also a good prognosticator when used in conjunction with biopsy Gleason score and clinical T-stage, and several pretreatment prostate cancer risk stratification systems are based on these indices. D’Amico et al. proposed a three-group risk stratification system in 1998, which categorized nonmetastatic (M0) carcinomas as low risk, intermediate risk and high risk. Low-risk prostate cancer was defined as 1992 AJCC T1/T2a, PSA ≤10 ng/mL and Gleason score ≤6. Intermediate-risk prostate cancer was defined as 1992 AJCC T2b, and/or PSA 10–20 ng/mL and/or Gleason 7 disease. High-risk disease included any one of the following: 1992 AJCC ≥T2c, PSA >20 ng/mL or Gleason 8–10 disease. In 2001, the GUROC published the results of a consensus meeting which categorized the groups as follows: low risk – 1997 AJCC T1–T2a, PSA ≤10 ng/mL and Gleason ≤6; intermediate risk – 1997 AJCC T1–T2, PSA ≤20 ng/mL and Gleason ≤7 not otherwise low risk and high risk – 1997 AJCC T3–T4 or PSA >20 ng/mL or Gleason 8–10. In due course, newer classification systems have been developed (Table 11.12.3), including the National Comprehensive Cancer Network (NCCN, USA), National Institute for Health and Clinical Excellence (NICE, UK), European Society of Medical Oncology (ESMO), American Urological Association (AUA) and the European Association of Urology (EAU). The NCCN guidelines also incorporate very low-risk (T1c, and Gleason score ≤6, PSA ≤10 ng/mL, 10–20 not PSA ≤10 low risk T1–T2a T2b or T2c and GS and/or GS = 7 2–6 and and/or PSA PSA ≤10 >10–20 not not very low risk low risk AND very lowrisk category: T1c and GS ≤6 and PSA 20 or GS 8– 10 T3–T4 or PSA >20 or GS 8–10 T3a or PSA >20 or GS 8– 10 not very high risk AND very high-risk category: T3b–T4

T3–T4 or PSA >20 or GS 8–10

AUA, American Urological Association; EAU, European Association of Urology; GUROC, Genitourinary Radiation Oncologists of

Canada; NICE, National Institute for Health and Clinical Excellence; CAPSURE, Cancer of the Prostate Strategic Urologic Research Endeavour; NCCN, National Comprehensive Cancer Network; ESMO, European Association of Urology; T, T-stage; GS, Gleason score; PSA, prostate-specific antigen. Note: Use of the 1997 TNM staging system (T2a one lobe involvement, T2b two lobes involvement, no T2c category). PSA, DRE and TRUS form the diagnostic triad for prostatic carcinoma. It has been well established that manipulations of the prostate gland, including prostatic massage, cystoscopy and perineal biopsy cause a potential increase in serum PSA levels. This raised the question of TRUS affecting PSA levels and it was found to cause a very small rise in PSA only in patients with prostatitis. The effect of DRE on serum PSA levels is also controversial, while some studies found a transient increase in PSA, others found no significant rise in PSA levels after DRE. Therefore, it is advisable to obtain blood samples for PSA testing either prior to DRE and TRUS or after at least 7 days. PSA-V refers to the change in PSA over time using serial measurements. Ideally, at least three consecutive measurements over at least 18–24 months should be used. Carter et al. first defined PSA-V and found that a value of 0.75 ng/mL per year or greater was indicative of carcinoma with a high sensitivity and specificity. Consequently, several studies disproved a definite relationship between PSA-V and prostate cancer, stating that there was no rationale behind a single threshold value for PSA-V. Further, it was found that calculating PSA-V was arduous and while elevated PSA values on serial examinations should raise alarm, there was no added benefit of formally calculating PSA-V. As per NCCN guidelines, the PSA-V cut-off should be based on the initial PSA value with a PSA-V of 0.35 ng/mL/y, when the PSA is ≤2.5 ng/mL and 0.75 ng/mL/y, when the PSA is 4–10 ng/mL PSAD was developed in order to correlate prostate volume and PSA values. The basis of PSAD was that cancer cells produce more PSA per unit volume than normal cells. It is calculated as PSA value divided by the prostate volume as determined by TRUS. This reliance on TRUS leads to interobserver variability and hence PSAD values would differ with the performing sonologist. The chief utility of PSAD is in the diagnostic grey zone of PSA values between 4 and 10 ng/mL and the most commonly used cut-off value is 0.15 ng/mL/cc. However, more recent studies have shown that a value of 0.08 ng/mL/cc has an NPV of 95% in predicting prostate cancer. Additionally, PSAD in conjunction with MRI (PI-RADS score) has proved to be a reliable prognosticator for Gleason score upgrading. The most significant application being avoiding unnecessary biopsies as PI-RADS scores of 1–3 along with PSAD values 2 ng/mL with choline PET/CT, it has been brought down to less than 0.5 ng/mL with PSMA PET/CT, which is a major achievement indeed as localized salvage therapies for suspected local failure such as salvage external beam radiation therapy (EBRT) after RP are most effective if instituted during early PSA recurrence, while the PSA is less than 0.5 ng/mL. PSMA-based radiotracers PSMA is a type II transmembrane protein with intracellular (19 amino acids), transmembrane (24 amino acids) and extracellular (707 amino acids) domains, which functions biochemically as a glutamate carboxypeptidase. After a ligand binds to PSMA, internalization occurs and it is either retained in lysosomal compartments or released into the cytoplasm. PSMA expression and localization in the normal human prostate is associated with cytoplasm and apical side of the epithelium surrounding prostatic ducts but not basal epithelium and neuroendocrine or stromal cells. Neoplastic transformation of prostate tissue results in the transfer of PSMA from the apical membrane to the luminal surface of the

ducts. PSMA is an ideal target for molecular imaging of prostate cancer as its expression is significantly upregulated in prostatic carcinoma cells compared to benign prostatic tissue, in density (100 to 1000 times) as well as activity (8 to 10 times). PSMA expression increases with increase in Gleason score, stage and grade of tumour, with further increased expression with transition to androgenindependent/castration-resistant prostate cancer. PSMA-binding analogues, because of their high sensitivity and specificity, possess precise imaging characteristics required for critical decisions in the management of prostate cancer (PCa). The most commonly used PSMA radiotracer is 68Gallium-PSMA-11, followed by 18F-PSMA. The availability of 18F-labelled PSMA radiopharmaceutical has helped to advance the reach of PSMA PET imaging to wider locations owing to higher available amount of the radiotracer due to its production from a cyclotron, compared to 68Ga-PSMA which is eluted from individual in-house generator. Additional benefit is accrued with excellent image quality owing to optimized radiotracer doses, higher imaging statistics and favourable decay properties of 18F radioisotope. Normal distribution The normal physiological biodistribution of PSMA-based radiotracers is seen in lacrimal and salivary glands, liver, spleen, kidneys and intestine. Physiological activity is also seen in celiac and cervicothoracic ganglia. Unbound PSMA radiotracer is excreted by the kidneys into the urinary bladder. Where can we use PSMA PET/CT? PSMA PET/CT has established roles of varying degrees in the imaging of different aspects of prostate cancer including primary diagnosis, staging, BCR after primary prostate cancer treatment (prostatectomy), identification and significance of oligometastasis, restaging and treatment response assessment and monitoring. PSMA PET/CT is useful at the stage of diagnosis in that subset of patients with tumour-negative biopsy samples, by contributing the useful molecular information to mpMRI, helping to precisely delineate suspicious lesions for targeted biopsies. In intermediaterisk to high-risk primary prostate cancer patients, PSMA-based imaging has shown improvement in detection of metastatic disease compared to the CT and mpMRI, which has led to reduced demand and dependence on additional cross-sectional imaging or bone scintigraphy. Furthermore, PSMA PET/CT has also established its clear advantage over conventional imaging in patients with biochemically recurrent prostate cancer with improved and increased detection of metastatic sites even at low serum PSA values. Initial/primary diagnosis

As it happens in cancer, biopsy is the standard of diagnosis and likewise in PCa, it is the multicore biopsy, which is the gold standard. However, because of its size, location, approach and sensitive and delicate nature, yield and accuracy can often be restricted, especially in inexperienced hands. The diagnostic yield of biopsy can go down as low as 40% and false negative (FN) rate can climb as high as 25%–30%. PSMA overexpression follows highgrade PCa cells and increases with Gleason score. In normal prostate tissue, PSMA to PSA ratio is about 1, which decreases in BPH, increases in primary PCa cells, further increases with intratumoural angiogenesis, higher in metastatic lesions than in primary PCa cells and further upregulated in castration-resistant situation. In a study by Litwin and Tan in 2017, the FN rate of multicore biopsy was around 21%–28% and about 15% of the cases were undergraded vis-à-vis final prostatectomy results. While the diagnostic accuracy of random multicore biopsy was around 76.3%, that of 68Ga-PSMA PET/CT was upward in the range of 85.5%. The role of PSMA PET/CT in the primary/initial diagnosis of prostate cancer is generally limited to clinically intermediate-risk to highrisk patients with negative biopsy or reluctance to biopsy or noncooperation or nonfeasibility and for confirmation and staging in clinically high-risk patients. In low-risk patients, metastatic spread is very unlikely and hence it is a relative indication at the time of initial diagnosis in low-risk patients. And, its role in screening is variable and debatable (Fig. 11.12.10).

FIG. 11.12.10 68/M with primary intraprostatic lesion with no metastases. PSMA PET/CT reveals abnormal high uptake of radiotracer PSMA in the left PZ (black arrows). No abnormal high uptake of radiotracer PSMA is observed in the rest of the body. Staging Staging is crucial as it has considerable influence on deciding further line of management and treatment choices, which includes RP, radiotherapy or palliative systemic treatment, deciding on the

extent of the pelvic nodal dissection during surgery, planning the radiotherapy field and consideration of multimodal therapy. Accurate staging helps to make the most appropriate choice of treatment modality (Fig. 11.12.11).

