Maingot's Abdominal Operations. 13th edition [13 ed.] 0071843078, 9780071843072

Table of contents :
Cover
Cover
Title Page
Copyright Page
Contents
Contents
Contributors
Preface
I Introduction
1. Gastrointestinal Surgery: A Historical Perspective
2. Preoperative and Postoperative Management
3. Enhanced Recovery Programs for Gastrointestinal Surgery
4. Performance Measurement and Improvement in Surgery
5. Endoscopy and Endoscopic Intervention
6. Fundamentals of Laparoscopic Surgery
7. Minimally Invasive Approaches to Cancer
8. Robotics in Gastrointestinal Surgery
9. Pediatric GI Surgery
II Abdominal Wall
10. Incisions, Closures, and Management of the Abdominal Wound
11. Inguinal Hernia
12. Perspective on Inguinal Hernias
13. Ventral and Abdominal Wall Hernias
14. Perspectives on Laparoscopic Incisional Hernia Repair
15. Intestinal Stomas
16. Abdominal Abscess and Enteric Fistulae
17. Gastrointestinal Bleeding
18. Lesions of the Omentum, Mesentery, and Retroperitoneum
19. Abdominal Trauma
20. Abdominal Vascular Emergencies
III Esophagus
21. Esophageal Diverticula and Benign Tumors
22. Achalasia and Other Motility Disorders
23. Gastroesophageal Reflux Disease, Hiatal Hernia, and Barrett Esophagus
24. Paraesophageal Hernia Repair
25. Perspectives Regarding Benign Foregut Diseases and Their Surgeries
26. Cancer of the Esophagus
27. Surgical Procedures to Resect and Replace the Esophagus
28. Perspective on Cancer of the Esophagus and Surgical Procedures to Resect and Replace the Esophagus
IV Stomach and Duodenum
29. Benign Gastric Disorders
30. Gastric Atony
31. Gastric Adenocarcinoma and Other Neoplasms
32. Perspective on Gastric Cancer
33. Gastrointestinal Stromal Tumors
34. Perspective on Gastrointestinal Stromal Tumors
35. Stomach and Duodenum: Operative Procedures
36. Morbid Obesity, Metabolic Syndrome, and Nonsurgical Weight Management
37. Surgical Treatment of Morbid Obesity and Type 2 Diabetes
V Intestine and Colon
38. Small Bowel Obstruction
39. Tumors of the Small Intestine
40. Carcinoid Tumors and Carcinoid Syndrome
41. Appendix and Small Bowel Diverticula
42. Short Bowel Syndrome and Intestinal Transplantation
43. Diverticular Disease and Colonic Volvulus
44. Colonic Volvulus
45. Crohns Disease
46. Ulcerative Colitis
47. Perspective on Inflammatory Bowel Disease
48. Hereditary Colorectal Cancer and Polyposis Syndromes
49. Tumors of the Colon
50. Laparoscopic Colorectal Procedures
51. Perspective on Colorectal Neoplasms
VI Rectum and Anus
52. Benign Disorders of the Anorectum (Pelvic Floor, Fissures, Hemorrhoids, and Fistulas)
53. Constipation and Incontinence
54. Cancer of the Rectum
55. Cancer of the Anus
VII Liver
56. Hepatic Abscess and Cystic Disease of the Liver
57. Benign Liver Neoplasms
58. Malignant Liver Neoplasms
59. Treatment of Hepatic Metastasis
60. Perspective on Liver Resection
61. Portal Hypertension
VIII Gallbladder and Bile Ducts
62. Cholelithiasis and Cholecystitis
63. Choledocholithiasis and Cholangitis
64. Choledochal Cyst and Benign Biliary Strictures
65. Cancer of the Gallbladder and Bile Ducts
66. Laparoscopic Biliary Procedures
67. Perspective on Biliary Chapters
IX Pancreas
68. Management of Acute Pancreatitis
69. Complications of Acute Pancreatitis
70. Perspective on Management of Patients with Acute Pancreatitis
71. Chronic Pancreatitis
72. Cystic Neoplasms of the Pancreas
73. Cancers of the Periampullary Region and Pancreas
74. Endocrine Tumors of the Pancreas
75. Perspective on Pancreatic Neoplasms
76. Complications of Pancreatectomy
X Spleen and Adrenal
77. The Spleen
78. Adrenal Anatomy and Physiology
Index
Index

Citation preview

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CONTENTS Contributors Preface

INTRODUCTION 1. Gastrointestinal Surgery: A Historical Perspective David L. Nahrwold 2. Preoperative and Postoperative Management Zara Cooper / Edward Kelly 3. Enhanced Recovery Programs for Gastrointestinal Surgery Anthony J. Senagore 4. Performance Measurement and Improvement in Surgery Andrew M. Ibrahim / Justin B. Dimick 5. Endoscopy and Endoscopic Intervention Nabil Tariq / Jeff Van Eps / Brian J. Dunkin 6. Fundamentals of Laparoscopic Surgery Fernando Mier / John G. Hunter 7. Minimally Invasive Approaches to Cancer Jonathan C. King / Herbert J. Zeh, III 8. Robotics in Gastrointestinal Surgery

Yanghee Woo / Yuman Fong 9. Pediatric GI Surgery Tina Thomas / Cabrini Sutherland / Ronald B. Hirschl

ABDOMINAL WALL 10. Incisions, Closures, and Management of the Abdominal Wound Robert E. Roses / Jon B. Morris 11. Inguinal Hernia Natalie Liu / Jacob A. Greenberg / David C. Brooks 12. Perspective on Inguinal Hernias Parth K. Shah / Robert J. Fitzgibbons, Jr. 13. Ventral and Abdominal Wall Hernias Andrew Bates / Mark Talamini 14. Perspectives on Laparoscopic Incisional Hernia Repair Camille Blackledge / Mary T. Hawn 15. Intestinal Stomas Cindy Kin / Mark Lane Welton 16. Abdominal Abscess and Enteric Fistulae Joao B. Rezende Neto / Jory S. Simpson / Ori D. Rotstein 17. Gastrointestinal Bleeding Eric G. Sheu / Ali Tavakkoli 18. Lesions of the Omentum, Mesentery, and Retroperitoneum Tara A. Russell / Fritz C. Eilber 19. Abdominal Trauma L.D. Britt / Jessica Burgess

20. Abdominal Vascular Emergencies John J. Ricotta / Cameron M. Akbari

ESOPHAGUS 21. Esophageal Diverticula and Benign Tumors Marco E. Allaix / Marco G. Patti 22. Achalasia and Other Motility Disorders Jeffrey A. Blatnik / Jeffrey L. Ponsky 23. Gastroesophageal Reflux Disease, Hiatal Hernia, and Barrett Esophagus Robert D. Bennett / David M. Straughan / Vic Velanovich 24. Paraesophageal Hernia Repair Jeffrey A. Blatnik / L. Michael Brunt 25. Perspectives Regarding Benign Foregut Diseases and Their Surgeries Lee L. Swanstrom / Silvana Perretta 26. Cancer of the Esophagus Daniel King Hung Tong / Simon Law 27. Surgical Procedures to Resect and Replace the Esophagus Jon O. Wee / Shelby J. Stewart / Raphael Bueno 28. Perspective on Cancer of the Esophagus and Surgical Procedures to Resect and Replace the Esophagus Joshua A. Boys / Tom R. DeMeester

STOMACH AND DUODENUM 29. Benign Gastric Disorders

Ian S. Soriano / Kristofell R. Dumon / Daniel T. Dempsey 30. Gastric Atony Rian M. Hasson / Scott A. Shikora 31. Gastric Adenocarcinoma and Other Neoplasms Waddah B. Al-Refaie / Young K. Hon / Jennifer F. Tseng 32. Perspective on Gastric Cancer Hisashi Shinohara / Mitsuru Sasako 33. Gastrointestinal Stromal Tumors Nicole J. Look Hong / Chandrajit P. Raut 34. Perspective on Gastrointestinal Stromal Tumors Michael J. Cavnar / Ronald P. DeMatteo 35. Stomach and Duodenum: Operative Procedures Joyce Wong / David I. Soybel / Michael J. Zinner 36. Morbid Obesity, Metabolic Syndrome, and Nonsurgical Weight Management Ali Tavakkoli 37. Surgical Treatment of Morbid Obesity and Type 2 Diabetes Bruce D. Schirmer

INTESTINE AND COLON 38. Small Bowel Obstruction Kristina L. Go / Janeen R. Jordan / George A. Sarosi, Jr. / Kevin E. Behrns 39. Tumors of the Small Intestine Michael M. Reader / Barbara Lee Bass 40. Carcinoid Tumors and Carcinoid Syndrome

Teresa S. Kim / Liliana G. Bordeianou / Richard A. Hodin 41. Appendix and Small Bowel Diverticula Arin L. Madenci / William H. Peranteau / Douglas S. Smink 42. Short Bowel Syndrome and Intestinal Transplantation Diego C. Reino / Douglas G. Farmer 43. Diverticular Disease and Colonic Volvulus Timothy Eglinton / Frank A. Frizelle 44. Colonic Volvulus Christina M. Papageorge / Eugene F. Foley 45. Crohn’s Disease Heather Yeo / Alessandro Fichera / Roger D. Hurst / Fabrizio Michelassi 46. Ulcerative Colitis Christina W. Lee / Freddy Caldera / Tiffany Zens / Gregory D. Kennedy 47. Perspective on Inflammatory Bowel Disease Patricia L. Roberts 48. Hereditary Colorectal Cancer and Polyposis Syndromes Jennifer L. Irani / Elizabeth Breen / Joel Goldberg 49. Tumors of the Colon Trevor M. Yeung / Neil J. Mortensen 50. Laparoscopic Colorectal Procedures Dorin Colibaseanu / Heidi Nelson 51. Perspective on Colorectal Neoplasms Martin R. Weiser

RECTUM AND ANUS

52. Benign Disorders of the Anorectum (Pelvic Floor, Fissures, Hemorrhoids, and Fistulas) James W. Fleshman, Jr. / Anne Y. Lin 53. Constipation and Incontinence Alexander T. Hawkins / Liliana G. Bordeianou 54. Cancer of the Rectum Joel Goldberg / Ronald Bleday 55. Cancer of the Anus Najjia N. Mahmoud

LIVER 56. Hepatic Abscess and Cystic Disease of the Liver Nikolaos A. Chatzizacharias / Kathleen K. Christians / Henry A. Pitt 57. Benign Liver Neoplasms Kevin C. Soares / Timothy M. Pawlik 58. Malignant Liver Neoplasms Sameer H. Patel / Guillaume Passot / Jean-Nicolas Vauthey 59. Treatment of Hepatic Metastasis Sean M. Ronnekleiv-Kelly / Sharon M. Weber 60. Perspective on Liver Resection Jordan M. Cloyd / Timothy M. Pawlik 61. Portal Hypertension Douglas W. Hanto / Sunil K. Geevarghese / Christopher Baron

GALLBLADDER AND BILE DUCTS

62. Cholelithiasis and Cholecystitis Ezra N. Teitelbaum / Nathaniel J. Soper 63. Choledocholithiasis and Cholangitis Yu Liang / David W. McFadden / Brian D. Shames 64. Choledochal Cyst and Benign Biliary Strictures Purvi Y. Parikh / Keith D. Lillemoe 65. Cancer of the Gallbladder and Bile Ducts Jason S. Gold / Michael J. Zinner / Edward E. Whang 66. Laparoscopic Biliary Procedures Alexander Perez / Theodore N. Pappas 67. Perspective on Biliary Chapters Steven M. Strasberg

PANCREAS 68. Management of Acute Pancreatitis Thomas E. Clancy 69. Complications of Acute Pancreatitis John A. Windsor / Benjamin P.T. Loveday / Sanjay Pandanaboyana 70. Perspective on Management of Patients with Acute Pancreatitis Stefan A.W. Bouwense / Hjalmar C. van Santvoort / Marc G.H. Besselink 71. Chronic Pancreatitis Marshall S. Baker / Jeffrey B. Matthews 72. Cystic Neoplasms of the Pancreas Michael J. Pucci / Charles J. Yeo 73. Cancers of the Periampullary Region and Pancreas

Csaba Gajdos / Martin McCarter / Barish Edil / Alessandro Paniccia / Richard D. Schulick 74. Endocrine Tumors of the Pancreas Mary E. Dillhoff / E. Christopher Ellison 75. Perspective on Pancreatic Neoplasms Douglas B. Evans 76. Complications of Pancreatectomy Mu Xu / O. Joe Hines

SPLEEN AND ADRENAL 77. The Spleen Liane S. Feldman / Amani Munshi / Mohammed Al-Mahroos / Gerald M. Fried 78. Adrenal Anatomy and Physiology David Harris / Daniel Ruan Index

CONTRIBUTORS Cameron M. Akbari, MD, MBA, FACS Senior Attending Physician, Vascular Surgery Director, Vascular Diagnostic Laboratory Medstar Washington Hospital Center Washington, DC Marco E. Allaix, MD, PhD Assistant Professor in General Surgery Department of Surgical Sciences University of Torino Torino, Italy Mohammed Al-Mahroos, MD Fellow, Minimally Invasive Surgery McGill University Montreal, Quebec, Canada Waddah B. Al-Refaie, MD, FACS John S. Dillon Professor and Chief of Surgical Oncology MedStar Georgetown University Hospital Georgetown Lombardi Comprehensive Cancer Center Washington, DC Marshall S. Baker, MD, MBA Clinical Associate Professor of Surgery Loyola University Chicago Stritch School of Medicine

Maywood, Illinois Christopher Baron, MD Assistant Professor Department of Interventional Radiology Vanderbilt University Hospital Nashville, Tennessee Barbara Lee Bass, MD Bookout Distinguished Presidential Endowed Chair Chair, Department of Surgery Houston Methodist Hospital Professor of Surgery Weill Cornell Medical College and Houston Methodist Institute for Academic Medicine Full Member Houston Methodist Research Institute Houston, Texas Andrew Bates, MD Department of Surgery Stony Brook University Hospital Stony Brook, New York Kevin E. Behrns, MD Vice President Medical Affairs Dean, School of Medicine St. Louis University St. Louis, Missouri Robert D. Bennett, MD Resident in General Surgery Department of Surgery University of South Florida Tampa, Florida

Marc G. H. Besselink, MD, MSc, PhD Professor of Pancreatic and Hepatobiliary Surgery Department of Surgery, Cancer Center Amsterdam Amsterdam UMC, University of Amsterdam Amsterdam, the Netherlands Camille Blackledge, MD Fellow, Division of Gastrointestinal Surgery Department of Surgery University of Alabama at Birmingham School of Medicine Birmingham, Alabama Jeffrey A. Blatnik, MD Assistant Professor of Surgery Department of Surgery, Section of Minimally Invasive Surgery Washington University School of Medicine St. Louis, Missouri Ronald Bleday, MD Chief Section of Colon and Rectal Surgery Associate Chair for Quality and Safety Department of Surgery Brigham and Women’s Hospital Associate Professor of Surgery Harvard Medical School Boston, Massachusetts Liliana G. Bordeianou, MD, MPH Chair, Colorectal Surgery Center Massachusetts General Hospital Associate Professor of Surgery Harvard Medical School Boston, Massachusetts Stefan A. W. Bouwense, MD, PhD

Fellow, Gastrointestinal Surgery Radboud University Medical Center Department of Surgery Nijmegen, the Netherlands Joshua A. Boys, MD Cardiothoracic Surgery Fellow General Thoracic Surgery Section University of Virginia Department of Surgery Division of Cardiothoracic and Vascular Surgery University of Virginia School of Medicine Charlottesville, Virginia Elizabeth Breen, MD Colon and Rectal Surgeon Lahey Hospital and Medical Center Program Director Colon and Rectal Surgery Residency Lahey Hospital and Medical Center Burlington, Massachusetts L. D. Britt, MD, MPH, DSc (Hon), FACS, FCCM, FRCSEng(Hon), FRCSEd(Hon), FWACS(Hon), FRCSI(Hon), FSC(SA)(Hon), FRCS(Glasg)(Hon) Henry Ford Professor and Edward J. Brickhouse Chairman Eastern Virginia Medical School Norfolk, Virginia David C. Brooks, MD, FACS Director of Minimally Invasive Surgery Senior Surgeon Brigham and Women’s Hospital Associate Professor of Surgery Harvard Medical School Boston, Massachusetts L. Michael Brunt, MD

Section Chief, Minimally Invasive Surgery Department of Surgery Washington University School of Medicine St. Louis, Missouri Raphael Bueno, MD Fredric G Levin Distinguished Chair in Thoracic Surgery and Lung Cancer Research Chief, Division of Thoracic Surgery Co-Director, The Lung Center and the Lung Research Center Brigham and Women’s Hospital Professor of Surgery Harvard Medical School Boston, Massachusetts Jessica Burgess, MD, FACS Assistant Professor Department of Surgery Eastern Virginia Medical School Norfolk, Virginia Freddy Caldera, DO, MS Assistant Professor Department of Gastroenterology and Hepatology University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Michael J. Cavnar, MD Assistant Professor Department of Surgery Section of Surgical Oncology University of Kentucky Lexington, Kentucky Nikolaos A. Chatzizacharias, MD, PhD Medical College of Wisconsin

Milwaukee, Wisconsin Kathleen K. Christians, MD Medical College of Wisconsin Milwaukee, Wisconsin Thomas E. Clancy, MD Division of Surgical Oncology Brigham and Women’s Hospital Dana-Farber Cancer Institute Assistant Professor of Surgery, Harvard Medical School Boston, Massachusetts Jordan M. Cloyd, MD Assistant Professor of Surgery Division of Surgical Oncology The Ohio State University Wexner Medical Center Columbus, Ohio Dorin Colibaseanu, MD Vice Chair of Education Department of Surgery Assistant Professor of Surgery Mayo Clinic Jacksonville, Florida Zara Cooper, MD, MSc, FACS Associate Professor Department of Surgery Associate Chair of Faculty Development Department of Trauma Burn and Surgical Critical Care Brigham and Women’s Hospital Boston, Massachusetts Ronald P. DeMatteo, MD, FACS John Rhea Barton Professor and Chair

Department of Surgery Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania Tom R. DeMeester, MD The Jeffrey P. Smith Professor of General and Thoracic Surgery Chairman Department of Surgery, Emeritus Keck School of Medicine University of Southern California Los Angeles, California Daniel T. Dempsey, MD, MBA Professor of Surgery Perelman School of Medicine University of Pennsylvania Assistant Director of Perioperative Services Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Mary E. Dillhoff, MD, MS Assisatnt Professor of Surgery Department of Surgery The Ohio State University Columbus, Ohio Justin B. Dimick, MD, MPH George D. Zuidema Professor of Surgery Chief of the Division of Minimally Invasive Surgery Director, Center for Healthcare Outcomes and Policy Associate Chair for Strategy and Finance Department of Surgery, University of Michigan Ann Arbor, Michigan Kristofell R. Dumon, MD, FACS

Associate Professor of Surgery Department of Surgery Hospital Penn Medicine Philadelphia, Pennsylvania Brian J. Dunkin, MD, FACS Professor of Surgery Weill Cornell Medical College John F., Jr. and Carolyn Bookout Chair in Surgical Innovation & Technology Medical Director Houston Methodist Institute for Technology, Innovation, and Education (MITIE) Houston Methodist Hospital Houston, Texas Barish Edil, MD, FACS Associate Professor of Surgery Chief, Section of Surgical Oncology University of Colorado at Denver Denver, Colorado Timothy Eglinton, MBChB, MMedSc, FRACS, FACS, FCSSANZ Associate Professor Department of Surgery University of Otago Christchurch, New Zealand Fritz C. Eilber, MD Professor of Surgery Professor of Molecular and Medical Pharmacology Director UCLA—JCCC Sarcoma Program UCLA Division of Surgical Oncology Los Angeles, California E. Christopher Ellison, MD Academy Professor

Robert M. Zollinger Professor Emeritus Department of Surgery The Ohio State University College of Medicine Columbus, Ohio Douglas B. Evans, MD Professor and Chair Department of Surgery Medical College of Wisconsin Milwaukee, Wisconsin Douglas G. Farmer, MD, FACS Professor of Surgery Surgical Director, Pediatric Liver Transplantation Surgical Director, Intestinal Transplantation Division of Liver and Pancreas Transplantation David Geffen School of Medicine at UCLA Los Angeles, California Liane S. Feldman, MD Steinberg-Bernstein Chair of Minimally Invasive Surgery and Innovation McGill University Health Centre Director, Division of General Surgery McGill University Montreal, Quebec, Canada Alessandro Fichera, MD, FACS, FASCRS Professor and Division Chief Gastrointestinal Surgery Department of Surgery University of North Carolina Chapel Hill, North Carolina Robert J. Fitzgibbons, Jr., MD, FACS Harry E. Stuckenhoff Professor and Chairman Department of Surgery Creighton University School of Medicine

Co-editor in Chief, Hernia CHI Health Creighton University-Bergan Mercy Omaha, Nebraska James W. Fleshman, Jr., MD Sparkman Endowed Chair in Surgery Chairman, Department of Surgery Baylor University Medical Center Professor of Surgery Texas A&M Health Science Center Dallas, Texas Eugene F. Foley, MD, FACS Susan Behren’s MD, Professor and Chair of Surgical Education Vice Chair for Education Chief, Division of Colon and Rectal Surgery Department of Surgery University of Wisconsin Madison, Wisconsin Yuman Fong, MD, Sc.D. (Hon) Chairman Department of Surgery City of Hope Medical Center Duarte, California Gerald M. Fried, MD Edward W. Archibald Professor and Chair Department of Surgery McGill University Surgeon-in-Chief, McGill University Health Centre Montreal, Quebec, Canada Frank A. Frizelle, MBChB, MMedSci, FRACS, FACS, FASCRS, FRCSI (Hon), FNZMA Professor Head of University Department of Surgery

Department of Surgery Christchurch Hospital University of Otago Christchurch, New Zealand Csaba Gajdos, MD, FACS Clinical Associate Professor of Surgery Department of Surgery Jacobs School of Medicine and Biomedical Science Buffalo, New York Sunil K. Geevarghese, MD, MSCI, FACS Medical Director, Acute Operations and Transplant Perioperative Services Program Director, Vanderbilt ASTS Transplant and Hepatobiliary Surgery Fellowship Associate Professor of Surgery, Radiology and Radiological Sciences Division of Hepatobiliary Surgery and Liver Transplantation Vanderbilt University Medical Center Nashville, Tennessee Kristina L. Go, MD Chief Resident University of Florida Department of Surgery Gainesville, Florida Jason S. Gold, MD Chief of Surgical Oncology, VA Boston Healthcare System Associate Professor of SurgeryHarvard Medical School Brigham and Women’s Hospital West Roxbury, Massachusetts Joel Goldberg, MD, MPH, FACS Assistant Professor of Surgery Harvard Medical School Colon and Rectal Surgery

Brigham and Women’s Hospital Boston, Massachusetts Jacob A. Greenberg, MD, EdM Associate Professor of Surgery General Surgery Residency Program Director University of Wisconsin Department of Surgery Madison, Wisconsin Douglas W. Hanto, MD, PhD Deputy Chief of Surgery VA St. Louis Health Care System St. Louis, Missouri Lewis Thomas Professor of Surgery Emeritus Harvard Medical School Boston, Massachusetts David Harris, MD Clinical Fellow in Surgery (EXT) Brigham and Women’s Hospital Department of Surgery Boston, Massachusetts Rian M. Hasson Charles, MD Assistant Professor of Surgery Department of Surgery, Section of Thoracic Surgery Dartmouth-Hitchcock Medical Center Geisel School of Medicine at Dartmouth Lebanon, New Hampshire Alexander T. Hawkins, MD, MPH Assistant Professor of Surgery Vanderbilt University Medical Center Nashville, Tennessee

Mary T. Hawn, MD, MPH Professor, Chief of Gastrointestinal Surgery Department of Surgery University of Alabama at Birmingham School of Medicine Birmingham, Alabama O. Joe Hines, MD, FACS Professor and Chief Division of General Surgery Robert and Kelly Day Chair in General Surgery Vice Chair for Administration Department of Surgery David Geffen School of Medicine University of California at Los Angeles Los Angeles, California Ronald B. Hirschl, MD, MS Professor of Pediatric Surgery Department of Surgery Mott Children’s Hospital University of Michigan Ann Arbor, Michigan Richard A. Hodin, MD Chief of Academic Affairs Department of Surgery Massachusetts General Hospital Professor of Surgery, Harvard Medical School Boston, Massachusetts Nicole J. Look Hong, MD, MSc, FRCSC Division of Surgical Oncology Sunnybrook Health Sciences Centre Assistant Professor of Surgery University of Toronto

Toronto, Canada Young K. Hong, MD Surgical Oncology Fellow Division of Surgical Oncology University of Louisville Louisville, Kentucky John G. Hunter, MD, FACS Executive Vice President and Chief Executive Officer, OHSU Health System Mackenzie Professor, OHSU School of Medicine Oregon Health & Science University Portland, Oregon Roger D. Hurst, MD Professor of Surgery University of Chicago Pritzker School of Medicine Chicago, Illinois Andrew M. Ibrahim, MD, MSc Robert Wood Johnson Clinical Scholar Institute for Healthcare Policy & Innovation, University of Michigan House Staff, General Surgery University Hospitals Case Medical Center Ann Arbor, Michigan Jennifer L. Irani, MD Assistant Professor of Surgery Harvard Medical School Associate Surgeon, General and Gastrointestinal Surgery Brigham and Women’s Hospital and Dana-Farber Cancer Institute Boston, Massachusetts Janeen R. Jordan, MD Critical Care (Intensivist) General Surgery

Orange Park Surgical Associates Orange Park, Florida Edward Kelly, MD, FACS Assistant Professor of Surgery Department of Trauma Burn and Surgical Critical Care Brigham and Women’s Hospital Boston, Massachusetts Gregory D. Kennedy, MD, PhD John H. Blue Chair in General Surgery and Professor of Surgery Director, Division of Gastrointestinal Surgery University of Alabama at Birmingham School of Medicine Birmingham, Alabama Teresa S. Kim, MD Assistant Professor Surgical Oncology, Department of Surgery University of Washington Seattle, Washington Cindy Kin, MD, MS, FACS, FASCRS Assistant Professor of Surgery Stanford University Department of Surgery Stanford, California Jonathan C. King, MD David Geffen School of Medicine at UCLA Department of Surgery Los Angeles, California Santa Monica General Surgery Santa Monica, California Simon Law, MBBChir (Cantab), MA, MS (HK), PhD (HK), FRCSEd, FCSHK, FHKAM, FACS Cheung Kung-Hai Endowed Chair

Chair Professor in Esophageal and Upper Gastrointestinal Surgery Department of Surgery The University of Hong Kong Hong Kong, the People’s Republic of China Christina W. Lee, MD Resident Physician University of Wisconsin School of Medicine and Public Health Department of Surgery Madison, Wisconsin Yu Liang, MD Assistant Professor Department of General Surgery UConn Health Farmington, Connecticut Keith D. Lillemoe, MD Surgeon-in-Chief Chief, Department of Surgery Massachusetts General Hospital W. Gerald Austen Professor of Surgery Harvard Medical School Boston, Massachusetts Anne Y. Lin, MD, MSHS Assistant Professor of Surgery Department of Surgery Section of Colon and Rectal Surgery University of California Los Angeles Los Angeles, California Natalie Liu, MD General Surgery Resident University of Wisconsin Department of Surgery

Madison, Wisconsin Benjamin P.T. Loveday, MBChB, PhD, FRACS Senior Lecturer in Surgery University of Auckland Consultant HBP Surgeon Auckland City Hospital Auckland, New Zealand Arin L. Madenci, MD, MPH Resident, General Surgery Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts Najjia N. Mahmoud, MD Emilie and Roland T. DeHellebranth Professor of Surgery Chief, Division of Colon and Rectal Surgery University of Pennsylvania Health System Philadelphia, Pennsylvania Jeffrey B. Matthews, MD, FACS Dallas B. Phemister Professor of Surgery and Chairman Department of Surgery The University of Chicago Chicago, Illinois Martin McCarter, MD, FACS Professor of Surgery, Section of Surgical Oncology University of Colorado at Denver Denver, Colorado David W. McFadden, MD, MBA Murray-Heilig Professor and Chairman Department of Surgery The University of Connecticut

Farmington, Connecticut Fabrizio Michelassi, MD Lewis Atterbury Stimson Professor Chairman, Department of Surgery Weill Cornell Medicine Surgeon-in-Chief New York-Presbyterian Weill Cornell Medical Center New York, New York Fernando Mier, MD Division of General and Gastrointestinal Surgery Department of Surgery and the Digestive Health Center Oregon Health and Science University Portland, Oregon Jon B. Morris, MD The Ernest F. Rosato—William Maul Measey Professor in Surgical Education Vice Chair for Education, Department of Surgery Hospital University of Pennsylvania Philadelphia, Pennsylvania Neil J. Mortensen, MA, MBChB, MD, FRCS Eng, Hon FRCPS Glas, Hon FRCS Edin, Hon FRCSI Professor of Colorectal Surgery Nuffield Department of Surgery University of Oxford Hon Consultant Surgeon Department of Colorectal Surgery, Churchill Hospital Oxford University Hospitals, Oxford England, United Kingdom Amani Munshi, MD, FRCSC, FACS Clinical Assistant Professor Department of Surgery

University Hospitals, St. John Medical Center Westlake, Ohio David L. Nahrwold, MD Emeritus Professor of Surgery Department of Surgery Feinberg School of Medicine Northwestern University Chicago, Illlinois Heidi Nelson, MD Fred C. Andersen Professor of Surgery Chair, Department of Surgery Mayo Clinic Rochester, Minnesota Sanjay Pandanaboyana, MBBS, MPhil, FRCS Consultant HBP Surgeon Auckland City Hospital Auckland, New Zealand Alessandro Paniccia, MD Chief Resident in General Surgery Department of Surgery University of Colorado Anschutz Medical Campus Denver, Colorado Christina M. Papageorge, MD, MS General Surgery Resident University of Wisconsin Hospital and Clinics Department of Surgery Madison, Wisconsin Theodore N. Pappas, MD, FACS Distinguished Professor of Surgical Innovation Chief of Advanced Oncologic and Gastrointestinal Surgery

Duke University School of Medicine Durham, North Carolina Purvi Y. Parikh, MD, FACS Hepato-Pancreato-Biliary Surgeon Director, Center of Excellence for HPB Care The Permanente Medical Group, Inc. Kaiser–Sacramento Medical Center Department of Surgery Sacramento, California Guillaume Passot, MD, PhD Department of Surgical Oncology CHU Lyon Sud, Pierre Bénite, France Professor of Surgery Lyon 1 University Lyon, France Sameer H. Patel, MD, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston, Texas Marco G. Patti, MD, FACS Professor of Medicine and Surgery Co-Director, Center for Esophageal Diseases and Swallowing University of North Carolina School of Medicine Chapel Hill, North Carolina Timothy M. Pawlik, MD, MPH, MTS, PhD, FACS, FRACS (Hon) Professor and Chair, Department of Surgery The Urban Meyer III and Shelley Meyer Chair for Cancer Research Professor of Surgery, Oncology, and Health Services Management and Policy Surgeon in Chief The Ohio State University Wexner Medical Center Columbus, Ohio

William H. Peranteau, MD Assistant Professor of Surgery The Division of Pediatric General, Thoracic, and Fetal Surgery The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Alexander Perez, MD, FACS Assistant Professor of Surgery Chief of Pancreatic Surgery Duke University School of Medicine Durham, North Carolina Silvana Perretta, MD Professor of Surgery Department of Digestive and Endocrine Surgery NHC University Hospital Director of Education IRCAD-IHU Strasbourg, France Henry A. Pitt, MD Temple University Philadelphia, Pennsylvania Jeffrey L. Ponsky, MD, MBA, FACS Lynda and Marlin Younker Chair in Developmental Endoscopy Professor of Surgery Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland, Ohio Michael J. Pucci, MD, FACS Associate Professor of Surgery Sidney Kimmel Medical College of Thomas Jefferson University Co-Director, Advanced Gastrointestinal Surgery Fellowship Associate Director, Undergraduate Education Division of General Surgery, Department of Surgery

Philadelphia, Pennsylvania Chandrajit P. Raut, MD, MSc, FACS Associate Surgeon Division of Surgical Oncology, Brigham and Women’s Hospital Surgery Director, Center for Sarcoma and Bone Oncology Dana-Farber Cancer Institute Associate Professor of Surgery Harvard Medical School Boston, Massachusetts Michael M. Reader, MD, FACS General Surgery Houston Methodist Surgical Associates Assistant Professor of Clinical Surgery Weill Cornell Medical College Houston, Texas Diego C. Reino, MD Cleveland Clinic Florida Transplant and Hepatobiliary Surgery Department of Solid Organ Transplantation Weston, Florida Joao B. Rezende Neto, MD, PhD, FRCSC, FACS Associate Professor Department of Surgery University of Toronto Trauma and Acute Care Surgery Division of General Surgery St. Michael’s Hospital Surgeon Investigator—Keenan Research Center for Biomedical Sciences Toronto, Ontario Canada John J. Ricotta, MD, FACS