FIG. 11.12.11 67/M with primary intraprostatic lesion with extraprostatic spread, nodal and osseous metastases. PSMA PET/CT reveals abnormal high uptake of radiotracer PSMA in the prostate gland, epicentered in the left lobe (white arrows) with extension into the right lobe, extracapsular spread, associated with focal abnormal uptake of radiotracer PSMA in the left external and right common iliac nodes and a sclerotic osseous lesion in the right ischiopubic ramus. In a meta-analysis of five studies with histopathology as gold standard, which included 216 patients, the per-lesion sensitivity of 68Ga-PSMA PET/CT ranged from 33% to 92% (33% value being an outlier due to the retrospective analysis based only on the reports, in absence of the images) with higher specificity of 82%–100%. For Tstaging, PSMA PET/CT showed a significantly higher tumour detection rate of 92% vis-à-vis 66% with MR alone. In regard with N-staging, the majority of metastatic nodes from prostate cancer are small subcentimetre-sized, less than 8 mm, which are overlooked, missed or inconclusive on morphological imaging (CT and MRI) (falling below size criteria for morphological imaging). Accurate Nstaging is important because lymph node involvement is a critical prognostic factor in cancer management, and precise pelvic nodal clearance could be curative and could make a difference in treatment success and long-term outcome in prostate cancer (Fig. 11.12.12). Also, accurate prediction of pelvic nodal metastases may spare nodal dissection, shorten surgical time and in turn help to reduce undesirable complications. In one study from 2016 involving 130 patients with intermediate-risk to high-risk prostate cancer, the

metastatic nodal detection rate by 68Ga-PSMA PET was around 66% compared to 44% with MRI. PSMA PET has shown superior predictive value for surgical response over Gleason score, pT stage and PSA (at the time of imaging). In a literature overview by Luiting et al. in 2019 involving 9 retrospective and 2 prospective studies, the specificity of PSMA PET/CT in detection of pelvic nodal metastases before initial treatment reached as high as 80%–100%. PSMA PET/CT increases the confidence level in the evaluation of nodal metastases and an NPV reaching up to 86%. With imaging becoming more precise and adding different modalities together, the question arises about the tiny nodes less than 5 mm size. In a study by van Leeuwen et al. in 2017, the mean size of missed lymph node metastases was 2.7 mm. In a recent study by Ferraro et al. in 2020, about the impact of PSMA PET staging on clinical decisionmaking in intermediate-risk to high-risk prostate cancer patients, PSMA PET provided new information in 36% of patients and this helped to change treatment decision in nearly 27% of patients, which means in every fourth patient they studied.

FIG. 11.12.12 75/M with a large primary intraprostatic lesion with extraprostatic spread, nodal and extensive sclerotic osseous metastases. PSMA PET/CT reveals abnormal high uptake of radiotracer PSMA in the prostate gland (white arrow) with extracapsular spread and rectal wall invasion (yellow arrow), along with focal abnormal high uptake of radiotracer PSMA in the left internal iliac node and extensive sclerotic osseous lesions in the axial and appendicular skeleton (yellow arrows). PSMA PET in combination with CT or MRI can achieve complete and precise Tumor, Nodes and Metastases (TNM) staging including staging of local tumour, nodal assessment and bone and organ/visceral metastases, in one single imaging session, with improved accuracy and better outcome, and in turn leading to

precise treatment planning, eventually superseding conventional imaging. Biochemical recurrence Accurate localization of prostate cancer lesions in patients with BCR is a major challenge. Especially at low serum PSA values (as low as less than 0.5 ng/mL), the precise determination of localized disease and metastatic spread is of great importance for further disease management. Conventional imaging modalities including CT scan or bone scintigraphy have limited detection rate for metastatic disease at low serum PSA values in this setting of BCR. PSMA PET/CT imaging plays a very valuable role in the evaluation of BCR (Fig. 11.12.13), which is indeed very critical and important aspect in prostate cancer management. The international consensus on BCR includes PSA >0.2 ng/mL for two times after prostatectomy, or PSA nadir + 2 ng/mL after radiotherapy or brachytherapy. With the incorporation of PSMA PET/CT in the imaging armamentarium, the overall detection rate for local recurrence as well as metastases with BCR after prostatectomy reached up to 90%. The detection rate increases with rising PSA level, jumping over 90% with PSA level going above 1 ng/mL. In a homogeneous consecutive cohort of 248 patients with BCR after RP with mean serum PSA value of 1.99 ng/mL, studied by Eiber et al., 68Ga-PSMA PET/CT showed detection rates of 57.9%, 72.7%, 93.0% and 96.8% for patients with serum PSA values of 0.2–3 mm) Malpositioned adnexa: In the midline, paramidline or contralateral side Free fluid: Haemoperitoneum or ascites USG CT MRI • In the initial stages of oedema and congestion, ovarian stroma appears hypoechoic • In the later stages of haemorrhagic infarction, appears mixed echogenic or hyperechoic • Internal echoes within a cyst or follicle due to haemorrhage

• In the initial stages of oedema and congestion, appears hypodense • In the later stages of haemorrhagic infarction: Intraovarian haemorrhage, haematosalpinx and haemoperitoneum (>50 HU on CT)

• In the initial stages of oedema and congestion, appears hypointense on T1WI and hyperintense on T2WI • In the later stages of haemorrhagic infarction: Intraovarian haemorrhage, haematosalpinx and haemoperitoneum may be seen – hyperintense on T1WI and FST1WI, hyperintense/hypointense on T2WI, hypointense on GRE Peripheral T1 and FST1 hyperintense rim of an ovarian haematoma

Other appearances of the twisted pedicle with/without fallopian tubes include target or beaked appearance (echogenic mass with multiple concentric hypoechoic stripes)/snail-shell appearance/an enlarged hypoechoic or echogenic mass/ellipsoid or tubular mass with heterogeneous internal echoes

Other appearances of the twisted pedicle with/without fallopian tubes include solid amorphous/target-like/beaked or serpentine-like protrusion extending from the uterus and partially covering the adnexa

Eccentric wall thickening leading into thickened tubes suggests haemorrhagic infarction Ipsilateral deviation of the uterus

Ovarian tenderness on transducer pressure – not elicitable on other modalities Abnormal location of the ovary at Abnormal placed ovary at or near the midline with or near the midline, superior to the far anterior or posterior location, or on the

uterine fundus or on the contralateral side contralateral side. ‘Double bladder’ sign if midline location. Engorged vessels on the ipsilateral side distal to the torsion Periadnexal fat infiltration Poor to absent adnexal enhancement – necrosis DOPPLER • Reduced or absent ovarian venous flow • Reduced or absent ovarian arterial flow – is usually associated with abnormal venous flow • Swirling appearance of vessels within a twisted vascular pedicle • Absence of reversal of diastolic flow in the ovaries • Lack of flow within the twisted vascular pedicle and absence of central venous flow within the ovaries – favours nonviability • Normal arterial or venous flow within the ovaries does not exclude torsion – this may be due to intermittent torsion (with the imaging performed during the stage of detorsion) or be related to dual arterial supply to the ovaries 1 1 .1 6 . 2

BENIGN OVARIAN LESIONS K. Geetha

Introduction Benign ovarian lesions are commonly seen in day-to-day practice and may be incidentally seen or diagnosed in symptomatic patients by imaging techniques. Imaging characterization of an ovarian lesion is significant to plan the management. Ultrasound is the first-line imaging modality in evaluating ovarian lesions. Both transabdominal and endovaginal ultrasound should be done to rule out the lesion. Magnetic resonance imaging (MRI) may be valuable for the further characterization of few benign ovarian lesions if ultrasound is equivocal. In this topic, we classified benign ovarian lesions into four groups based on morphological appearance and described the imaging features in ultrasound, computed tomography (CT) and MRI.

Approach to benign ovarian lesions Optimal assessment of benign ovarian lesions often need multidisciplinary approach, which will be based on clinical history, physical examination, serum markers and imaging techniques. As some benign and malignant ovarian lesion have overlapping or similar imaging features, multidisciplinary approach, such as clinical history, serum markers and imaging techniques, helps to derive the probable diagnosis. It is important to diagnose the type of benign ovarian lesions as it changes the patient management. Certain lesions such as endometrioma, mature cystic teratoma and paraovarian cysts have to be diagnosed since they affect patient’s fertility and sometimes can lead to torsion of ovary. Clinical history such as reproductive age, infertility, dysmenorrhea in cases of endometriosis and ovulation induction for ovarian hyperstimulation syndrome are important. The most commonly used serum tumour marker for epithelial tumours is cancer antigen (CA)-125. In postmenopausal women, CA-125 is highly sensitive and specific but it has less specificity in premenopausal women as it is elevated in other benign conditions. Imaging has significant role in detection, characterization of benign ovarian lesions. Ultrasound, colour Doppler MRI are useful in characterization of benign ovarian lesions. CT helps to identify lesions containing fat tissue and calcifications, like mature teratoma. Imaging features in general suggestive of benignity are size less than 4–7 cm, thin regular wall (35 • Perifollicular VFI – vascularity flow index – perfusion

FIG. 11.20.1.13 3DPD of perifollicular blood flow.

Assessment of endometrium for receptivity in preovulatory USG

1. Thickness – 6 to 14 mm – high negative predictive value 2. Endometrial volume – better when more than 7 cc or at least 2 to 2.5 cc 3. Endometrial morphology – indicates level of oestrogen According to Gonen and Gasper – 3 grades (Fig. 11.20.1.14) According to Sher et al. – 2 grades (multilayered/nonmultilayered) • Fluffy margin indicates early exposure to progesterone (as in recent ovulation) • Echogenic margin means the endometrium is already exposed to progesterone 4. Endometrial vascularity Endometrial vascularity is an important prognosticator of implantation than its thickness or morphology. Scoring is done depending on assessment of vascularity by power Doppler Applebaum’s scoring (Fig. 11.20.1.15) Zone 1 – vascularity reaches myometrium/junctional zone Zone 2 – reaches up to the outer hyperechoic endometrial line Zone 3* – vascularity up to the intervening hypoechoic layer of the endometrium Zone 4* – vascularity reaches the central line (endometrial cavity) • RI 40, VFI >20 – good prognosticator • Spiral artery RI 35

FIG. 11.20.1.19 Ideal follicular parameters before triggering (HCG).