Clinical Professor of Surgery George Washington University Washington, DC Patricia L. Roberts, MD Chair, Division of Surgery Senior Staff Surgeon, Department of Colon and Rectal Surgery Lahey Hospital and Medical Center Burlington, Massachusetts Professor of Surgery Tufts University School of Medicine Boston, Massachusetts Sean M. Ronnekleiv-Kelly University of Wisconsin Hospital and Clinics Department of Surgery Clinical Science Center Madison, Wisconsin Robert E. Roses, MD Assistant Professor Department of Surgery Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Ori D. Rotstein, MD Professor and Associate Chair of Surgery University of Toronto Surgeon-in-Chief, St. Michael’s Hospital Toronto, Ontario Canada Daniel Ruan, MD General Surgeon Department of Surgery Tampa General Hospital

Tampa, Florida Tara A. Russell, MD, MPH, PhD Resident Physician UCLA Department of General Surgery Los Angeles, California George A. Sarosi, Jr., MD Professor and Program Director Vice Chair of Education Department of Surgery University of Florida Gainesville, Florida Mitsuru Sasako, MD, PhD Special Consultant Surgeon Department of Surgery Yodogawa Christian Hospital Osaka Professor Emeritus Hyogo College of Medicine Nishinomiya, Japan Bruce D. Schirmer, MD Stephen H. Watts Professor of Surgery University of Virginia Health System Department of Surgery Charlottesville, Virginia Richard D. Schulick, MD, MBA, FACS Aragón/Gonzalez-Gíustí Endowed Chair Chair, Department of Surgery Director, Cancer Center Professor of Surgery University of Colorado School of Medicine Aurora, Colorado

Anthony J. Senagore, MD, MS, MBA Professor, Vice Chair for Research Department of Surgery Western Michigan University - Homer Stryker MD School of Medicine Kalamazoo, Michigan Parth K. Shah, MBBS Fellow in Complex General Surgical Oncology H. Lee Moffitt Cancer Center University of South Florida Tampa, Florida Brian D. Shames, MD Associate Professor of Surgery Division Chief General Surgery Program Director General Surgery Residency University of Connecticut School of Medicine Farmington, Connecticut Eric G. Sheu, MD, D.Phil Associate Surgeon Brigham and Women’s Hospital Assistant Professor of Surgery Harvard Medical School Boston, Massachusetts Scott A. Shikora, MD, FACS Professor of Surgery Harvard Medical School Director, Center for Metabolic and Bariatric Surgery Department of Surgery Brigham and Women’s Hospital Boston, Massachusetts Hisashi Shinohara, MD, PhD Chairman, Upper GI Division

Department of Surgery Hyogo College of Medicine Nishinomiya, Japan Jory S. Simpson, MD, MEd, FRCSC Assistant Professor Department of Surgery University of Toronto Division of General Surgery St. Michael’s Hospital Toronto, Canada Douglas S. Smink, MD, MPH Program Director General Surgery Residency Associate Chair of Surgery Department of Surgery Brigham and Women’s Hospital Associate Professor of Surgery Harvard Medical School Boston, Massachusetts Kevin C. Soares, MD Resident in General Surgery Department of Surgery The Johns Hopkins School of Medicine Baltimore, Maryland Nathaniel J. Soper, MD, FACS Loyal and Edith Professor and Chairman of Surgery Surgeon-in-Chief, Northwestern Memorial Hospital Northwestern Medicine Chicago, Illinois Ian S. Soriano, MD, FACS, FASMBS, FPALES Clinical Assistant Professor of Surgery

Perelman School of Medicine University of Pennsylvania Pennsylvania Hospital Philadelphia, Pennsylvania Visiting Assistant Professor of Surgery University of the Philippines College of Medicine Philippine General Hospital Manila, Philippines David I. Soybel MD, FACS David L. Nahrwold Professor of Surgery Division Chief, General Surgery Specialties & Surgical Oncology Vice-Chairman (Research) Department of Surgery Penn State Hershey Medical Center Hershey, Pennsylvania Shelby J. Stewart, MD Assistant Professor Department of Thoracic surgery University of Maryland Baltimore, Maryland Steven M. Strasberg, MD Pruett Professor of Surgery Section of HPB Surgery Washington University in Saint Louis Siteman Cancer Center and Barnes-Jewish Hospital Saint Louis, Missouri David M. Straughan, MD Resident in General Surgery Department of Surgery University of South Florida Morsani College of Medicine

Tampa, Florida Cabrini L. Sutherland, MD, MPH Acute Care Surgery Service Trauma Trust Tacoma, Washington Lee L. Swanström, MD Professor of Surgery The Oregon Clinic Portland, Oregon Mark A. Talamini, MD, MBA Professor and Chair Department of Surgery School of Medicine, SUNY Stony Brook Chief of Surgical Services Stony Brook Medicine Stony Brook, New York Nabil Tariq, MD, FACS Assistant Professor of Surgery Department of Surgery Houston Methodist Hospital Houston, Texas Ali Tavakkoli, MD Interim Chief, Division of General and GI Surgery Brigham and Women’s Hospital Co-Director, Center for Weight Management and Metabolic Surgery Associate Professor of Surgery, Harvard Medical School Boston, Massachusetts Ezra N. Teitelbaum, MD, MEd Assistant Professor of Surgery and Medical Education Northwestern University

Feinberg School of Medicine Chicago, Illinois Tina Thomas, MD Clinical Lecturer, Pediatric Surgery Research Fellow, Newman Lab Department of Pediatric Surgery C. S. Mott Children’s Hospital University of Michigan Ann Arbor, Michigan Daniel King Hung TONG, MBBS, MS, PhD, FRACS, FACS, FCSHK, FHKAM Honorary Clinical Associate Professor The University of Hong Kong Hong Kong Jennifer F. Tseng, MD, MPH Utley Professor and Chair, Department of Surgery Boston University Surgeon-in-Chief, Boston Medical Center Boston, Massachusetts Jeff Van Epps, MD Fellow Colon and Rectal Surgery University of Minnesota Minneapolis, Minnesota Hjalmar C. van Santvoort, MD, PhD Hepato-Pancreato-Biliary Surgeon Associate professor Regional Academic Cancer Center Utrecht St. Antonius Hospital Nieuwegein and University Medical Center Utrecht, the Netherlands

Jean-Nicolas Vauthey, MD, FACS Professor of Surgery Chief, Hepato-Pancreato-Biliary Section Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston, Texas Vic Velanovich, MD Professor of Surgery Department of Surgery University of South Florida Tampa, Florida Sharon M. Weber, MD, FACS Tim and MaryAnn McKenzie Chair of Surgical Oncology Director for Surgical Oncology UW Carbone Cancer Center Professor of Surgery Department of Surgery University of Wisconsin Madison, Wisconsin Jon O. Wee, MD Section Chief, Esophageal Surgery Director of Robotics in Thoracic Surgery Co-Director of Minimally Invasive Thoracic Surgery Associate Program Director Division of Thoracic Surgery Brigham and Women’s Hospital Assistant Professor of Surgery Harvard Medical School Boston, Massachusetts Martin R. Weiser, MD

Stuart H. Quan Chair in Colorectal Surgery Vice Chair, Faculty Affairs Department of Surgery Memorial Sloan Kettering Cancer Center Professor of Surgery Weill Cornell Medical College New York, New York Mark Lane Welton, MD, MHCM Chief Medical Officer Fairview Health Services Professor of Surgery Section of Colon and Rectal Surgery University of Minnesota Minneapolis, Minnesota Edward E. Whang, MD Associate Professor of Surgery Department of Surgery Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts John A. Windsor, MD, MBChB, FRACS, FACS, FRSNZ Professor of Surgery University of Auckland Consultant HBP/Upper GI Surgeon Auckland City Hospital Auckland, New Zealand Joyce Wong, MD Assistant Professor of Surgery Zucker School of Medicine at Hofstra/Northwell Lenox Hill Hospital New York, New York

Yanghee Woo, MD, FACS Associate Clinical Professor Vice Chair, International Surgery Director, GI Minimally Invasive Therapies Division of Surgical Oncology Department of Surgery City of Hope National Medical Center Duarte, California Mu Xu, MD, PhD Resident in Surgery David Geffen School of Medicine at UCLA Los Angeles, California Charles J. Yeo, MD, FACS Samuel D. Gross Professor and Chairman Department of Surgery Jefferson Pancreas, Biliary and Related Cancer Center Department of Surgery Sidney Kimmel Medical College Thomas Jefferson University Senior Vice President and Enterprise Chair, Surgery Jefferson Health Co-Director Jefferson Pancreas, Biliary, and Related Cancer Center Co-Editor in Chief, Emeritus Journal of Gastrointestinal Surgery Official Publication of the SSAT Editor in Chief, Journal of Pancreatic Cancer Philadelphia, Pennsylvania Heather Yeo, MD, MHS Assistant Professor of Surgery Weill Cornell Medical College Assistant Professor of Public Health

Weill Cornell Medical College New York, New York Trevor M. Yeung, MA, MBBChir, D.Phil, FRCS Specialty Registrar Department of Colorectal Surgery Oxford University Hospitals Oxford, United Kingdom Herbert J. Zeh, III, MD University of Pittsburgh Medical Center Department of Surgery Pittsburgh, Pennsylvania Tiffany Zens, MD University of Wisconsin School of Medicine and Public Health Department of Surgery Madison, Wisconsin Michael J. Zinner, MD, FACS CEO and Executive Medical Director Miami Cancer Institute Miami, Florida Moseley Professor of Surgery, Emeritus Harvard Medical School Boston, Massachusetts

PREFACE For the editors, the production of the newest edition of Maingot’s Abdominal Operations represents a labor of love. Maingot’s has always filled a unique niche. This text has consistently offered a comprehensive discussion of surgical diseases of the abdomen with a focus on operative strategy and technique. The book has served as a needed reference to refresh our knowledge before a common operation or in preparation for a novel one. Our intended audience for this edition is the same as for the original publication; the book is meant for the surgical trainee as well as the practicing surgeon, and for the American surgeon as well as for our international colleagues. We continue to have a significant international audience and have made every effort to develop a product that is equally valuable to readers in India as well as Indiana. This is the fifth effort together for the senior editors, joined this time by a new editor (O.J.H.) with a fresh vision; it continues to be not only a pleasure but an honor and a privilege to have the opportunity to co-edit the 13th edition of this classic textbook. Abdominal surgery has clearly evolved since Rodney Maingot’s first edition of this text in 1940. Not only has our knowledge base increased substantially, but the procedures themselves have become both more complex and less invasive. The current subspecialization in abdominal surgery, a consequence of these changes, continues to challenge the need for a comprehensive text. Abdominal disease has been increasingly parceled between foregut, hepatobiliary, pancreatic, colorectal, endocrine, acute care, and vascular specialists. The editors continue to believe, however, that the basic principles of surgical care in each of the anatomic regions have more similarities than differences. Experience in any one of these organs can inform and strengthen the approach to each of the others. In fact, in community hospitals and rural settings both nationally and internationally, practices spanning multiple subspecialties remain the norm. Few would

question the need for the abdominal surgeon to be well versed in dealing with any unexpected disease that is encountered in the course of a planned procedure. For many of us, Maingot’s Abdominal Operations has consistently helped to fill that need. This textbook remains primarily disease focused, in addition to maintaining its organ/procedure format. The new edition of this textbook is a significant revision and, in many areas, a completely new book. We have continued to focus some chapters on technical operative procedures, whereas others elucidate new and continuing concepts in diagnosis and management of abdominal disease. The new edition is expanded compared with previous versions, and we have continued to present the opinions and knowledge of more than one expert. In areas where opinions and approaches differ, we have added even more “Perspective” commentaries by experts in the field who we expected might have distinct opinions about approaches and/or operative techniques. In response to recent developments, we have added chapters on quality metrics, enhanced recovery after surgery, and robotic surgery. We have attempted to maintain an international flavor and have included a cross-section of both seasoned senior contributors and new leaders in gastrointestinal surgery. We continue to provide a contemporary textbook on current diagnostic procedures and surgical techniques related to the management and care of patients with all types of surgical digestive disease. An extensive artwork program was undertaken for this edition. Many line drawings have been recreated to reflect the contributors’ preferred method for performing certain surgical procedures. Some of these drawings are new and give the book a more consistent look. In addition, this edition continues fullcolor text and color line art. In the preface to the sixth edition, Rodney Maingot noted, “As all literature is personal, the contributors have been given a free hand with their individual sections. Certain latitude in style and expression is stimulating to the thoughtful reader.” Similarly, we have tried to maintain consistency for the reader, but the authors have also been given a free hand in their chapter submissions. We would like to thank the publisher, McGraw-Hill, and in particular Christie Naglieri and Andrew Moyer, for their unwavering support during the lengthy time of development of this project. Their guidance was invaluable to completing this project in a single comprehensive volume. Their suggestions and attention to detail made it possible to overcome the innumerable

problems that occur in publishing such a large textbook. Finally, we want to acknowledge the expertise of each chapter and perspective contributor. Without their effort, this book would not have been possible. We acknowledge our editorial assistant, Linda Smith, who has survived the trials of this book; she has been invaluable, and we never would have been able to do it without her. Patrina Tucker and Heather Couture have also stepped up and made this project possible. We owe them a great debt of gratitude for helping with every step of the work. To all of those who have participated in the creation and publication of this text, we thank you very much. Michael J. Zinner, MD, FACS Stanley W. Ashley, MD, FACS O. Joe Hines, MD, FACS

INTRODUCTION

GASTROINTESTINAL SURGERY: A HISTORICAL PERSPECTIVE David L. Nahrwold

INTRODUCTION Surgeons continue to have brilliant ideas and use amazing technology to bring safe and effective surgery to people all over the world, but it was not always so. The evolution of surgery to its present state has taken at least 200 years, and surgery is still evolving. Each of the many abdominal operations surgeons now performed has its own special history, from the idea that spawned it to the present state of its art. Abdominal operations were brought to fruition by innovative surgeons who carefully planned them and had the courage to perform them and the wisdom to modify and improve them. Although the histories of all abdominal operations are interesting, a broader view of abdominal surgery puts those stories into perspective. The broader view is best obtained by asking: What enabled abdominal surgery to evolve to its present state? What were the barriers to the evolution of abdominal surgery? How were the barriers overcome, and who overcame

them? Although recognizing the individuals who developed and perfected individual operations is important, the perspective of this chapter is on how modern abdominal surgery came about and how it was enabled.

THE EARLY PROBLEMS Prior to the middle of the 19th century, few operations were done with the expectation that the patient would live and be cured of the disease for which it was performed. The fundamental barrier was the excruciating pain caused by opening the abdomen and manipulating its contents, even when tempered by the administration of alcohol or derivatives of opium such as laudanum and morphine. Patients often died from postoperative bleeding, dehydration, or malnutrition. But it was infection that was the bane of surgeons. Infections followed almost all operations. Wound infection and peritonitis were the killers of patients who had abdominal surgery. Without antibiotics or even standardized methods of dressing infected wounds, the consequences of infection were disastrous. Except in a few isolated instances, physicians knew that surgery was not a realistic therapeutic option until infection, hemorrhage, dehydration, and malnutrition could be alleviated or eliminated. Remarkable progress was made during the second half of the 19th century, enabling surgeons to bring hope to a large number of patients with diseases or conditions that swiftly became amenable to surgery.

ANESTHESIA The modernization of abdominal surgery was dependent on the patient’s loss of sensation, anesthesia, during the procedure. The development of anesthesia eliminated the cruelty of surgery and enabled surgeons to incise, manipulate, and suture tissue in a disciplined manner without the urgency and disorder that surrounded operations in the conscious patient. Dr. Crawford Long was the first to use ether for general anesthesia, in 1842, but he did not report it until 1849.1 Meanwhile, in 1846, the Boston dentist William T.G. Morton demonstrated the use of ether as a general anesthetic in the amphitheater of the Massachusetts General Hospital in a patient with a tumor of the neck, which was removed by Dr. John Collins Warren, former Dean of the Harvard Medical School (1816-1819).2

OVERCOMING INFECTION Louis Pasteur conducted experiments between 1860 and 1864 showing that “pyogenic vibrio” caused puerperal fever and that fermentation of wine and milk did not proceed in the absence of living organisms. Heating milk and wine, now called pasteurization, killed the bacteria, but not the yeast, and made them safe to drink.3 Robert Koch, the German physician and microbiologist who in 1876 identified Bacillus anthracis as the cause of anthrax, learned how to grow bacteria on media and, in 1884, isolated Vibrio cholerae, the agent that causes cholera. In 1882, Koch identified the slow-growing Mycobacterium tuberculosis as the cause of tuberculosis. Between 1879 and 1889, he also isolated the organisms that caused typhoid fever, diphtheria, pneumonia, tetanus, meningitis, and gonorrhea. He found organisms in wound infections. Koch proved that the germs in the germ theory of disease were organisms that could be isolated and identified.4 The English physician Joseph Lister, professor of surgery at the University of Glasgow, soaked surgical dressings in carbolic acid (phenol) and applied them to the open leg wound of a boy who had suffered a compound fracture (Fig. 1-1). No infection ensued, and to his surprise, the bones healed solidly together. He published the results in a series of articles in The Lancet in 1867. He returned to the University of Edinburgh in 1869 and continued to develop methods of asepsis and antisepsis. Soon, surgeons performed operations under a mist of dilute carbolic acid that was sprayed in the operating room, instruments were dipped in carbolic acid before use, and the surgical wound was covered in dressings saturated with it.5 This routine, with variations, became known as listerism, which Joseph Lister introduced to the United States during a visit in 1876.

FIGURE 1-1 Joseph Lister. (Used with permission from Wellcome Images.) Surgeons learned from listerism of the need to maintain sterile conditions at the operating table. Although the steam autoclave was invented in 1879, it was not used routinely for sterilization of instruments and supplies until early in the 20th century. Dr. William Halsted, who embraced listerism, introduced the use of surgical gloves at Johns Hopkins Hospital. However, the original use of the gloves made by the Goodyear Company was to protect the hands of the surgical team from the carbolic acid.6 Measures to control infection have been used routinely since the first half of the 20th century and affect hospital construction, all invasive procedures, interactions with patients, and behaviors in hospitals and other medical

facilities. The medicinal use of sulfa drugs in the late 1930s, the discovery of penicillin in 1928 by Fleming, and its clinical use by Florey and his colleagues in the early 1940s began the successful search for many other antibiotics to combat infections by almost all known bacteria. During the second half of the 20th century and beyond, surgical infections have been ameliorated or cured by the large array of antibiotics that became available, although antibiotic-resistant bacteria from antibiotic overuse have recently become a problem. In recent decades, the evidence-based prophylactic use of antibiotics in abdominal surgery has almost eliminated surgical site infections.

THE SURGEON’S WORKPLACE Hospitals were built to provide clinical material for the faculties and students of the country’s original medical schools. They included the Pennsylvania Hospital (1752), the New York Hospital (1771), and the Massachusetts General Hospital (1811), all of which became the workplaces of innovative physicians and surgeons who taught and conducted research (Fig. 1-2). However, most cities had no hospitals; instead, almshouses, poorhouses, and poor farms, living facilities for indigent people in the community were established by charitable organizations and wealthy individuals. Over time, many of them became hospitals for the sick and poor. Some physicians also established hospitals, often by converting a large home into a place for their sick patients. Many hospitals were dirty and poorly kept, and because some of the occupants had infectious diseases for which there were no cures, the other occupants also became infected and often died.

FIGURE 1-2 The Pennsylvania Hospital. (Reproduced with permission from The Library of Congress.)

Because hospitals were known as dangerous places, middle- and upperclass families kept sick relatives at home. The typical horse-and-buggy doctor made rounds to the homes of his patients, and minor procedures, such as drainage of a carbuncle or suture of a wound, were performed in the home. Occasionally, a physician whose patient was in desperate straits would attempt an abdominal operation on the kitchen table, usually with disastrous results. As medical diagnosis and treatment advanced, medical care in the home was no longer practical. Beginning in the latter half of the 19th century, religious organizations, civic groups, and municipalities began aggressive programs to build hospitals modeled after those in Europe, and by 1900, there were more than 4000 hospitals in the United States. However, the management, medical staffs, nursing, and other services of these hospitals varied from excellent to poor.

THE HOSPITAL STANDARDIZATION PROGRAM IMPROVES HOSPITALS

Dr. Franklin H. Martin, a Chicago gynecologist, led the founding of the American College of Surgeons (ACS) in 1912 (Fig. 1-3). He and other leaders of the ACS were concerned about the marked variation in the quality of hospitals throughout the country and began a program to standardize hospitals in 1916 by establishing standards that hospitals were required to meet.7 Surveyors visited the hospitals to determine their compliance and to offer help in meeting the standards. The ACS also held annual hospital standardization conferences to educate hospital personnel. The American Hospital Association, which initiated institutional memberships in 1918, also contributed to the modernization of hospital management.

FIGURE 1-3 Dr. Franklin H. Martin, Founder of the American College of Surgeons. (Image courtesy of the Archives of the American College of Surgeons.)

Only 13% of the 692 hospitals surveyed in 1918 were approved by the ACS, but by 1939, 76% of the 3564 hospitals surveyed were approved.8 Over the years, the standards proliferated, and in 1951, the ACS transferred the program to what is now The Joint Commission. The Hospital Standardization Program and The Joint Commission were largely responsible for the current organization and functions of the modern hospital. The standards they set have saved many lives and made surgery safe.

NURSING AND HOSPITAL ADMINISTRATION Although hospitals proliferated early in the 20th century, few of them hired nurses to care for patients. Graduate nurses were hired by middle- and upperclass patients as “special nurses” to care for them in their homes or in the hospital during illnesses. To serve patients who could not afford special nurses, hospitals established schools of nursing in which the students were taught by a faculty of 1 or 2 graduate nurses and the medical staff of the hospital. Student nurses were assigned to wards to care for patients, often with very little supervision. Many of these schools closed during the Great Depression, and later, colleges and universities established degree programs, which now educate most of the country’s nurses. Prior to World War II, the supply of graduate nurses became sufficient for hospitals to hire nursing staffs to care for their patients. As the complexity of medical care escalated, nurses assumed many roles other than hospital care, and they continue to be indispensable to the healthcare system. During the first half of the 20th century, when hospitals were simple organizations, hospital administrators learned from a mentor or on the job. By the middle of the century, hospitals had become departmentalized and complex, requiring expertise in finance, personnel management, construction, and many other fields of management. This led to the development of advanced degree programs in hospital administration, the first of which was established at the University of Chicago in 1934. Within a few decades, many universities had established such programs.

APPLYING THE BASIC SCIENCES

Although the gross structure of the human body and its organs had been delineated by the middle of the 19th century, the functions of organs remained mysterious. Concurrent development of the basic sciences of pathology, microbiology, physiology, and chemistry during the second half of the 19th century led to an understanding of organ function and disease. During this period, Rudolph Virchow, using the ever-improving optics of the microscope, introduced histopathology to the medical sciences, and Friedrich von Recklinghausen described embolism, infarction, tissue degeneration, and many diseases and conditions such as uterine adenomyomata. Improved techniques for fixing, embedding, and staining tissue facilitated more accurate diagnoses in the early 20th century, and the process of preparing frozen sections of tissues, reported by Dr. Louis Wilson of the Mayo Clinic in 1905, enabled pathologists to accurately diagnose diseases during operations.9 New techniques enabled investigators to understand normal and abnormal gastrointestinal physiology. Between the 1890s and his death in 1936, the Russian physiologist Ivan Pavlov used Heidenhain pouches and gastric and esophageal fistulas in dogs to study salivary and gastric secretions as well as conditioned reflexes, work for which he received the Nobel Prize.10 His experiments inspired many surgical investigators to use similar methods to study gastrointestinal hormonal physiology and motility during the 20th century. Their work, and the work of others, resulted in a comprehensive understanding of the biochemistry, physiology, and pharmacology of the hepatobiliary and digestive systems in health and disease. Army surgeon Dr. William Beaumont performed the first human experiments in gastric physiology during the first half of the 19th century,11 but it was not until Dr. Lester Dragstedt studied gastric secretion in ulcer patients that gastrointestinal physiology was applied to the development of surgical procedures to combat excessive acid secretion. He introduced vagotomy to reduce gastric acid secretion.12 Upon finding that vagotomy inhibited gastric emptying, he and others added pyloroplasty or antrectomy. Beginning with the administration of intravenous fluids to surgical patients by Dr. Rudolph Matas in 1924, many advances in biochemistry and physiology led to a greater understanding of body composition, nutrition, and fluid, electrolyte, and acid-base balance. The studies of Dr. Francis Moore and others culminated in his magisterial text, Metabolic Care of the Surgical

Patient, which taught surgeons how to deliver the highest level of pre- and postoperative care.13 Drs. Jonathan Rhoads and Stanley Dudrick emphasized the importance of nutrition in surgical patients and demonstrated that intravenous alimentation could support normal growth and development of puppies and babies.14 The basic science of immunology matured during the 20th century, enabling the first kidney transplantation by Dr. Joseph Murray and his associates in 1954 and the first liver transplantation by Dr. Thomas Starzl in 1963.

BLOOD, TRAUMA, AND SHOCK After Karl Landsteiner identified the major blood groups A, B, and O in 1901, transfusion of blood and blood products became safer. Dr. George W. Crile, professor of surgery at Case-Western Reserve University, and Dr. William Halsted of The Johns Hopkins Hospital employed blood transfusions during surgical procedures. Reactions to transfusions were frequent until 1940, when the Rh system was discovered and taken into account in matching donor blood to patients. Dr. Bernard Fantus established the first hospital blood bank in the United States at Cook County Hospital in Chicago in 1937.15 Liquid and reconstituted dried plasma was used extensively for resuscitation from wounds during World War II. Lessons learned from the Korean conflict, the Vietnam War, and subsequent conflicts have been applied to the management of civilian trauma and burns, especially the techniques of resuscitation from shock, which were studied extensively by Dr. G Thomas Shires and his colleagues.16 The wartime concepts of rapid evacuation for resuscitation and early transport to a major healthcare facility are embodied in the existing trauma system in the United States. The military experience has also informed the management of abdominal gunshot and knife wounds and blunt abdominal injuries in the civilian population.

THE SURGEON’S TOOLS More than 200 years have elapsed since Ephraim McDowell performed the first abdominal operation in the United States to remove a huge ovarian

tumor from a woman in Danville, Kentucky.17 Subsequently, and especially during the latter half of the 19th century, operations were developed in Europe and the United States to deal with almost every abdominal disease or condition. The need to design and manufacture surgical instruments spawned an entirely new field, biomedical engineering, which became institutionalized in the late 1960s when universities began degree programs in biomedical engineering. The manufacture of surgical instruments and supplies is now vested in a huge industry that produces products ranging from silk sutures to robots. Manufacture of most surgical instruments was routine by the beginning of the 20th century, including retractors, hemostats, scissors, forceps, and a variety of tools designed to grasp, hold, or manipulate abdominal organs and tissues. Improvements such as the disposable scalpel blade in the 1920s and disposable instruments in the 1970s have reduced labor costs of hospitals. The introduction of staplers for gastrointestinal side-to-side and end-to-end anastomoses by Russian investigators, brought to the United States and developed by Ravitch and Steichen18 in the 1960s, was a major advance. Hemostasis was facilitated by the development of a diathermy machine for electrosurgical cutting and cautery by William T. Bovie and introduced into clinical use by Harvey Cushing at the Peter Bent Brigham Hospital in 1920, eliminating the need to clamp and ligate small vessels. Since then, topical preparations, clips, electrical energy, and ultrasonic energy have been incorporated into various devices that have enabled minimally invasive surgery.

TECHNOLOGY DRIVES SURGERY Development of minimally invasive surgery was dependent on the visualization of organs in the abdominal cavity through a scope. In 1806, Phillipp Bozzini made a major contribution by constructing a “lichtleiter,” a scope that incorporated mirrors to reflect light back to the eye. It was used primarily for gynecologic examinations (Fig. 1-4). The development of small bulbs illuminated by electric current enabled laparoscopy for diagnosis beginning in the first half of the 20th century, and flexible fiberoptic scopes for examining the interior of the gastrointestinal tract followed in the 1950s.

FIGURE 1-4 Bozzini’s lichtleiter. (Image courtesy of the Archives of the American College of Surgeons.)

Numerous advances in technology, many driven by the computer and the computer chip television camera, enabled laparoscopic surgery, which revolutionized abdominal surgery. Laparoscopic surgery had its origin in obstetrics and gynecology, with the first laparoscopic organ removal, salpingectomy, performed by Tarasconi in 1975.19 This was followed by laparoscopic cholecystectomy, first performed by Muhe in Germany in 1985, by Mouret in France in 1987, and Reddick in the United States in 1988.20 Since then, every abdominal organ has been subjected to laparoscopic procedures. The most recent technological development is the use of robots in surgery. After years of research and development by many organizations, the da Vinci surgery system was approved by the US Food and Drug Administration in 2000 for general laparoscopic surgery. The surgeon sits at a console where the interior of the abdomen is projected on a screen and uses a computer to control a robotic arm to which are attached various instruments. Newer versions, including a console for an assistant, have been used in general

surgery and the surgical specialties. The advantages and disadvantages of robotic surgery are still under evaluation as experience accumulates and the technology continues to improve.

SUMMARY Early abdominal surgery was enabled by the discovery of general anesthesia, means to control or eliminate infection, and the evolution of the hospital, where patients could be housed and surgeons could work in a supportive environment that included nurses and hospital administrators. Later, development of the basic sciences enabled the development of new operations and methods to deal with altered physiology and body chemistry caused by illness, trauma, and complex surgical procedures. Most recently, striking advances in technology have enabled the development of minimally invasive and robotic surgery.

REFERENCES 1. Long CW. An account of the first use of sulphuric ether by inhalation as an anesthetic in surgical operations. South Med Surg J. 1849;5:705-713. 2. Keys TE. William Thomas Green Morton (1819-1868). Anesth Analg. 1973;52(2):166. 3. Schwartz M. The life and works of Louis Pasteur. J Appl Microbiol. 2001;91(4):597-601. 4. Blevins SM, Bronze MS. Robert Koch and the “golden age” of bacteriology. Int J Infect Dis. 2010;14(9):e744-e751. 5. Lister Centenerary Celebration. American College of Surgeons. Detroit, MI, October, 1927; Descriptive Catalogue. Lister Collection. 1927; Wellcome Historical Medical Museum. 6. Cameron JC. William Stewart Halsted: our surgical heritage. Ann Surg. 1997;225(5):445-458. 7. Nahrwold DL, Kernahan PJ. A Century of Surgeons and Surgery. The American College of Surgeons 1913-2012. Chicago, IL: American College of Surgeons; 2012. 8. Twenty-second annual hospital standardization report. Bull Am Col Surg. 1939;24(5):316. 9. Wilson LB. A method for the rapid preparation of fresh tissues for the microscope. JAMA. 1905;45:1737. 10. Babkin BP. Pavlov, a Biography. Chicago, IL: The University of Chicago Press; 1939. 11. Myer JS. Life and Letters of Dr. William Beaumont. St. Louis, MO: CV Mosby Company; 1939:327. 12. Dragstedt LR, Owens FM Jr. Supra-diaphragmatic section of the vagus nerves in treatment of duodenal ulcer. Proc Soc Exp Biol Med. 1943;53:152-154. 13. Moore FD. Metabolic Care of the Surgical Patient. Philadelphia, PA: WB Saunders; 1959. 14. Dudrick SJ, Rhoads JE. New horizons for intravenous feeding. JAMA. 1971;215(6):939-949. 15. Fantus B. The therapy of the Cook County Hospital: blood preservation. JAMA. 1938;111(4):317. 16. Shires GT. Shock and Related Problems. London, United Kingdom: Churchill Livingstone; 1984.

17. Rutkow IM. The History of Surgery in the United States, 1775-1900. Vol 2. Novato, CA: Norman Publishing; 1988. 18. Steichen FH, Ravitch MM. Stapling in Surgery. Chicago, IL: Year Book Medical; 1971. 19. Tarasconi JC. Endoscopic salpingectomy. J Reprod Med. 1981;26(10): 541-545. 20. Blum CA, Adams DB. Who did the first laparoscopic cholecystectomy? J Minim Access Surg. 2011;7(3):165-168.