Signs of ovulation (Figs. 11.20.1.20 and 11.20.1.21) 1. Disappearance of follicle/reduction in size/collapsed follicle 2. Fluffy/homogenous endometrium 3. Free fluid in POD (1–3 mL of fluid is normal in POD irrespective of menstrual phase) The intraperitoneal fluid resulting from ovulation is typically 4–5 mL. This fluid may be present even outside the posterior cul-de-sac (in the lower abdomen, upper pelvis or in the anterior cul-de-sac superior to the uterine fundus) 4. Visualization of corpus luteum

TABLE 11.20.1.3 Modified Version of Applebaum Uterine Scoring System Parameter Endometrial thickness ≤7 mm

Score =0

>7 to ≤9 mm

=2

>9 to ≤14 mm

=3

>14 mm

=1

Endometrial morphology No layering

=0

Hazy five-line appearance

=1

Distinct five-line appearance

=3

Endometrial vascularization Within zone 3

=0

Absent

=2

Present, but sparse

=5

Present multifocally Myometrial echogenicity Coarse/inhomogeneous echogenicity

=1

Relatively homogeneous echogenicity

=2

Uterine artery Doppler flow evaluated by PI ≥3

=0

2.5–2.99

=0

2.2–2.49

=1

4 follicles larger than 16 mm or >8 follicles larger than 12 mm. USG features massive cystic ovarian enlargement with multiple large follicles arranged in centre as well as periphery (whereas in PCO, the follicles are small and arranged in periphery with increased stromal thickness). While doing follicular study, familiarity with OHSS is essential to avoid incorrect diagnosis (of polycystic ovaries, theca lutein cysts or cystic ovarian neoplasm) as well as to reduce the morbidity.

Suggestion for a standardized report • LMP • Date and day of cycle on the day of visit • Natural or stimulated cycle • Relevant clinical features if any (previous history of oophorectomy) • Technique (real time 2D/sono AVC, etc.) used for evaluation and maximum frequency of probe 1. Baseline scan: • Apart from documentation of routine pelvic USG findings, • Mention FNPO and total AFC ([2–10 mm-sized follicles in each ovary and also sum of follicles considering both ovaries). • Measure ovarian volume. • Spectral Doppler study of ovarian stromal blood flow and categorize the patient as hyper/normal/poor responder. • Note the presence of dominant follicle (as in early recruitment). • Comments on accessibility of each ovary is made for transvaginal egg collection (e.g. ovaries which are fixed to posterior serosa of uterus or ovaries situated cranially are difficult/risky for transvaginal puncture). This has to be commented to IVF centres. • Look for intactness of endomyometrial junction and normal absence of endometrial blood flow. 2. Preovulatory scan • Look for response on the fifth day of stimulated cycle or seventh day of natural cycle. • Do serial monitoring with interval based on response. • Do daily monitoring, once the dominant follicle reaches 15 mm diameter. • Assess perifollicular Doppler grading and spectral flow. • Assess uterine scoring system for endometrial receptivity. • Advise on trigger based on perifollicular flow and favourable endometrial score. • Advise to consult with gynaecologist for natural intercourse/IUI/IVF. • Look for signs of ovulation. 3. Secretory scan • Look for formation of healthy corpus luteum. • Look for findings of anovulatory cycles if any,

1 1 .20. 2

ROLE OF ULTRASOUND IN IVF PROCEDURES Yuva Bala Kumaran Ultrasound is an essential tool for the assessment and management of women undergoing assisted reproductive technique (ART).

Introduction Transvaginal ultrasound (TVS)/transabdominal ultrasound (TAS) is the first line of investigation for infertility cases. It determines morphology, thickness, volume and vascularity of the uterus/endometrium. There are five broad areas where USG is used in assisted reproductive techniques. It includes i) monitoring of ovulation and reserve assessment, ii) endometrial growth assessment, iii) assessment of ovarian, uterine and adnexal factors, iv) outcome prediction in ART cycles and v) interventional procedures.

Infertility Defined as the inability of a couple to conceive after 12 months of unprotected sexual intercourse and inability to conceive after 6 months in women after 35 years. Approximately 15% of the couples are infertile. USG plays a vital role in the evaluation of male and female infertility. It helps to screen and evaluate the couple to identify the cause and to follow up their response to ARTs.

Oocyte retrieval During the early days of IVF, oocyte retrieval was performed systematically by laparoscopy, requiring a hospital admission, anaesthesia and surgical procedure. Oocyte retrieval was almost always performed with transvaginal US, after the first reports on transvaginal oocyte retrieval (TVOR) in the early 1980s. But in those patients in whom the ovaries were transposed or enlarged above the pelvic brim, transabdominal USG was performed. So, transabdominal-guided oocyte retrieval was used at some centres for patients who have inaccessible ovaries by transvaginal US. Nowadays, oocyte retrieval by transvaginal US is a procedure performed widely with lower complication rate.

Advantages of transvaginal oocyte retrieval When compared with transabdominal or laparoscopic approach, transvaginal route has the following advantages: • Shorter distance of ovary from transducer and better visualization. • Minimal discomfort with high oocyte recovery rate. • Using local anaesthesia instead of general anaesthesia. • Low risk of intestinal trauma. • Learnt easily especially by trained operators in US. • Cost effective. • Quick recovery in postintervention period.

Prerequisites The following equipments for oocyte pick-up (OPU) should be available on a sterile operation table. Small sterile gauzes and speculum which is disposable or reusable for cervical examination and to look at the site of bleeding. A heating block (at 37°C), and test tube warmer should be available and culture medium should be ready at 37°C for flushing. Additional equipment and consumables such as ovary clamps, sponge holder, vaginal surgery equipment and absorbable sutures should be also available in the procedure room that might be used during OPU. Resuscitation equipment, aesthetic drugs for reversal, shock treatment kit for anaphylaxis and oxygen should be also available in proximity of procedure room. USG machine and transducer probe: The USG machine with a high-frequency transvaginal US transducer used for OPU should offer the best quality in real time imaging. The adjustments of field of view, depth and zoom, adjusting the focal zone to the region of interest, adjusting the acoustic power, colour and power Doppler abilities, displaying the mechanical and thermal indices, displaying the needle guide superimposed on the field of view and printing or saving images/cine loops in the system’s hard drive or a central PACS. Probe: The transvaginal probe should have a frequency range of 5–8 MHz and an abdominal probe with a frequency range of 2–6 MHz, or their contemporaneous equivalents are used. Needle: A single-lumen 17- or 18-gauge needle is the most commonly used one for OPU. Nonetheless, different sized and shaped needles with different flexibility do exist. The

needles with a smaller diameter provoke less discomfort to the patient. Edged needles are recommended. The operator must be able to see the needle tip with edges and recognize it during the US procedure. Translucent tubing is attached to the needle which enables the operator to see the nature (content and colour) of the fluid aspirated. The guide of the needle is ideally attached to the tip and bottom of the transducer. Disposable guide is preferred. Needles with double lumen or varied ones can also be used. Oocyte collection media is infused into the follicle through the needles while follicular fluid is being aspirated at the same time. Patency of the needle and ability to aspirate must be checked before insertion into the guide. Suction pump and pressure: For aspiration of follicles, negative pressure is provided by suction pump. Since, predetermined single optimal pressure level is not available now, pressure range of 100–200 mmHg are used.

FIG. 11.20.2.1 Equipment for OPU.

FIG. 11.20.2.2 Transvaginal probe.

FIG. 11.20.2.3 Aspiration needle.

FIG. 11.20.2.4 Aspiration needle. Transabdominal oocyte retrieval The patient is put under light IV sedation with anaesthesia in transabdominal oocyte retrieval (TAOR). A long needle is passed from the surface of the abdomen into the follicles of each ovary using an abdominal ultrasound probe. After aspirating fluid from follicles, scanning is done to check for eggs. Transvaginal oocyte retrieval It is the highly recommended method worldwide, as it is less invasive with less complications. HCG is administered 34–36 h before oocyte retrieval. Position: TVOR is done with the patient in the lithotomy position. Sterilizing the vagina: Recommended method of cleansing is the use of vaginal povidone-iodine disinfection and subsequent saline douching to prevent infection.

Anaesthesia/analgesia can be performed under sedation, general anaesthesia, paracervical block or spinal anaesthesia. Local anaesthetics are not used because they interfere with follicular cleavage and the technique requires multiple needle punctures. Procedure: A transvaginal ultrasound transducer with an attached needle is used for the procedure. The operator inserts a (21 gauge) 7 cm single lumen needle into the vaginal wall into an ovarian follicle without injuring adjacent blood vessels, organs located between the vaginal wall and the ovary. The suction device is attached to the other end of the needle. After entering the follicle, suction is applied for aspiration of follicular fluid along with the cellular material which includes ‘the oocyte’. For examining the ova, the follicular fluid is delivered to the IVF laboratory. Aspiration of other follicles is done next. After completing the aspiration from one ovary, the procedure is repeated in other ovary. The needle is withdrawn and haemostasis is achieved after completing the procedure. The procedure usually lasts from 20–60 min.

FIG. 11.20.2.5 Suction pump.

Role of colour doppler In oocyte retrieval during IVF, 3D colour Doppler USG is used to guide the aspiration needle to avoid puncturing blood vessels, thereby reducing the risk of peritoneal and vaginal bleeding after the procedure.

Complications Infection

Contamination from vaginal bacteria into intraperitoneal space originates from vaginal puncture during the OPU procedure. Other contributing factors will be the presence of pre-existent latent pelvic infection. In some difficult cases, septicaemia can occur due to the puncture of hydrosalpinx or an accidental puncture of an attached bowel loop. The patient presents with fever, dysuria and lower abdominal pain more than a week after the procedure. Presence of pelvic endometriosis and ovarian teratoma can add difficulties to the procedure.

FIG. 11.20.2.6 (A and B) Technique of abdominal oocyte retrieval.

FIG. 11.20.2.7 Technique of transvaginal oocyte retrieval.

FIG. 11.20.2.8 Hyperstimulated follicles.