PREOPERATIVE AND POSTOPERATIVE MANAGEMENT Zara Cooper • Edward Kelly

Surgeons of every specialty face increasingly complex surgical challenges. In addition, modern surgical treatment can be offered to more fragile patients, with successful outcomes. Mastery of the scientific fundamentals of perioperative management is required to achieve satisfactory results. The organ system–based approach presented here allows the surgeon to address the patient’s pre- and postoperative needs with a comprehensive surgical plan. This chapter will serve as a summary guide to best practices integral to conducting surgical procedures in the modern era.

MANAGEMENT OF PAIN AND DELIRIUM The most common neuropsychiatric complications following abdominal surgery are pain and delirium. Moreover, uncontrolled pain and delirium prevent the patient from contributing to vital aspects of his or her care, such as ambulation and respiratory toilet, and promote an unsafe environment that may lead to the unwanted dislodgment of drains and other supportive

devices, with potentially life-threatening consequences. Pain and delirium usually coexist in the postoperative setting, and each can contribute to the development of the other. Despite high reported rates of overall patient satisfaction, pain control is frequently inadequate in the perioperative setting,1 with high rates of complications such as drowsiness from overtreatment and unacceptable levels of pain from undertreatment. Therefore, it is mandatory that the surgical plan for every patient include close monitoring of postoperative pain and delirium and regular assessment of the efficacy of pain control. Pain management, like all surgical planning, begins in the preoperative assessment. In the modern era, a large proportion of surgical patients will require special attention with respect to pain control. Patients with preexisting pain syndromes, such as sciatica or interspinal disc disease, or patients with a history of opioid use may have a high tolerance for opioid analgesics. Every patient’s history should include a thorough investigation for chronic pain syndrome, addiction (active or in recovery), and adverse reactions to opioid, nonsteroidal, or epidural analgesia. The pain control strategy may include consultation with a pain control anesthesiology specialist, but it is the responsibility of the operating surgeon to identify complicated patients and construct an effective pain control plan.

Opioid Analgesia Postoperative pain control using opioid medication has been in use for thousands of years. Hippocrates advocated the use of opium for pain control. The benefits of postoperative pain control are salutary and include improved mobility and respiratory function and earlier return to normal activities. The most effective strategy for pain control using opioid analgesia is patientcontrolled analgesia (PCA), wherein the patient is instructed in the use of a preprogrammed intravenous pump that delivers measured doses of opioid (usually morphine or meperidine). In randomized trials, PCA has been shown to provide superior pain control and patient satisfaction compared to interval dosing,2 but PCA has not been shown to improve rates of pulmonary and cardiac complications3 or length of hospital stay,4 and there is evidence that PCA may contribute to postoperative ileus.5 In addition, PCA may be unsuitable for patients with a history of substance abuse, high opioid

tolerance, or those with atypical reactions to opioids.

Regional Analgesia Due to the limitations of PCA, pain control clinicians have turned to regional analgesia as an effective strategy for the management of postoperative pain. Postoperative epidural analgesia involves the insertion of a catheter into the epidural space of the lumbar or thoracic spine, enabling the delivery of local anesthetics or opioids directly to the nerve roots. The insertion procedure is generally safe, with complication rates of motor block and numbness between 0.5% and 7%,6 and an epidural abscess rate of 0.5 per thousand.7 Potential advantages of epidural analgesia include elimination of systemic opioids, and thus less respiratory depression, and improvement in pulmonary complications and perioperative ileus. There have been several large trials,810 a meta-analysis,6 and a systematic review11 comparing PCA with epidural analgesia in the setting of abdominal surgery. These studies indicate that epidural analgesia provides more complete analgesia than PCA throughout the postoperative course. Furthermore, in randomized prospective series of abdominal procedures, epidural analgesia has been associated with decreased rates of pulmonary complications12,13 and postoperative ileus.14,15 Epidural analgesia requires a skilled anesthesia clinician to insert and monitor the catheter and adjust the dosage of neuraxial medication. Some clinicians may prefer correction of coagulopathy before inserting or removing the catheter, although the American Society of Anesthesiologists (ASA) has not issued official guidelines on this issue. Peripheral nerve blocks are also effective in perioperative pain control and do not carry the same potential morbidities as the epidural approach. Using ultrasound guidance, a skilled practitioner can deliver a long-acting local anesthetic into the transversus abdominis plane (TAP) or in the rectus sheath to establish analgesia both intraoperatively and postoperatively. Randomized clinical data have confirmed the efficacy of regional blocks in controlling pain and reducing use of opioid analgesia.16,17

Analgesia with Nonsteroidal Anti-Inflammatory Drugs

Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for postoperative analgesia in the outpatient setting and, with the development of parenteral preparations, have come into use in the inpatient population. This class of medication has no respiratory side effects and is not associated with addiction potential, altered mental status, or ileus. In addition, these medications provide effective pain relief in the surgical population. However, use of NSAIDs has not been universally adopted in abdominal surgery due to concerns regarding the platelet dysfunction and erosive gastritis associated with heavy NSAID use. In prospective trials, NSAIDs were found to provide effective pain control without bleeding or gastritis symptoms following laparoscopic cholecystectomy,18 abdominal hysterectomy,19 and inguinal hernia repair.20,21 NSAIDs have also been shown to improve pain control and decrease morphine dosage when used in combination following appendectomy.22 The sensation of pain is very subjective and personal. Accordingly, the surgeon must individualize the pain control plan to fit the needs of each patient. The pain control modalities discussed above can be used in any combination, and the surgeon should not hesitate to use all resources at his or her command to provide adequate relief of postoperative pain.

Postoperative Delirium Delirium, defined as acute cognitive dysfunction marked by fluctuating disorientation, sensory disturbance, and decreased attention, is an all too common complication of surgical procedures, with reported rates of 11% to 25%, with the highest rates reported in the elderly population.23,24 The postoperative phase of abdominal surgery exposes patients, some of whom may be quite vulnerable to delirium, to a large number of factors that may precipitate or exacerbate delirium (Table 2-1). These factors can augment one another: postoperative pain can lead to decreased mobility, causing respiratory compromise, atelectasis, and hypoxemia. Escalating doses of narcotics to treat pain can cause respiratory depression and respiratory acidosis. Hypoxemia and delirium can cause agitation, prompting treatment with benzodiazepines, further worsening respiratory function and delirium. This vicious cycle can result in serious complications or death. Preoperative recognition of high-risk patients and meticulous monitoring of every patient’s

mental status are the most effective ways to prevent postoperative delirium; treatment can be remarkably difficult once the cycle has begun. TABLE 2-1: CAUSES OF PERIOPERATIVE DELIRIUM

Pain Narcotic analgesics Sleep deprivation Hypoxemia Hyperglycemia Acidosis Withdrawal (alcohol, narcotics, benzodiazepines) Anemia Dehydration Electrolyte imbalance (sodium, potassium, magnesium, calcium, phosphate) Fever Hypotension Infection (pneumonia, incision site infection, urinary tract infection) Medication (antiemetics, antihistamines, sedatives, anesthetics) Postoperative myocardial infarction Patient factors that are associated with high risk of perioperative delirium include age greater than 70 years, preexisting cognitive impairment or prior episode of delirium, history of alcohol or narcotic abuse, and malnutrition.22,25 Procedural factors associated with high delirium risk include operative time greater than 2 hours, prolonged use of restraints, presence of a urinary catheter, addition of more than 3 new medications, and reoperation.26 Once the patient’s risk for postoperative delirium is identified, perioperative care should be planned carefully to decrease other controllable factors. Epidural analgesia has been associated with less delirium than PCA after abdominal surgery.26 Sedation or “sleepers” should be used judiciously, if at all, with high-risk patients. If the patient requires sedation, neuroleptics such as haloperidol and the atypical neuroleptics such as olanzapine are

tolerated much better than benzodiazepines.27 The patient’s mental status, including orientation and attention, should be assessed with every visit and care should be taken to avoid anemia, electrolyte imbalances, dehydration, and other contributing factors. Once the diagnosis of postoperative delirium is established, it is important to recognize that some of the causes of delirium are potentially lifethreatening, and immediate action is necessary. Evaluation begins with a thorough history and physical examination at the bedside by the surgeon. The history should focus on precipitating events such as falls (possible traumatic brain injury), recent procedures, use of opioids and sedatives, changes in existing medications (eg, withholding of thyroid replacement or antidepressants), and consideration of alcohol withdrawal. The vital signs and fluid balance may suggest sepsis, hypovolemia, anemia, or dehydration. The exam should include brief but complete sensory and motor neurologic examinations to differentiate delirium from stroke. Pay attention to common sites of infection such as the surgical wound, the lungs, and intravenous catheters. Urinary retention may be present as a result of medication or infection. Deep venous thrombosis may be clinically evident as limb swelling. Postoperative myocardial infarction (MI) may often present as acute cardiogenic shock. The history and physical examination should then direct the use of lab tests. Most useful are the electrolytes, blood glucose, and complete blood cell count. Pulse oximetry and arterial blood gases may disclose hypercapnia or hypoxemia. Chest x-ray may disclose atelectasis, pneumonia, acute pulmonary edema, or pneumothorax. Cultures may be indicated in the setting of fever or leukocytosis, but will not help immediately. Electrocardiogram (ECG) and cardiac troponin may be used to diagnose postoperative MI. Resuscitative measures may be required if life-threatening causes of delirium are suspected. Airway control, supplemental oxygen, and fluid volume expansion should be considered in patients with unstable vital signs. The patient should not be sent out of the monitored environment for further tests, such as head computed tomography (CT), until the vital signs are stable and the agitation is controlled. Treatment of postoperative delirium depends on treatment of the underlying causes. Once the underlying cause has been treated, delirium may persist, especially in elderly or critically ill patients, who regain orientation and sleep cycles slowly. In these patients, it is important to provide orienting communication and mental stimulation during

the day and to promote sleep during the night. The simplest ways are the most effective: contact with family members and friends, use of hearing aids, engagement in activities of daily living, and regular mealtimes. Sleep can be promoted by keeping the room dark and quiet throughout the evening and preventing unnecessary interruptions. If nighttime sedation is required, atypical neuroleptics or low-dose serotonin reuptake inhibitors such as trazodone are better tolerated than benzodiazepines. If agitation persists, escalating doses of neuroleptics (or benzodiazepines in the setting of alcohol withdrawal) can be used to control behavior, but underlying organic causes of delirium must be investigated.

CARDIAC EVALUATION Risk Assessment It has been estimated that 1 million patients have a perioperative MI each year, and the contribution to medical costs is $20 billion annually.28 Thoracic, upper abdominal, neurologic, and major orthopedic procedures are associated with increased cardiac risk. Diabetes, prior MI, unstable angina, and decompensated congestive heart failure (CHF) are most predictive of perioperative cardiac morbidity and mortality, and patients with these conditions undergoing major surgery warrant further evaluation29 (Table 22). Patient factors conferring intermediate risk include mild angina and chronic renal insufficiency with baseline creatinine ≥2 mg/dL.30 It is worth noting that women were underrepresented in the studies on which the American College of Cardiology and the American Heart Association (ACC/AHA) guidelines are based.31 A retrospective study in gynecologic patients found that hypertension and previous MI were major predictors of postoperative cardiac events, as opposed to the ACC/AHA guidelines, which indicate that they are minor and intermediate criteria, respectively.32 Vascular surgical patients are at highest risk because of the prevalence of underlying coronary disease in this population.29,33 Other high-risk procedural factors include emergency surgery, long operative time, and high fluid replacement volume. Intraperitoneal procedures, carotid endarterectomy, thoracic surgery, head and neck procedures, and orthopedic procedures carry an intermediate

risk and are associated with a 1% to 5% risk of a perioperative cardiac event.30 TABLE 2-2: CLINICAL PREDICTORS OF INCREASED RISK FOR PERIOPERATIVE CARDIAC COMPLICATIONS

Major Recent myocardial infarction (within 30 days) Unstable or severe angina Decompensated congestive heart failure Significant arrhythmias (high-grade atrioventricular block, symptomatic ventricular arrhythmias with underlying heart disease, supraventricular arrhythmias with uncontrolled rate) Severe valvular disease Intermediate Mild angina Any prior myocardial infarction by history or electrocardiogram Compensated or prior congestive heart failure Diabetes mellitus Renal insufficiency Minor Advanced age Abnormal electrocardiogram Rhythm other than sinus (eg, atrial fibrillation) Poor functional capacity History of stroke Uncontrolled hypertension (eg, diastolic blood pressure >10 mm Hg) Perioperative evaluation to identify patients at risk for cardiac complications is essential in minimizing morbidity and mortality. Workup should start with history, physical exam, and ECG to determine the existence of cardiac pathology. Screening with chest radiographs and ECG is required for men over 40 and women over 55. According to the ACC/AHA guidelines, initial preoperative cardiac risk can be assessed using a clinical calculator, the

Revised Cardiac Risk Index (RCRI).34 This index includes history of ischemic heart disease, CHF, cerebrovascular disease, diabetes, chronic kidney disease, and planned high-risk procedure. Advanced or invasive testing is reserved for patients with 2 or more of these risk factors. Overall functional ability is the best clinical measure of cardiac fitness. Patients who can exercise without limitations can generally tolerate the stress of major surgery.35 Limited exercise capacity may indicate poor cardiopulmonary reserve and the inability to withstand the stress of surgery. Poor functional status is the inability to perform activities such as driving, cooking, or walking less than 5 km/h. Intraoperative risk factors include operative site, inappropriate use of vasopressors, and unintended hypotension. Intra-abdominal pressure exceeding 20 mm Hg during laparoscopy can decrease venous return from the lower extremities and thus contribute to decreased cardiac output,36 and Trendelenburg positioning can result in increased pressure on the diaphragm from the abdominal viscera, subsequently reducing vital capacity. Intraoperative hypertension has not been isolated as a risk factor for cardiac morbidity, but it is often associated with wide fluctuations in pressure and has been more closely associated with cardiac morbidity than intraoperative hypotension. Preoperative anxiety can contribute to hypertension even in normotensive patients. Patients with a history of hypertension, even medically controlled hypertension, are more likely to be hypertensive preoperatively. Those with poorly controlled hypertension are at greater risk of developing intraoperative ischemia, arrhythmias, and blood pressure derangements, particularly at induction and intubation. Twenty-five percent of patients will exhibit hypertension during laryngoscopy. Patients with chronic hypertension may not necessarily benefit from lower blood pressure during the preoperative period because they may depend on higher pressures for cerebral perfusion. Those receiving antihypertensive medications should continue them up until the time of surgery. Patients taking β-blockers are at risk of withdrawal and rebound ischemia. Key findings on physical examination include retinal vascular changes and an S4 gallop consistent with left ventricular hypertrophy. Chest radiography may show an enlarged heart, also suggesting left ventricular hypertrophy. ECG should be obtained in patients with chest pain, diabetes, prior revascularization, prior hospitalization for cardiac causes, all men age 45 or

older, and all women age 55 or older with 2 or more risk factors. High- or intermediate-risk patients should also have a screening ECG. A lower-thannormal ejection fraction demonstrated on echocardiography is associated with the greatest perioperative cardiac risk and should be obtained in all patients with symptoms suggesting heart failure or valvular disease. Tricuspid regurgitation indicates pulmonary hypertension and is often associated with sleep apnea. The chest x-ray is used to screen for cardiomegaly and pulmonary congestion, which may signify ventricular impairment. Exercise testing demonstrates a propensity for ischemia and arrhythmias under conditions that increase myocardial oxygen consumption. Numerous studies have shown that performance during exercise testing is predictive of perioperative mortality in noncardiac surgery. ST-segment changes during exercise including horizontal depression greater than 2 mm, changes with low workload, and persistent changes after 5 minutes of exercise are seen in severe multivessel disease. Other findings include dysrhythmias at a low heart rate, an inability to raise the heart rate to 70% of predicted, and sustained decrease in systolic pressure during exercise. Unfortunately, many patients are unable to achieve adequate workload in standard exercise testing because of osteoarthritis, low back pain, and pulmonary disease. In this case, pharmacologic testing is indicated with a dobutamine echocardiogram. Dobutamine is a β-agonist that increases myocardial oxygen demand and reveals impaired oxygen delivery in those with coronary disease. Echocardiography concurrently visualizes wall motion abnormalities due to ischemia. Transesophageal echocardiography may be preferable to transthoracic echocardiography in obese patients because of their body habitus and has been shown to have high negative predictive value in this group.37 Nuclear perfusion imaging with vasodilators such as adenosine or dipyridamole can identify coronary artery disease and demand ischemia. Heterogeneous perfusion after vasodilator administration demonstrates an inadequate response to stress. Wall motion abnormalities indicate ischemia, and an ejection fraction lower than 50% increases the risk of perioperative mortality. Angiography should only be performed if the patient may be a candidate for revascularization.

Coronary Disease Most perioperative MIs are caused by plaque rupture in lesions that do not

produce ischemia during preoperative testing.38 This presents an obvious challenge for detecting patients at risk. Stress testing has a low positive predictive value in patients with no cardiac risk factors and has been associated with an unacceptably high rate of false-positive results.39 Preoperative optimization may include medical management, percutaneous coronary interventions (PCIs), or coronary artery bypass grafting (CABG).40 The ACC/AHA guidelines29 recommend revascularization for patients whose preoperative testing reveals severe disease that warrants intervention according to practice guidelines for coronary artery disease, independent of their perioperative status. Patients warranting emergent CABG will be at greatest risk for that procedure. A recent study from the Veterans Administration hospitals recommends against revascularization in patients with stable cardiac symptoms.41 Preoperative PCI does not decrease the risk of future MI or mortality in patients with stable coronary disease, and only targets stenotic lesions, rather than those most likely to rupture. One retrospective study found no reduction in morbidity or perioperative MI after percutaneous transluminal coronary angioplasty, and the authors proposed that surgery within 90 days of balloon angioplasty increased the risk of thrombosis.42 However, PCI done more than 90 days before surgery did provide benefit when compared to those who had no intervention at all. Another retrospective study found that patients who have surgery within 2 weeks of stenting had a high incidence of perioperative MI, major bleeding, or death.43 Although a retrospective review from the Coronary Artery Surgery Study registry showed a lower mortality rate in patients with coronary artery disease who were post-CABG than those without CABG (0.09% vs 2.4%), this benefit did not include the morbidity associated with CABG itself. Unfortunately, the benefit was overwhelmed by the 2.3% morbidity rate seen with CABG in this cohort.44 Survival benefit of CABG over medical management is realized at 2 years or more after surgery,45 so preoperative mortality may decrease overall short-term survival. Revascularization and bypass grafting should be restricted to patients who would benefit from the procedure independent of their need for noncardiac surgery. One of the disadvantages of PCI in the preoperative setting is the need for anticoagulation to prevent early stent occlusion. The use of platelet inhibitors to prevent stent occlusion must be included in the overall risk assessment, especially for surgery of the central

nervous system. Catecholamine surges can cause tachycardia, which may alter the tensile strength of coronary plaques and incite plaque rupture.46,47 Catecholamine surges can also increase blood pressure and contractility, contributing to platelet aggregation and thrombosis after plaque rupture and increasing the possibility of complete occlusion of the arterial lumen.48 Perioperative βblockade mitigates these effects and has been shown to reduce MI and mortality from MI by over 30% in vascular surgical patients with reversible ischemia.46 Patients at highest risk still have a cardiac event rate of 10%, even with adequate perioperative β-blockade.29 In 1998, a landmark study49 demonstrated a 55% reduction in mortality in noncardiac surgical patients with known coronary disease who were given atenolol perioperatively. This was followed by the DECREASE trial,50 which showed a 10-fold reduction in perioperative MI and death compared to placebo. Thereafter, perioperative β-blockade was widely adopted as a quality measure. However, additional later investigations have shown that although perioperative β-blockers benefit patients with known ischemia, lowrisk patients may in fact be harmed.51 Tight rate control has been associated with increased risk of hypotension and bradycardia requiring intervention and stroke without any significant decrease in mortality.52-55 Furthermore, critical analysis of the literature shows that studies have been inconsistent in the type of medication administered, the duration and timing of administration, and the target for heart rate control.56 Consequently, results are difficult to interpret. Thus, prophylactic perioperative β-blockade should be restricted to patients with cardiac ischemia and has a limited role in patients with low or moderate risk of postoperative cardiac events.29

Congestive Heart Failure and Arrhythmia CHF is associated with coronary disease, valvular disease, ventricular dysfunction, and all types of cardiomyopathy. These are all independent risk factors that should be identified prior to surgery. Even compensated heart failure may be aggravated by fluid shifts associated with anesthesia and abdominal surgery and deserves serious consideration. Perioperative mortality increases with higher New York Heart Association class and preoperative pulmonary congestion. CHF should be treated to lower filling

pressures and improve cardiac output before elective surgery. β-Blockers, angiotensin-converting enzyme inhibitors, and diuretics can be employed to this end. The patient should be stable for 1 week before surgery.57 Arrhythmias and conduction abnormalities elicited in the history, on exam, or on ECG should prompt investigation into metabolic derangements, drug toxicities, or coronary disease. In the presence of symptoms or hemodynamic changes, the underlying condition should be reversed and then medication given to treat the arrhythmia. Indications for antiarrhythmic medication and cardiac pacemakers are the same as in the nonoperative setting. Nonsustained ventricular tachycardia and premature ventricular contractions have not been associated with increased perioperative risk and do not require further intervention.58,59

Valvular Disease Valvular disease should be considered in patients with symptoms of CHF, syncope, and a history of rheumatic heart disease. Aortic stenosis (AS) is a fixed obstruction to the left ventricular outflow tract, limiting cardiac reserve and an appropriate response to stress. History should elicit symptoms of dyspnea, angina, and syncope; examination may reveal a soft S2, a latepeaking murmur, or a right-sided crescendo–decrescendo murmur radiating to the carotids. AS is usually caused by progressive calcification or congenital bicuspid valve. Critical stenosis exists when the valve area is less than 0.7 cm2 or transvalvular gradients are greater than 50 mm Hg and is associated with an inability to increase cardiac output with demand. If uncorrected, AS is associated with a 13% risk of perioperative death. Valve replacement is indicated prior to elective surgery in patients with symptomatic stenosis.29 Myocardial ischemia may occur in the absence of significant coronary artery occlusion in the presence of aortic valve disease. Perioperative management should include optimizing the heart rate to between 60 and 90 beats per minute and avoiding atrial fibrillation if possible. Because of the outflow obstruction, stroke volume may be fixed and bradycardia will lower cardiac output. Similarly, hypotension is also poorly tolerated. Aortic regurgitation (AR) is associated with backward flow into the left ventricle during diastole and reduced forward stroke volume. Bradycardia

facilitates regurgitation by increased diastolic time. Chronic AR causes massive left ventricular dilatation (cor bovinum) and hypertrophy, which is associated with decreased left ventricular function at later stages. AR is most often caused by rheumatic disease or congenital bicuspid valve. Medical treatment includes rate control and afterload reduction. Without valve replacement, survival is approximately 5 years once patients become symptomatic. This is an obvious consideration when planning any other surgical procedures. Tricuspid regurgitation is usually caused by pulmonary hypertension secondary to severe left-sided failure. Other causes include endocarditis, carcinoid syndrome, and primary pulmonary hypertension. Hypovolemia, hypoxia, and acidosis can increase right ventricular afterload and should be avoided in the perioperative period. Mitral stenosis is an inflow obstruction that prevents adequate left ventricular filling. The transvalvular pressure gradient depends on atrial kick, heart rate, and diastolic filling time. Tachycardia decreases filling time and contributes to pulmonary congestion. Mitral regurgitation is also associated with pulmonary hypertension with congestion, as the pathologic valve prevents forward flow, causing left atrial dilatation and subsequent atrial arrhythmias. History and physical exam should focus on signs of CHF such as orthopnea, pedal edema, dyspnea, reduced exercise tolerance, and auscultatory findings such as murmurs and an S3 gallop. Neurologic deficits may signify embolic sequelae of valve disease. Perioperative rate control is essential for maintaining adequate cardiac output. ECG findings will reflect related arrhythmias and medications but will not be specific for valve disease. Laboratory studies should identify secondary hepatic dysfunction or pulmonary compromise. Left ventricular hypertrophy is an adaptive response, which may cause subsequent pulmonary hypertension and diastolic dysfunction. Prosthetics in the mitral position pose the greatest risk for thromboembolism, and the risk increases with valve area and low flow. Mechanical valves pose a higher risk than tissue valves in patients with a history of valve replacement. Diuretics and afterload-reducing agents will enhance forward flow and minimize cardiopulmonary congestion. Patients with mitral valve prolapse (MVP) should receive antibiotics. Mitral regurgitation may also impair left ventricular function and lead to pulmonary hypertension. Stroke volume is reduced by backward flow into the

atrium during systole. The left ventricle dilates to handle increasing endsystolic volume, eventually causing concentric hypertrophy and decreased contractility. The end result may be decreased ejection fraction and CHF. A decrease in systemic vascular resistance and increase in atrial contribution to the ejection fraction can both improve forward flow and reduce the amount of regurgitation. Echocardiography can clarify the degree of valvular impairment. Medical treatment centers on afterload reduction with vasodilators and diuretics. MVP is present in up to 15% of women and is usually associated with a midsystolic click and late systolic murmur on physical exam. Murmur is indicative of prolapse. Although MVP is associated with connective tissue disorders, it usually occurs in otherwise healthy, asymptomatic patients. Echocardiography is used to confirm the diagnosis and evaluate the degree of prolapse. Chronically, MVP may be associated with mitral regurgitation, emboli, and increased risk of endocarditis. Prolapse may be aggravated by decreased preload, which should be minimized in the perioperative period. Patients with MVP are at risk of ventricular arrhythmias with sympathetic stimulation and endocarditis, which can be addressed with pain control and antibiotic prophylaxis, respectively. Individuals with underlying structural cardiac defects are at increased risk for developing endocarditis after invasive procedures. Surgical procedures involving mucosal surfaces or infected tissues may cause transient bacteremia that is usually short-lived. Certain procedures are associated with a greater risk of endocarditis and warrant prophylaxis (Table 2-3). Abnormal valves, endocardium, or endothelium can harbor the bloodborne bacteria for a longer period of time, and infection and inflammation can ensue. Although there are no randomized trials regarding endocarditis prophylaxis, the AHA recommends prophylaxis for those60 at high and moderate risk for developing the condition. The highest-risk patients have prosthetic heart valves, cyanotic congenital heart disease, or a history of endocarditis (even without structural abnormality).61 Conditions associated with moderate risk include congenital septal defects, patent ductus arteriosus, coarctation of the aorta, and bicuspid aortic valve. Hypertrophic cardiomyopathy and acquired valvular disease also fall into this category. MVP is a prevalent and often situational condition. Normal valves may prolapse in the event of tachycardia or hypovolemia and may reflect normal growth patterns in young people. Prolapse without leak or regurgitation seen on Doppler studies is not associated with risk greater than that of the general population, and no antibiotic prophylaxis is necessary.62,63

However, the jet caused by the prolapsed valve increases the risk of bacterial adherence and subsequent endocarditis. Leaky valves detected by physical exam or Doppler warrant consideration for prophylactic antibiotics.64 Patients with significant regurgitation are more likely to be older and men, and other studies have shown that older men are more likely to develop endocarditis.6466 Some advocate prophylaxis for men older than 45 years with MVP even in the absence of audible regurgitation.66 Prolapse secondary to myxomatous valve degeneration also warrants prophylactic antibiotics.67,68 TABLE 2-3: AHA ENDOCARDITIS PROPHYLAXIS RECOMMENDATIONS

Antibiotic Coverage Recommended Respiratory: tonsillectomy/adenoidectomy; bronchoscopy with biopsy; procedures involving respiratory mucosa Gastrointestinal tract: any procedure in the setting of infected tissue in the gastrointestinal tract Genitourinary tract: any procedure in the setting of established infection Antibiotic Coverage Not Recommended Respiratory: endotracheal intubation; bronchoscopy without biopsy; tympanostomy Gastrointestinal tract: transesophageal echocardiography; endoscopy without biopsy In uninfected tissue: urethral catheterization; uterine dilation and curettage; therapeutic abortion; manipulation of intrauterine devices Other: cardiac catheterization; pacemaker placement; circumcision; incision or biopsy on prepped skin For patients at risk, the goal should be administration of antibiotics in time to attain adequate serum levels during and after the procedure. For most operations, a single intravenous dose given 1 hour prior to incision will achieve this goal. Antibiotics should generally not be continued for more than 6 to 8 hours after the procedure to minimize the chance of bacterial resistance. In the case of oral, upper respiratory, and esophageal procedures, α-hemolytic Streptococcus is the most common cause of endocarditis, and

antibiotics should be targeted accordingly. Oral amoxicillin, parenteral ampicillin, and clindamycin for penicillin-allergic patients are suitable medications. Erythromycin is no longer recommended for penicillin-allergic patients because of gastrointestinal side effects and variable absorption.69 Antibiotics given to those having genitourinary and nonesophageal gastrointestinal procedures should target enterococci.69 While gram-negative bacteremia can occur, it rarely causes endocarditis. Parenteral ampicillin and gentamicin are recommended for highest-risk patients. Moderate-risk patients may receive amoxicillin or ampicillin. Vancomycin may be substituted in patients allergic to penicillin.