FIG. 11.20.2.9 (A–C) Colour Doppler examination of iliac vessels and ovary. Vaginal bleeding Haemoperitoneum after OPU is identified when haemoglobin reduces >2 g/day, increasing pelvic-free fluid of >200 mL or a total blood loss of >500 mL. Intra-abdominal haemorrhage Occurs due to accidental puncture of ovarian vessels, capsule puncture sites and other pelvic vessels. Patients with high risk are lean patients with PCOS, lower BMI and previous history of surgeries. These patients present with weakness, dizziness, dyspnoea, abdominal pain, tachycardia and low blood pressure. Management includes early hemodynamic monitoring, blood transfusion, laparoscopic aspiration and laparotomy. Retroperitoneal bleeding Occurs due to injury to the sacral vein. It presents several hours after the procedure and it is difficult to diagnose. Periumbilical haematoma (Cullen’s sign) following UG-guided TVOR reflects a retroperitoneal haematoma of benign course. Rare complications

• Rupture of endometriotic or dermoid cyst. • Injury to the ureter: Ureterovaginal fistula, acute ureteral obstruction. Conclusion Research continues to improve egg retrieval for patients and providers. Ultrasound-guided oocyte retrieval coupled with new needle technology will ensure oocyte retrieval at the optimal time point and an overall decrease in the patient discomfort. Overall, the result is less anxiety for patients and more effective tools for providers. *Zones

3 and 4 are good prognosticators.

11.21: Genital tuberculosis

ENDOVAGINAL ULTRASOUND IN GENITAL TUBERCULOSIS P.K. Srivastava, Yashodhara Pradeep Genital tuberculosis is common problem in India, however, it is very much underdiagnosed because of innocuous symptoms. It is one of the major causes of female infertility in India. The disease has varied presentations therefore; it is the biggest diagnostic dilemma. India accounts for one-fourth of the global burden of tuberculosis. About 300 million population is infected by tuberculosis. Genital tuberculosis was first diagnosed by Morgagni in 1744, when he did autopsy of a 20-year-old girl who died of tubercular peritonitis. Hager in 1886 conducted the detailed study of genital tuberculosis. Genital tuberculosis is always secondary to the tubercular focus elsewhere in the body. The most common affected organs are fallopian tubes and endometrium. Genital tuberculosis should be suspected and excluded in every woman who is infertile. Amenorrhoea or menstrual irregularities cannot be explained by other causes. Adolescent girl or an unmarried woman having suspected symptoms of chronic pelvic infections. Any pelvic infection which is slow to respond to the given medical treatment, exacerbation of symptoms after invasive procedures like dilatation and curettage (D&C), hysterosalphigogram (HSG) and previous history of peritonitis, appendicectomy, poor healing of the wound and prolonged illness in the childhood strongly suggests abdominal tuberculosis (Fig. 11.21.1) or genital tuberculosis. The spread of genital tuberculosis is focus present in the body, may be in lung, kidney, GIT, bones or joints. In 90% of the cases the spread is by haematogenous route. The rest 10% of cases may be due to ascending, descending or direct contiguous spread.

FIG. 11.21.1 (A) EVS – early findings in genital TB. Endovaginal sonography (EVS) shows matted bowel loops in the pelvis. (B) The 3D ultrasound shows a thick covering around the matted bowel loops forming a pseudo capsule and makes a cocoon. (C) Loculated ascites is also seen in the pelvis.

Clinical presentation The most common clinical presentation are: • Menstrual irregularity • Secondary amenorrhoea • Infertility: 40%–80% • Pelvic Pain: 20%–50% • Tubo-ovarian mass (Fig. 11.21.2) • Pelvic abscesses (Figs. 11.21.3 and 11.21.4) • Vaginal discharge • Poor general condition • Asymptomatic • A group of patients remain asymptomatic

FIG. 11.21.2 (A and B) Tubercular T.O. mass. A complex echo mass is seen in the Lt ovarian fossa with thick echo collection. The mass is seen adherent with posterior wall of uterus. The adhesions seen pulling the uterus. The repeated spillage of tubercular exudates provoke adhesions between the tubes, ovaries and round ligament and bowel loops forming the mass. Fluid is also seen in pouch of Douglas.

FIG. 11.21.3 (A and B) Tubercular tuboovarian abscess – transvaginal ultrasound shows complex echo mass in both ovarian fossae in a case of pulmonary tuberculosis. The uterus is seen sandwiched between the masses. The normal anatomic relation is distorted. The bowel loops are also seen adherent. (C) The CT of the pelvis also shows the same findings seen on EVS.

FIG. 11.21.4 (A and B) Tubercular tuboovarian abscess: EVS shows heterogeneous complex mass. The mass shows thick exudation. They are multiloculated with particulates. Thick

capsule of the mass shows retention cyst and adhesive band formation.

Common site of infection The common sites of infection are as follows: • Fallopian tube: 90%–100% (Figs. 11.21.5–11.21.7) • Endometrium: 50%–60% (Figs. 11.21.8–11.21.10) • Ovary: 20%–30% (Fig. 11.21.11) • Cervix: 5%–15% • Vulva and vagina

FIG. 11.21.5 (A and B) EVS findings – fallopian tube. The first site of involvement is fallopian tube. The tube involvement is of two types: (A) Exosalpingitis – EVS shows thickened inner tubal wall. Club-shaped ampullary end of the tube is seen. The tube is dilated and the mouth is blocked by the exudates. Cogwheel appearance is seen. (B) Endosalpingitis – EVS shows thickened tubal wall. Low level exudates are seen in the dilated tube.

FIG. 11.21.6 (A) Exosalpingitis: EVS shows dilated convoluted tube. The convoluted tubal wall is seen as echogenic bands. (B) Endosalpingits: The tube is dilated. It is more than 13 cm in caliber. Low level echo collection is seen in the tube.

FIG. 11.21.7 (A and B) Endosalpingitis: A patient was investigated for infertility. EVS shows markedly dilated tube. Thick echo collection is seen in the tube resulting into blocked hydrosalpinx. The tube is seen adherent with posterior wall of uterus. The uterine wall is also irregular in outline.

FIG. 11.21.8 (A and B) Tubercular endometritis: A patient came for evaluation of primary infertility. There was history of irregular scanty periods. EVS shows dense echogenic calcified linear shadow along the line of the endometrial cavity suggestive of dense calcified plaque. The margins are jagged and the plaque is accompanied with acoustic shadowing. Normal endometrial appearance is lost.

FIG. 11.21.9 (A–C) Tubercular calcified plaque on 3D imaging: 3D ultrasound with TUI imaging shows well-defined echogenic plaques in the upper part and lower part of endometrium. They are accompanied with dense acoustic shadowing. Part of the endometrium shows triple line endometrial pattern.

FIG. 11.21.10 (A and B) Chronic Tubercular endometritis: The acute changes of endometritis are rarely seen in genital TB. The chronic changes show irregular echogenic endometrium. EVS shows calcified plaques at the fundus and the lower part of endometrium in a patient of infertility.

FIG. 11.21.11 (A and B) A case of primary infertility on EVS shows a complex echo mass in Lt ovarian fossa. The ovary is ill defined. The Lt tube is adherent with the mass and it is dilated. Normal anatomic relation is distorted. The mass is also seen adherent with the bowel loops.

Routine investigations The routine investigations in suspected cases of genital tuberculosis are as follows: • Hb%, TLC, DLC • ESR, PPD • Sputum and urine for M.T.B. • Lymph node biopsy • X-ray chest PA view

• X-ray pelvis • Elisa test for detection of antigen The specific investigations are as follows: • Cytology, histopathology and culture of AFB in menstrual blood • Premenstrual endometrium • Aspiration biopsy in premenstrual endometrium The specificity of endometrial biopsy is 10%. The PCR of endometrial tissue: BACTEC: 460/nucleic acid probes (2–3 weeks). H.S.G. laparoscopy and hysteroscopy are the invasive procedures. The endovaginal sonography (EVS) is an important noninvasive imaging modality for evaluation of genital tuberculosis involving fallopian tubes, ovaries and the uterus (Fig. 11.21.12).

FIG. 11.21.12 (A) Genital TB varied presentation – abdominal and transvaginal ultrasound show uterus. (B) The uterus outline is ill defined. (C) The myometrium is inhomogeneous. Endometrium shows thickening. A complex echo mass is seen in Lt ovarian fossa. (D) Thick echoes are seen in the mass. The mass is seen adherent with the uterus. Small amount of fluid is seen in the pelvis. It is very useful for visualization of tubes, ovaries, uterus, cul-desac, bowel and urinary bladder wall. EVS is indicated in the cases of chronic pelvic pain, menstrual irregularity, unexplained infertility, suspected case of genital tuberculosis and in the cases of negative culture of Mycobacterium and menstrual blood is negative. It is also very helpful for evaluating tubal block by sonosalpingography (SSG) (Figs. 11.21.13–11.21.15) and tubo-ovarian masses.

FIG. 11.21.13 Intrauterine synache or Asherman’s syndrome due to genital tuberculosis (GTB). On sonosalpingography (SSG), EVS shows distended endometrial cavity. Fine thin strands are seen in endometrial cavity. The fluid from the endometrial cavity does not go out easily suggestive of Asherman’s syndrome.

FIG. 11.21.14 Intrauterine synache in Asherman’s syndrome due to GTB – tomographic ultrasound imaging shows holdup of the fluid in the endometrial cavity with multiple echogenic synache clearly seen in endometrial cavity.

FIG. 11.21.15 (A and B) Asherman’s syndrome on 3D SSG. 3D imaging shows clearly the uterine synache in distended endometrial cavity. On power Doppler imaging, the uterine cavity and both tubes are clearly seen. Fine synache is seen in uterine cavity.

Conclusion High resolution ultrasound and EVS is an excellent noninvasive imaging modality for evaluation of genital tuberculosis. It can easily identify the nature of problem, organ involvement and also surrounding spread (Fig. 11.21.16).

FIG. 11.21.16 (A and B) Frozen pelvis. Repeated tubercular infection and spillage of tubercular exudates in peritoneal cavity results into multiple adhesions. Normal anatomy is grossly distorted. Abdominal and transvaginal ultrasound show grossly distorted uterus. Normal outlines are lost. Normal pelvis relations are lost. The tubes are distended. The bowel loops are adherent with the pelvic organs and a complex dense mass is formed resulting into frozen pelvis. It is noninvasive cost effective and does not require any preparation. It is easy in follow-up of the cases.

11.22: Genitourinary interventions

VASCULAR GENITOURINARY INTERVENTIONS Pushpinder Khera

Introduction Renal artery embolization (RAE) was first described by Almgard et al. in 1973 in relation to a renal cell carcinoma. Over the years the indications for renal artery embolization have expanded to comprise management of iatrogenic complications, renal trauma and renal tumours. Genitourinary vascular interventions are frequently required in clinical practice with increasing number of renal and prostatic surgeries, renal transplants and biopsies of the genitourinary tract. Venous interventions and procedures are also discussed in this chapter.