PERIOPERATIVE MANAGEMENT OF ANTITHROMBOTIC MEDICATION Estimates suggest that 250,000 patients receiving chronic anticoagulation require surgery in the United States each year. Operative bleeding risk must be balanced against thromboembolic risk for the patient off of anticoagulation and requires careful judgment. Factors that influence the risk of thromboembolism include the condition requiring chronic anticoagulation, the duration of the procedure, time expected off of anticoagulation, and the duration of perioperative immobility. Thromboembolic risk increases with the amount of time that the patient’s anticoagulation is subtherapeutic. Primary indications for chronic anticoagulation include arterial embolism associated with mechanical valves and atrial fibrillation and venous thromboembolism (VTE). Arterial events precipitate stroke, and valvular and atrial clot and systemic emboli are higher risk for morbidity and mortality than venous events. Patients at highest risk for perioperative embolism include those with mechanical prosthetic mitral valves, aortic caged-ball and tilted valves, rheumatic heart disease, or history of stroke or transient ischemic attacks (TIAs) in the past 3 months. The risk of thromboembolism without anticoagulation is higher than 10% per year in these high-risk patients. Patients at moderate risk of thromboembolism without anticoagulation (4%-10% per year) have atrial fibrillation, a bileaflet valve, or history of stroke or TIA. The CHADS2 score (CHF, hypertension, age, diabetes, and stroke) further stratifies embolic risk for patients with atrial fibrillation based

on comorbidities. One point is assigned for hypertension, diabetes, CHF, and age >75 years; 2 points are assigned for history of stroke or TIA. Patients with a cumulative score of 5 to 6 are highest risk; those with a score of 3 to 4 are moderate risk; and those with a score of 0 to 2 without history of stroke or TIA are low risk. Chronic anticoagulation is indicated for VTE. Patients with VTE within 3 months of surgery and severe thrombophilia are at highest risk for perioperative events and should receive bridging anticoagulation with therapeutic doses of low-molecular-weight heparin (LMWH) or intravenous unfractionated heparin (UFH). Patients at moderate risk include those with a thromboembolic event 3 to 12 months before surgery and less severe thrombophilias. They can receive therapeutic or subtherapeutic doses of anticoagulation depending on the risk of bleeding associated with the procedure. Patients with a remote event are at lowest risk and do not require bridging anticoagulation. It is generally recommended to stop warfarin 5 days prior to surgery if a normal international normalized ratio (INR) is desired. Vitamin K may be administered in the days leading up to the event if the INR is not correcting quickly enough. LMWH should be held 24 hours before surgery, and intravenous UFH should be held 4 hours before surgery. Oral anticoagulants may be started 12 to 24 hours postoperatively because they take at least 48 hours to affect coagulation. The timing of resuming intravenous and subcutaneous anticoagulants should be determined on a case-by-case basis. Low-risk patients receiving clopidogrel or aspirin should have it held 5 to 10 days before surgery. Patients with coronary stents are chronically treated with clopidogrel and aspirin to mitigate the risk of stent thrombosis. Interruptions in therapy are associated with high risk of thrombosis and infarct. Patients with bare metal stents placed within 6 weeks of surgery or drug-eluting stents placed within 12 months of surgery should continue clopidogrel and aspirin in the perioperative period. The perioperative antithrombotic guidelines70 from the American College of Chest Physicians are summarized in Table 2-4. TABLE 2-4: GUIDELINES FOR PERIOPERATIVE MANAGEMENT OF ANTITHROMBOTIC MEDICATIONS

PULMONARY EVALUATION Pulmonary complications are common after surgery and can prolong hospital stays for 1 to 2 weeks.71 Complications include atelectasis, pneumonia, exacerbations of chronic pulmonary disorders, and respiratory failure requiring mechanical ventilation. Smoking, underlying chronic obstructive pulmonary disease (COPD), and poor exercise tolerance are the greatest risk factors for postoperative pulmonary complications. Physicians should ask about a history of smoking, decreased exercise capacity, dyspnea, and chronic cough. Examination should note pursed lip breathing, clubbing, and chest wall anatomy that could impair pulmonary function. Pulmonary testing is unnecessary in patients without a clear history of smoking or pulmonary disease. The predictive value of screening spirometry is unclear, and no threshold value has been identified to guide surgical decision-making. Forced expiratory volume in 1 second less than 50% of predicted is indicative of exertional dyspnea and may herald the need for further testing. Preoperative chest x-ray abnormalities are associated with postoperative pulmonary complications,71 but to this point, there are no recommendations for screening radiographs in patients without pulmonary disease. Any

preoperative chest x-ray must be examined for signs of hyperinflation consistent with COPD. While compensated hypercapnia has not been shown to be an independent predictor for postoperative ventilatory insufficiency in patients undergoing lung resection, preoperative arterial blood gas analysis provides useful baseline information for perioperative management of patients with chronic carbon dioxide retention. Transverse and upper abdominal incisions are associated with a higher rate of postoperative pulmonary complications than longitudinal midline incisions and lower abdominal incisions.72 Surgery longer than 3 hours is also associated with higher risk.73 General anesthesia is also associated with a higher risk of pulmonary complications than spinal, epidural, or regional anesthesia.74 Physiologic changes can be seen in the postoperative period, especially after thoracic and upper abdominal procedures. Vital capacity may decrease by 50% to 60%, and is accompanied by an increased respiratory rate to maintain tidal volumes. Normally, functional residual capacity usually exceeds the closing capacity of the alveoli so they remain open throughout the respiratory cycle. Prolonged effects of anesthetics and narcotics reduce functional reserve capacity postoperatively, causing alveolar collapse. These changes can last for weeks to months. A distended abdomen can impair diaphragmatic excursion; painful incisions around the diaphragm and other respiratory muscles contribute to splinting and inadequate pulmonary toilet. Narcotics can inhibit sighing and coughing reflexes, which normally prevent alveolar collapse during periods of sleep and recumbency. Analgesics must be titrated carefully to permit deep breathing and avoid impairing respiratory effort. Inspired nonhumidified oxygen and halogenated anesthetics are cytotoxic and interfere with surfactant production and mucociliary clearance. Depressed respiratory reflexes, diaphragm dysfunction, and decreased functional reserve capacity all contribute to alveolar collapse and pooling of secretions. Aspiration risk is also increased. Excess secretions cause further alveolar collapse and create a milieu ripe for bacterial infection and pneumonia. Intubated patients should receive antacid prophylaxis and gastric drainage to minimize the risk of aspiration. Multiple analyses have found that poor exercise tolerance is the greatest predictor of postoperative pulmonary impairment. The ASA risk classification is a gauge of general status and is highly predictive of both

cardiac and pulmonary complications.75,76 Although advanced age is associated with increased incidence of chronic pulmonary disease and underlying impairment, it is not an independent risk factor for pulmonary complications. Clearly, all smokers should be urged to stop before surgery. Even in the absence of coexisting pulmonary disease, smoking increases the risk of perioperative complications. Smoking confers a relative risk of 1.4 to 4.3, but a reduced risk of pulmonary complications has been shown in patients who stop smoking at least 8 weeks before cardiac surgery.77 Even 48 hours of abstinence can improve mucociliary clearance, decrease carboxyhemoglobin levels to those of nonsmokers, and reduce the cardiovascular effects of nicotine. A nicotine patch may help some patients with postoperative nicotine withdrawal but may not be advisable in patients at risk for poor wound healing. COPD confers a relative risk of 2.7 to 4.7 in various studies. Symptoms of bronchospasm and obstruction should be addressed before surgery, and elective procedures should be deferred in patients having an acute exacerbation. Preoperative treatment may include bronchodilators, antibiotics, steroids, and physical therapy to increase exercise capacity. Patients with active pulmonary infections should have surgery delayed if possible. Asthmatics should have peak flow equivalent to their personal best or 80% of predicted and should be medically optimized to achieve this goal. Pulse corticosteroids may be used without an increased risk of postoperative infection or other complication.78,79 Malnourished patients may not be able to meet the demands of the increased work of breathing, increasing their risk for respiratory failure. Obese patients have higher rates of oxygen consumption and carbon dioxide production, which increases their work of breathing. They may also exhibit restrictive physiology due to a large, stiff chest wall. A complete history should inquire about sleeping difficulty and snoring. Obesity increases the amount of soft tissue in the oropharynx, which can cause upper airway obstruction during sleep. Fifty-five percent of morbidly obese patients may have sleep-related breathing disorders such as obstructive sleep apnea and obesity-hypoventilation syndrome.80 Symptoms include snoring and daytime sleepiness, and formal sleep studies are employed for definitive diagnosis. Sleep-disordered breathing is associated with hypoxia, hypercapnia, changes

in blood pressure, nocturnal angina, and increased cardiac morbidity and mortality including stroke and sudden death.81 Arterial blood gas with partial arterial oxygen pressure less than 55 mm Hg or partial arterial carbon dioxide pressure greater than 47 mm Hg confirms the diagnosis. An increased incidence of pulmonary hypertension and right-sided heart failure is seen in patients with obesity hypoventilation syndrome, and these patients should have an echocardiogram before surgery. In severe cases, intraoperative monitoring with a pulmonary artery catheter may be prudent. In the patient who is awake, postoperative care should include coughing and deep breathing exercises, and in nonambulatory patients, early mobilization should include turning every 2 hours. Early ambulation prevents atelectasis and pooling of secretions and increases the ventilatory drive. Upright position distributes blood flow and minimizes shunting. Preoperative medications should be resumed expeditiously. Incentive spirometry and pulmonary toilet are pulmonary expansion maneuvers, which reduce the relative risk of pulmonary complications by 50%.81 Patients should receive preoperative education about these techniques. Inhaled ipratropium and βagonists, used together, may prevent postoperative wheezing and bronchospasm and should be prescribed in patients at risk. Intermittent positive-pressure ventilation and nasal bilevel positive airway pressure may be enlisted for secondary prevention. Epidural analgesia is superior to parenteral narcotics in abdominal and thoracic procedures for preventing pulmonary complications.

GASTROINTESTINAL EVALUATION Stress ulceration has been a well-recognized complication of surgery and trauma since 1932, when Cushing reported gastric bleeding accompanying head injury. With later research in gastric physiology and shock, it has been recognized that the appearance of gastric erosion results from failure of the protective function of gastric mucosa and back diffusion of hydrogen ion, enabling gastric acid to injure the mucosa. Once the mucosa is injured, the defenses are further weakened, leading to further injury in a vicious cycle. The protective functions of the mucosa rely on the stomach’s rich blood flow to maintain high oxygen saturation. The most critical factor in the development of erosive ulceration now appears to be mucosal ischemia. Once

the rich blood supply of the mucosa is compromised, the protective mechanisms are impaired, and gastric acid causes erosion, bleeding, and perforation. In the late 1970s,82 the incidence of gastric bleeding in critically ill patients was 15%. Recognition of the importance of organ perfusion has resulted in decreased rates of erosive stress gastritis. Factors often cited for this observation are improvement in resuscitation and monitoring technology, nutritional support, and effective agents for medical prophylaxis. The prophylactic medicines are targeted to reduce gastric acid secretion. Antacids have been shown to provide effective protection against erosive ulceration; however, there is increased risk of aspiration pneumonia. Antagonists of the histamine-2 (H2) receptors of the parietal cells impair gastric acid secretion and are effective prophylaxis for erosive ulceration. With the emergence of proton pump inhibitor (PPI) medications, more effective control of gastric acid secretion was available, leading to widespread use of PPIs for stress ulcer prophylaxis. In high-risk, critically ill patients, PPIs have been shown to decrease the incidence of gastrointestinal bleeding as compared to H2 blockers, but both carry increased risk of ventilator-associated pneumonia and pseudomembranous colitis.83 In the setting of elective operations when the patients are not critically ill, the incidence of stress ulceration is now very low, and routine use of ulcer prophylaxis medication has been questioned. In addition, the routine use of antisecretory medication, in particular in the elective setting, may lead to increased risk of pneumonia and pseudomembranous colitis.

Postoperative Ileus Ileus is a condition of generalized bowel dysmotility that frequently impairs feeding in the postoperative setting. Ileus typically occurs after abdominal surgery, even if the bowel itself is not altered. It has been shown that laparotomy alone, without intestinal manipulation, leads to impaired gastrointestinal motility. The small bowel is typically affected the least and can maintain organized peristaltic contractions throughout the perioperative period. The stomach usually regains a normal pattern of emptying in 24 hours, and the colon is last to regain motility, usually in 48 to 72 hours. The exact mechanism that causes postoperative ileus is not known;

however, physiologic studies have demonstrated the significant contribution of both inhibitory neural reflexes and local mediators within the intestinal wall. Inhibitory neural reflexes have been shown to be present within the neural plexuses of the intestinal wall itself and in the reflex arcs traveling back and forth from the intestine to the spinal cord. These neural pathways may account for the development of ileus during laparotomy without bowel manipulation. In addition, inflammatory mediators such as nitric oxide are present in manipulated bowel and in peritonitis and may play a role in development of ileus. Ileus can be recognized from clinical signs, such as abdominal distension, nausea, and the absence of bowel sounds and flatus, which should prompt the diagnosis. Abdominal x-ray imaging typically shows dilated loops of small bowel and colon. Bowel obstruction must also be considered with these clinical findings, however, and CT or other contrast imaging may be required to rule out obstruction. Ileus can also appear following nonabdominal surgery and can result from effects of medications (most often narcotics), electrolyte abnormalities (especially hypokalemia), and a wide variety of other factors. Occasionally, the patient sustains a prolonged period of postoperative ileus. This can be due to a large number of contributing factors, such as intraabdominal infection, hematoma, effects of narcotics and other medications, electrolyte abnormalities, and pain. In addition, there can be prolonged dysmotility from certain bowel operations, such as intestinal bypass. The role of laparoscopic surgery in prevention of ileus is controversial. In theory, with less handling of the bowel laparoscopically and with smaller incisions, there should be less stimulation of the local mediators and neural reflexes. Animal studies comparing open and laparoscopic colon surgery indicate earlier resumption of normal motility studies and bowel movements with the laparoscopic approach. Human trials have not been conclusive. Several series demonstrate earlier tolerance of postoperative feeding with the laparoscopic approach to colon resection; however, these have been criticized for selection bias, and such studies are impossible to conduct in a blinded fashion. Early mobilization has long been held to be useful in prevention of postoperative ileus. While standing and walking in the early postoperative period have been proven to have major benefits in pulmonary function and prevention of pneumonia, mobilization has no demonstrable effect on

postoperative ileus. In the expected course of uncomplicated abdominal surgery, the stomach is frequently drained by a nasogastric tube for the first 24 hours after surgery, and the patient is not allowed oral intake until there is evidence that colonic motility has returned, usually best evidenced by the passage of flatus. Earlier feeding and no gastric drainage after bowel surgery can be attempted for healthy patients undergoing elective abdominal surgery and has a high rate of success provided clinical symptoms of ileus are not present. In such patients, the use of effective preventive strategies is highly effective. These include maintenance of normal serum electrolytes, use of epidural analgesia, and avoidance of complications such as infection and bleeding. The routine use of nasogastric tubes for drainage in the postoperative period after abdominal surgery has come into question since the mid-1990s. The most effective strategy for management of postoperative ileus following abdominal surgery has been the development of epidural analgesia. Randomized trials have shown that the use of nonnarcotic (local anesthetic– based) epidural analgesia at the thoracic level in the postoperative period results in a decreased period of postoperative ileus in elective abdominal surgery. Ileus reduction is not seen in lumbar-level epidural analgesia, suggesting that inhibitory reflex arcs involving the thoracic spinal cord may play a major role in postoperative ileus. Narcotic analgesia, while effective for postoperative pain, has been shown to lengthen the duration of postoperative ileus, especially when used as a continuous infusion or as PCA. Patients report better control of postoperative pain with continuous infusion or PCA as compared to intermittent parenteral dosing. Many studies have been done comparing various types of opioid analgesics, in attempts to find a type that does not prolong ileus. There has been no clearly superior drug identified; all currently available opioids cause ileus. Opioid antagonists such as naloxone have been used in trials to decrease ileus in chronic narcotic use, and there is evidence that antagonists are effective in that setting; however, in postoperative ileus, the antagonists have not been shown to be clinically useful, again suggesting that other mechanisms are contributing to postoperative ileus.

Early Postoperative Bowel Obstruction Early postoperative bowel obstruction refers to mechanical bowel

obstruction, primarily involving the small bowel, which occurs in the first 30 days following abdominal surgery. The clinical picture may frequently be mistaken for ileus, and these conditions can overlap. The clinical presentation of early postoperative bowel obstruction is similar to that of bowel obstruction arising de novo: crampy abdominal pain, vomiting, abdominal distention, and obstipation. The incidence of early postoperative bowel obstruction has been variable in published series, due to difficulty in differentiating ileus from early postoperative bowel obstruction, but the reported range is from 0.7% to 9.5% of abdominal operations. Retrospective large series show that about 90% of early postoperative bowel obstruction is caused by inflammatory adhesions. These occur as a result of injury to the surfaces of the bowel and peritoneum during surgical manipulation. The injury prompts the release of inflammatory mediators that lead to formation of fibrinous adhesions between the serosal and peritoneal surfaces. As the inflammatory mediators are cleared and the injury subsides, these adhesions eventually mature into fibrous, firm, bandlike structures. In the early postoperative period, the adhesions are in their inflammatory, fibrinous form and, as such, do not usually cause complete mechanical obstruction. Internal hernia is the next most common cause of early postoperative bowel obstruction and can be diagnosed with a CT scan but may not be recognized until laparotomy. Internal hernia occurs when gaps or defects are left in the mesentery or omentum or blind gutters or sacs are left in place during abdominal surgery. The typical scenario is colon resection involving extensive resection of the mesentery for lymph node clearance. If the resulting gap in the mesentery is not securely closed, small bowel loops may go through the opening and not be able to slide back out. A blind gutter may be constructed inadvertently during the creation of a colostomy. When the colostomy is brought up to the anterior abdominal wall, there is a space between the colon and the lateral abdominal wall, which may also trap the mobile loops of small bowel. Defects in the closure of the fascia during open or laparoscopic surgery can cause obstruction from incarcerated early postoperative abdominal wall hernia. Fortunately, internal hernia is a rare occurrence in the early postoperative period; however, it must be suspected in cases in which bowel anastomoses or colostomies have been constructed. Unlike adhesive obstruction, internal hernia requires operative intervention due to the high potential for complete obstruction and strangulation of the

bowel. Intussusception is a rare cause of early postoperative bowel obstruction in adults but occurs more frequently in children. Intussusception occurs when peristalsis carries a segment of the bowel (called the lead point) up inside the distal bowel like a rolled up stocking. The lead point is usually abnormal in some way and typically has some intraluminal mass, such as a tumor or the stump of an appendix after appendectomy. Other rare causes for early postoperative bowel obstruction include missed causes of primary obstruction at the index laparotomy, peritoneal carcinomatosis, obstructing hematoma, and ischemic stricture. Management of early postoperative bowel obstruction depends on differentiation of adhesive bowel obstruction (the majority) from internal hernia and the other causes and from ileus. Clinicians generally rely on radiographic imaging to discern ileus from obstruction. For many years, plain x-ray of the abdomen was used: if the abdominal plain film showed airdistended loops of bowel and air-fluid levels on upright views, the diagnosis of obstruction was favored. However, plain radiographs can be misleading in the postoperative setting, and the overlap of ileus and obstruction can be confusing. Upper gastrointestinal contrast studies using a water-soluble agent have better accuracy, and abdominal CT using oral contrast has been shown to have 100% sensitivity and specificity in differentiating early postoperative bowel obstruction from postoperative ileus. However, unlike late adhesive bowel obstruction, contrast passage into the colon has not been shown to predict success for nonoperative management. Once the diagnosis is made, management is tailored to the specific needs of the patient. Decompression via nasogastric tube is usually indicated, and ileus can be treated as discussed. Adhesive bowel obstruction warrants a period of expectant management and supportive care, as the majority of these problems will resolve spontaneously. Most surgical texts recommend that the waiting period can be extended to 14 days. If the early bowel obstruction lasts longer than 14 days, less than 10% resolve spontaneously, and exploratory laparotomy is indicated. The uncommon causes of early postoperative bowel obstruction, such as internal hernia, require more early surgical correction and should be suspected in the setting of complete obstipation, or when abdominal CT suggests internal hernia or complete bowel obstruction.

Renal Evaluation Patients without a clinical history suggesting renal disease have a low incidence of significant electrolyte disturbances on routine preoperative screening.84 However, patients with renal or cardiac disease who are taking digitalis or diuretics or those with ongoing fluid losses (ie, diarrhea, vomiting, fistula, and bleeding) do have an increased risk of significant abnormalities and should have electrolytes measured and replaced preoperatively. Preoperative urinalysis can be a useful screen for renal disease. Proteinuria marks intrinsic renal disease or CHF. Urinary glucose and ketones are suggestive of diabetes and starvation in the ketotic state, respectively. In the absence of recent genitourinary instrumentation, microscopic hematuria suggests calculi, vascular disease, or infection. A few leukocytes may be normal in female patients, but an increased number signifies infection. Epithelial cells are present in poorly collected specimens. Patients with renal insufficiency or end-stage renal disease often have comorbidities that increase their overall risk in the perioperative period. Hypertension and diabetes correlate with increased risk of coronary artery disease and postoperative MI, impaired wound healing, wound infection, platelet dysfunction, and bleeding. Preoperative history should note the etiology of renal impairment, preoperative weight as a marker of volume status, and timing of last dialysis and the amount of fluid removed routinely. Evaluation should include a cardiac risk assessment. Physical exam should focus on signs of volume overload such as jugular venous distention and pulmonary crackles. In patients with clinically evident renal insufficiency, a full electrolyte panel (calcium, phosphorus, magnesium, sodium, and potassium) should be checked preoperatively, along with blood urea nitrogen and creatinine levels. Progressive renal failure is associated with catabolism and anorexia. Such patients need aggressive nutritional support during the perioperative periods to minimize the risk of infection and poor healing. Dialysis-dependent patients should have dialysis within 24 hours before surgery and may benefit from monitoring of intravascular volume status during surgery. Blood samples obtained immediately after dialysis, before equilibration occurs, should only be used in comparison to predialysis values to determine the efficacy of dialysis.85

Postoperatively, patients with chronic renal insufficiency or end-stage renal disease will need to have surgical volume losses replaced, but care should be taken to avoid excess. Replacement fluids should not contain potassium, and early dialysis should be employed to address volume overload and electrolyte derangements. Patients with impaired creatinine clearance should have their medications adjusted accordingly. For example, meperidine should be avoided because its metabolites accumulate in renal impairment and can lead to seizures. The choice of postoperative fluid therapy depends on the patient’s comorbidities, the type of surgery, and conditions that affect the patient’s fluid balance. There is no evidence that colloid is better than crystalloid in the postoperative period, and it is considerably more expensive.86 Sepsis and bowel obstruction will require ongoing volume replacement rather than maintenance. Ringer’s solution provides 6 times the intravascular volume as an equivalent amount of hypotonic solution. In patients with normal renal function, clinical signs such as urine output, heart rate, and blood pressure should guide fluid management. Once the stress response subsides, fluid retention subsides and fluid is mobilized from the periphery, and fluid supplementation is unnecessary. This fluid mobilization is evident by decreased peripheral edema and increased urine output. Diuretics given in the period of fluid sequestration may cause intravascular volume depletion and symptomatic hypovolemia. Postoperative management includes close monitoring of urine output and electrolytes, daily weight, elimination of nephrotoxic medications, and adjustment of all medications that are cleared by the kidney. Hyperkalemia, hyperphosphatemia, and metabolic acidosis may be seen and should be addressed accordingly. Indications for renal replacement therapy include severe intravascular overload, symptomatic hyperkalemia, metabolic acidosis, and complicated uremia (pericarditis and encephalopathy) (Table 25). TABLE 2-5: OLIGURIA IN THE PERIOPERATIVE PATIENT

Postoperative renal failure increases perioperative mortality. Risk factors for postoperative renal failure include intraoperative hypotension, advanced age, CHF, aortic cross-clamping, administration of nephrotoxic drugs or radiocontrast, and preoperative elevation in renal insufficiency. Up to 10% of patients may experience acute renal failure after aortic cross-clamping. Postoperative renal failure rates are higher in hypovolemic patients, so preoperative dehydration should be avoided. Contrast nephropathy is a common cause of hospital-acquired renal failure and manifests as a 25% increase in serum creatinine within 48 hours of contrast administration. Nephropathy is caused by ischemia and direct toxicity to the renal tubules. Diabetes and chronic renal insufficiency are the greatest risk factors for dye nephropathy. Early trials87 indicated that patients receiving contrast have a lower incidence of contrast-induced nephropathy when treated with a sodium bicarbonate infusion or N-acetylcysteine. However, recent evidence from multicenter trials and meta-analyses shows no benefit in any pharmacologic intervention in reducing the incidence of radiocontrast nephropathy.88 Rising blood urea nitrogen and creatinine and postoperative oliguria (8 involved lymph nodes; (2) the transhiatal resection is less able to remove involved lymph nodes in patients with ≤8 involved lymph nodes; and (3) a combination of both explanations. To investigate these possible explanations, a multinational study was performed in 2008 by Peyre and associates to determine if the number of involved lymph nodes could predict the risk of systemic disease after esophagectomy irrespective of the resection technique.14 The study showed that patients with systemic disease were more likely to have T3 tumors, and 3 or more involved lymph nodes. Patients with only 1 or 2 involved lymph nodes were significantly less likely to develop

systemic disease compared to patients with 3 to 7 involved lymph nodes (44% vs 69%, respectively; P < .001). The relationship of nodal disease to systemic disease in this study indicated that when 3 or more nodes are involved, the likelihood of systemic disease is >50% and approaches 100% with 8 or more involved lymph nodes. Based on the above studies, the goal to improve the survival of patients with esophageal cancer by surgery should be to remove all diseases in patients with 48 hours, or dangerous medical comorbidity (eg, recent MI, pulmonary hypertension, multisystem organ failure [MSOF], cirrhosis), definitive ulcer operation should be eschewed. In the stable patient, definitive operation may be considered for chronic ulcer which has failed medical management and if postoperative elimination of risk factors is unlikely.

Though simple omental patch with postoperative Helicobacter treatment has been shown to eliminate recurrent or persistent ulcer symptoms in most patients with perforated duodenal ulcer, some patients will fail H pylori eradication or have other significant risk factors such as smoking and NSAID use. Furthermore, extrapolation from duodenal ulcer to gastric or marginal ulcer may be inappropriate. Thus it is reasonable to consider definitive operation on a case-by-case basis in the stable patient with peptic ulcer perforation. For perforated duodenal ulcer, definitive procedures include parietal cell vagotomy, truncal vagotomy and drainage (pyloroplasty incorporating the perforation or gastrojejunostomy), and truncal vagotomy and antrectomy (perhaps most appropriate for giant duodenal perforations). For perforated gastric ulcer, definitive operations include distal gastrectomy to include the ulcer, and wedge resection with vagotomy and drainage. For marginal ulcer, definitive operation includes resection of the gastrojejunostomy with the perforation, along with additional stomach if deemed appropriate.

Obstructing Peptic Ulcer By far the most common cause of gastric outlet obstruction is cancer (pancreas, duodenum, stomach), and it is worthwhile keeping this in mind when treating patients for peptic ulcer obstruction. All three peptic ulcer varieties (duodenal, gastric, marginal) can cause chronic scarring resulting in intractable gastric outlet obstruction manifested by chronic nausea, vomiting, epigastric pain, weight loss, food intolerance, and even sitophobia. Patients with suspected obstructing peptic ulcer should have upper endoscopy with biopsy and CT scan. Traditional barium fluoroscopic studies may also be revealing. Endoscopic balloon dilation can be transiently helpful in up to half of these patients, but multiple dilations are usually necessary and most patients eventually require operation. The gold standard procedure for obstructing duodenal or prepyloric gastric ulcer is distal gastrectomy with Billroth 2 gastrojejunostomy, and truncal vagotomy. An acceptable alternative operation is laparoscopic gastrojejunostomy and selective vagotomy, which can be done minimally invasively. If the obstructing ulcer disease is primarily prepyloric, attempt should be made to obtain lumenal biopsies at the site of obstruction. Subsequently, if indicated, the gastrojejunostomy can be reversed (eg, for severe dumping if the pyloric

channel is patent) or converted to distal gastrectomy with Billroth 2 or Roux gastrojejunostomy (eg, for persistent symptoms or concern about malignancy). However, this “lesser operation” may miss or delay the diagnosis of an unexpected obstructing cancer. The hospital mortality for patients with obstructing peptic ulcer is 2% to 3%.

Bleeding Peptic Ulcer Although bleeding remains the most common reason for hospitalization in peptic ulcer patients, with a hospital mortality around 3%, it is no longer a common indication for surgery due to the efficacy of endoscopic treatment and occasionally radiologic embolization. Aggressive treatment with IV acid suppression is important too. Bleeding peptic ulcer is the most common cause of clinically significant upper GI bleeding. Most patients (75%) have low-risk bleeds, but 25% of patients have high-risk bleeds, and essentially all the deaths from bleeding ulcer occur in this latter group. Clinical and endoscopic parameters can identify this high-risk group (Table 29-6), which should be managed by a multidisciplinary team in a special unit or intensive care unit. After initial resuscitation, early endoscopy should be performed and bleeding sites treated with epinephrine injection and an energy source. Endotracheal intubation for airway protection is considered on a case-by-case basis. Rebleeding should prompt repeat endoscopic treatment or angiography. Surgery should be considered for refractory bleeding requiring multiple transfusions, especially if associated with episodes of hemodynamic instability, and for high-risk lesions, such as deep penetrating ulcer with a subjacent named artery. Bleeding from erosion of the ulcer into the gastroduodenal, left gastric, or splenic artery is very likely to persist or recur after endoscopic therapy alone. TABLE 29-6: ULCER STIGMATA AND REBLEEDING IN PEPTIC ULCERS

Bleeding marginal ulcers are best treated with resection. Occasionally the ulcer has eroded into named vessels such as the splenic artery or middle colic artery, so the surgeon should be prepared for these contingencies. Bleeding gastric ulcer can be treated with oversewing, wedge resection, or definitive gastrectomy to include the ulcer. Traditionally, vagotomy for gastric ulcer has been deemed unnecessary. Though hemigastrectomy and damage control remains an option, it is best to avoid definitive ulcer operation in the setting of shock or profound coagulopathy. Surgical options for the management of bleeding duodenal ulcer include oversewing, either alone or with definitive ulcer operation, usually vagotomy and drainage. Classically the pyloroduodenotomy, which is made to access the bleeding ulcer, is incorporated into a pyloroplasty. Alternatively, the pyloric incision is closed and gastrojejunostomy performed. Then truncal vagotomy is done. Antrectomy with truncal vagotomy can be considered in stable patients, especially those with giant bleeding duodenal ulcer. However, management of the duodenal stump can be challenging since the ulcer must be securely oversewn or resected. Regardless of operation performed, certain and secure ulcer hemostasis by suture ligation should be the most important goal of any operation for bleeding peptic ulcer. Much has been written about the proverbial and useful “U-stitch” to secure hemostasis in a deep duodenal ulcer with a hole in the gastroduodenal artery near a large pancreatic side branch. Deep “over-andover” sutures may accomplish the same thing. Extralumenal ligation of the gastroduodenal or left gastric artery may occasionally also be helpful. Compared to simple oversewing and vagotomy and drainage, rebleeding may

be less common after distal gastrectomy for bleeding peptic ulcer, but the operative mortality is higher. Overall, current hospital mortality in patients requiring operation for bleeding peptic ulcer is 10% to 20%.

Intractable or Nonhealing Peptic Ulcer Operation for nonhealing peptic ulcer should be performed only after careful deliberation and diagnostic evaluation. Nonhealing or intractability should indeed be a rare indication for ulcer operation today, and the patient referred for surgical evaluation of intractable peptic ulcer disease should raise red flags for the surgeon. Since acid secretion can be totally blocked and H pylori eradicated with modern medication, it is important to ask why the patient has a persistent ulcer diathesis. All causes of nonhealing peptic ulcer should be considered prior to operative treatment (Table 29-7). TABLE 29-7: DIFFERENTIAL DIAGNOSIS OF INTRACTABILITY OR NONHEALING PEPTIC ULCER DISEASE

Surgical treatment may be considered in patients with nonhealing or intractable peptic ulcer disease who have multiple recurrences, large ulcers

(>2 cm), complications (obstruction, perforation, or hemorrhage), or suspected gastric cancer. Though nonhealing ulcers may represent an undiagnosed malignancy, this is unusual nowadays. Typically patients with intractable or nonhealing peptic ulcer experience suboptimal outcomes after ulcer operation, which may result in chronic weight loss of up to 10% to 20%. Before embarking on an ulcer operation in a patient for intractability or nonhealing, it is prudent for the surgeon to envision this degree of weight loss, since this is what the patient might look like after an ill-conceived ulcer operation. The obvious corollary is that operation for intractability or nonhealing ulcer should be avoided in asthenic patients. Sadly, the thin patient can be an easy target for a big ulcer operation in the hands of the inexperienced ulcer surgeon. Prior to operation for intractable or nonhealing peptic ulcer, empiric Helicobacter treatment should be administered; smoking and NSAIDs should be stopped. Patient, family, surgeon, and gastroenterologist should understand the risks and likely outcomes of operation. It is important to realize that operative results for ulcer intractability today will not mirror those obtained 40 to 50 years ago, since the surgical populations are different. Formal distal gastric resection should be avoided if possible. For intractable duodenal ulcer, consideration should be given to parietal cell vagotomy, with or without gastrojejunostomy, which is reversible. For intractable or nonhealing gastric ulcer, wedge excision with or without parietal cell vagotomy should be considered as an alternative to distal gastrectomy when technically feasible. It is important that the surgeon not fall into the trap of performing a large, irreversible operation on these patients based on the unproven theory that if all other methods have failed, a larger operation is required. Today’s patients are different than those of three or four decades ago. One might argue that modern medical care has healed the minor ulcer, and that patients presenting with true intractability or nonhealing will be more difficult to treat and are likely to have chronic problems after a major ulcer operation. If surgery is necessary, less is often better. It is the practice of the authors never to perform a gastrectomy as the initial elective operation for intractable duodenal ulcer in the thin or asthenic patient. Instead, the preferred operation for this group of patients is HSV. In patients with nonhealing gastric ulcer, wedge resection with HSV should be considered in thin or frail patients. Otherwise distal gastrectomy (to include the ulcer) is recommended. It is

unnecessary to add a vagotomy in patients with type I gastric ulcer.

Technical and Physiological Considerations Transection of both vagal trunks at the esophageal hiatus, termed truncal vagotomy, severs vagal input to the abdominal viscera. Truncal vagotomy eliminates the cephalic phase of gastric acid secretion and alters antral and pyloric motor function, often (but not always) resulting in delayed gastric emptying. Thus, truncal vagotomy is usually combined with a procedure to eliminate or bypass pyloric sphincter function, for example pyloroplasty or gastrojejunostomy. Several methods of pyloroplasty have been developed. The Heineke−Mikulicz pyloroplasty (Fig. 29-2) consists of a longitudinal incision of the pyloric sphincter extending into the antrum and the duodenum. The incision is closed transversely, eliminating sphincteric closure and increasing the lumen of the pyloric channel. The Finney pyloroplasty (Fig. 29-3) extends the pyloric incision 5 cm onto the duodenal wall, forming an inverted U-shaped incision after the placement of superior and inferior traction sutures. Once traction is applied, the two limbs of the inverted Ushaped incision are lined up and sutured to each other to complete the procedure, with the inferior suture line forming the posterior wall and the superior suture line forming the anterior wall of the pyloroplasty. A Jaboulay gastroduodenostomy (Fig. 29-4) requires more extensive dissection, beginning with a Kocher maneuver followed by corresponding incisions on the stomach and the duodenum proximal and distal to the pylorus, respectively. Traction sutures are then placed between the stomach and duodenum to approximate the two incisions, and the anastomosis is then performed.

FIGURE 29-2 Heinecke-Mikulicz pyloroplasty. (Reproduced with permission from Zinner MJ. Atlas of Gastric Surgery. New York, NY: Churchill Livingstone; 1992. Illustrated after Gwynne Gloege.)