Vascular anatomy and technical considerations The kidneys are one of the most highly perfused organs in the body (receiving 15% of cardiac output while accounting for 5% of total body weight). In 70% of individuals, they are supplied by a single renal artery originating laterally from abdominal aorta, just caudal to origin of the superior mesenteric artery (SMA) at L1/L2 discal level. The right renal artery (RRA) originates from the anterolateral aspect of the aorta whereas the left renal artery (LRA) originates from the posterolateral aspect (Fig. 11.22.1). A total of 30% of cases have variant renal arterial anatomy which may be presence of accessory renal arteries (more common) or double renal arteries (less common). Accessory renal arteries usually originate from abdominal aorta but can originate from any of its branches till the pelvis. If present, they enter the renal pelvis and perfuse the poles of the kidney. This is relevant while performing procedures, especially embolizations since evaluation of only the main renal artery and its branches may lead to failure to locate a bleeder arising from an accessory renal artery.

FIG. 11.22.1 Relative origins of the renal arteries from the aorta as seen on an axial maximum intensity projection CT image (A) and on a volume rendered image (B). The right artery (black arrowhead) originates slightly anteromedially whereas the left artery (white arrowhead) arises from posterolateral aspect of the aorta. The main renal arteries are 4–6 cm in length (the left RA being shorter) and 5–6 mm in diameter. The schematic branching of renal artery is shown in Fig. 11.22.2 and the branches as seen on a selective renal digital subtraction angiogram (DSA) are shown in Fig. 11.22.3. Each renal artery divides into anterior and posterior branch at the renal hilum, each of which divide into upper, inter and lower polar segmental arteries. These segmental arteries branch into lobar arteries which upon entering the renal parenchyma divide into interlobar arteries. These arteries give rise to the arcuate arteries which lead into afferent arterioles of the glomeruli.

FIG. 11.22.2 Schematic diagram of typical renal artery anatomy. 1: Main renal artery, 2: inferior adrenal artery, 3: ureteric artery, 4: capsular artery, 5: anterior division, 6: posterior division, 7: segmental artery, 8: lobar artery, 9: interlobar artery, 10: arcuate artery, 11: interlobular artery.

FIG. 11.22.3 Selective angiogram of the left kidney. 1: Main renal artery, 2: anterior division, 3: posterior division, 4: segmental artery, 5: lobular artery, 6: interlobar artery, 7: arcuate artery. The renal arteries are end arteries, hence, embolization proximal to the site of bleeding stops haemorrhage. This is in contrast to the bowel where abundant collateral supply requires embolization on both sides of the bleeder (i.e. ‘front door’ and ‘back door’ embolization). Ultrasound and Doppler are excellent modalities to diagnose and characterize vascular complications of renal surgeries as evident in the various examples shown later in the chapter. With advancements in diagnostic modalities, DSA is usually performed with a goal to intervene. Hence a good quality CT urography study is used in most cases to plan the procedure (see Table 11.22.1).

TABLE 11.22.1 Phases of a CT Urography Study Phase Noncontrast

Delay Time of Acquisitiona Precontrast injection

Corticomedullary 25–35 s (late arterial)

Nephrographic

120–180 s

Delayed

7–10 min

Areas to Structures/Pathologies Be Well Visualized Covered Kidneys Haematomas and proximal ureters Kidneys, • Pseudoaneurysms ureters • Arterial transections and • Arteriovenous fistulas bladder • Arterial thrombosis • Lacerations Kidneys and proximal ureters Kidneys, ureters and bladder

Renal masses, venous structures, perirenal planes Urinary leaks

aPostinjection

of 1–1.5 mL/kg of iodinated contrast at rate of 4–5 mL/s through a peripheral vein. Renal interventions are mostly done by a retrograde right or left femoral approach with placement of a 5Fr-6Fr sheath in the artery. A brachial or radial artery approach can be used in cases of iliac occlusion or unfavourable angle between the aorta and renal artery. Whereas conventional aortogram is the first injection used, in cases when the indication is embolization of a bleeder, the prior CT study usually gives enough information so as to obviate the aortogram and directly proceed with cannulation of the bleeding artery. In cases where aortogram needs to be obtained for renal arteries, contrast must be injected through a pig tail catheter at a rate of 15–20 mL/s (using a pressure injector) for a total of 1–2 s. The side holes of the pigtail catheter should be positioned at the L1– L2 level. This is necessary to prevent the contrast filling the superior mesenteric artery and hence causing overlapping of images. Selective cannulation of the renal arteries is usually achieved using 4Fr/5Fr Cobra 1/Cobra 2 catheters. A reversed curve catheter such as Simmons 1 is used for a renal artery arising at an acute angle from the aorta. Positioning the detector-tube assembly in a slight LAO position (8–10 degrees) enables the renal arteries to be imaged

in profile position. The renal embolization can be either nonselective (in case of tumour or trauma) or selective (tumour haemorrhage/tumours at risk of haemorrhage such as angiomyolipomas and focal arterial injuries). Nonselective embolization is done after placement of the 4Fr/5Fr catheter into the main renal artery and confirming that there is no reflux into the aorta. If superselective embolization is the target, a 2-Fr or 3-Fr microcatheter and microwire (014″/018″) system is placed coaxially via the 4-Fr or 5-Fr catheter. The microcatheter is then advanced subselectively into the vessel/vessels of choice under road map guidance. Intermittent runs are obtained to confirm microcatheter position and embolization is performed. A final completion angiogram is performed through the microcatheter or parent catheter. The renal veins drain into the inferior cava vein. Left renal vein is longer and receives tributary veins such as left gonadal vein, suprarenal vein and phrenic vein. Right renal vein, on the other hand, is shorter, and generally does not receive tributaries. Renal venous interventions can be done from jugular as well as femoral approach.

Renal arterial injury Renal vascular (arterial) injury can be caused by percutaneous renal biopsy, laparoscopic or robotic partial nephrectomy for renal tumours, percutaneous nephrostomy tube placement, percutaneous nephrolithotomy (PCNL), abdominal trauma and open surgery. The guiding principles for treatment for all these entities remain the same and include initial imaging by ultrasound followed by acquisition of a CT angiography study to localize the bleeder and DSA for embolization. Although most cases of renal artery bleeding are mild and self-limiting and do not require intervention, immediate treatment is indicated in cases of massive bleeding manifested by a deterioration of patient’s vitals, an expanding retroperitoneal haematoma, or persistent haematuria with or without clinical symptoms. Endovascular embolization is considered the most appropriate technique to treat renal bleeders because of its less invasive nature and high success rate. Coils are the embolizing agents most suited to treat renal bleeders (Figs. 11.22.4 and 11.22.5) with NBCA (N-butyl cyanoacrylate) glue also useful in certain situations such as inability to reach close to the intended position of embolization or absence of a stump to hold the coils (Fig. 11.22.6). Use of gelfoam should be avoided in renal embolizations. The embolization should be done using superselective coaxial catheters in order to preserve noninvolved renal artery branches.

FIG. 11.22.4 Post-PCNL bleeder of right kidney presenting 12 days after procedure with drop in haemoglobin. Ultrasound (A) and Doppler (B) images show an anechoic lesion in interpolar location (arrow in a) with bidirectional colour fill in on Doppler consistent with a pseudoaneurysm. (C) Corticomedullary phase CT and nonselective renal angiogram (D) confirm the same at a lobular artery (arrows). (E) Coiling of the injured branch is done in a superselective manner with postcoiling DSA image showing occlusion of the injured artery.

FIG. 11.22.5 Post-PCNL bleeder of left kidney presenting 6 days after procedure with haematuria and drop in haemoglobin. (A) Noncontrast CT image shows a hyperdense perinephric collection (asterisk) and hyperdense contents within the collecting system (arrow) consistent with perinephric haematoma and blood in collecting system, respectively. (B) Coronal MIP image shows no obvious PSA. (C) Left renal DSA shows a small PSA arising from a lobular artery in interpolar location. (D) The injured artery is blocked using a pushable coil.

FIG. 11.22.6 Use of glue for post-PCNL bleeder. A 61-year-old man with severe haematuria 6 days after left PCNL procedure. (A) Noncontrast CT image shows acute haemorrhage (arrows) within the pelvicalyceal system, ureter and urinary bladder. (B) CT angiography image shows a large central pseudoaneurysm (arrow) at the lower pole. (C) Superselective glue injection is done into the pseudoaneurysm and the injured artery after two coils (arrows) prolapsed into the aneurysmal sac due to small stump of sac. (D)

Postembolization image shows cessation of sac filling. A) Post-PCNL arterial injury Renal haemorrhage requiring intervention is a rare complication of PCNL, and its frequency is 0.6%–1.4%. Incidence of postpercutaneous nephrolithotomy (PCNL) renal vascular injury is 0.5%–1% with significant blood loss requiring blood transfusion during or after PCNL reported at a rate of 11%– 23%. Post-PCNL arterial bleeding usually presents few weeks after PCNL. Clinical findings in such cases include severe postoperative haematuria/bleeding through the drain leading to haemodynamic instability and moderate to severe persistent postoperative haematuria. CT urography should be done to rule out intrarenal arterial injury since most cases of severe post-PCNL haemorrhage usually have an arterial cause. The study mostly reveals the pathology (pseudoaneurysm, extravasation, arteriovenous fistula, segmental arterial branch interruption, etc.) and its location and number. It also shows any renal arterial variations and helps in planning the DSA procedure. Angioembolization is highly effective in controlling bleeding from a post-PCNL bleeder. The study must include a proximal angiogram of the main renal artery in order to include any early branching of the vessel. The findings must be correlated with the CT angiography study for location, number and anatomy of the pathology. The findings may include pseudoaneurysm (in most cases), arterial transection and arteriovenous fistula formation. These may be present in isolation or be coexisting in the same case. As mentioned earlier the embolisation must be done in a superselective manner using coaxial catheters in order to preserve noninvolved renal artery branches. Both coils and NBCA-lipiodol mixture can be used to achieve embolization and the choice depends upon the anatomy and flow dynamics (Figs. 11.22.4–11.22.6). It is always important to look for lower intercostal and the lumbar arteries on DSA in case no bleeding focus is seen on renal angiogram. B) Postrenal biopsy bleeding Renal and perirenal haematomas are the most common complications to occur after percutaneous renal biopsies. Majority of these are self-limiting with no need for active intervention in

most cases. Their prevalence has reduced mainly due to the widespread use of ultrasound guidance during the procedure and use of automated biopsy devices. Potential risk factors for bleeding complications include elevated baseline blood pressure, disturbed coagulation parameters and low haemoglobin level before biopsy. The rate of major bleeding varies from 2% to 3% with transfusion required in close to 2%, and embolization in 0.4% of cases. The angiographic findings and management is similar to a postoperative arterial bleeder with embolization using coils or glue being the mainstay of endovascular treatment (Fig. 11.22.7).

FIG. 11.22.7 Endovascular management for postrenal biopsy renal bleeder. A 61-year-old lady with IgA nephropathy underwent renal biopsy following which she developed haematuria and drop in haemoglobin. (A and B) Noncontrast CT images show heterogeneity and hyperdensity in perinephric space (white arrows) consistent with an acute haematoma displacing the kidney superiorly (black arrow in b). (C) Selective left renal artery DSA shows a pseudoaneurysm (arrow) with an early draining vein (block arrow) indicating a AV fistula at the lower pole. (D) The injured artery is coiled thereby closing the pseudoaneurysm and AV fistula.

Vascular complications in transplant kidney Transplanted kidney can have various vascular complications such as arterial or venous thrombosis, arterial stenosis, postbiopsy AVF and pseudoaneurysm formation. Since grafts are placed in the iliac fossa, they are quite superficial and hence allow good penetration of the ultrasound beam. Doppler sonography is therefore extremely useful in evaluation of vascular complications in a transplant kidney. Furthermore, nonenhanced MR angiography should be considered rather than CT angiography for evaluation of the vessels in case it is needed after a Doppler examination (Fig. 11.22.8). Due to the superficial and altered axis of the graft kidney it is prone to injury of the main renal artery during biopsy and same must be guarded.

FIG. 11.22.8 Postbiopsy bleeder in a transplanted kidney. A 30-year-old man with continuing haematuria postbiopsy of a transplanted kidney underwent a MR angiography (A) which shows a small area of irregularity (arrow) in a lower pole lobular artery. (B) Nonselective DSA image does not show any abnormality but a super selective injection of the artery (C) depicts an abnormal contrast blush (arrow) which is coiled (D).

Trauma Renal injury occurs in 1%–5% of all traumas, mainly due to blunt trauma abdomen, it is usually mild and is managed conservatively.

The renal vasculature is injured in 7% of penetrating abdominal wounds and 15% of blunt trauma abdomen cases. In the majority of abdominal trauma cases (75%–80%), the renal injuries are mild and include only small renal contusions or small lacerations with preserved capsule: grades I–III AAST (American Association for the Surgery of Trauma) renal injuries. As per various studies the consensus indication to perform RAE in abdominal trauma are the presence of blunt kidney trauma grades II–IV, combined with a gross haematuria that cannot be stopped conservatively. Angiographic findings in such cases includes frank extravasation, pseudoaneurysms and arteriovenous fistulas and the treating principles for them are the same as for iatrogenic bleeders which involves selective and super selective embolization using agents such as coils, glue and PVA particles so as to spare more renal parenchyma than open surgery would do.

Arteriovenous malformations (AVMs) and arteriovenous fistulas (AVF) Renal AVMs are mostly congenital and are extremely rare with reported incidence of 0.04% at autopsy. Renal AVFs are almost always acquired with trauma and iatrogenic procedures being the causes in an overwhelming number of cases. Most AVMs remain asymptomatic throughout the life span of the patient. Symptomatic cases can present with haematuria (most common symptom), hypertension (due to steal phenomenon), flank pain, congestive cardiac failure (due to arteriovenous shunting) and haemorrhage into retroperitoneum iatrogenic renal AVFs present with haematuria. In case of AVMs, the embolization procedure aims at permanent occlusion of the nidus of the AVM and all the arterial feeders. Each of the several feeding arteries which are involved at the segmental and interlobar level needs to be examined angiographically to determine feasibility of embolization. Liquid embolizing agents such as NBCA glue and Onyx are mostly used for treatment of AVMs. Alcohol has also been used in the past for treatment of AVMs and it is an excellent sclerosant but its systemic side effects in some cases have precluded its use as the primary agent for treatment. Embolization with coils, plugs and NBCA glue is the mainstay of treatment for renal AVFs with excellent results (Fig. 11.22.9).

FIG. 11.22.9 Post-PCNL pseudoaneurysm and arteriovenous fistula. (A) DSA shows a right lower pole pseudoaneurysm (black arrow) and an arteriovenous fistula (white arrow). The renal vein shows early opacification due to the fistula. (B) Coiling of the feeding artery treats the pseudoaneurysm and fistula.

Renal artery embolization (RAE) for tumours Indications for RAE in setting of renal tumours includes palliation for advanced stage renal cell carcinoma (RCC); preoperative embolization before nephrectomy; treatment for angiomyolipoma; and as an adjunctive therapy to ablation for RCC. a) Preoperative embolization for RCC: Benefits of RAE in the preoperative setting for a large RCC include a decrease in perioperative blood loss and reduction in tumour bulk and extent of vascular thrombus, if present. There is no consensus regarding case selection for RCC for preoperative RAE but the large tumours especially those with venous extension which can be difficult to resect owing to the vascular nature of the mass are the ones most suitable for RAE (Fig. 11.22.10). Goal of embolization is devascularization of the tumour and in most cases of the involved kidney as well. Hence small gelfoam pledgets and PVA particles are the embolization agents of choice. The tumour must be embolized within 24 hours of the scheduled surgery in order to minimize chances of postembolization

syndrome. Postprocedure flank pain may be severe enough to warrant prophylactic use of analgesics. b) Renal angiomyolipoma embolization: Whereas small (4 cm). RAE is an effective nephron sparing method to treat ruptured AMLs as well as to prophylactically devascularize AMLs with size >4 cm in order to prevent complications due to rupture. Superselective embolization with PVA particles should be done in such cases (Fig. 11.22.11). With effective embolization the risk of future bleeding is reduced to 5%– 6%. About 10% cases may require repeat embolization due to tumour expansion or rebleeding in follow up.

FIG. 11.22.10 Preoperative embolization for a large left RCC. (A and B) Nephrographic phase CT images show a large infiltrative mass involving almost the entire left kidney except the lower pole with perinephric invasion and a tumour thrombus within the left renal vein (arrow in b). (C) Left renal artery was cannulated with a 5-Fr C1 catheter. The nonselective angiogram shows a large hypervascular mass at upper and interpolar regions (black arrows) corresponding to the CT study with small area of normal vascularity at lower pole (white arrow). (D) Superselective run of the upper pole shows cork screw-shaped tumour vessels with areas of microaneurysms (arrows). (E) Embolization was done for the mass using 200–300 micron size PVA particles and gelfoam. Postembolization angiogram shows devascularized upper pole and interpolar regions with preserved lower pole vascularity.

FIG. 11.22.11 Embolization for a bleeding renal angiomyolipoma in a case of tuberous sclerosis. A 32-year-old man with no previous medical history presented with acute right flank pain. (A and B) Coronal and axial contrast enhanced CT of the abdomen show multiple bilateral renal masses having areas of soft tissue and fat within consistent with bilateral angiomyolipomas (arrows). In addition note fluid within the right perinephric space (asterisk in B) reflecting haemorrhage. (C) Clinical image showing nodular lesions over the face and forehead consistent with adenoma sebaceum. (D) Axial FLAIR MR sequence of the brain shows a cortical tuber (arrow) in right high parietal lobe. (E) Right renal DSA image shows irregular arteries coursing towards the upper pole. (F) Microcatheter run of the upper pole artery shows multiple microaneurysms (arrows). (G) Post 200–300 micron size PVA and gelfoam particle embolization of the tumour there is marked reduction in its vascularity. Further course of the patient was uneventful.

Adrenal venous sampling (AVS)

AVS is performed in cases of primary aldosteronism (PA) where cross-sectional imaging is inconclusive in assessing whether endogenous hormone production is unilateral or bilateral. The differentiation is important since those with unilateral secretion (mostly due to an adenoma) can be offered surgery whereas caused of bilateral hypersecretion are managed medically. Rarely AVS may also be done in biochemically proven cases of pheochromocytoma when no secreting source is seen on cross-sectional imaging. Potassium sparing diuretics and mineralocorticoid receptor antagonists should be withheld for at least 2 weeks preceding the procedure. The patient should be adequately heparinized after obtaining venous access in the femoral vein. In the simultaneous method, both femoral veins are accessed followed by placement of a short 5/6-Fr sheaths. Catheters are then positioned in both adrenal veins (C2 or a reversed curve catheter such as Simmons 1 for left AV and a C1 for right AV) and gentle venograms obtained to confirm the positions (Fig. 11.22.12) since too strong an injection may lead to adrenal vein rupture. Using a coaxial microcatheter is also an option for selective cannulation of AVs. It is important to remember that majority of left AVs arise from proximal left renal vein whereas the right AV arises directly from the IVC and hence cannulation for the same should be tried in the appropriate areas.

FIG. 11.22.12 Bilateral adrenal venous sampling for a 40-year-old hypertensive lady with primary aldosteronism and no clear adrenal adenoma detected on cross-sectional imaging. (A) Right and (B) left adrenal venograms show the characteristic branching venous tributaries of adrenal gland. Note opacification of the renal capsular vein (arrow in a) and the inferior phrenic vein (arrow in b). Adrenal venography can have multiple appearances: a welldefined wedge-shaped glandular structure with branching veins, a delta-shaped pattern of veins, a triangular pattern of veins, spiculated veins in the shape of the gland or a nonspecific shape of veins in the expected location of the adrenal vein. On the right, collateral drainage into a hepatic vein should suggest that the selected vein is an accessory hepatic rather than the adrenal vein. Samples are obtained sequentially or simultaneously from both adrenal veins and a peripheral (usually femoral) vein. In the sequential method, the two AVs are sequentially cannulated and only a single femoral vein access is obtained.