FIGURE 29-3 Finney pyloroplasty. (Reproduced with permission from Zuidema GD: Shackelfords Surgery of Alimentary Tract. Vol II, 5th edition. Philadelphia, PA: WB Saunders; 2001.)

FIGURE 29-4 Jaboulay gastroduodenostomy. Truncal vagotomy can be combined with resection of the gastric antrum to further reduce acid secretion by removing antral sources of gastrin. The limits of antral resection are defined by external landmarks. The stomach is divided proximally along a line from a point above the incisura angularis on the lesser curvature to a point somewhere along the greater curvature midway between the pylorus and the inferior tip of the spleen. Reconstruction via a gastroduodenostomy is called a Billroth I procedure. A Billroth II procedure

uses a gastrojejunostomy to restore GI continuity. Proximal gastric vagotomy, also termed highly selective vagotomy (HSV), differs from truncal vagotomy in that only the nerve fibers to the acidsecreting fundic mucosa are transected (Fig. 29-5). The hepatic and celiac divisions are not divided, and vagal nerve fibers to the antrum and pylorus remain intact. The operation has also been called parietal cell vagotomy to emphasize the intended functional consequence. Proximal gastric vagotomy is a safe operation with an elective operative mortality rate of less than 0.1% in a good risk patient. Truncal vagotomy and pyloroplasty has an accepted mortality rate of 0.5% to 0.8%, whereas operative mortality after truncal vagotomy and antrectomy approximates 1.5%. Note that these statistics, acquired decades ago, represent the results of elective operations on mostly good risk patients with peptic ulceration and may not accurately reflect expected results when similar procedures are performed urgently in patients with multiple comorbidities.

FIGURE 29-5 Technique of proximal gastric vagotomy. The distal 6 cm of the esophagus is skeletonized. Denervation spares the antrum and pylorus by stopping 7 cm proximal to the pylorus. Division of vagal nerve fibers alters gastric acid secretion by reducing cholinergic stimulation of parietal cells. Vagal denervation also decreases parietal cell responsiveness to gastrin and histamine. Basal acid secretion is diminished by approximately 80% in the immediate postoperative period and

is maintained over time. The maximal acid output in response to secretagogues such as pentagastrin is reduced by approximately 70%. After 1 year, pentagastrin-stimulated maximal acid output increases to 50% of prevagotomy values but remains at this level on subsequent testing. Acid secretion due to meal stimulation is reduced by 60% to 70% relative to normal subjects. The inclusion of antrectomy to truncal vagotomy further reduces acid secretion. Maximal acid output is reduced by 85% relative to values recorded before antrectomy. Operations that involve vagotomy affect gastric emptying. Both truncal vagotomy and proximal gastric denervation abolish vagally mediated receptive relaxation that normally allows the ingestion of a meal with no increase in intragastric pressure. After vagotomy, the intragastric pressure rise is greater for any given volume ingested, and the gastroduodenal pressure gradient is higher than in normal subjects. As a result, emptying of liquids, which depends on the gastroduodenal pressure gradient, is accelerated. Because nerve fibers to the antrum and pylorus are preserved with proximal gastric vagotomy, the function of the distal stomach to mix solid food is preserved, and emptying of solids is nearly normal. Truncal vagotomy affects the motor activity of the distal stomach, and solid and liquid emptying rates are usually increased when truncal vagotomy is accompanied by pyloroplasty. Though uncommonly performed today, gastric ulcer in the good risk wellnourished patient is perhaps best treated with distal gastrectomy (including the ulcer in the specimen) (Fig. 29-6) with either gastro-duodenal (Billroth I) or gastrojejunal (Billroth II) anastomosis. Performed electively, operative mortality approximates 2% to 3%, and ulcer recurrence rates are less than 5%. Unlike antrectomy for duodenal ulcer, inclusion of vagotomy does not decrease recurrence rates for gastric ulcer, which is not surprising given the variability of acid secretion in patients with gastric ulcers. The occurrence of a benign ulcer near the gastroesophageal junction (type IV ulcer) represents a difficult surgical problem. The ulcer may be excised via a distal gastrectomy with an extension along the lesser curvature into the cardia and reconstruction with Roux gastrojejunostomy (Csendes operation). Alternative procedures to deal with proximal gastric ulcers include the Pauchet gastrectomy and the Kelling-Madlener procedure (Fig. 29-7). Type V gastric ulcers occur along the greater curvature and are best treated with wedge resection.

FIGURE 29-6 Points of transection for distal gastrectomy performed to resect a gastric ulcer along the lesser curvature. d, the approximate diameter of the duodenum.

FIGURE 29-7 Operations for gastric ulcer. (Reproduced with permission from Feldman M, Scharschmidt BF, Sleisenger MH: Gastrointestinal and Liver Disease, 6th ed. Philadelphia, PA: WB Saunders; 1998.)

POSTGASTRECTOMY SYNDROMES Perhaps up to 30% of patients who have had operations on the stomach have some chronic symptoms, commonly referred to as “postgastrectomy syndromes.” However, the occurrence of permanent disabling postgastrectomy syndromes is uncommon (5% or less) and usually unpredictable. Symptoms typically include one or more of the following: diarrhea, vomiting, abdominal pain, and malnutrition or nutritional deficiency. These patients have had operations on the stomach for peptic ulcer, cancer, obesity, or gastroesophageal reflux disease (GERD). The frequency with which post-gastrectomy symptoms and syndromes are found

depends on how hard they are looked for. The incidence is high early postoperatively, but most patients report improvement within 1 year after surgery. The management of patients with these symptoms can be challenging but appropriate therapy can have a significant impact on the patient’s long-term outcome.

Dumping Syndrome Dumping syndrome (DS) is a constellation of gastrointestinal and vasomotor symptoms that present postprandially due to rapid gastric emptying. It is caused by loss of pyloric regulation of gastric emptying and/or decreased gastric compliance. Early dumping symptoms occur within 1 hour of ingestion of a meal and include nausea, epigastric discomfort, tremulousness, and sometimes dizziness or syncope. Late dumping symptoms follow a meal by 1 to 3 hours. Late symptoms are usually due to reactive hypoglycemia. The human stomach has the capability of adapting to large volumes of orally administered liquids and solids through vagally mediated accommodation and receptive relaxation. Procedures that alter the normal intragastric pressure/volume relationship (proximal gastric vagotomy, sleeve gastrectomy, fundoplication) or outflow resistance (pyloroplasty, gastrojejunostomy) predispose to DS. Procedures that alter both have the highest incidence of dumping (eg, distal gastrectomy, gastric bypass). Dumping symptoms have been reported in up to 70% of Billroth II patients and up to 75% of patients after RYGBP for obesity. Similarly, after gastrectomy for cancer, 67% of patients present with early dumping symptoms and 38% with late dumping. The role of surgically induced microbiome changes in the etiology of DS is unknown. Early dumping is more common and includes systemic and abdominal symptoms. Systemic manifestations include palpitations, tachycardia, fatigue, a need to lie down following meals, flushing or pallor, diaphoresis, lightheadedness, hypotension, headache, and possibly syncope. Abdominal symptoms include early satiety, epigastric fullness or pain, diarrhea, nausea, cramps, bloating, and borborygmi. Early dumping begins within 30 min following a meal and is attributable to bowel distention, relative hypovolemia, gastrointestinal hormone hypersecretion, and autonomic dysregulation. Late dumping is characterized by symptoms that occur 1 to 3 h postprandial. Symptoms of late dumping consist of perspiration, faintness,

decreased concentration, and altered levels of consciousness, among others. These symptoms are related to a reactive hypoglycemia that occurs 1 to 3 h postprandial. Patients with late dumping often have early dumping as well. Most patients with DS have mild to moderate symptoms, but some patients have disabling symptoms that may be severe enough to cause protein–energy malnutrition. An oral glucose challenge will confirm the diagnosis of DS. The diagnosis can also be made with a scintigraphic gastric emptying study, in which greater than 50% of an isotope-labeled solid meal has emptied within 1 hour. Early dumping tends to improve with time, whereas late dumping tends to persist or exacerbate. In most patients with DS, symptoms are not severe and medical management is successful. Dietary modification such as frequent small meals and separating liquids and solids are the first line of treatment. Diets should be high in protein and fiber. Fat, milk, and simple sugars should be avoided. A number of pharmacologic options exist for the treatment of DS. Octreotide, a somatostatin analogue, should be considered for patients with severe postgastrectomy DS refractory to diet therapy (Table 29-8). Octreotide can markedly improve the quality of life in DS patients. Long-term octreotide therapy may lose efficacy over time, as side effects, such as diarrhea and steatorrhea, and cost lead to lack of compliance. Acarbose is an α-glycosidase hydrolase inhibitor that delays carbohydrate digestion and absorption and is efficient in the treatment of late dumping. Diazoxide is a potassium channel activator that inhibits the secretion of insulin. Thus, diazoxide has showed success in treating late dumping hypoglycemia and can be used when acarbose and lifestyle modifications are insufficient. TABLE 29-8: OCTREOTIDE IN DUMPING SYNDROME

Delay in the accelerated gastric emptying Delay in small intestine transit time Inhibition of enteral hormone secretion Inhibition of insulin release Inhibition of postprandial vasodilation/splanchnic vasoconstriction Increase in intestinal absorption of water and sodium

Reproduced with permission from Ukleja A. Dumping syndrome: pathophysiology and treatment, Nutr Clin Pract 2005 Oct;20(5):517–525.

Most patients improve with time (months and even years), dietary management, and medication. Therefore, the surgeon should not rush to reoperate on the patient with DS. Only a small percentage of patients with dumping symptoms ultimately require surgery. The results of remedial operation for dumping are variable and unpredictable. A variety of surgical approaches exist, none of which work consistently well. In addition, there is not a great deal of experience reported in the literature with any of these methods and long-term follow-up is rare. Patients with disabling refractory dumping after gastrojejunostomy can be considered for simple takedown of this anastomosis provided that the pyloric channel is patent endoscopically. For dumping following pyloroplasty, distal gastrectomy with Roux reconstruction is an option. For severe dumping after BI or BII gastrectomy, conversion to Roux-en-Y gastrojejunostomy may be considered, since dysmotility of the Roux limb tends to slow gastric emptying. In the presence of a sizable (>40%) gastric pouch with intact vagal innervation, lifelong acid suppression may be prudent in the setting of Roux gastrojejunostomy.

Postvagotomy Diarrhea Truncal vagotomy is initially associated with clinically significant diarrhea in 5% to 10% of patients, but symptoms improve with time. The incidence of long-lasting postvagotomy diarrhea is 1% to 2%. The cause of postvagotomy diarrhea is unclear. Contributing factors include intestinal dysmotility with accelerated small bowel transit, bile acid malabsorption, rapid gastric emptying, altered microbiome, and bacterial overgrowth. Some patients with postvagotomy diarrhea respond to cholestyramine, while for others codeine or loperamide may be useful. In the rare patient who is debilitated by postvagotomy diarrhea unresponsive to maximal medical management for at least 1 year, surgery might be considered, but outcomes can be problematic. The 10-cm reversed jejunal interposition placed in continuity 100 cm distal to the ligament of Treitz has been described but can cause obstructive symptoms and/or bacterial overgrowth.

Gastric Stasis

In the rare patient with acute gastric stasis after gastric surgery, persistent nausea and vomiting prevent removal of the nasogastric tube in the absence of mechanical obstruction. If the symptoms persist beyond a period of 7 to 10 days after surgery, a gastrostomy can be placed and a J tube should be considered for enteral nutrition. In patients who are not candidates for enteral nutrition, total parenteral nutrition is an alternative. Reoperation should generally be delayed for at least 3 months, as the majority of patients will regain satisfactory GI function without surgery. Chronic gastric stasis following gastric surgery may be due to a problem with gastric motor function or caused by an obstruction. Chronic gastric stasis presents with vomiting (often of undigested food), bloating, epigastric pain, and weight loss. Symptoms are usually improved by a liquid diet, and always improved by prolonged fasting. The evaluation includes EGD, upper GI series, gastric emptying scan (scintigraphy), and gastric motor testing. Endoscopy shows gastritis and retained food or bezoar in the stomach. The gastroenteric anastomosis and efferent limb should be evaluated for stricture or narrowing. A dilated efferent limb suggests chronic stasis, either from a motor abnormality (eg, Roux syndrome) or mechanical small bowel obstruction (eg, chronic adhesion). If the problem is thought to be primarily a disorder of intrinsic motor function, newer diagnostic techniques such as electrogastrography and GI manometry should be considered. Once mechanical obstruction has been ruled out, medical treatment is successful in most patients. Management consists of dietary modification and promotility agents such as metoclopramide, domperidone, and erythromycin. Intermittent oral antibiotic therapy may be helpful in treating bacterial overgrowth. Probiotics should be tried, since alterations in gut microbiome are likely. Operation is reasonable when chronic postoperative gastric stasis is severe and resistant to medical management. At operation, small bowel obstruction and efferent limb obstruction should always be ruled out. Gastroparesis following vagotomy and drainage procedures may be treated with subtotal (75%) gastrectomy. Billroth II anastomosis with Braun enteroenterostomy may be preferable to Roux-en-Y reconstruction after subtotal gastrectomy in this setting, since Roux reconstruction may result in persistent gastric emptying problems (Roux syndrome). Gastroparesis following subtotal gastric resection is best treated with near-total (95%) or total gastric resection and Roux-en-Y reconstruction. High-frequency gastric electrical stimulation (GES) may be an effective treatment for patients with

postsurgical gastroparesis who failed standard medical therapy, but long-term data are lacking.

Afferent and Efferent Loop Obstruction Afferent loop obstruction is a mechanical complication that typically occurs after Billroth II or loop gastrojejunostomy. Etiologies include (1) entrapment, compression, and kinking of the afferent loop by postoperative adhesions; (2) internal herniation, volvulus, and intussusception of the afferent loop; (3) scarring due to marginal ulceration of the gastrojejunostomy; (4) locoregional recurrence of cancer (lymph nodes, peritoneum, gastric remnant, anastomotic sites); (5) radiation enteritis of the afferent loop; and (6) enteroliths, bezoars, and foreign bodies impacted in the afferent loop. Although both acute and chronic forms of afferent loop syndrome have been described, chronic partial obstruction is the more common clinical manifestation. The classic presentation of chronic afferent loop syndrome is postprandial abdominal pain relieved by bilious vomiting. A meal elicits pancreatic, biliary, and duodenal secretion into the obstructed afferent limb. Eventually the pressure in the partially obstructed afferent limb overcomes the obstruction (usually 30-60 minutes postprandial), delivering a large volume of bilious secretions into the stomach or Roux limb. This leads to bilious vomiting and prompt relief of the pain, which was caused by the afferent limb distention. Obstruction of the biliopancreatic limb following RYGBP must also be considered an afferent loop obstruction and typically presents with postprandial abdominal pain; bilious vomiting is usually lacking because of the long Roux limb. If the obstruction is high grade or complete, the distended afferent loop may not sufficiently decompress, leading to acute afferent loop obstruction. In this scenario, vomiting, if present, will be nonbilious, and a clinical picture of “closed loop obstruction” manifested as an acute abdomen will result. If this condition is not recognized early, the afferent loop may actually perforate and result in peritonitis. Urgent intervention or surgery is necessary to correct this problem. Abdominal CT is the diagnostic study of choice. CT appearance of the obstructed afferent loop consists of a C-shaped, fluid-filled tubular mass located in the midline between the abdominal aorta and the superior mesenteric artery (c-loop sign) with valvulae conniventes projecting into the lumen (keyboard sign).

Although endoscopic interventions and/or percutaneous approaches may be useful in special cases (eg, carcinomatosis or extremely high operative risk), the cornerstone of treatment for afferent loop obstruction is operation. In contrast to the relatively stereotypical manifestation of afferent loop obstruction, efferent loop obstruction generally mimics proximal small bowel obstruction. It is most commonly caused by adhesions, but internal hernia must also be considered.

Alkaline (Bile) Reflux Gastritis Alkaline reflux gastritis is presumably caused by the longstanding presence of an abnormal amount of duodenal content in the stomach or gastric remnant, a situation that often occurs in patients after pyloroplasty or loop gastrojejunostomy with or without gastric resection. A distinction must be made between histologic bile gastritis, which is present in many patients after gastric surgery (up to 85% in Billroth II patients), most of whom are asymptomatic, and the presence of clinical bile gastritis leading to significant symptoms, a much more unusual situation. Gastric stasis may potentiate the damaging effects of duodenal contents on the gastric mucosa. Smoking and NSAIDs also may contribute. In a subset of patients, bile gastritis leads to metaplasia and dysplasia, and some of these patients progress to gastric cancer (“stump cancer”). Many patients have histologic gastritis after gastric surgery, but clinically significant bile reflux gastritis is not common and the relationship of chronic gastric mucosal inflammation to symptoms in this setting is not well defined. The most common symptoms attributed to chronic bile gastritis are abdominal pain and bilious vomiting. The pain is typically not relieved by antacids or acid suppressive medication. Unlike afferent limb syndrome, the pain does not resolve after vomiting. The diagnosis of alkaline reflux gastritis is essentially a diagnosis of exclusion and is largely based on symptomatology. The first step in patient evaluation is endoscopy. Inflammatory changes in the stomach involving more than just the peristomal area are supportive, but not specific for bile reflux. Mucosal biopsies will show the characteristic histologic features of bile reflux. However, the endoscopic and histological features of bile gastritis are frequently observed in asymptomatic patients, and the extent of the findings does not correlate well with the severity of symptoms. Hepatobiliary iminodiacetic acid (HIDA) scans can provide a semiquantitative assessment

of bile reflux/stasis in the stomach. Upper gastrointestinal barium study, ultrasound, and CT scan may also be useful. Medical management includes cholestyramine, antacids, H2 blockers, proton pump inhibitors, sucralfate, or promotility agents to enhance clearance of refluxate from the gastric remnant. When these measures fail, surgery is considered for patients with incapacitating symptoms, a reasonably secure clinical diagnosis, and realistic expectations. Preoperative nutritional support may be required and jejunostomy tube placement should be considered strongly during remedial operation, the aim of which is diversion of duodenal contents away from the stomach. The Roux-en-Y gastrojejunostomy is the surgical reconstruction most frequently chosen to treat patients with alkaline reflux gastritis (Fig. 29-8). Conversion of BI or BII to Roux-en-Y gastrojejunostomy with a 60-cm Roux limb reliably diverts intestinal contents from the gastric remnant and improves symptoms in up to 85% of patients. This procedure also results in significant improvement of endoscopic findings. Although Roux-en-Y gastrojejunostomy achieves satisfactory symptom relief following surgery, during long-term follow-up epigastric pain may persist, particularly in those patients using narcotics preoperatively. The only symptom that is consistently relieved is bilious vomiting, but some patients develop worsening delayed gastric emptying. Other surgical options for postoperative bile gastritis include Braun enteroenterostomy between the afferent and efferent limbs of BII or loop gastrojejunostomy, Henley isoperistaltic jejunal interposition between stomach and duodenum, and duodenal switch. The latter was described to treat primary bile reflux gastritis, which occurs rarely, and absent any previous operation of the stomach or duodenum, but it might be a reasonable surgical option in the rare patient who has acquired debilitating bile reflux gastritis after pyloroplasty or B-I gastroduodenostomy.

FIGURE 29-8 Roux-en-Y gastrojejunostomy used to treat alkaline reflux gastritis. (Reproduced with permission from Schwartz SI, Ellis H: Maingot’s Abdominal Operations, 9th ed. Stamford, CT: Appleton & Lange; 1989.)

Roux Stasis Syndrome After distal gastrectomy with Roux-en-Y reconstruction, some patients experience symptomatic delayed gastric emptying of solids. This phenomenon has been termed the “Roux stasis syndrome” since it has generally been attributed to measurable abnormalities in Roux limb motility.

Of note, Roux syndrome is more common in the presence of a large gastric remnant or after vagotomy, and quite uncommon after Roux-en-Y gastric bypass. Symptoms of Roux syndrome include abdominal pain and distention, postprandial bloating, nausea, and vomiting. Typically the vomitus contains solid food and is nonbilious. Bacterial overgrowth, with diarrhea and nutrient malabsorption, may result. Endoscopically, the gastric remnant may be dilated with retained food and mucosal irritation. The anastomosis is patent and the Roux limb may also be dilated. There is no evidence of mechanical obstruction on CT or upper GI series. Scintigraphy shows markedly delayed emptying of solids. Liquid emptying is usually not delayed. Most patients with the Roux syndrome can be successfully managed conservatively with dietary manipulations and use of prokinetic agents, but some patients require revisional operation in an attempt to relieve debilitating symptoms and improve nutritional status. In general, the operation of choice is near-total or total gastrectomy with anastomosis to a new Roux limb (usually the original Roux should be resected). The addition of a feeding jejunostomy is prudent. Pacing of the intestine and/or stomach has been investigated as potential nonsurgical treatment, but this has not yet been proven effective as long-term treatment.

Marginal Ulcers Marginal ulceration (ie, juxta-anastomotic ulceration) is a well-described complication of gastrojejunostomy and must be considered as part of the differential diagnosis for many of the more traditional post-gastrectomy syndromes. The incidence of marginal ulcer ranges from 0.6% to 25%. It is more common after Roux-en-Y anastomosis than after Billroth II because the former arrangement lacks the buffering afferent limb contents that counteract the noxious effect of gastric acid on the jejunal mucosa (usually the ulceration is on the jejunal side of the anastomosis). Chronic ischemia and permanent suture material may also be contributing factors. NSAIDs (including aspirin) and smoking predispose to marginal ulcer. Incomplete vagotomy, Helicobacter infection, and hypergastrinemia must also be considered. In most cases, marginal ulcers can be adequately treated with PPIs, the elimination of NSAIDs, Helicobacter treatment, and smoking cessation. Vagotomy and/or lifelong PPI therapy should also be considered.

Hypergastrinemia after distal gastrectomy can be caused by gastrinoma or retained antrum. In the latter there is residual antral tissue left in continuity with the duodenal stump after gastric resection with Billroth II anastomosis. A similar situation can be created inadvertently during revisional gastric bypass operation if the proximal bypassed stomach is resected and the distal bypasses stomach left in situ. Clinical suspicion of retained antrum may be confirmed by technetium 99 scan, and resection is curative. Gastrinoma is suspected when secretin infusion leads to significant further elevation of gastrin level. CT, endoscopic ultrasound (EUS), and octreotide scan may be helpful, but exploration by an experienced surgeon is the best way to find the tumor(s) if operation is indicated.

Nutritional Abnormalities Weight loss is common in patients who have had a gastric operation for tumor or ulcer. The degree of weight loss tends to parallel the magnitude of the operation and should be considered as part of the preoperative decision making. Anemia is also a common finding in postgastrectomy patients, occurring in up to one-third of patients. This is generally secondary to nutrient malabsorption, but can also be caused by decreased nutrient intake or chronic blood loss due to ulcer, tumor, or mucosal inflammation. Iron, B12, and folate deficiencies are the most common cause of chronic nutritional anemia after gastric surgery. Chronic calcium deficit and osteoporosis may occur after gastric operation. Calcium absorption occurs primarily in the duodenum, so any gastric operation that diverts the food stream away from the duodenum will disturb calcium homeostasis. Finally, any gastric procedure that predisposes to bacterial overgrowth or inadequate mixing of food and digestive enzymes may interfere with the absorption of fat-soluble vitamins, including vitamin D. Thus, it is likely that both calcium and vitamin D malabsorption contribute to metabolic bone disease in patients following gastric surgery.

STRESS ULCER DISEASE Gastritis and gastric ulceration can be induced by physiologic stress, which compromises mucosal defenses against acid peptic injury. Though some

acute stressors (eg, intracranial hypertension) may be surprisingly associated with increased gastric acid secretion, decreased gastric mucosal blood flow is a major factor in the development of “stress gastritis,” which has largely disappeared as an indication for operation owing to advances in critical care and probably also to stress ulcer prophylaxis. Usually occurring in hospitalized patients with critical illness (Table 29-9), stress gastritis can be demonstrated endoscopically in the majority of patients recovering from shock. While occult bleeding in this population is common, clinically significant hemorrhage defined by the need for blood transfusion, hypotension, or alteration in other vital signs occurs in only 0.5% to 5% of patients. In four recent surgical series comprising more than 28,000 patients, the incidence of clinically significant stress ulceration was 0.4%. In another series of 16,612 hospitalized patients, the incidence of overt stress bleeding was only 0.1%. In a review of patients admitted to both surgical and medical intensive care units (ICUs), the incidence of clinically significant and endoscopically proven stress ulceration was 0.17%. TABLE 29-9: RISK FACTORS FOR STRESS ULCER BLEEDING

Respiratory failure Coagulopathy Hypotension Sepsis Hepatic failure Renal failure Steroids Injury Severity Score >16 Spinal cord injury Age >55 y Major trauma (especially if accompanied by hypotension) sepsis, respiratory failure, hemorrhage, or multiple injuries predispose to acute stress gastritis. Acute stress gastritis is also common after thermal injury with greater than 35% total body surface area burned. A form of gastritis similar to that following trauma may complicate central nervous system (CNS) injury

or intracranial hypertension. When viewed endoscopically, multiple ulcerations are observed in the proximal, acid-secreting portion of the stomach. Fewer lesions are found in the antrum, and only rare ulcerations in the duodenum. The major complication of stress gastritis is hemorrhage. Patients with coagulopathy and those requiring mechanical ventilation are at increased risk of hemorrhage. Patients without these two risk factors have been reported to have an overall risk of hemorrhage of only 0.1%, while those with both demonstrate clinically significant bleeding in 3.7% of cases. Respiratory failure is defined as greater than 48 hours on a mechanical ventilator. Coagulopathy is defined as a platelet count less than 50,000/μL, an international normalized ratio greater than 1.5, or a partial thromboplastin time greater than two times control. Admission to an ICU does not by itself place patients at risk for hemorrhage, and patients undergoing major GI surgery do not have an increased risk of stress-related bleeding in the absence of complications. Increased patient age, emergency surgery, need for reoperation, and the occurrence of hypotension are risk factors for postoperative gastric bleeding. The occurrence of sepsis and respiratory failure are also risk factors. Multiple regression analysis has shown that mechanical ventilation and coagulopathy impart the greatest risk. The diagnosis of stress ulceration requires endoscopic examination. Acute mucosal ulcerations may be observed as early as 12 hours post-insult— lesions appear as multiple shallow areas of erythema and friability, accompanied by focal hemorrhage. Histologically, the lesions consist of coagulation necrosis of the superficial surface epithelium with infiltration of leukocytes into the lamina propria. Signs of chronicity, such as fibrosis and scarring, are absent. With resolution of injury or sepsis, healing is accomplished by mucosal restitution and regeneration. Stress ulcer prophylaxis is unnecessary in most elective surgery patients but should be considered in ICU patients with mechanical ventilation >48 hours, coagulopathy, burns, CNS injury, recent history of peptic ulcer or upper GI bleeding, and shock. Most commonly H2 blockers or PPIs are used; both enteral or parenteral routes of administration are acceptable. Suppression of gastric acid secretion has been implicated in the development of nosocomial pneumonia and Clostridium difficile infection, so indiscriminate or unnecessary use of these agents in hospitalized patients should be avoided.

A survey of Society of Critical Care Medicine members showed that ranitidine, famotidine, sucralfate, and cimetidine were the drugs used most commonly for prophylaxis. The presence of bright red blood in the nasogastric tube was considered by most to define prophylaxis failure, and the addition of a second drug from a different therapeutic class was the preferred mode of treatment. Because hemorrhage does not occur in all patients, studies that use bloody nasogastric discharge as a sign of stress gastritis underestimate the true incidence in critically ill patients. In one endoscopically controlled study, 100% of patients with life-threatening injuries had evidence of gastric erosions by 24 hours. A high prevalence of gastric erosions is also noted in burn patients, while GI hemorrhage occurs in only 25% to 50% of patients with burn wound infection. Barium contrast examinations have no role in the diagnosis of stress gastritis and interfere with endoscopic examination.

GASTRIC EPITHELIAL POLYPS Gastric epithelial polyps (Table 29-10) are the most common benign tumors of the stomach, and they are usually found incidentally on EGD or upper GI. The two most common gastric polyps are fundic gland polyps and hyperplastic polyps. Both tend to be multiple. TABLE 29-10: MANAGEMENT OF COMMON GASTRIC EPITHELIAL POLYPS

Fundic gland polyps are most commonly associated with chronic PPI use but they may occur as part of polyposis syndromes. They are thought to have very low malignant potential, but a substantial percentage of fundic gland polyps arising in patients with familial adenomatous polyposis (FAP) may show dysplasia. Progression to cancer is rare. Polyposis syndrome should be considered when numerous fundic gland polyps are encountered in young

patients and/or when concomitant distal gastric polyps or duodenal adenomas are found. Fundic gland polyps should be removed and PPIs stopped if the polyp(s) exceeds 1 cm in size or is ulcerated, or is distally located (we also stop PPIs for >20 fundic gland polyps). Otherwise, simple confirmatory biopsy is adequate. Routine endoscopic surveillance is unnecessary unless the patient has a polyposis syndrome or there is something unusual about the findings (large or distal polyps). Hyperplastic polyps occur in the setting of chronic inflammation; eg, chronic gastritis or around a gastrojejunostomy. Up to 20% of hyperplastic polyps may have a focus of dysplasia, and larger polyps (>1 cm) or pedunculated lesions may contain cancer. Lesions >0.5 cm should be completely removed and the stomach should be assessed for metaplasia and dysplasia. H pylori should be eradicated, and follow-up endoscopy exam performed in about 6 months to assess any missed or new polyps. Subsequent endoscopic surveillance is based on the assessment of gastric cancer risk using a risk assessment tool (eg, OLGA) since virtually all of these patients have chronic gastritis. Adenomatous gastric polyps (gastric adenomas) are usually solitary and most often occur in a background of chronic gastritis. Like colon adenomas, gastric adenomatous polyps have malignant potential and should be completely resected. The stomach should be diligently assessed endoscopically for metaplasia and dysplasia. Synchronous gastric cancer is not unusual with gastric adenomas, particularly if the adenoma contains a focus of adenocarcinoma. Helicobacter should be eradicated if present. Sessile and larger lesions are more likely to harbor dysplasia or cancer. Repeat endoscopy should be performed to ensure that other synchronous lesions were not missed and to assess adequacy of polypectomy. Subsequent endoscopic surveillance should be considered with frequency based on assessed gastric cancer risk. Hamartomas can occur in the stomach in patients with Peutz−Jeghers (PJ) syndrome and PTEN hamartoma tumor syndrome (includes Cowden syndrome). If amenable to endoscopic removal this is not unreasonable, since carcinoma arising from hamartoma has clearly been described. Patients with PJ syndrome are at increased risk for gastric cancer (about 30% lifetime risk) but there is no evidence that removal of hamartomas decreases this risk, and the lifetime risk for colon cancer or pancreas cancer is even higher.

GASTRIC SUBEPITHELIAL TUMORS Subepithelial gastric tumors include GIST (see Chapter 33), leiomyoma, lipoma, cyst, schwannoma, ectopic pancreas, and carcinoid (see below). They are identified on EGD or barium upper GI, and can best be evaluated by EUS and endoscopic needle biopsy with specimen evaluation by specialized immunohistochemical techniques. Symptomatic lesions should be removed. Incidentally discovered lipoma and cyst have characteristic EUS findings and do not require removal or close follow-up. GIST and leiomyoma have similar echo characteristics and both are spindle cell tumors on standard H&E stain, as is the less common schwannoma. These lesions are differentiated by immunohistochemistry: GIST is positive for c-kit; leiomyoma for desmin; and schwannoma for S100 protein. Regardless of symptoms, GIST is removed whenever possible either by endoscopic submucosal resection for small lesions, or laparoscopic or open gastric wedge resection. In the absence of worrisome EUS features such as irregular borders and internal heterogeneity, small leiomyomas (5 cm) should be removed because of the risk of current or future malignancy. Intermediate lesions (2-5 cm) should be removed unless inconveniently located for wedge resection (eg, gastric cardia or prepyloric antrum), in which case diligent follow-up may be recommended on a caseby-case basis. Any change in the tumor is an indication for resection.

GASTRIC NEUROENDOCRINE TUMORS (CARCINOIDS) The majority of gastric carcinoids (70%) are type 1 carcinoids and are enterochromaffin-like (ECL) neuroendocrine tumors that occur in the presence of hypergastrinemia due to atrophic gastritis, usually autoimmune (Table 29-11). They tend to be small and multiple with a low risk of malignancy. Endoscopic removal with biopsy of background gastric mucosa to confirm atrophic gastritis, and surveillance, is recommended. Antrectomy to remove the source of tumor-stimulating gastrin may be considered when there are multiple type 1 carcinoids larger than 1 cm or when recurrence is problematic. Type 2 carcinoids occur in the setting of gastrinoma and MEN1. These lesions also tend to be multiple with a slightly higher risk of

malignancy, and the oxyntic mucosa is hyperplastic, not atrophic. Treatment is removal of the gastrinoma. If EUS and biopsy of type 1 or type 2 carcinoid show high- risk features (invasion of muscularis propria, angioinvasion, high mitotic count), gastrectomy is indicated. Type 3 carcinoid tumors are sporadic solitary tumors that occur in the setting of normogastrinemia. Malignant potential is high, and treatment is surgical resection with lymphadenectomy after clinical staging. Interestingly, there have been a few case reports of solitary and sizable gastric carcinoid tumors occurring in patients with hypergastrinemia without atrophic gastritis, associated with long-term PPI use. TABLE 29-11: MANAGEMENT OF GASTRIC NEUROENDOCRINE TUMORS (CARCINOIDS)

GASTROPARESIS Gastroparesis is a chronic gastric motility disorder defined by delayed gastric emptying of solids without evidence of mechanical obstruction. Diabetes is a recognized cause of gastroparesis. Primary idiopathic gastroparesis affects mostly young and middle-aged women who present with nausea, abdominal pain, early satiety, vomiting, fullness, bloating, anorexia, and weight loss, with nausea and vomiting being the most disquieting of all the symptoms.

Gastroparesis is diagnosed by symptom assessment and delayed gastric emptying of a solid meal. Gastric retention of more than 10% of the standard solid test meal at 4 hours is abnormal, with retention of more than 30% at 4 hours indicating severe gastroparesis. Severe gastroparesis may result in recurrent hospitalizations, malnutrition, and significant mortality. Patients failing medical therapy (special diet and trial of promotility agents such as metoclopramide, erythromycin, and domperidone) are often considered for a variety of endoscopic and/or surgical interventions. In general, the therapeutic progression should start with the least aggressive interventions. Recent emphasis has been on reducing pyloric resistance with Botox, laparoscopic pyloromyotomy, or per oral endoscopic pyloromyotomy. Implantable gastric stimulators have helped some patients. Other options include gastrostomy, jejunostomy, gastrojejunostomy, and sleeve gastrectomy. Completion gastrectomy seems to provide symptom relief in post-surgical gastroparesis but this is generally considered a last resort.

BEZOARS AND FOREIGN BODIES Bezoars are collections of undigestible matter that accumulate in the stomach and small bowel. They are the most common foreign body found in the stomach and may be seen in patients who have undergone prior gastric surgery, including after bariatric surgery. The most common bezoar is composed of hair (trichobezoars). It occurs most commonly in young women. Phytobezoars are composed of vegetable matter and are usually seen in association with gastroparesis or gastric outlet obstruction. Other types of bezoars include lactobezoars (concentrated milk formula), mixed medication bezoars (pharmacobezoars), and food bolus bezoars. Bezoars may present with obstruction, ulceration, or bleeding, and rarely as intussusception. Diagnosis is suggested by upper GI series and confirmed by endoscopy. Enzyme therapy with papain, cellulase, or acetylcysteine may be used, but most patients will need endoscopic or surgical disruption and extraction. Foreign body ingestion in adults is usually associated with psychiatric or developmental disorder, intoxication, or incarceration. Repeated episodes of foreign body ingestion are common in some patients. Ingested foreign bodies are usually asymptomatic, but removal of sharp or large objects in the

stomach should be considered to avoid bleeding, perforation, or obstruction. Endoscopic removal of ingested foreign bodies is usually possible and is thought to be necessary in about 70% of intentional ingestions, while it is less frequently performed for accidental ingestion. Operation, open or laparoscopic, is performed in about 15% of adult patients with ingested foreign bodies, which most often are retrieved from the stomach. AP and lateral radiographs, and CT scan are helpful localizing studies. Contrast studies are avoided until the need for urgent endoscopy or operation is determined. For gastric foreign bodies, urgent removal is typically recommended for sharp pointed objects, objects longer than 6 cm, and magnets. Prompt but nonurgent removal is recommended for batteries and objects >2.5 cm. Airway protection is key, since aspiration of the foreign body during removal may occur. Retrieval of drug packets from the stomach of drug smugglers (“body packers”) is usually done surgically rather than endoscopically because the risk of rupture and dangerous overdose is thought to be lower with operation.

MISCELLANEOUS GASTRIC CONDITIONS Dieulafoy Lesion Dieulafoy lesion is a congenital arteriovenous malformation of the proximal stomach, typically on the lesser curve where it derives its supply from branches of either the left or right gastric artery. It is seen in middle-aged or elderly men and characterized by an unusually large, tortuous submucosal artery. Prior to widespread endoscopy, Dieulafoy lesions were diagnosed postoperatively but are now becoming diagnosed and treated routinely via endoscopy.57 It clinically presents as an upper GI bleed if eroded, and on endoscopy appears as a stream of arterial blood emanating from what appears grossly to be a normal gastric mucosa. Patients may also present with intermittent episodes of mild upper GI bleeding, and endoscopy can miss the lesion if it is not actively bleeding. Most lesions are now treated via endoscopic therapy (injection of epinephrine or other sclerosants, electrocoagulation, hemoclipping, rubber band ligation, and photocoagulation) or via angiographic embolization. Surgery is sometimes necessary, at which time the lesion may be oversewn or resected. Endoscopic

submucosal resection has also been reported. Dieulafoy lesions may occasionally be seen in the duodenum and jejunum as well as in the colon. These lesions have also been successfully managed via endoscopy or surgery.

Gastric Diverticula Gastric diverticula are typically solitary and may either be congenital or acquired. Congenital diverticula are rare, true diverticula that typically occur near the gastroesophageal junction and are found on the lesser curve or in the posterior area. They will demonstrate all three layers of the gastric wall on endoscopic ultrasound. Acquired or pseudodiverticula usually have a negligible outer muscle layer and are due to either pulsion or traction, and most are found in the antrum. Symptoms are due to inflammation and may produce pain or bleeding, but perforation is rare. Symptomatic lesions should be removed, and this can be done laparoscopically.

Mallory−Weiss Syndrome The Mallory−Weiss lesion is a longitudinal tear in the mucosa of the gastroesophageal junction, usually due to forceful vomiting and/or retching, and is commonly seen in alcoholics. It has also been reported after instrumentation of the esophagus and stomach. It typically presents with impressive upper GI bleeding. Endoscopy confirms the diagnosis and may be useful in controlling the bleeding, but 90% of patients stop bleeding spontaneously. In patients who continue to bleed, balloon tamponade, angiographic embolization, or selective infusion of vasopressin, systemic vasopressin, and surgery are other treatment options. At surgery, the bleeding lesion is oversewn via a long gastrotomy.

Gastric Volvulus Gastric volvulus occurs when the stomach twists around one of its axes, usually seen with a large hiatal hernia. It can also occur in the unusually mobile stomach without a hiatal hernia. Typically, the stomach twists along its long axis (organoaxial volvulus), and the greater curvature flips up. Less frequently, it occurs around the transverse axis, called mesoaxial volvulus. It

is usually a chronic condition that can be surprisingly asymptomatic, and expectant nonoperative management is usually advised, especially in the elderly. The risk of strangulation and infarction has been overestimated in asymptomatic patients. Surgery is recommended for symptomatic patients, especially if symptoms are severe and/or progressive. These patients complain of pain and pressure related to the intermittently distending and poorly emptying twisted stomach. Dyspnea, palpitations, and dysphagia may be seen due to compressive effects of the distended stomach on the surrounding organs. Symptoms are often relieved with vomiting or, if possible, passage of a nasogastric tube. The patient who presents moribund most likely has an infarcted stomach requiring urgent operation and resection, but this is quite unusual. Elective operation may often be done laparoscopically and usually involves reduction of the stomach, repair of hiatal hernia, and gastropexy. Gastropexy alone may be considered for high-risk patients or patients with short esophagus.

MINIMALLY INVASIVE GASTRIC OPERATIONS The use of minimally invasive surgery in benign gastric diseases has seen a significant increase over the past decade. Minimally invasive techniques combined with either intraoperative endoscopic or radiologic localization are now routinely used for most localized, benign lesions such as leiomyomas, gastrointestinal stromal tumors (GISTs), and gastric diverticula. Combined endoscopic and laparoscopic techniques have also been described. The number and location of ports are determined by triangulating around the target organ, and most procedures can be performed using four to five ports. The benefits of laparoscopic surgery (less postop pain, quicker recovery, and decreased hospital stay) are all realized without compromising surgical principles of adequate resection and tension-free suture lines for many benign gastric disorders. Vagotomy (any type), patch closure of perforation, gastrojejunostomy, pyloroplasty, pyloromyotomy, and gastric wedge resection are all procedures that can and should be considered by the surgeon with advanced laparoscopic skills for the appropriate indication. Also, laparoscopic intragastric resection of large polyps or subepithelial tumors is a good option for lesions that are close to the pylorus or GE junction. An

anterior gastrotomy is made, the lesion identified and elevated, a GIA stapler placed across the base with apparent grossly negative margin, and then a 50Fr bougie is passed per os through the GE junction to confirm patency. The stapler is fired, the lesion removed, and the anterior gastrotomy closed. With the introduction followed by rapid improvements of the da Vinci robotic platform, the use of robotic technology, first in urology and gynecology, has now found increasing use in general surgical procedures. Despite its size, cost, and the lack of tactile feedback, the reported advantages over conventional laparoscopic surgery of improved ergonomics, tremor filtering, motion scaling, stable visual platform, and (wrist-like) instrument articulation, especially with the latest generation models (Xi system) have led to widespread adaptation in practice. Decreased conversions rates to open surgery (compared to laparoscopy) as well as expanding indications for a minimally invasive approach in more complex procedures (intracorporeal suturing, mediastinal/pelvis procedures) may be additional reasons for using the robot in gastric resection and reconstruction procedures, particularly those close to the pylorus or GE junction.

FURTHER READING Helicobacter Pylori Infection; Functional Dyspepsia Amieva M, Peek RM Jr. Pathobiology of Helicobacter pylori-induced gastric cancer. Gastroenterology. 2016 Jan;150(1):64-78. Atherton JC, Blaser MJ. Co-adaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest. 2009;119(9):2475-2487. Atkinson NS, Braden B. Helicobacter pylori infection: diagnostic strategies in primary diagnosis and after therapy. Dig Dis Sci. 2016 Jan;61(1):19-24. Bode G, Brenner H, Adler G, et al. Dyspeptic symptoms in middle-aged to old adults: the role of Helicobacter pylori infection, and various demographic and lifestyle factors. J Intern Med. 2002;252:41-47. Burucoa C, Delhier JS, Courillon-Mallet A, et al. Comparative evaluation of 29 commercially available Helicobacter pylori serology kits. Helicobacter Serology Study Group. Helicobacter. 2013;14:428-433. Dore MP, Lu H, Graham DY. Role of bismuth in improving Helicobacter pylori eradication with triple therapy. Gut. 2016 May;65(5):870-878. Gatta L, Vakil N, Vaira D, Scarpignato C. Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ. 2013 Aug 07;347:f4587. Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology. 2015 Apr;148(4):719-731.e3.

Li BZ, Threapleton DE, Wang JY, et al. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ. 2015 Aug 19;351:h4052. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut. 2017;66:6-30. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311-1315. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for nonulcer dyspepsia [review]. Cochrane Database Sys Rev. 2006;2:CD002096. Senatore FJ, Wilmot J, Birk JW. Helicobacter pylori treatment: still a work in progress. Postgrad Med. 2016;128(1):152-157. Shiota S, Reddy R, Alsarraj A, et al. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clin Gastroenterol Hepatol. 2015;13:1616-1624. Sugano K, Tack J, Kuipers EJ, et al; faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015 Sep;64(9):1353-1367. Suzuki H, Moayyedi P. Helicobacter pylori infection in functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2013;10:168-174. Talley NJ, Ford AC. Functional dyspepsia. N Engl J Med. 2015 Nov 05;373(19):1853-1863. Wildner-Christensen M, Hansen JM, De Muckadell OBS. Risk factors for dyspepsia in a general population: non-steroidal anti-inflammatory drugs, cigarette smoking and unemployment are more important than Helicobacter pylori infection. Scand J Gastroenterol. 2006;41:49-54. Yazbek PB, Trindade AB, Chin CM, Dos Santos JL. Challenges to the treatment and new perspectives for the eradication of Helicobacter pylori. Dig Dis Sci. 2015;60(10):2901-2912.

Atrophic Gastritis Capelle LG, deVries AC, Haringsma J, et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-1158. Carrasco G, Corvalan AH. Helicobacter pylori-induced chronic gastritis and assessing risks for gastric cancer. Gastroenterol Res Pract. 2013;1-8. Correa P, Piazuelo MB, Wilson KT. Pathology of gastric intestinal metaplasia—clinical implications. Am J Gastroenterol. 2010;105:493-498. Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev. 2015;20:25-40.

Peptic Ulcer Disease Buck DL, Vester-Andersen M, Moller MH, et al. Surgical delay is a critical determinant of survival in perforated peptic ulcer. Br J Surg. 2013;100:1045-1049. Byrge N, Barton RG, Enniss TM, Nirula R. Laparoscopic versus open repair of perforated gastroduodenal ulcer: a National Quality Improvement Program analysis. Am J Surg. 2013;206:957-963. Cheng H-C, Wu C-T, Chang W-L, et al. Double dose esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high risk patients: a randomized controlled trial. Gut. 2014;63:1864-1872. Cryer B. Mucosal defense and repair. Gastroenterol Clin North Am. 2001;30:877-894.

Dubois F. New surgical strategy for gastroduodenal ulcer: laparoscopic approach. World J Surg. 2000;24:270-276. Espat NJ, Ong ES, Helton WS, et al. 1990-2001 U.S. General Surgery chief resident operative experience: analysis of paradigm shift. J Gastrointest Surg. 2004;8:471-477. Gilliam AD, Speake WJ, Lobo DN, Beckingham IJ. Current practice of emergency vagotomy and Helicobacter pylori eradication for complicated peptic ulcer in the United Kingdom. Br J Surg. 2003;90:88-90. Gisbert JP, Calvet X, Faust F, et al. Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding. Helicobacter. 2007;12:279-286. Gisbert JP, Khorrami S, Carballo F, et al. H pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer [review]. Cochrane Database Syst Rev. 2004;2:CD004062. Hepworth CC, Swain CP. Mechanical endoscopic methods of haemostasis for bleeding peptic ulcers: a review. Baillieres Best Pract Res Clin Gastroenterol. 2000;14:467-476. Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal antiinflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet. 2002;359:14-22. Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology. 1996;110:1244-1252. Johnson AG. Proximal gastric vagotomy: does it have a place in the future management of peptic ulcer? World J Surg. 2000;24:259-263. Kleeff J, Friess H, Büchler MW. How Helicobacter pylori changed the life of surgeons. Dig Surg. 2003;20:93-102. Lagoo J, Pappas TN, Perez A. A relic or still relevant: the narrowing role for vagotomy in the treatment of peptic ulcer disease. Am J Surg. 2014;207:120-126. Lal P, Vindal A. Controlled tube duodenostomy in the management of giant duodenal ulcer perforation. Am J Surg. 2009;198:319-323. Lee CW, Sarosi Jr GA. Emergency ulcer surgery. Surg Clin North Am. 2011;91:1001-1013. Machicado GA, Jensen DM. Thermal probes alone or with epinephrine for the endoscopic haemostasis of ulcer haemorrhage. Baillieres Best Pract Res Clin Gastroenterol. 2000;14:443-458. Matsuda M, Nishiyama M, Hanai T, et al. Laparoscopic omental patch repair for perforated peptic ulcer. Ann Surg. 1995;221:236-240. Millat B, Fingerhut A, Borie F. Surgical treatment of complicated duodenal ulcers: controlled trials. World J Surg. 2000;24:299-306. Moller MH, Adamsen S, Thomsen RW, et al. Multicenter trial of a perioperative protocol to reduce mortality in patients with perforated peptic ulcer. Br J Surg. 2011;98:802-810. Parasher G, Eastwood GL. Smoking and peptic ulcer in the Helicobacter pylori era. Eur J Gastroenterol Hepatol. 2000;12:843-853. Peskar BM, Maricic N, Gretzer B, et al. Role of cyclooxygenase-2 in gastric mucosal defense. Life Sci. 2001;69:2993-3003. Schroder VT, Pappas TN, Vaslef SN, et al. Vagotomy/drainage is superior to local oversew in patients who require emergency surgery for bleeding peptic ulcers. Ann Surg. 2014;259:1111-1118. Sharma VK, Sahai AV, Corder FA, et al. Helicobacter pylori eradication is superior to ulcer healing with or without maintenance therapy to prevent further ulcer haemorrhage. Ailment Pharmacol Ther. 2001;15:1939-1947. Soreide K, Thorsen K, Harrison EM, et al. Perforated peptic ulcer. Lancet. 2015;386:1288-1298. Wang, YR, Ritcher JE, Dempsey DT. Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993-2006. Ann Surg. 2010;251(1):51-58. Wilhelmsen M, Moller MH, Rosenstock S. Surgical complications after open and laparoscopic surgery

for perforated peptic ulcer in a nationwide cohort. Br J Surg. 2015;102:382-387.

Postgastectomy Syndromes Abell TL, Minocha A. Gastrointestinal complications of bariatric surgery: diagnosis and therapy. Am J Med Sci. 2006;331(4):214-218. doi:10.1097/00000441-200604000-00008. Berg P, McCallum R. Dumping syndrome: a review of the current concepts of pathophysiology, diagnosis, and treatment. Dig Dis Sci. 2016;61(1):11-18. doi:10.1007/s10620-015-3839-x. Daram SR, Tang SJ, Vick K, et al. Novel application of GI electrical stimulation in Roux stasis syndrome (with video). Gastrointest Endosc. 2011;74(3):683-686. doi:10.1016/j.gie.2011.05.023. Dempsey DT, Kitagawa Y. Stomach. In: Schwartz’s Principles of Surgery. New York, NY: McGraw Hill Education; 2015:1059. Didden P, Penning C, Masclee AA. Octreotide therapy in dumping syndrome: analysis of long-term results. Aliment Pharmacol Ther. 2006;24(9):1367-1375. doi:10.1111/j.1365-2036.2006.03124.x. Forstner-Barthell AW, Murr MM, Nitecki S, et al. Near-total completion gastrectomy for severe postvagotomy gastric stasis: analysis of early and long-term results in 62 patients. J Gastrointest Surg. 1999;3(1):15-21, NaN-3. doi:10.1016/S1091-255X(99)80003-1. Hejazi RA, Patil H, McCallum RW. Dumping syndrome: establishing criteria for diagnosis and identifying new etiologies. Dig Dis Sci. 2010;55(1):117-123. doi:10.1007/s10620-009-0939-5. Kojima K, Yamada H, Inokuchi M, Kawano T, Sugihara K. A comparison of Roux-en-Y and Billroth-I reconstruction after laparoscopy-assisted distal gastrectomy. Ann Surg. 2008;247(6):962-967. doi:10.1097/SLA.0b013e31816d9526. McAlhany JC, Hanover TM, Taylor SM, Sticca RP, Ashmore JD. Long-term follow-up of patients with Roux-en-Y gastrojejunostomy for gastric disease. Ann Surg. 1994;219(5):451-5-7. /pmc/articles/PMC1243166/?report=abstract. McCallum R, Lin Z, Wetzel P, Sarosiek I, Forster J. Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis. Clin Gastroenterol Hepatol. 2005;3(1):49-54. doi:S1542356504006056 [pii]. Mine S, Sano T, Tsutsumi K, et al. Large-scale investigation into dumping syndrome after gastrectomy for gastric cancer. J Am Coll Surg. 2010;211(5):628-636. doi:10.1016/j.jamcollsurg.2010.07.003. Navarro X, Sancho J, Simo-Deu J, Segura R. Bile reflux in postoperative alkaline reflux gastritis. Ann Surg. 1990;211(2):239-243. doi:10.1097/00000658-199002000-00018. Patel RA, Brolin RE, Gandhi A. Revisional operations for marginal ulcer after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2009;5(3):317-322. doi:10.1016/j.soard.2008.10.011. Pedrazzani C, Marrelli D, Rampone B, et al. Postoperative complications and functional results after subtotal gastrectomy with Billroth II reconstruction for primary gastric cancer. Dig Dis Sci. 2007;52(8):1757-1763. doi:10.1007/s10620-006-9655-6. Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R. Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol. 2009;6(10):583-590. doi:10.1038/nrgastro.2009.148. Vecht J, Lamers CBHW, Masclee AA. Long-term results of octreotide-therapy in severe dumping syndrome. Clin Endocrinol (Oxf). 1999;51(5):619-624. doi:10.1046/j.1365-2265.1999.00819.x.

Stress Ulcer Disease Alshamsi F, Belley-Cote E, Cook D, et al. Efficacy and safety of proton pump inhibitors for stress ulcer

prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care. 2016;20(1):120. Hiramoto JS, Terdiman JP, Norton JA. Evidence-based analysis: postoperative gastric bleeding: etiology and prevention. Surg Oncol. 2003;12:9-19. Krag M, Perner A, Moller MH. Stress ulcer prophylaxis in the intensive care unit. Curr Opin Crit Care. 2016;22(2):186-190. Pimental M, Roberts DE, Bernstein CN, et al. Clinically significant gastrointestinal bleeding in critically ill patients in an era of prophylaxis. Am J Gastroenterol. 2000;95:2801-2806. Shears M, Alhazzani W, Marshall JC, et al. Stress ulcer prophylaxis in critical illness: a Canadian survey. Can J Anaesth. 2016;63(6):718-724.

Gastric Epithelial Polyps ASGE Standards of Practice Committee; Evans JA, Chandrasekhara V, Chathadi KV, et al. The role of endoscopy in the management of premalignant and malignant conditions of the stomach. Gastrointest Endosc. 2015;82(1):1-8. Goddard AF, Badreldin R, Pritchard DM, Walker MM, Warren B; British Society of Gastroenterology. The management of gastric polyps. Gut. 2010;59(9):1270-1276. Jalving M, Koornstra JJ, Wesseling J, et al. Increased risk of fundic gland polyps during long-term proton-pump inhibitor therapy. Aliment Pharm Ther. 2006 Nov;24(9):1341-1348. Kelly PJ, Lauwers GY. Clinical guidelines: consensus for the management of patients with gastric polyps. Nat Rev Gastroenterol Hepatol. 2011;8(1):7-8. Shaib YH, Rugge M, Graham DY, Genta RM. Management of gastric polyps: an endoscopy-based approach. Clin Gastroenterol Hepatol. 2013;11(11):1374-1384.

Gastric Subepithelial Tumors Cho JW; Korean ESD Study Group. Current guidelines in the management of upper gastrointestinal subepithelial tumors. Clin Endoscop. 2016;49:235-240. Lee M, Min B-H, Lee H, et al. Feasibility and diagnostic yield of EUS guided fine needle biopsy with a new core biopsy needle device in patients with gastric subepithelial tumors. Medicine. 2015;94:17. Zhang S, Chao G-Q, Li M, et al. Endoscopic submucosal dissection for gastric submucosal tumors originating from the muscularis propria layer. Dig Dis Sci. 2013;58:1710-1716.

Gastric Neuroendocrine Tumors (Carcinoids) Kim BS, Oh ST, Yook JH, et al. Typical carcinoids and neuroendocrine carcinomas of the stomach: differing clinical courses and prognoses. Am J Surg. 2010;200:328-333. LaRosa S, Vanoli A. Gastric neuroendocrine neoplasms and related precursor lesions. J Clin Pathol. 2014;67:938-948. Nandy N, Hanson JA, Strickland RG, McCarthy DM. Solitary gastric carcinoid tumor associated with long term use of omeprazole: a case report and review of the literature. Dig Dis Sci. 2016;61:708712.

Gastroparesis Heckert J, Sankineni A, Hughes WB, Harbison S, Parkman H. Gastric electric stimulation for refractory gastroparesis: a prospective analysis of 151 patients at a single center. Dig Dis Sci. 2016 Jan;61(1):168-175. Khashab MA, Ngamruengphong S, Carr-Locke D, et al. Gastric per-oral endoscopic myotomy for refractory gastroparesis: results of the first multicenter study on endoscopic pyloromyotomy. Gastrointest Endosc. 2017;85:123-128. Pasricha PJ, Yates KP, Nguyen L, et al. Outcomes and factors associated with reduced symptoms in patients with gastroparesis. Gastroenterology. 2015 Dec;149(7):1762-1774.e4. Toro JP, Lytle NW, Patel AD, et al. Efficacy of laparoscopic pyloroplasty for the treatment of gastroparesis. J Am Coll Surg. 2014;218(4):652-660.

Bezoars and Foreign Bodies ASGE. Management of ingested foreign bodies and food impactions. Gastrointest Endosc. 2011;73:1085-1091. Erzurumlu K, Malazgirt Z, Bektas A, et al. Gastrointestinal bezoars: a retrospective analysis of 34 cases. World J Gastroenterol. 2005;11(12):1813-1917. Iwamuro M, Okada H, Matsueda K, et al. Review of the diagnosis and management of gastrointestinal bezoars. World J Gastrointest Endosc. 2015;7:336-345. Pinto D, Carrodeguas L, Soto F, et al. Gastric bezoar after laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2006;16:365-368.

Miscellaneous Gastric Conditions Bryant RV, Kuo P, Williamson K, et al. Performance of the Glasgow-Blatchford score in predicting clinical outcomes and intervention in hospitalized patients with upper GI bleeding. Gastrointest Endosc. 2013;78(4):576-583. Custodio Lima J, Garcia Montes C, Kibune Nagasako C, et al. Performance of the Rockall scoring system in predicting the need for intervention and outcomes in patients with nonvariceal upper gastrointestinal bleeding in a Brazilian setting: a prospective study. Digestion. 2013;88(4):252257. Halland M, Young M, Fitzgerald MN, et al. Characteristics and outcomes of upper gastrointestinal hemorrhage in a tertiary referral hospital. Dig Dis Sci. 2010;55(12):3430-3435. Lara LF, Sreenarasimhaiah J, Tang SJ, et al. Dieulafoy lesions of the GI tract: localization and therapeutic outcomes. Dig Dis Sci. 2010;55(12):3436-3441. Ljubicic N, Budimir I, Pavic T, et al. Mortality in high-risk patients with bleeding Mallory-Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study. Scand J Gastroenterol. 2014;49(4):458-464. MaCauley M, Bollard E. Gastric diverticulum: a rare cause of refractory epigastric pain. Am J Med. 2010 May;123(5):e5-e6. Mohan P, Ananthavadivelu M, Venkataraman J. Gastric diverticulum. CMAJ. 2010;182(5):E226. Parikh K, Ali MA, Wong RC. Unusual causes of upper gastrointestinal bleeding. Gastrointest Endosc Clin North Am. 2015 Jul;25(3):583-605.

Saleh R, Lucerna A, Espinosa J, Scali V. Dieulafoy lesions of the GI tract: localization and therapeutic outcomes. Am J Emerg Med. 2016 Dec;34(12):2464.e3-2464.e5. Simon M, Zuber-Jerger I, Schölmerich J. True gastric diverticulum. Dig Liver Dis. 2009;41:370. Sleiwah A, Thomas G, Crawford I, Stanek A. Gastric volvulus: a potentially fatal cause of acute abdominal pain. BMJ Case Rep. 2017 Mar 08.

Minimally Invasive Gastric Operations Diez del Val I, Martinez Blazquez C, Loureiro Gonzalez C, et al. Robot-assisted gastroesophageal surgery: usefulness and limitations. J Robotic Surg. June 2014;8(2):111-118. Hur H, Kim JY, Cho YK, Han SU. Technical feasibility of robot-sewn anastomosis in robotic surgery for gastric cancer. J Laparoendosc Adv Surg Tech A. 2010;20:693-697. Omori T, Nakajima K, Ohashi S, et al. Laparoscopic intragastric surgery under carbon dioxide pneumostomach. J Laparoendosc Adv Surg Tech A. 2008;18(1):47-51.

GASTRIC ATONY Rian M. Hasson • Scott A. Shikora

INTRODUCTION In addition to being essential for adequate nutrient absorption, normal gastrointestinal motility is crucial for maintaining an appropriate balance of microorganisms and proper function within the gut.1 It also serves as a major defense mechanism against infection of the gut, and limits the propagation of bacteria to pathologic levels.1 Gastric atony, also referred to as gastroparesis, can be defined as the inability of the stomach to contract normally, causing a delay in the movement of food out of the stomach. Causal factors for gastric atony can be classified as either medical or idiopathic. The most common medical cause is diabetes mellitus, whereas less common medical conditions include neurologic disorders, connective tissue disorders, critical illness, and surgery. In the nonsurgical patient with medical comorbidities, disruption of the normal motility can lead to atony, resulting in often devastating symptoms that severely impact nutrition and quality of life. Diabetic gastroparesis is thought to be the result of the dysregulation of the autonomic nervous system, a system that is intimately related to the neural functioning of the stomach. Similarly, the impact of neurologic disorders on gastric motility is often a

consequence of the parallel functioning of neurotransmitters within the central nervous system and those found in enteric neurons. Disturbance of the former can lead to disruption of the latter and gastric atony. With connective tissue disorders, gastric atony is of critical importance, given the tendency of these patients to develop severe and complicated reflux resulting from lower esophageal sphincter hypotension and significantly impaired esophageal peristaltic amplitude. Critical illness greatly impairs the use of enteral nutrition and results in a sustained catabolic state that depletes the patient’s caloric reserves, leading to decreased immune function, impaired wound healing, and ultimately increased morbidity and mortality.2 This disruption can further result in bacterial overgrowth, translocation, pneumonia, and sepsis. While multiple therapeutic options exist for medical gastric atony, patients may often spend a majority of their life with discomfort and in search of the appropriate management. In the postoperative setting, gastric atony, or failure of the stomach to empty, must, by definition, not be related to any other common postsurgical complication such as wound infection, intraperitoneal abscess, electrolyte disturbances, pancreatitis, thromboembolic disorders, pneumonitis, or cardiovascular complications. While a variety of factors may cause postoperative ileus, the specific categorization of atony must include “dysfunction causing a prolonged postoperative course defined as more than 14 days elapsing between the primary surgical intervention and planned discharge of the patient from the hospital.”3 In general, there are a variety of techniques employed to treat gastric atony including medical management, endoscopic techniques, and surgical intervention. Future directions will focus on greater development of these treatment strategies either alone or in combination to improve the daily functioning of these patients. The purpose of this chapter is to review the biology, physiology, diagnosis, treatment options, and persistent clinical challenges that describe this often complex and debilitating disorder.

NORMAL GASTRIC MOTILITY Research investigating the specific mechanisms through which the intestinal tract functions has revealed a well-designed balance between management of the intestinal microbiome and intestinal motility.

Historical Perspective The role of the stomach in nutrient digestion and health maintenance has interested man since early times.4-6 The ancient Greeks often detailed the “bitter-sour” nature of gastric contents, and in the 16th century, both Paracelsus7 and van Helmont8 believed acid to be present in the stomach and a necessity for digestion. Subsequent observations by Reaumur9 and Spallanzani10 further described the “solvent” effects of gastric juices. However, the role of gastric acid was not well understood until 1823 when William Prout published his work on the effects of gastric acid secretion.4 Three years later, observations made by William Beaumont of his patient afflicted with a gastrocutaneous fistula, Alexis St Martin, were published in 1826.10 His detailed observations over almost a decade of the gastrocutaneous fistula described gastric digestion in a human during normal life experiences including the effects of stress. In the early 20th century, the multifaceted nature of the control of gastric acid secretion was explored by experiments using ablation of the celiac axis and vagotomy as therapeutic intervention for peptic ulcer disease. This led to a rapid increased interest in gastric acid secretion and spurred the work of Dale and Laidlaw on histamine.12 This seminal research led to the critical discovery by Popielski of histamine’s effect on gastric secretion,13 Bayliss and Starling’s discovery of secretin,14 and Edkins’ discourse on gastrin.15 These discoveries ushered in a new era in our understanding of gastric disease and specifically led to remarkable advances in the pharmacologic management of peptic ulcer disease starting with the discovery of the H2receptor antagonists by Sir James Black in 1972.16 The emphasis on acid-related disease preoccupied research in the middle and latter half of the 20th century until the groundbreaking discovery of Helicobacter pylori in 1983 by Marshall and Warren.17 This was counterintuitive to the then current thinking that the stomach was microbiologically sterile, despite the many observations of numerous bacterial populations in gastric secretions described by Jaworski18 and the Nobel Prize–winning contribution of Metchnikoff in 1908 for his work describing Lactobacillus and gut immunity.19 As a consequence, the importance of the gastric microbiome and its relationship to H pylori revolutionized our understanding of gastric diseases, specifically cancer,

especially in terms of prevention. Current neurohormonal research has led to a better understanding of the control of appetite, food absorption, metabolism and obesity. Furthermore, increasing evidence supports a vital role for gastric motility in the maintenance of the several processes mentioned earlier in completing digestion and ultimately absorbing nutrients.