Varicocele embolization In males, reflux of blood through incompetent gonadal veins leads to dilatation of pampiniform plexus (varicocele) which can present with infertility and scrotal pain. The condition is quite common with prevalence ranging from 5% to 20% of normal males, 30%–35% of males with primary infertility and in up to 80% of males with secondary infertility. A total of 90% of the cases are left sided since the angle of left gonadal vein with left renal vein leads to increased hydrostatic pressure within the former compared to the right gonadal vein. However, most patients are asymptomatic.

Confirmation is done by performing a Doppler examination which should demonstrate reflux into the dilated scrotal veins during Valsalva. The surgical method of treatment involves open or laparoscopic ligation of internal spermatic vein in retroperitoneum or a subinguinal microsurgical ligation. Percutaneous embolization is an excellent choice for patients having recurrence following surgery since the operative field has increased vasculature due to collaterals which can be difficult to ligate surgically as well the patient who presents with scrotal pain without infertility. On the other hand, primary surgery should be offered to varicocele presenting with infertility since data from various studies show that in presence of varicocele with reduced sperm counts, pregnancy rates improve following surgery but not so much with embolization. Surgery should also be the first choice in paediatric and young adults due to radiation concerns. The endovascular method of treatment involves cannulation of the offending gonadal vein (usually the left) with a C1 catheter. After reflux during Valsalva procedure is confirmed angiographically the gonadal vein should be embolized with either coils alone or coils along with a liquid sclerosant such as sodium tetradecyl sulphate (Fig. 11.22.13). Percutaneous pressure should be applied at the level of ipsilateral inguinal ligament while the sclerosant is injected so as to minimize the changes of pampiniform phlebitis. Care must be taken to occlude the gonadal vein and its tributaries (usually two: medial and lateral) completely so as to minimize chances of recurrence. NBCA glue can also be used to occlude the vein but is favoured less by most authors.

FIG. 11.22.13 Left varicocele embolization. (A) The left gonadal vein is cannulated using a right jugular venous access. (B) Left gonadal venogram shows the dilated pampiniform plexus of veins (white arrow) and medial and lateral tributaries of the gonadal vein (black arrows). (C) The gonadal vein was embolized with coils. (D) Postembolization venogram shows complete occlusion of the distal gonadal vein and the varicocele.

Pelvic congestion syndrome

Chronic pelvic pain has varied causes. The gynaecologic causes include fibroids, endometriosis, pelvic adhesions, chronic infections, adenomyosis and pelvic venous congestion. Pelvic congestion syndrome is a diagnosis of exclusion. This entity presents in young women of childbearing age with symptoms such as pelvic pain, dyspareunia and menstrual abnormalities. It is important to look for vulvar varices and lower extremity varicose veins which are commonly present and reflect reflux in pelvic veins. Symptoms are typically worse when standing, with sexual arousal, towards the end of the days and during menstruation. Mere presence of dilated pelvic veins on ultrasound, CT and MRI does not suggest pelvic congestion syndrome and typical unequivocal symptoms must be present and other causes of pelvic pain must be ruled out to make this diagnosis. The underlying anatomic cause is reflux in the ovarian veins with about 50% of the patients also having reflux in iliac veins and embolization of the refluxing veins is indicated in symptomatic patients in whom other causes of pelvic pain have been excluded. The surgical alternative of venous ligation and hysterectomy is less favoured since most patients are young and in premenopausal age group. After cannulation of the ovarian veins, an injection should be obtained to demonstrate retrograde flow within them along with the presence of prominent uterine venous plexus with outflow into the hypogastric veins or the contralateral normal ovarian vein. Embolization with sclerosant (sodium tetradecyl sulphate) followed by coils or plug usually achieve complete obliteration of the vein (Fig. 11.22.14). If the patient does not improve and the iliac vein also shows reflux, the same should be embolized in follow up sitting. Studies have shown an improvement in up to 70% of cases at 5 years if patient selection is good.

FIG. 11.22.14 Bilateral ovarian vein embolization for pelvic congestion syndrome. A 28-year-old lady with last child birth 2 years earlier presented with symptoms consistent with pelvic congestion syndrome. (A) Transverse axis ultrasound image of the left adnexa shows prominent tortuous channels which became prominent on performance of Valsalva (B). (C) Left ovarian venogram confirms presence of dilated veins in left parametrium with some channels coursing towards the vulva (arrow). (D) Coiling is done for the left ovarian vein. (E and F) Right ovarian venogram followed by coiling is also done.

Posttrauma priapism An uncommon presentation of pelvic trauma can be high flow priapism due to arteriocavernosal communication (fistula). It should be suspected when the patient presents with mildly painful persistent erection of the penis postperineal trauma. Its primary treatment is conservative such as ice compression for 2–3 weeks. If

it fails and the fistula persists endovascular treatment by means of coiling is an effective method to treat it while preserving potency in the majority of patients (Fig. 11.22.15). The surgical option of ligating internal pudendal artery or its branches leads to a loss of potency in a significant majority of patients.

FIG. 11.22.15 Posttrauma case of priapism treated by coiling. A 28-year-old man sustained genitoperineal trauma and presented with high flow priapism consequent to an arteriocavernosal fistula. (A and B) Ultrasound and Doppler images depict cystic spaces in right corpus cavernosum with high velocity arterial waveform within. (C) Axial CT angiography image shows contrast extravasation from the pudendal branch of the right internal iliac artery in right copora cavernosa. (D) Selective right internal iliac arteriography demonstrates contrast extravasation (arrow) from the pudendal branches in right copora cavernosa, suggesting arteriocavernosal communication. (E) Postcoiling (arrow) DSA of the artery shows cessation of the extravasation.

11.23: Genitourinary nonvascular interventions

UROGENITAL NONVASCULAR INTERVENTIONS Amithavikrama

Introduction Fallopian tube recanalization (FTR) and transrectal ultrasound guided prostatic biopsy are discussed in this chapter. Both of them are minimally invasive and less expensive procedures which make a big difference to the patients. They are usually done as an outpatient procedure.

Fallopian tube recanalization Infertility is defined as the failure to conceive after 12 months of unprotected coitus. Tubal factor is the most common cause of female infertility. Fallopian tubal adhesions or occlusions and peritoneal adhesions are usual sequel of prior pelvic inflammatory disease or endometriosis. Fallopian tubal occlusion can be proximal or distal. Distal tubal occlusions are difficult to treat by IR Techniques. However, proximal tubal occlusions are amenable for recanalization with high technical success rates of 70%–90%. FTR is a simple, cost effective and minimally invasive procedure which can be done as an OPD procedure. Indications • Proximal tubal blocks with normal distal tube. Patient preparation Procedure is done during first half of the menstrual cycle, preferably between 7–12 days. Six hours of fasting is needed. Preprocedural appropriate antibiotics to be given 2 days prior to the procedure. Mild sedation is usually helpful. Patient is placed supine as for the hysterosalphingography (HSG) procedure with slight pelvic elevation. A metallic speculum is used to visualize the cervix. Using the fallopian tube recanalization kit from Cook, a 9 French balloon catheter is passed into the uterine cavity and inflated which provides a sterile access to the cavity through which other catheters and wires can be passed. A 5F curved tip catheter and an 035 terumo wire assembly is passed through the balloon catheter and the catheter is wedged against the ostium of the fallopian tube. Contrast injection can be done to demonstrate the tubal occlusion after which the wire is gently attempted to negotiate

the occluded tube. In some difficult cases, a microcatheter and a microwire can be used to cannulate the tube. Once the wire has crossed the occluded segment, final contrast injection can be done to demonstrate the patency (Fig. 11.23.1).

FIG. 11.23.1 Fallopian tube recanalization in a young lady with primary infertility. (A) Hysterosalpingogram showing normal uterine cavity with normal and patent right fallopian tube. Left tubal ostial occlusion seen (arrow). (B) A 0.014 wire (arrow) seen within the proximal segment of the left fallopian tube. (C and D) Final HSG showing patent and normal appearing left fallopian tube (arrow) with peritoneal spillage. Patient can be discharged the same day and the antibiotics are to be continued for another 3 days. Complications • Tubal rupture • Infections like salpingitis, endometritis, adnexal infection, pelvic abscesses, etc. Tips for difficult cases

• Forceful contrast injection with the catheter wedged against the occluded ostium itself will recanalize in many cases. • Do not attempt balloon plasty of the tube as it may cause tubal rupture and epithelial damage. • Using soft tip wires prevents tubal damage. • Use premedications to avoid vasovagal attack.

Transrectal ultrasound guided prostatic biopsy TRUS guided biopsy of prostate is one of the common procedures performed in patients suspected with prostatic malignancy. Indications • To rule out malignancy in patients with raised PSA. • Patients with hard nodule in prostate on digital rectal examination. Contraindications • Uncorrectable coagulopathies • Acute urinary tract infection (UTI) including prostatitis • Immunocompromised patients • Painful rectal conditions is a relative contraindication. Patient preparation Appropriate antibiotics are started 1–2 days before the procedure and continued for 5 days. Antiplatelets and anticoagulants are stopped at least 3 days before the procedure. Patients are asked to come fasting for solid foods. Clear liquids are allowed. Enema is given to the patient 2 hours before the procedure. IV antibiotic is also given. We generally use Injection gentamicin 80 mg IV stat. Per rectal examination done and the tone of the anal sphincter is assessed. Lignocaine gel is inserted into the anal canal with a 10 mL syringe which is left behind so that it acts like a dilator prior to inserting the transrectal probe. The probe is placed at the anal orifice and slight but gradually increasing forward pressure is applied to the probe so that the tip of the probe dilates and sphincter and enters inside. After inserting the transrectal probe into the rectum, the prostate is imaged to look for any suspicious nodules in the peripheral zone. The biopsy is usually done under periprostatic block which is usually given at the base of the prostate, just inferior to the seminal vesicle, using 22G chiba needle. A study by Mustafa Hiros has shown significant reduction in the pain score in patients who underwent TRUS biopsy of prostate after periprostatic block. At our

institution, we take the standard 12 core biopsies, two in each sextant of the prostate, one of them being as peripheral as possible (Fig. 11.23.2). In our experience, if the PSA value is more than 100, six core biopsy is sufficient. Biopsies are done using 18G core biopsy needle (Fig. 11.23.3).

FIG. 11.23.2 Illustration showing 6 core and 12 core biopsy sites within the peripheral zone of prostate.

FIG. 11.23.3 TRUS image guided prostatic biopsy. Image showing the needle trajectory (arrow) into the peripheral zone of the right lobe of prostate.

Postprocedure, patient is counselled about the haematochezia/haematuria/haematospermia which usually subsides in a day or two. In case of urinary retention due to significant bladder clots, patient is asked to return to the emergency department for catheterization. Advancements in prostatic biopsy: MR imaging directed prostatic biopsy: In this technique, prior MR imaging of prostate is performed to localize the suspicious lesion. The standard T2W imaging, diffusion weighted imaging and dynamic contrast imaging sequences are routinely used. Additional MR spectroscopy provides more accurate characterization of the lesion. Then real time ultrasound guidance is used to biopsy the suspicious lesion. MR imaging guided prostatic biopsy: In this technique, MR imaging is used to localize the abnormal lesion and targeted biopsy of the lesion is done by using real time MR imaging guidance. This is made possible by the availability of MR compatible biopsy needle, biopsy device with attached needle guides and faster MR sequences. In this method, different studies have been done with transgluteal, transperineal or transrectal approaches for targeting the lesions. Complications • Bleeding – haematochezia/haematuria/haematospermia. • Urinary clots and bladder outlet obstruction. • Infection. Tips for difficult cases • Use serial anal dilators in case of severe spasm of sphincters. • General anaesthesia helps in relaxing the sphincters. • Valsalva will sometimes help in targeting small nodules which otherwise slip away.

11.24: Recent advances in reproductive system 1 1 .24 .1

MULTIPARAMETRIC MRI OF THE PROSTRATE Dayala Sundaram

Introduction Worldwide prostate cancer is the most common solid organ malignancy and the second most common cancer in men. The incidence of prostate cancer in India is 3.9 per 100,000 men and contributes 9% of all cancer-related mortality. Traditionally, serum prostate specific antigen (PSA) and digital rectal examination (DRE) are used as screening tools, and systematic transrectal ultrasound (TRUS)-guided biopsy is considered as the gold standard for confirmation for the detection of cancer prostate. Nevertheless, this combined approach has led to the risk of overdiagnosis and overtreatment of clinically insignificant low volume and indolent tumours. On the other hand, tumour in the anterior aspect of the gland tends to be missed by TRUS-guided biopsy until they grow to a substantial size and reach within 15–20 mm from the posterior margin, leading to delayed diagnosis. Moreover, systematic TRUS biopsy has also proven to underestimate the final Gleason score of the tumour following radical prostatectomy, leading to inaccurate triaging and selection of therapeutic options. Multiparametric magnetic resonance imaging (mpMRI) changed the paradigms on prostate cancer detection. It struck a balance between underdiagnosis and overdiagnosis with a clinical priority not to miss any clinically significant cancer (Gleason score ≥4 + 3, and/or volume ≥0.5 cc, and/or extraprostatic extension). Initially, MRI was not used for the primary detection of the tumour, but it was mainly used for locoregional staging in biopsy-proven patients since it provided only morphologic information with T1-weighted imaging (TIW) and T2-weighted imaging (T2WI). Ever since the introduction

of mpMRI, which combines the morphological assessment of T2WI and molecular and physiologic assessment by diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging, it has been used in primary tumour detection as well as staging. Over the period, mpMRI has been proven to have high sensitivity and negative predictive value (NPV) in diagnosing clinically significant prostate cancer, however, with more variable specificity. A positive association has also been established between abnormal mpMRI and increased tumour volume and high grade. Overall, the introduction of mpMRI has changed the traditional diagnostic pathway in the management of prostate cancer (Fig. 11.24.1.1).

FIG. 11.24.1.1 Diagnostic pathway of cancer prostate. Efforts were taken to improve the global standardization in image acquisition, interpretation and reporting of mpMRI of prostate and prostate imaging reporting and data system (PI-RADS) was introduced in 2012. T1WI, T2WI, DWI, DCE and spectroscopy were identified as the key sequences. In 2015, PI-RADS version 2 (v2) was released with the inclusion of key advancements in image acquisition and incorporation of a five-point final assessment scoring system for peripheral zone (PZ) and transition zone (TZ). Spectroscopy was excluded in PI-RADS v2. The recent update, PI-RADS version 2.1 (v2.1), proposed in 2019, endorses small adjustments to obviate ambiguities in the scoring system and reduces inter-reader variability. PI-RADS is intended for detection, localization and risk stratification in patients with suspected cancer in the prostate gland and staging the confirmed cases. However, detection of recurrence,

progression during active surveillance and evaluation of other parts of the body (e.g. skeletal system) are not included in PI-RADS.

Indications for mpMRI a. Patients with raised PSA, strong family history, known genetic predispositions, elevated urinary genomics scores – mpMRI may precisely localize the suspicious area for a targeted biopsy. b. Patients with prior negative biopsies with an unexplained rise in PSA values – mpMRI may help to diagnose a previously missed lesion on random biopsy. c. In patients with low-risk malignancy who are on active surveillance, presents with fast PSA doubling times – mpMRI is the decision-making tool for continued surveillance or definitive treatment. d. In patients with prior prostate interventions known to change prostate morphology (TRUS/TURP/hormonal therapy/radiotherapy) – mpMRI will be more useful to diagnose the hidden tumour. e. In biopsy-proven patients, mpMRI can be used for local staging. Preoperative mpMRI is a useful tool in patients with high-risk disease to evaluate the extracapsular extension; however, in patients with the low-risk disease, it may not have any added advantage over the standard staging tools.

Contraindications a. Contraindications to MRI examination: MRI unsafe pacemakers, implantable cardioverter defibrillators (ICDs), ferromagnetic metallic vascular clips, neurostimulation systems, cochlear implants, medication pumps, metallic foreign bodies and severe claustrophobia. b. Contraindications for gadolinium chelate contrast agents: Prior adverse reaction to MRI contrast agent and poor renal function (estimated glomerular filtration rate [eGFR] 4 cm but ≤7 cm in greatest dimension, limited to the kidney T2 Tumour >7 cm in greatest dimension, limited to the kidney T2a Tumour >7 cm but ≤10 cm in greatest dimension, limited to the kidney T2b Tumour >10 cm, limited to the kidney T3 Tumour extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond the Gerota’s fascia T3a Tumour grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumour invades perirenal and/or renal sinus fat but not beyond the Gerota’s fascia T3b Tumour grossly extends into the vena cava below the diaphragm T3c Tumour grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava T4 Tumour invades beyond the Gerota’s fascia (including contiguous extension into the ipsilateral adrenal gland) REGIONAL LYMPH NODE (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in regional lymph node(s) DISTANT METASTASIS (M) M0 No distant metastasis M1 Distant metastasis

TABLE 11.25.1.3 Anatomic Stage/Prognostic Groups Stage I

T T1

N N0

M M0

II

T2

N0

M0

III

T1–2

N1

M0

T3

NX, N0 or N1

M0

T4

Any N

M0

Any T

Any N

M1

IV

Localized renal cancer Localized renal cancer is defined as a disease confined to the renal capsule and refers mainly to stage I and II disease. Nearly 70% of RCCs, especially the lower-stage lesions, are incidentally diagnosed on cross-sectional imaging. Also, amongst incidentally diagnosed renal lesions less than 4 cm in size, about 20% turn out to be benign on histopathology. Asymptomatic incidentally diagnosed small renal masses have an indolent course and better prognosis. Nephron-sparing surgery (NSS) has gathered momentum in recent years due to promising results and prognoses in small lesions. The 2017 AUA guidelines for localized renal masses describe restricted and well-defined indications for radical nephrectomy, bigger role of nephron-sparing procedures such as partial nephrectomy, tumour enucleation and thermal ablation, as well as increasing role for biopsy as well as active surveillance of such lesions. Hence, imaging findings in these lesions become critical in charting management of these patients. The imaging features of common histopathological subtypes of RCCs have already been discussed above. Signal intensity on T2W images and corticomedullary phase enhancement have been seen to be independent predictors of clear cell and papillary RCCs. Further, T2 signal homogeneity can be a predictor for slower growth rate. Hence, in general, multiparametric MRI studies have been shown to be effective in small renal mass characterization and can subsequently guide decisions regarding biopsy, surgery or surveillance. CT is a good alternative in patients with contraindication to MRI. For cystic renal lesions, the Bosniak classification, which stratifies the risk of neoplasia in cystic renal lesions based on the complexity of their appearance (wall thickness, septations, solid

component), can be used effectively to decide further course of management. The Bosniak classification originally applies to CT findings but can logically be extrapolated to MRI, USG and Contrast Enhanced Ultrasound (CEUS) as well. Bosniak I and II cysts are benign while Bosniak IIF, III and IV cysts show progressively increasing risk of neoplasia. Given the more indolent course of cystic RCCs as compared to solid lesions and possible complications of interventions, lately there has been a case for even the type III and IV cysts, which previously would be operated, to be followed up, especially if patient has existing comorbidities or if the solid component is minimal. Initial follow-up would be at 6 months, followed by annual imaging. AUA 2017 guidelines recommend considering renal mass biopsy if haematologic, metastatic, inflammatory or infectious aetiology is suspected. Once the need for surgery is established in a localized disease, NSS may be considered for stage Ia and Ib disease. To predict perioperative outcomes in NSS, various scoring systems have been proposed for preoperative renal mass evaluation, such as R.E.N.A.L. nephrometry score, PADUA score (Preoperative aspects and dimensions used for anatomical classification), C-index method and mathematical tumour contact surface area (CSA). The popular R.E.N.A.L. nephrometry score takes into account various tumour descriptors that help decide the technical feasibility of NSS and predict surgical outcomes. These include tumour radius, exo/endophytic location, nearness to collecting system or renal sinus, anterior/posterior location and location with reference to polar lines. These descriptors need to be commented upon diligently while reporting renal masses (Table 11.25.1.4). Higher scores are seen to correlate with ischaemia time, postoperative urologic complications, higher grade and mortality.

TABLE 11.25.1.4 R.E.N.A.L. Nephrometry Score Component R (radius, maximal diameter) (cm) E (exophytic/endophytic) N (nearness to collecting system/renal sinus) (mm) A (anterior/posterior locator)

L (location relative to polar lines)

1 Point ≤4 ≥50% exophytic ≥7

SCORE 2 Points >4 but