Current Understanding and the Migrating Motor Complex Despite these many advances demonstrating the complexity of the stomach, it is still often viewed as “just” the hollow muscular organ that initiates the second phase of digestion4 (the first being mastication and transport of the food bolus through the esophagus). However, all ingested materials, specifically nutrients and orally dosed medications, have to negotiate the stomach, and as such, the stomach is now recognized to be one of the most important components within the gastrointestinal (GI) tract. Furthermore, the stomach facilitates many unique functions that are crucial to the continued transport of ingested materials, digestion, and the uptake of nutrition, roles that may also have a secondary purpose of maintaining homeostasis.1,19,20 It is now confirmed that gastric motility is one of the most important factors necessary for normal digestion. In the interdigestive state, upper GI motility can be described by the recurrent contractility pattern of the migrating motor complex (MMC) (Fig. 30-1).21 The MMC is thought to serve a “housekeeping” role by sweeping residual undigested material through the digestive tract, out of the stomach, and into the small intestine. The MMC is a distinct 4-stage pattern of electromechanical activity that takes place in GI smooth muscle between meals. Although well preserved across mammalian species, the specific role of the MMC in humans has remained unclear. However, using manometry, Björnsson and Abrahamsson22,23 demonstrated that apart from the intestinal contractions migrating in the distal direction observed in phase II, phase III of the MMC also behaves as a retroperistaltic pump in the duodenum, creating intermittent alkalinization of the stomach. While acidity of the stomach has always been a key component of homeostasis, recent observations have also identified a role for this alkalinization in maintaining normal physiologic balance and signaling the return of hunger after meals.24,25 Conversely, impaired GI motility impedes

the absorption of drugs and nutrients introduced into the stomach, decreases the hunger stimulus, and can also be the nidus from which the symptoms of poor digestion, including nausea, vomiting, distention, and early satiety, begin.

FIGURE 30-1 Migrating motor complex (MMC). The 2 panels refer to the gastric and intestinal wall, respectively. Black arrows indicate induction (full line) or permissive effects (dotted line). Red arrows indicate inhibitory effects. Interestingly, it seems that phase III contractions of the MMC with gastric and duodenal origin are under different control mechanisms. The peptide hormones motilin and ghrelin and the vagus nerve seem to be important regulators for phase III contractions originating in the antrum, while somatostatin and serotonin seem to be involved in the regulation of phase III contractions with a duodenal origin. Peaks in xenin concentration are also associated with duodenal phase III activity in humans. Motilin levels (or activity) are inhibited by pancreatic polypeptide, somatostatin, 5-HT3 antagonists, and low pH. 5-HT, 5-hydroxytryptamine (serotonin; this could originate either from enterochromaffin cells or from neurons in the enteric nervous system); ACh, acetylcholine; M, motilin-producing M cell; NOR, noradrenaline; P/D1, ghrelin-producing P/D1 cell; PP, pancreatic polypeptide; SOM, somatostatin-producing cell; X, putative xenin producing cell. (Reproduced with permission from Deloose E, Janssen P, Depoortere I, et al: The migrating motor complex: control mechanisms and its role in health and disease, Nat Rev Gastroenterol Hepatol. 2012 Mar 27;9(5):271-285.) GI motility serves as a major means to prevent infection of the intestinal tract. Normally, microorganisms are rarely encountered in the esophagus, stomach, and duodenum because of peristaltic contractions that continually move their contents toward the colon. While fairly low in the esophagus and stomach, the quantity of bacteria increases significantly as the GI contents reach the terminal ileum and eventually the bacterial-laden colon. Multiple “normal” physiologic processes within the gut limit the proliferation of these microorganisms to pathologic levels.26 While gastric acid is directly toxic to bacteria, resulting in minimized overgrowth, inhibiting gastric acid secretion in the face of normal motility does not seem to affect bacterial counts. Conversely, when motility is disrupted, with or without normal acid secretion, small intestinal bacterial overgrowth occurs. Hence, it is now recognized that patients with impaired GI motility are also at risk of bacterial overgrowth in the proximal gut with pathogenic organisms and subsequent translocation of these organisms or their toxins into the bloodstream. We can conclude that normal GI motility is vital to the initial desire to eat, natural and timely digestion, the specific uptake of nutrients to maintain

health and well-being, and the regulation of bacterial flora whose structured concentration is also necessary for digestive stability. Disruption in motility at any step can have major consequences impacting overall health and nutrition in multiple ways.

CLASSIFICATION, PATHOPHYSIOLOGY, AND EPIDEMIOLOGY OF GASTRIC ATONY Gastric atony can arise in multiple situations, including medical, postsurgical, and idiopathic settings, each related to specific derangements in normal motility (Table 30-1). The management of these patients presents several challenges and is best conducted in the context of a dedicated and skilled multidisciplinary team. TABLE 30-1: DIFFERENTIAL DIAGNOSES OF GASTRIC ATONY

Medically Related Atony DIABETES MELLITUS Even though the relationship between diabetic gastroparesis and other complications of longstanding diabetes mellitus (DM) is incompletely understood, it has been established that there is an association with autonomic neuropathy.27 Additionally, although acute hyperglycemia delays gastric emptying,28 the relationship between long-term control of glycemia

and gastric emptying is unclear, and results from investigation have been conflicting at best. For example, although increased glycosylated hemoglobin (HbA1c) levels have been associated with GI symptoms in people with type 2 DM (T2DM),29 HbA1c levels were not found to be significantly different among patients with T2DM with GI symptoms and delayed gastric emptying, patients with T2DM with GI symptoms and normal gastric emptying, and patients with T2DM without GI symptoms. In addition, improved glycemic control did not improve gastric emptying in subjects with delayed gastric emptying and type 1 DM or patients with T2DM and delayed gastric emptying.30 These findings are in contrast to those of the Diabetes Control and Complications Trial (DCCT),31 in which 6.5 years of intensive insulin therapy reduced the risk of other complications such as diabetic retinopathy, nephropathy, and peripheral and cardiac autonomic neuropathy by 40% to 60% when compared with conventional insulin therapy. Furthermore, the differences between the former intensive and conventional treatment groups persisted for as long as 14 years despite the loss of glycemic separation.32-34 In the only community-based study, symptoms of peripheral or autonomic neuropathy were not associated with diabetic gastroparesis.35 Nevertheless, despite uncertainty in the causal factors for gastric atony, diabetic patients are still the cohort most commonly afflicted with medically related gastric atony, and are often most afflicted with gastric atony–related symptoms second only to patients with postsurgical gastric atony.36

NEUROLOGIC DISORDERS As populations age, the prevalence of neurologic disease continues to increase and consultations involving GI motility problems in the patient diagnosed with a neurologic disorder become ever more common. The high prevalence of gastric atony and other disturbances of gut motor function in neurologic diseases is based on similarities in morphology and function of the neuromuscular apparatus of the gut and that of the somatic nervous system.36 Furthermore, the basic organization of the enteric nervous system (ENS) (neurons, ganglia, glia, and ENS-blood barrier) and the ultrastructure of its components are similar to those of the central nervous system (CNS). Almost all neurotransmitters identified within the CNS are also found in enteric neurons. Thus, the concept of ENS involvement in neurologic disease should not come as a great surprise.

Dysfunction of the autonomic nervous system (an important modulator of enteric neuromuscular function) can be commonly seen in several neurologic syndromes. In addition to the presence of several primary and secondary disorders of autonomic function, disturbed autonomic modulation of gut motor function, in some cases, may be an important factor that contributes to symptom development. It is also evident that the gut has important sensory functions. Sensory input is fundamental to several reflex events in the gut, such as the viscerovisceral reflexes that coordinate function along the gut. Even though these functions are usually subconscious, gut sensation may be relayed to and perceived within the CNS. Because the role of sensory dysfunction in the mediation of common symptoms such as abdominal pain and nausea in the patient with CNS disease with GI manifestations has not been extensively investigated, this does offer a future area of study.36 The two predominant neurologic disorders often encountered in GI practice are cerebrovascular disease and parkinsonism. In addition, patients with multiple sclerosis, autonomic and peripheral neuropathies including that associated with diabetic autonomic neuropathy, Guillain-Barré syndrome, myotonic dystrophy, and Duchenne muscular dystrophy have all been shown to demonstrate signs and symptoms suggestive of gastric atony. Regardless of the specific neurologic diagnosis, the use of a multidisciplinary team that is aware of the wishes and needs of the family and mindful of the nature and the natural history of the underlying disease process is best practice. Together, the team, including a neurologist and/or neurosurgeon, nutritionist, gastroenterologist, and specialty nurse, can assess and manage gastric atony and other GI problems in the patient with neurologic disease.36

CONNECTIVE TISSUE DISORDERS Gastric atony is also seen with scleroderma, one of the most common causes of pseudo-obstruction. Gastric involvement in scleroderma tends to parallel the same clinical course as the esophagus.37 In the Olmstead County study,38,39 10.8% of all cases of definite gastric atony were associated with the presence of a connective tissue disorder. In scleroderma, gastric involvement has been documented in anywhere from 10% to 75% of all patients, and delayed gastric emptying has been seen in 50% to 75% of those patients with scleroderma who demonstrated GI symptoms.36 Gastric atony in itself has important clinical consequences in scleroderma, including

exacerbation of gastroesophageal reflux and malnutrition. The former is of critical importance, given the tendency of these patients to develop severe and complicated reflux resulting from significantly impaired esophageal peristaltic amplitude and lower esophageal sphincter hypotension. Using the relatively noninvasive 13C-octanoic acid breath test, Marie et al40 documented delayed gastric emptying in 47% of 57 consecutive patients with scleroderma. Furthermore, they described a close correlation between GI symptoms and a delay in gastric emptying.40 Using the same approach, Hammar et al41 discovered atony in 29% of their 28 patients with primary Sjögren syndrome. Most recently, a reported association between Ehlers-Danlos syndrome type III (the joint hypermobility syndrome) and a variety of functional GI symptoms, including those that may be based on gastric emptying delay, have begun to emerge,4244 with the frank documentation of gastric atony in some of the studies.42

CRITICAL ILLNESS The prevalence of delayed gastric emptying in the intensive care unit (ICU) setting has been estimated to range from 38% to 57%, depending on the method used to define it.45,46 Using the 13C-octanoate acid breath test and measuring 13CO2 in end-expiratory breath samples, Ritz et al,47 found that 40% to 45% of the patients in an intensive care setting had delayed gastric emptying. Factors that can contribute to delayed gastric emptying in critical care patients include the supine position, coughing, suctioning, obesity, and advanced age, and the extent of the delay is directly related to the severity of critical illness. Nguyen et al48 found that, after controlling for other factors, admission diagnoses had only a modest impact on the risk for gastric atony in the ICU, with those at the highest risk being patients with head injuries, multisystem trauma, sepsis, and burns. That being said, a number of comorbid conditions may increase gastric emptying time, including raised intracranial pressure, hiatal hernia, gastric cancer, gastric resection, liver cirrhosis, and chronic pancreatitis. Interestingly, Lam et al49 observed in a retrospective study that a history of diabetes was not an independent risk factor for gastric emptying delay in critically ill patients despite its high prevalence in modern hospital populations. Additionally, proximal gastric motor responses to feeding were similar in diabetic patients to those of

healthy individuals.50 Nevertheless, hyperglycemia does impair gastric contractility and, along with electrolyte disturbances, may lead to gastric atony.51,52 Hence, in the critically ill setting, the continued need for optimization of both of these parameters is vital. Treatment has thus focused on the correction of electrolyte disturbances, withdrawal of medications that may impair gut motility, hypoglycemic monitoring, the addition of prokinetics, and the placement of feeding tubes (gastrostomy or jejunostomy) as needed.

Postsurgical Atony Although many surgical procedures originally associated with gastroparesis or gastric atony are less commonly performed today, several more recently developed upper abdominal procedures may be complicated by the development of gastric atony (Table 30-1). Acute gastric atony may be the result of the “ileus syndrome,” which can complicate many surgical procedures. Most often, it is a transient event that usually resolves in a short period of time. Occasionally, this gastric dysmotility can become chronic and result in significant symptoms. In contrast to chronic medical gastric atony, whose pathophysiology is often poorly understood, in the acute form of postsurgical atony, inflammatory processes seem central to the inhibition of motility. The frequency of postsurgical gastric atony can vary widely depending on many factors including the site and nature of the surgical procedure.36 Again citing the prominent Olmstead County studies of the community prevalence of gastric atony, 7.2% of all cases were related to prior gastrectomy or fundoplication.39 More specifically, Dong and colleagues53 noted that the rates of atony ranged from 0.4% to 5% after gastrectomy, 20% to 50% after pylorus-preserving pancreaticoduodenectomy, and 50% to 70% after cryoablation therapy for pancreatic cancer.

VAGOTOMY Although vagotomy is now infrequently performed for the management of peptic ulcer disease, the effect of inadvertent vagal injury underscores the continued relevance of a complete understanding of the complex effects of

vagotomy on gastric motor function.36 Loss of vagally mediated reflexes impairs receptive relaxation of the gastric fundus, leading to acceleration of the early phase of liquid emptying. This acceleration causes rapid emptying of hyperosmolar solutions into the proximal small intestine and may result in dumping syndrome. Conversely, and as a consequence of impaired antropyloric function, vagotomy prolongs the later phases of liquid and solid emptying. Other motility effects of vagotomy include impairment of the motor response to feeding, which contributes to the pathophysiologic mechanisms of postvagotomy diarrhea, and a suppression of the antral component of the MMC, which is particularly common among individuals with symptomatic postvagotomy gastroparesis.36,46,52,53 Currently, standard practice includes the addition of a drainage procedure, such as a pyloroplasty or gastroenterostomy, which tends to only negate the effects of vagotomy and results in little alteration in the gastric emptying of liquids or solids. Interestingly, prolonged postoperative gastroparesis (ie, lasting longer than 3-4 weeks) is, in fact, rare (90% gastric retention at 1 hour, >60% at 2 hours, and >10% at 4 hours.107-109 This test is noninvasive, widely available, and easy to perform. Other routine tests include upper abdominal x-ray and esophagogastroduodenoscopy (EGD) to rule out mechanical obstruction. Real-time magnetic resonance imaging (MRI) has also been shown to be a reliable tool for the assessment of gastric motion; however, the study itself is

expensive, time intensive, and not widely available.108,110,111

Manometry and Electrogastrography Gastric manometry is an invasive test that measures motility patterns of the gut. This test requires expertise to perform and evaluate the results. Gastric manometry can reveal characteristic patterns that suggest a neuropathy, myopathy, or intestinal mechanical obstruction.111 Electrogastrography, a noninvasive measurement of electrical activity of the gastric smooth muscle, is used predominantly in research to evaluate for gastric arrhythmias.109 Electrogastrography measures electrical rhythms, but because it requires expertise to evaluate results, it is not widely available.108,111

TREATMENT OPTIONS Optimal treatment can only be achieved once a careful investigation has taken place to properly diagnose gastric atony, exclude iatrogenic causes, correct electrolyte or metabolite imbalances, and modify eating habits and diet to achieve the peak level of noninvasive symptom relief possible. While medical management has been the gold standard initial treatment for most cases of gastric atony, the emergence of minimally invasive techniques has created attractive alternative options for patients who do not respond to medical management. When all else fails, conventional surgical remedies can be considered. Figure 30-2 offers a treatment algorithm for patients with symptomatic gastroparesis.

FIGURE 30-2 Treatment algorithm for gastric atony. While medical management has been the gold standard regarding initial treatment for most

cases of gastric atony, the emergence of minimally invasive techniques has created attractive alternative options for patients who do not respond to medical management. Conventional surgical remedies can be considered if other options fail. GES, gastric electrical stimulation.

Medical Therapy Although a multitude of pharmacologic therapies exist for the treatment of gastroparesis, prokinetic agents are by far the most recognized agents. It has been approximately 30 years since the first randomized controlled trials of the conventional prokinetic agents, metoclopramide, domperidone, and erythromycin, have been published. Despite this, they are still the first-line agents for the treatment of gastroparesis.112 Much like many other investigated areas of gastric atony, the majority of data regarding the efficacy of conventional prokinetic agents for the treatment of gastric atony are outdated.113-117 Metoclopramide has been the most extensively studied and has been associated with less improvement in gastric emptying when compared to the macrolide antibiotic erythromycin.117 A meta-analysis assessing the benefits of 4 different medications in 514 patients in 36 clinical trials reported erythromycin as the most potent stimulant of gastric emptying. Both erythromycin and the dopamine receptor antagonist domperidone (not available in the United States) are best at reducing the symptoms of gastric atony.118 Currently, several novel pharmacotherapies such as ghrelin receptor agonists (TZP-101, TZP-102, RM-131), mitemcinal, prucalopride, velusetrag, and levosulpiride are in development; however, their clinical efficacy and safety still need to be determined.112,119,120 While it is generally accepted that a significant percentage of patients require additional therapy beyond prokinetic agents, no clear data exist to determine the percentage of patients who fail medical management. Nevertheless, the use of promotility drugs in all patients is a relatively safe and effective means to circumvent the problem of gastric atony and improve patient recovery. Furthermore, understanding the drugs available and their interaction with the receptors involved in neuromuscular transmission within the GI tract can often aid the clinician in selecting the optimal therapy.

Endoscopic Techniques

Gastric atony has traditionally been a largely medically managed disease with refractory symptoms typically falling under the umbrella of the surgical domain. Advancements in the field have included the endoscopic management of gastroparesis, which most commonly involves intrapyloric botulinum toxin A injection and gastric electrical stimulation implantation. Furthermore, on the horizon are novel endoscopic approaches that have the potential to radically improve the standard of care. Endoscopic management of gastroparesis seeks to treat delayed gastric emptying with a less invasive approach compared to traditional surgical approaches.121 New endoscopic procedures offer a minimally invasive alternative to more radical options and should probably be more widely adopted. However, a progressive algorithm needs to be followed in challenging cases: starting with medical treatment and diet modification, then progressing through endoscopic treatments including new interventions such as per-oral pyloromyotomy, and finally using laparoscopic and/or open interventions including gastrectomy for truly refractory cases.122

BOTULINUM TOXIN A (BOTOX) Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications for several neurologic and nonneurologic conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the GI tract. The toxin blocks cholinergic nerve endings in the autonomic nervous system but does not block nonadrenergic noncholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions, including gastroparesis, easier in the outpatient setting, at a lower cost and without permanent complications.123 However, the benefits of botulinum toxin injections in gastric atony have been unclear. Several retrospective and openlabel studies have shown clinical advantages of intrapyloric botulinum toxin type A injections, whereas other smaller randomized trials did not show positive results. Overall, the available published studies have yielded conflicting results, leading to a fading out of Botox therapy for gastroparesis.124 Currently, the American Gastroenterological Association (AGA) does not recommend the use of endoscopic Botox for patients with

gastroparesis.125 However, given the small sample size of existing studies with conflicting data, there is a continued need for larger randomized trials in the future before a definitive decision or treatment guidelines can be established.

ENDOSCOPIC GASTRIC STIMULATOR IMPLANTATION In 2000, gastric electrical stimulation (GES) was approved by the US Food and Drug Administration (FDA) as a humanitarian device exemption in patients with refractory symptoms of diabetic or idiopathic gastroparesis.126 Often referred to as a gastric pacer, GES uses an implantable device consisting of a pulse generator that allows for electrical stimulation at a variety of frequencies. Permanent GES for gastroparesis typically requires a surgical implantation under general anesthesia. Several case series and small randomized controlled trials, the most important being the Worldwide AntiVomiting Electrical Stimulation Study (WAVESS), have shown clinical benefit from GES.127-133 A subsequent meta-analysis by Chu et al134 in 2012 confirmed significant improvement in symptom severity and gastric emptying times, although many of the analyzed studies were low-quality observational studies lacking control groups. A more recent study by McCallum et al130 also demonstrated improvement in weekly vomiting frequency among all patients with idiopathic gastric atony with a median reduction of 61.2%. The National Institute of Health and Care Excellence issued guidelines in 2014 that stated that the current evidence is adequate to support the use of GES.135 Up until 2012, surgery was the only available means to implant the GES device. Endoscopic placement of temporary gastric stimulators has been proven as a concept and is often used to determine whether a patient will respond to GES before undergoing a permanent implant surgery. The lack of a permanent endoscopic solution and the reliance on surgical implantation for symptomatic improvement has at present limited further endoscopic utilization.136,137 However, Deb et al138 designed 5 innovative endoscopic gastric implantation techniques and developed a novel, wirelessly powered miniature gastrostimulator. Although this early model has only been evaluated in pig investigations, the studies provide a promising prototype for

other dysmotility treatment paradigms and exciting new options that may translate in the future to less invasive endoscopic placement in gastroparetic patients.139

SURGICAL IMPLANTATION OF GASTRIC ELECTRICAL STIMULATION The implantation procedure of the GES can be performed via laparotomy or a laparoscopic approach. Two intramuscular leads containing electrodes (Model 4351; Medtronic) are inserted into the muscularis propria of the stomach.140,141 The 2 electrodes are sutured 9 and 10 cm from the pylorus on the greater curvature of the stomach and connected by leads of 35 cm in length to the pulse generator, which is placed subcutaneously in the abdominal wall, usually in the right upper quadrant. The programming parameters are usually set as the default at surgery and are then reevaluated approximately 3 months after surgery. While some investigators have proposed specially designed algorithms,142,143 due to the lack of any controlled trials, these have only been used for clinical nonresponders. In a 10-year observation,144 it has been shown that the electrical current is increased approximately 20% to 30% during follow-up interrogations based on a clinician observation that symptoms are not optimally controlled and more voltage might help. However, this practice has not been based on any supportive evidence.

ENDOSCOPIC PYLOROMYOTOMY Rao et al145 demonstrated that phasic motor activity in the antrum and duodenum can be stimulated by fundic balloon distention. While there are no such studies to determine the effect of pyloric channel distention on the interstitial cells of Cajal in the stomach or gastric emptying, endoscopic pyloromyotomy and manipulation of the pylorus may improve gastroparesis refractory to medical management. Khashab et al146 demonstrated the feasibility and efficacy of this approach with a case report of the first human gastric per-oral endoscopic myotomy in a patient with severe refractory gastroparesis. The procedure was well tolerated with vast improvement in gastroparetic symptoms noted at 12-week follow-up. This technique is similar in principle to the submucosal dissection and

myotomy performed for the treatment of achalasia.147 With this technique, endoscopy is performed and myotomies of the inner circular and oblique muscle bundles 2 to 5 cm proximal to the pylorus on the anterior wall of the stomach are performed. The longitudinal muscle layers are preserved. Endoscopic pyloromyotomy is then performed by dissecting the pylorus until deeper layers become evident with full separation of the pyloric ring.146,148 Complications of endoscopic pyloromyotomy include GI bleeding, leak, and pneumonia.148 Despite these complications, the endoluminal pyloromyotomy technique could provide an incision-less, less invasive alternative with similar functional outcome as compared to standard laparoscopic or open pyloroplasty.148 While the small number of cases certainly limits the ability to determine the true impact of this procedure in the management of gastroparesis, with more frequent use, increasing technical experience, and more data, endoscopic pyloromyotomy has exciting potential to be at the forefront in the endoscopic management of gastroparesis.

ENDOSCOPIC DECOMPRESSION OR BYPASS: PERCUTANEOUS GASTROJEJUNOSTOMY AND JEJUNOSTOMY Enteral nutrition and feeding is sometimes required for more severe symptoms of gastric atony and can be seen in up to 30% of patients with grade 3 gastric atony.149,150 Specifically, a feeding jejunostomy is a critical adjunct to the treatment of gastroparesis as a means to maintain hydration, nutrition, and glycemic control. While surgical gastrojejunostomy is a potential treatment option for patients with refractory gastric atony, the procedure is associated with substantial morbidity and mortality when patients are in a less than ideal clinical condition.151-154 Furthermore, although surgical gastrojejunostomy has been shown to improve gastroparetic symptoms, endoscopic ultrasound-guided gastrojejunostomy using a stent has been developed but warrants further investigation due to unknown long-term stent safety and patency issues.152 Ideally, the stent can be removed after an interval of time, leaving a permanent fistula tract. However, studies are needed to determine the necessary pressure gradient and initial gastrojejunostomy tract diameter in order to maintain long-term fistula

patency after stent removal. The minute amount of data available to date, while optimistic and potentially transformative, requires repeat analysis and trials with human study before implementation into the gastroenterologist’s everyday arsenal. However, given the technical success reported in the studies above, the future of endoscopic gastrojejunostomy using EUS-guided lumen-apposing metal stents is bright, with the potential to diminish the need for invasive surgeries and improve symptoms of gastroparesis refractory to medical management. Percutaneous endoscopic gastrostomies with jejunal extensions (PEGJ) are technically less demanding to perform but plagued with the difficulties of tube migration back into the stomach. One of the major negatives of percutaneous endoscopic jejunostomies (PEJs) is that the tube is generally positioned in the distal duodenum or very proximal jejunum and the force of active vomiting often leads to displacement or coiling of the tubing back into the proximal duodenum or the stomach, resulting in the enteral fluid being vomited. It also partially compromises the lumen size of the pylorus. This specific aspect is relevant because, as oral intake is introduced and PEJ feedings are being tapered off, the usually 14- to 16-Fr tube is still located in the pylorus, interfering with the gastric emptying process and the mechanism of the pylorus. The skin site is often also more difficult to manage because of the larger tube diameter with seeping or discharge of very acidic fluids onto the skin. The tube is large and needs to be secured to the skin and is painful and very cosmetically obtrusive.155 Direct percutaneous endoscopic jejunostomy (DPEJ) is a push enteroscopy technique that was first described by Shike et al156 and offers another option of providing direct postpyloric enteral nutritional support. In the largest cohort study to date, Maple et al157 reported clinical outcomes with DPEJ and included 307 attempts at PEJ placement with a success rate of 68%. Although this study included multiple indications for DPEJ placement, gastric atony comprised 21% of the cases. A case series by Toussaint et al158 showed a PEJ technical success rate of 78.6% with no immediate complications reported. However, this was based on a small sample size of only 14 patients. Based on these data, PEJ should be considered in the algorithm of enteral access for nutritional support before considering surgical jejunostomy. The main limitation of DPEJ is the technical difficulty of the procedure as the jejunum is narrow, making it more difficult to advance a needle directly into the

lumen.159 This difficulty can be alleviated with balloon-assisted enteroscopy (BAE).160 PEJs are technically more difficult to place but provide a more direct route for enteral alimentation without the need for laparotomy. Fan et al161 reported the outcomes of PEGJ versus PEJ with findings for reintervention rates of 39.5% versus 9.0%, respectively. Toussaint et al162 reported on the use of PEJ for gastroparesis with a success rate of 78.6% and a complication rate of 36.4%, including jejunal volvulus and jejunocolic fistula. In summary, jejunostomies are a critical adjunct to the management of gastroparesis but need knowledgeable medical support to minimize long-term complications.155

SURGICAL GASTROSTOMY AND JEJUNOSTOMY TUBE PLACEMENT The theory that gastric tube placement is needed to provide venting in patients with gastroparesis to alleviate symptoms has not been proven to be beneficial. The abdominal bloating that patients with gastric atony experience has now been determined to be secondary to small bowel bacterial overgrowth, rather than the accumulation of air. Tube venting may also cause electrolyte imbalance, particularly potassium, which can become a major health risk. More importantly, patients may claim they have the ability to eat a meal, but the process of draining their intestinal contents by suction or venting can be a misleading indication of the patients’ progress. Additionally, it can often become an addictive habit. Intestinal venting can compromise the patient’s nutritional status by draining out the consumed nutrients and may also inhibit the stomach itself by not allowing it to adequately reeducate itself and regain motor function.155 Gastrostomy and jejunostomy tubes can also be placed surgically through a mini-laparotomy, laparoscopically or endoscopically as previously mentioned. The largest series of gastroparesis (26 patients) followed with jejunostomy was studied by Fontana and Barnett,163 who demonstrated subjective perception of improved health with improved nutrition in 57% of patients and decreased hospitalizations in 52%. However, this series notably had 23 major complications requiring hospitalization and surgery, including intestinal obstruction, tube dislodgement, wound abscesses, and cellulitis,

reiterating that morbid complications can still occur despite the ease with which these tubes are placed.164 Surgical jejunostomy tube placement can be performed concomitant to gastric surgery for gastroparesis. The 3 most common techniques are a longitudinal Witzel tunnel, the Roux-en Y technique, and the needle catheter technique. The Witzel technique involves creating a longitudinal tunnel in the small bowel wall that covers a several-centimeter length of tube so that inadvertent tube dislodgement facilitates the collapse and sealing off of the enterostomy.165 Gerndt and Orringer166 demonstrated that the routine use of the Witzel tunnel resulted in complications in only 2.1% of 523 patients. These complications included intestinal obstruction, intraperitoneal leak, and local and intra-abdominal abscesses.166 The Roux-en-Y jejunostomy has few indications and is mostly used for pediatric patients with severe injury and neurologic malformations.167 However, a high rate of complications was described, with 15% stoma prolapse and 6% leakage rates. The needle catheter technique involves the use of the Seldinger technique whereby a needle is tunneled through the intestinal serosa and submucosal space for a distance of 5 cm before entering the enteric lumen. A wire is then passed through the needle followed by a narrow lumen catheter. Needle catheter jejunostomies are often used for feeding after oncologic procedures but are also plagued by complications, including tube blockage, tube dislodgement, and pneumatosis. However, Meyers and colleagues168 reported on the findings of 2022 patients with needle catheter jejunostomies and noted complications in only 1.5% of patients. The laparoscopic approach can also use the needle catheter technique for jejunostomy placement, resulting in small incisions and early return of bowel function with similar complications.

TRANSPYLORIC STENTING An innovative approach recently described by Clarke et al169 involves the use of through-the-scope transpyloric stent placement as a treatment for gastric atony. In this small case series (n = 3), double-layered, fully covered Niti-S self-expandable metallic stents (TaeWoong Medical, Seoul, South Korea) were used and shown to successfully improve symptoms of gastric atony. The procedure entails the placement of a self-expandable stent across the pyloric channel. The stent is placed using endoscopic guidance without fluoroscopy. The stent is then fully deployed in the transpyloric position with

its proximal end in the gastric antrum. In all 3 cases, patient symptoms markedly improved or became asymptomatic at 115, 122, and 174 days of follow-up, respectively. While this was a case series of only 3 patients, the stark improvement and lasting results at follow-up after the procedure suggest that transpyloric stent placement may improve symptoms associated with impaired gastric emptying.169 A major concern with transpyloric stenting is stent migration leading to intestinal obstruction or the recurrence of symptoms. Several stent-securing methods such as endoscopic clips (through-the-scope clip and over-the-scope clip) and endoscopic suturing have been described to reduce stent migration. However, at present, the question still remains regarding which stent-securing method is superior.170 Future studies are required to truly ascertain the longterm durability, utility, and preferred method for transpyloric stenting and fixation. Until that time, transpyloric stenting will remain a limited option for endoscopists in the management of patients with refractory gastroparesis.

SURGICAL TREATMENT Surgical therapies for patients with intractable gastric atony have traditionally been reserved for patients who have failed diet modification, medical therapy, and/or endoscopic therapy. However, depending on the precipitating factor, surgical treatment may at times be warranted. Surgical options including pyloroplasty and gastrectomy (subtotal or total), along with electrical stimulation, or placement of gastrojejunostomy or jejunostomy feeding tubes are viable solutions.171

Pyloroplasty Pyloroplasty is beginning to emerge as a successful drainage procedure for refractory gastric atony in the surgical management of diabetic and nondiabetic gastric atony. A retrospective study was performed of 46 patients undergoing pyloroplasty for refractory gastroparesis.172 Modifiers of improvement included pre- and postoperative assessment using gastric emptying scintigraphy and the Gastroparesis Cardinal Symptom Index. Laparoscopic pyloroplasty was performed in 42 patients, open pyloroplasty was performed in 3 patients, and 1 patient was converted from a laparoscopic

to open pyloroplasty. Studies were repeated during the 6- to 12-month postoperative intervals. The postoperative gastric emptying scintigraphy improved in 90% of patients and normalized in 60%. Postoperative halfemptying time was significantly reduced (P = .001), as was the 4-hour retention (P < .001). The Gastroparesis Cardinal Symptom Index showed statistically significant reduction in symptom severity for all 9 categories (P < .0005) as well as total symptom score (P < .005), and no patients developed dumping syndrome. This has led to the conclusion that pyloroplasty is a highly effective therapy for refractory gastroparesis, offering significant reduction in symptom severity, improvement in quality of life, and acceleration of gastric emptying.

Surgical Implantation of Gastric Electrical Stimulation with Pyloroplasty The lack of acceleration of the delayed gastric emptying by GES begs the question as to how much better the outcome would be if gastric emptying could be accelerated. This is the rationale for the addition of a surgical pyloroplasty (PP) performed at the time when GES is implanted. This approach can be supported by the following data in the literature: first, the injection of Botox into the pylorus causes a transient but substantial decrease in symptoms and gastric retention rate, with this effect being the most pronounced in the postvagotomy subset173; second, surgical investigation174,175 has suggested that PP alone could have a role in patients with gastroparesis; and finally, pyloric spasm is hypothesized to be present in diabetes.176 A subset of patients with idiopathic gastroparesis was suspected of having pyloric dysfunction based on pyloric motility findings.177 Only 1 clinical investigation has tested whether PP combined with GES could enhance the outcomes of GES.164 This study showed that gastric emptying improved in all subgroups, especially in postsurgical patients with gastroparesis. In fact, >50% of patients normalized their gastric emptying test. No adverse events related to the additional surgery were observed. In addition, oral intake and nutritional status were improved after PP with GES, along with a continued reduction in nausea and vomiting. A randomized, double-blind study would be beneficial to further confirm these excellent results. In general, it may be concluded that the addition of a Heineke-

Mikulicz PP to the standard GES procedure markedly improves and often normalizes delayed gastric emptying, especially in postvagotomy gastroparetic patients, thus enhancing long-term symptom control and augmenting the central mechanism of nausea and vomiting by GES.163 Furthermore, the data would support that PP should be recommended to be routinely added to the standard GES procedure.

Total and Subtotal Gastrectomy Gastrectomy has traditionally been reserved for patients who have experienced severe refractory postsurgical gastric atony.178,179 Common operations resulting in postsurgical gastric atony include vagotomy for ulcer disease, Nissen fundoplication for severe GI reflux, the Billroth I and II gastric reconstructions for ulcer disease and gastric cancer, and the Whipple procedure, as previously discussed. Forstner-Barthell et al180 reported that extensive subtotal or completion gastrectomy provides symptomatic improvement in 67% of gastroparesis patients but has not always been shown to be beneficial in terms of weight gain. Nausea, the need for total parenteral nutrition, and retained food at endoscopy were negative prognostic factors for patient outcome following the procedure. Like other surgical adjuncts, complications were common (40%) and included narcotic withdrawal syndrome (18%), ileus (10%), wound infection (5%), intestinal obstruction (2%), and anastomotic leak (5%). Symptoms were relieved in 43% of participants (Visick grade I or II); however, 57% of candidates remained in Visick grade III or IV. Nausea, vomiting, and postprandial pain were shown to be reduced from 93% to 50%, 79% to 30%, and 58% to 30%, respectively (P < .05); however, chronic pain, diarrhea, and dumping syndrome were not significantly affected.180 Subtotal gastrectomy involves resection of approximately 70% of the stomach including the antrum and pylorus, with closure of the duodenum and reestablishment of continuity with a Roux-en-Y jejunal segment. Watkins et al181 reported the largest longitudinal experience with subtotal gastrectomy in diabetic patients with gastric atony. They demonstrated that 6 of 7 patients had immediate resolution of vomiting symptoms and improvement in quality of life, which persisted up to 6 years postoperatively.181 Zehetner et al182 compared 2 groups treated with GES, laparoscopic subtotal gastrectomy, or a

combination of the 2 if GES failed. Thirty-one patients received laparoscopic subtotal gastrectomy, whereas 72 received GES. Evaluation demonstrated that 30-day morbidity was significantly greater in the gastrectomy group than the GES group (23% vs 8%), but this difference decreased over time. Although two-thirds (63%) of the GES group attained symptom improvement, 87% of those in the gastrectomy group reported significant improvement in nausea, vomiting, and epigastric pain. Nineteen (26%) of the GES group had to have the device removed because of device malfunction, infection, or failure to respond. These patients received laparoscopic subtotal gastrectomies, with 100% reported symptom improvement. This success with laparoscopic gastrectomy prompted Lipham and colleagues182 to propose this approach as first-line therapy for the surgical treatment of gastric atomy. Recent observations of increased gastric emptying in bariatric surgical patients have prompted multiple case reports and case series describing the use of longitudinal sleeve gastrectomy for the treatment of patients with atony. Sleeve gastrectomy involves removal of the body and fundus of the stomach and stapling along the lesser curvature to create a tubular stomach. Bagloo and colleagues183 reported an initial case series of sleeve gastrectomy in 4 patients with diabetes with atony. Three of the 4 patients had resolution of their symptoms after a minimum follow-up of 6 months. Similarly, Meyer and colleagues184 demonstrated, in 9 morbidly obese patients with diabetes and gastroparesis, that laparoscopic sleeve gastrectomy resulted in the resolution of gastroparesis symptoms and improved gastric emptying studies. The introduction of laparoscopic gastric resection with reconstruction has allowed for decreased morbidity in populations with complex diabetic histories prone to complications and morbidity secondary to chronic malnutrition. McCallum and colleagues166 reported their experience on 8 patients with gastroparesis who underwent completion gastrectomy after failing to respond to both available and experimental medical therapies with prokinetic agents. They concluded that although completion gastrectomy is a radical approach, it can provide reliable relief of symptoms in a select group of patients with chronic refractory gastroparesis after partial gastric resection for gastric outlet obstruction secondary to peptic ulcer disease. Subsequently, these authors reported on their own experience at a GI motility referral center. They reported on 9 of 200 patients (4.5%) who received GES for gastric atony who then underwent a total gastrectomy with placement of a jejunostomy tube as a

last resort to control their symptoms. Nausea and vomiting improved by an average of 55%; all patients became nutritionally stable, previously placed jejunostomy tubes were able to be removed, and the quality of life was such that they all would recommend the procedure. Furthermore, all patients had a significant reduction in the number of emergency room visits and hospitalizations.

OUTCOMES Natural History In the Olmsted County epidemiology study,39 one-third of all patients with incident gastric atony died, and another one-third required hospitalization, medications, or tube feeding related to atony. Furthermore, overall survival in patients with gastroparesis was significantly lower than that of the Minnesota white population, reiterating the vast impact it can have on patient morbidity and mortality.

Impact on Quality of Life As stated earlier, the impact of gastroparesis on quality of life can be severe and debilitating. Although nausea and vomiting are the cardinal symptoms of gastroparesis, data from the NIDDK Gastroparesis Clinical Research Consortium suggested that upper abdominal pain or discomfort is not uncommon and is often severe.185 Moderate to severe pain was associated with more severely delayed gastric emptying, worse quality of life, depression, and anxiety.185 Moreover, among patients with moderate to severe pain, 48% were chronically taking opiates. To what extent this impact is related to GI symptoms per se versus comorbid conditions (eg, depression) and/or medications (eg, opiates) is unclear. Data on the impact of GI symptoms on quality of life among patients with gastric atony in the community are limited. Among a community cohort of people with T2DM, the physical and mental quality of life as assessed by the Short Form-36 were lower in patients with diabetes with GI symptoms compared with population norms.186 The quality-of-life scores in all

subscales decreased markedly with increasing numbers of distinct GI symptoms, and the association between GI symptoms and poorer quality of life in DM was independent of age, sex, smoking, alcohol use, and type of DM.186 Race has also been shown to be associated with the impact of GI symptoms on quality of life in patients with DM. One study reported that nonwhite patients with gastroparesis had more severe symptoms, poorer quality of life, and used more health care resources than white patients.187 The 2 groups differed in health care use, with 49% of nonwhite patients reporting more than 4 gastroparesis-related emergency department visits and 42% reporting more than 4 gastroparesis-related hospitalizations, compared with 20% and 14% of white patients, respectively. In this study, nonwhite race, sex, age, and age of onset were independently associated with symptom scores, whereas the causes of gastroparesis and GE times were not. High unemployment rates, lower household income, and work absenteeism are also variably associated with gastroparesis.96,150

Mortality Rates Overall survival in patients with idiopathic gastroparesis was significantly lower than the age- and sex-specific expected survival computed from the Minnesota white population.39 A review of several case series observed that the mortality rates in patients with gastroparesis range from 4% and 38%.188 The best outcomes were observed in a largely outpatient-based group of patients followed for approximately 2 years, and the highest death rates were reported in patients with diabetes with gastroparesis requiring nutritional support.30,189-192 In a study of 86 patients with diabetes, approximately 25% had died during follow-up of at least 9 years, but gastroparesis was not associated with mortality after adjustment for other disorders.193 However, this study did not ascertain the relationship between diabetic gastroparesis and other medical conditions. Whether this increased mortality is driven by gastroparesis is unknown. Data on long-term natural history in the community are lacking.

FUTURE DIRECTIONS

Chronic disturbances of GI function encompass a wide spectrum of clinical disorders that range from common conditions with mild-to-moderate symptoms to rare diseases characterized by a severe impairment of digestive function, chronic pain, vomiting, bloating, and severe constipation.194 Patients at the clinically severe end of the spectrum such as those with gastric atony can specifically experience profound changes in gut transit and motility. In a subset of these patients, histopathologic analyses have revealed abnormalities of the gut innervation, including the ENS, termed enteric neuropathies, and offer a possible future direction of study to increase our arsenal of treatment targets.194 At the other end of the spectrum, medical treatment options continue to be first-line therapy for those with “manageable” symptoms. Nevertheless, acquisition of knowledge regarding this disease can hopefully enable the future development of novel targeted therapeutic approaches to help relieve the symptomatic and emotional burden of those afflicted.

CONCLUSION Gastric atony continues to be a medical problem with significant effects. The causes are multifactorial and may have mild to severe symptoms. Acquisition of consistent cure rates will undoubtedly require early diagnosis, prompt workup, and more effective, yet minimally invasive medical treatment options.

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GASTRIC ADENOCARCINOMA AND OTHER NEOPL ASMS Waddah B. Al-Refaie • Young K. Hon • Jennifer F. Tseng

INTRODUCTION Tumors of the stomach are diverse in presentation, symptoms, and prognosis. In this chapter, the authors will first describe the epidemiology, presentation, and management of gastric adenocarcinoma. Subsequently, gastric polyps, mesenchymal tumors (eg, gastrointestinal [GI] stromal tumors), and the rare gastric sarcoma and lymphoma will be discussed.

GASTRIC ADENOCARCINOMA Historic Background The first description of stomach cancer documented in Western literature is generally thought to be that of Avicenna (980-1037). Many years later, in

1761, Morgani published a manuscript on malignancies of the stomach. In 1879, Pean was believed to perform the first gastric resection for cancer, followed by Billroth performing the first described pyloric resection in 1881, and Schlatter successfully performing the first total gastrectomy (TG) in 1897. In 1951, McNeer et al recommended a more extensive resection for cancer, including TG with distal pancreatectomy and splenectomy.1

Incidence and Pathology While gastric cancer (GC) is the third leading cause of cancer-related death worldwide, significant differences in its incidence exist across the continents.2 Specifically, a higher incidence is found in Japan and Eastern Asia (approximately 18-25 cases/100,000) than in Europe and North America (approximately 8-10 cases/100,000).3 The incidence of GC in the United States is low as it is currently the 15th most prevalent cancer. In 2015, 24,500 patients were diagnosed with GC, and nearly 10,000 persons are projected to die from GC in 2016. The estimated overall 5-year survival approaches 30%.4 Gastric cancer is a malignant solid organ tumor of older adults (>65 years). The median age of diagnosis is 69 years of age. Similar to other solid organ cancers, older adults are primarily affected.5 In recent years, the incidence of GC has been rising in younger adults (age 5/HPF, tumor rupture at the time of surgery, or mitotic count >10 mitoses/50 HPF) for patients treated 3 years.120 The most recent trial looking at 5-year

adjuvant therapy, PERSIST-5, has now concluded. This single-arm, phase II, nonrandomized, open-label multicenter study analyzed the survival benefit of 5-year adjuvant imatinib mesylate in patients that underwent resection of primary KIT (+) GIST with high risk of recurrence within 12 weeks. The primary endpoint of the trial was recurrence-free survival. The 5- and 8-year estimated RFS rates were 90% (95% CI, 80-95) and 81% (95% CI, 62-91), respectively. The 5- and 8-year OS rate was 95% (95% CI, 86-99). Forty-five of 91 patients discontinued treatment; common reasons included patient choice (20%), adverse events (AEs, 17%), protocol deviation (4%), and loss to follow-up (4%). Of the patients that had recurrences, this occurred after discontinuing the imatinib.140 They concluded that patients with exon 9 or PDGFRA mutations should be started at the higher 800 mg daily dose since there was no significant benefit at 3 years at the 400 mg dose.141 Metastatic Disease. Patients with metastatic disease are candidates for imatinib mesylate as the primary targeted therapy with the option of secondline tyrosine inhibitor, sunitinib, for disease progression after dose escalation of imatinib from 400 to 800 mg regimen.142 The mode of imatinib resistance has been determined to be second c-kit exon mutations in exon 13 which can be targeted by sunitinib.143 Patients can also develop resistance to imatinib mesylate therapy through new BRAF mutations in patients with c-kit and PDGFRA-mutant GIST.144 A third-line TKI, Regorafenib, is an oral multitargeted inhibitor with activity against multiple kinases including KIT, RET, RAF1, BRAF, vascular endothelial growth factor (VEGF), and PDGFR that is recommended after progression through imatinib mesylate escalation and sunitinib.145,146 Select patients with GIST tumors that have a treatment response without signs of multifocal progressive disease (MPD) can undergo cytoreductive metastasectomy with an outcome comparable to sunitinib in highly select patients.147 The liver is the most common site of synchronous and metachronous metastases for patients; the incidence is 15% to 20% incidence and there is a solitary site of disease in 50% of cases.116 Patients selected for surgical metastasectomy are those that have stable disease who have primary or secondary resistance on first-, second-, and third-line of TKIs (imatinib mesylate, sunitinib, and regorafenib); those who have resectable disease with R0 margins; those who have good performance status (Eastern Cooperative

Oncology Group [ECOG] score 0); and those presenting with hemorrhage, perforation, obstruction, or abscess. The ability to obtain negative R0 margins enhances both progression-free survival (29 months vs 7 months; P = 0.002) and OS (100% vs 37.5% at 1 year; P = 0.001).148,149 While there is no consensus on the timing of metastasectomy, selection of patients who have favorable response to TKI is critical. Recent data suggests that patients who underwent resection at the period of maximum tumor response to TKIs had improved surgical outcome compared to those who were operated on after the development of primary or secondary resistance (1-year survival of 95% with stable disease, 86% with limited progression, and 0% for generalized progression; P < 0.0001).150–152 Given the morbidity of metastasectomy, it is critical to select patients with the best probability of progression-free and OS based on the type of mutation and response to TKI.

SARCOMA Leiomyoma and Leiomyosarcoma. Leiomyoma and leiomyosarcoma are rare mesenchymal tumors that arise from the muscularis propria and muscularis mucosa layers of the stomach and small intestine (Fig. 31-13). The diagnosis is made by immunohistochemistry. These tumors stain positive for desmin and actin but are negative for CD117 (c-kit and CD34) which distinguishes them from GIST. Leiomyoscarcoma can be distinguished from leiomyoma clinically—leiomyosarcomas are typically solitary, larger, and frequently display areas of hemorrhage and necrosis. Symptoms are often delayed due to their extramural growth until there is ulceration, bleeding, obstruction, or incidental finding of metastatic disease noted in the liver and peritoneum during imaging workup for a different cause. The prognosis of patients with metastatic disease at initial presentation is poor. Management should be focused on R0 resection.153,154

FIGURE 31-13 Hematoxylin and eosin staining of a leiomyoma. Fibrosarcoma and Angiosarcoma. Fibrosarcoma is a malignant tumor composed of fibroblasts with variable collagen production, classically with a herringbone architecture. Fibrosarcomas stain positively for vimentin and very focally for smooth muscle actin. Fibrosarcomas are rare, accounting for 1% to 3% of all sarcoma diagnoses. They present in the middle age but can also develop in infancy without any predilection for gender.155 They are more commonly in the extremities, head and neck, than in the viscera. Fibrosarcomas are the least differentiated type of mesenchymal malignancy and are defined as spindle cell malignant neoplasms lacking any specific differentiation and therefore are the least heterogeneous of the sarcomas.156 The tumors have a white or tan mass appearance with a firm texture due to the collagen content. Fibrosarcomas tend to exhibit resistance to systemic chemo- and radiotherapy. Angiosarcomas are malignant vascular tumors that arise from normal endothelium. They comprise only approximately 2% of all sarcomas and are highly aggressive with early recurrence and metastasis. The majority develop as cutaneous tumors associated with lymphedema; less than a quarter present as deep soft tissue masses of the arm, trunk, and abdominal cavity.

Histologically, angiosarcomas have components of both epithelioid and spindled areas with a predominance of the former and are composed of sheets, small nests, cords, or rudimentary vascular channels. Immunohistochemistry positive for CD31, CD34, and von Willebrand factor confirms the diagnosis.157 Hemangiopericytoma. Hemangiopericytoma is a diagnosis used to describe a wide array of neoplasms that have a thin-walled branching vascular pattern. Patients generally present with tumors of the deep soft tissue or abdominal cavity and less commonly in the limbs; symptoms are due to the mass effect from these slow growing tumors. Hypoglycemia noted in these patients when tumors secrete insulin-like growth factor.158 They are well-circumscribed masses with yellowish or tan cut surface and a fleshy or spongy consistency ranging in size from 5 to 15 cm in diameter at presentation. The overall prognosis of hemangiopericytoma is generally favorable as the majority are benign although an aggressive malignant clinical course is sometimes reported. Schwannoma. Schwannoma is a benign neoplasm of Schwann cell origin. These are benign lesions that have a rubbery, yellow trabeculated appearance macroscopically. They are characterized by lymph node aggregates around their periphery, with nuclear palisading Verocay bodies and hyalinized vessels similar to schwannomas found elsewhere in the body. They grow slowly along the outer covering of the myelin sheath of the peripheral nerves and are generally contained within a capsule, permitting successful surgical removal159 (Fig. 31-14). These tumors can be monitored if asymptomatic and the diagnosis is secure.

FIGURE 31-14 CT imaging of a gastric schwannoma (A) without and (B) with IV contrast.

GASTRIC LYMPHOMA Background There are two major types of Non-Hodgkin lymphoma—nodal involvement versus extranodal disease. Gastric lymphoma is an extranodal Non-Hodgkin lymphoma defined by the presence of the majority of the lymphoma in the stomach with variable involvement of the surrounding lymphatic drainage. The two main subtypes of gastric lymphoma are diffuse large B-cell lymphoma (DLBCL) (Fig. 31-15) or mucosa associated lymphoid tissue (MALT). Gastric lymphoma arises from the mucosa or submucosal layer, most often from the lymphoid tissue in the lamina propria.

FIGURE 31-15 Hematoxylin and eosin stain of a gastric diffuse large B cell lymphoma.

INCIDENCE There is estimated to be 500,000 new cases of gastric lymphoma in the United States each year; this comprises 5% of all lymphoma diagnoses.160 Gastric lymphoma is the most common site of GI lymphoma followed by small intestine, ileocecum, and colon/rectum.161 Patients initially present in their sixth decade of life with more males and Caucasians than females and blacks. There are several risk factors associated with gastric lymphoma including celiac disease, H. pylori infection, immunosuppression, human immunodeficiency virus (HIV) or Epstein-Barr virus (EBV), and inflammatory bowel disease.162,163

PRESENTATION AND DIAGNOSIS The clinical symptoms of patients with gastric lymphoma are nonspecific but not limited to fever, nausea, vomiting, epigastric abdominal pain, anorexia, unintentional weight loss, night sweats, hematemesis, and melena.164,165 Staging studies includes contrast-enhanced CT, MRI, EGD biopsies, EUS,

and 18F-fluorodeoxyglucose PET (18FDG-PET).163 Additionally, peripheral blood smear and bone marrow biopsy are required in the staging workup to exclude metastatic disease. Patients should also be tested for H. pylori given its essential role in the pathogenesis of MALT. There are several proposed staging systems that are available, including the Ann Arbor Staging System with Musshoff Modification and the Lugano Staging System. In the Ann Arbor Staging System with Musshoff Modification, stage IE is lymphoma restricted to the GI tract, stage IIE is lymphoma infiltrating lymph nodes on the same side of diaphragm, stage III is lymphoma involving both sides of the diaphragm, and stage IV is disseminated disease. Using the Lugano system, stage I is lymphoma confined to the GI tract, stage II is lymphoma extending into the abdomen, and stage III/IV is disseminated extranodal involvement or a GI tract lesion with supradiagphragmatic nodal involvement.166

MANAGEMENT The approach for patients with gastric lymphoma should be multidisciplinary, involving the medical oncologist, radiation oncologist, and surgical oncologist to determine the best treatment options. The treatment of choice for DLBCL is chemotherapy alone. A trial in Mexico randomized 589 patients to chemotherapy alone, chemotherapy plus surgery, surgery only, and surgery plus radiation therapy with 10-year survival rates of 96%, 91%, 54%, and 53%, respectively.167 In contrast, there was no difference in treatment outcomes in a randomized trial of 241 patients with low-grade MALT lymphoma comparing surgery, radiation therapy, and chemotherapy with 10-year survival rates of 80%, 75%, and 87%, respectively; P = 0.40). Therefore, patients with low-grade MALT are offered chemotherapy with or without radiation therapy if antibiotic treatment does not cause complete regression of the MALT lesion.168 MALT lymphoma was first associated with H. pylori infection in 1991; nearly 92% of patients with MALT lymphoma are positive for H. pylori infections. This association is based on the T-cell activation of MALT lymphoma by H. pylori itself.169 Treatment of H. pylori with triple therapy (amoxicillin or metronidazole, clarithromycin, and proton pump inhibitors) has produced complete remission of MALT lymphomas and is considered the first line treatment.170,171 Surgery is reserved for those with emergency presentation of uncontrolled refractory bleeding, perforation, and/or fistula

formation.

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analysis of a randomized clinical trial. JAMA Oncol. 2017;3(5):602–609. 142. Hsu JT, Le PH, Kuo CF, et al. Imatinib dose escalation versus sunitinib as a second-line treatment against advanced gastrointestinal stromal tumors: A nationwide population-based cohort study. Oncotarget. 2017;8(41):71128–71137. 143. Wada N, Kurokawa Y, Takahashi T, et al. Detecting secondary C-KIT mutations in the peripheral blood of patients with imatinib-resistant gastrointestinal stromal tumor. Oncology. 2016;90(2):112–117. 144. Agaram NP, Wong GC, Guo T, et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer. 2008;47(10):853– 859. 145. Ben-Ami E, Barysauskas CM, von Mehren M, et al. Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol. 2016;27(9):1794– 1799. 146. Rutkowski P, Stepniak J. The safety of regorafenib for the treatment of gastrointestinal stromal tumors. Expert Opin Drug Saf. 2016;15(1):105–116. 147. Fairweather M, Balachandran VP, Li GZ, et al. Cytoreductive surgery for metastatic gastrointestinal stromal tumors treated with tyrosine kinase inhibitors: A 2-institutional analysis. Ann Surg. 2017. 148. Zaydfudim V, Okuno SH, Que FG, et al. Role of operative therapy in treatment of metastatic gastrointestinal stromal tumors. J Surg Res. 2012;177(2):248–254. 149. Cananzi FC, Belgaumkar AP, Lorenzi B, et al. Liver surgery in the multidisciplinary management of gastrointestinal stromal tumour. ANZ J Surg. 2014;84(12):937–942. 150. Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24(15):2325–2431. 151. Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245(3):341–346. 152. Bamboat ZM, DeMatteo RP. Metastasectomy for gastrointestinal stromal tumors. J Surg Oncol. 2014;109(1):23–27. 153. Madan AK, Frantzides CT, Keshavarzian A, et al. Laparoscopic wedge resection of gastric leiomyoma. JSLS. 2004;8(1):77–80. 154. Soufi MA, Errougani, Chekkof RM. Primary gastric leiomyosarcoma in young revealed by a massive hematemesis. J Gastrointest Cancer. 2009;40(1-2):69–72. 155. Scott SM, Reiman HM, Pritchard DJ, et al. Soft tissue fibrosarcoma. A clinicopathologic study of 132 cases. Cancer. 1989;64(4):925–931. 156. Song B, Kim B, Choi SH, et al. Mesenchymal stromal cells promote tumor progression in fibrosarcoma and gastric cancer cells. Korean J Pathol. 2014;48(3):217–224. 157. Meis-Kindblom JM, Kindblom LG. Angiosarcoma of soft tissue: a study of 80 cases. Am J Surg Pathol. 1998;22(6):683–697. 158. Pavelic K, Glunčić V, Pavičić D, et al. The expression and role of insulin-like growth factor II in malignant hemangiopericytomas. J Mol Med (Berl). 1999;77(12):865–869. 159. Biswas D, Marnane CN, Mal R, et al. Extracranial head and neck schwannomas—a 10-year review. Auris Nasus Larynx. 2007;34(3):353–359. 160. Hashim D, Apostolova M, Lavotskin S, et al. The evolution in the management of gastric lymphoma. Gastroenterology Res. 2009;2(5):253–258. 161. Burke JS. Lymphoproliferative disorders of the gastrointestinal tract: a review and pragmatic guide to diagnosis. Arch Pathol Lab Med. 2011;135(10):1283–1297.

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PERSPECTIVE ON GASTRIC CANCER Hisashi Shinohara • Mitsuru Sasako

THEORETICAL BACKGROUND FOR D2 GASTRECTOMY Gastric cancer remains a major health problem in East Asia. In contrast, in the United States and Western Europe, the incidence of gastric cancer has declined but is often diagnosed at an advanced stage. Thus, the number of operations that a surgeon performs annually varies according to region, so it is not easy to define which type of gastric cancer surgery should be considered the global standard. Nevertheless, a consensus that D2 dissection is the most appropriate way to treat resectable advanced gastric cancer has been reached based on the results of long-term follow-up of the Dutch D1 versus D2 trial1 and the Japan Clinical Oncology Group (JCOG) 9501 study,2 which confirmed no survival benefit with more extensive lymphadenectomy. Radical surgery for gastrointestinal cancer focused on en bloc removal of the primary tumor along with lymphovascular drainage by excising organspecific mesenteries. This general concept is widely accepted in colorectal cancer surgery and is realized as total mesorectal excision (TME) or complete

mesocolic excision (CME).3,4 D2 gastrectomy entails systematic dissection of all the nodes along the celiac axis (CA) and its named branches as well as the perigastric nodes. Based on embryologic principles, D2 gastrectomy is essentially a realization of mesentery-based surgery despite the anatomic restrictions inherent to the mesogastrium.5

UNIQUE ANATOMIC STRUCTURE OF THE MESOGASTRIUM The basic technique of lymph node dissection is common for all gastrointestinal cancers. However, because of the high incidence of tumor deposits in the adipose tissue and significant tendency of developing peritoneal metastasis in gastric cancer, dissection without destroying the intact fascial package surrounding the fatty tissue where all nodes and tumor deposits are imbedded is of paramount importance.6 To perform a proper lymph node dissection of the stomach, an understanding of the unique anatomic structure of the mesogastrium is essential. The stomach has 2 mesenteries: the dorsal mesogastrium and the ventral mesogastrium. During the rotation of the intestinal system, the ventral mesogastrium becomes the lesser omentum and the dorsal mesogastrium becomes the greater omentum. The mesoduodenum and the transverse mesocolon are eventually overlaid by the greater omentum. The dorsal pancreas arises from the duodenal wall, grows into the mesoduodenum, and eventually extends into the dorsal mesogastrium. The anterior surface of the mesoduodenum is then overlaid by the proper transverse mesocolon and the greater omentum. These fetal events produce certain anatomic restrictions to conduct mesentery-based gastric cancer surgery. From the viewpoint of mesenteric structures, however, it is important to recognize that regional lymph node stations can be embedded in the dorsal or ventral mesogastrium, as shown in Figure 32-1A.

FIGURE 32-1. A. Development of omentum, mesogastrium, and mesoduodenum. Numbers in circles indicate lymph node stations according to the Japanese classification of gastric carcinoma. Blue nodes belong to the ventral mesogastrium, green nodes to dorsal mesogastrium, and yellow nodes

to mesoduodenum. B. The simplified mesogastrium whose embryonic concrescences were restored. The gastric mesentery can be divided into 3 sectors: the root (R), intermediate (I), and perigastric (P) sectors. C. D2 lymphadenectomy based on mesogastric excision concept by resection of the mesogastrium while excluding the pancreas and major branches of the celiac axis (CA). ASPDA, anterior superior pancreatoduodenal artery; CHA, common hepatic artery; DP, dorsal pancreas; GDA, gastroduodenal artery; IPA, infrapyloric artery; LGA, left gastric artery; LGEA, left gastroepiploic artery; PGA, posterior gastric artery; PHA, proper hepatic artery; SGA, short gastric artery; SMA, superior mesenteric artery; SPA, splenic artery; RGA, right gastric artery; TM, transverse mesocolon; VP, ventral pancreas.

D2 DISSECTION BASED ON MESOGASTRIC EXCISION CONCEPT The simplified mesogastrium after restoration of embryonic concrescences is shown in Figure 32-1B. The dorsal mesogastrium can be divided into 3 sectors: the root, intermediate, and perigastric sectors. Station no. 9 surrounding the CA would be equivalent to the root sector of the whole gastric mesentery. The intermediate sector, which envelopes the pancreas, would include nodes along the left gastric artery (no. 7), common hepatic artery (no. 8), splenic hilum (no. 10), and splenic artery (no. 11). The perigastric sector would include nodes situated at the right (no. 1) and left cardia (no. 2) and lesser (no. 3a) and greater curvature (no. 4). The no. 6 infrapyloric station lies within the mesoduodenum beyond the boundary of the mesogastrium. The remaining few stations, that is, nos. 3b and 5, along the right gastric artery, and 12, along the proper hepatic artery, are originally included in the ventral mesogastrium. The dissection of N2 nodes by “complete” mesogastric excision with central vascular ligation like CME is disturbed by the presence of the pancreas and some branches arising from the CA. Ligation of the CA in radical gastrectomy is anatomically possible since the blood supply to the liver is secured in most cases by the pancreatoduodenal arcades from the superior mesenteric artery. However, by preserving the gastroduodenal artery, even Appleby’s operation cannot realize complete mesogastric excision. Further, the division of the CA entails combined

splenopancreatectomy even when the organs are not directly invaded. Instead, as shown in Figure 32-1C, D2 gastric cancer surgery should aim at systematic mesogastric excision, that is, en bloc excision of the mesogastrium while excluding the pancreas and its associated vessels.5 This concept is expected to aid the universalization of the operative strategy for gastric cancer, as is currently the case for TME and CME in colorectal cancer.

PRACTICAL MODIFICATIONS OF D2 GASTRECTOMY Prognostic relevance of other components of the standard D2 dissection such as combined splenectomy in case of cancer of the upper third stomach (JCOG 0110) and bursectomy (JCOG 1001) has more recently been addressed by randomized phase III trials. In the past, when most of gastric cancers were large and accompanied by large nodal metastasis surrounding the left gastric, splenic, and celiac arteries, en bloc resection of the entire tumor required the combined resection of the pancreatic tail with the spleen. This procedure, which had been carried out for prophylactic dissection of the splenic artery and hilar lymph nodes, was abandoned because of the higher mortality and morbidity with limited survival benefit compared with pancreas-preserving total gastrectomy.7 Now, such extended surgery is used only for T4b tumors invading the pancreas or splenic vessels. JCOG 0110, a randomized controlled trial comparing a total gastrectomy with or without splenectomy for advanced gastric cancers not involving the greater curvature, proved the noninferiority of spleen preservation for such tumors,8 while 2 other small sized trials did not show any statistically reliable results.9,10 To carry out a D2 dissection without splenectomy, meticulous dissection along the splenic vessels is needed. For safe dissection of this area, accurate knowledge of the basic anatomy and its variations is essential. The branch-off point of the posterior gastric artery varies widely; it is sometimes at 3 to 4 cm from the root of the splenic artery and sometimes close to the splenic hilum. We should know that the upper pole artery to the spleen sometimes has a common trunk with the posterior gastric artery, which should be divided not at the root of the common trunk but at the branching off from the upper pole artery. There are 3 or 4 short gastric arteries, each of which tracks ventrally from the final branches of the splenic artery into the splenic parenchyma. The

left gastroepiploic artery is usually the most caudal branch of the splenic artery. Often, it has a common trunk with the inferior pole branch to the spleen. As demonstrated in Figure 32-2A, all nodes are included in the dorsal mesogastrium that expanded into the upper abdomen to form the omental bursa. The role of bursectomy dissecting the peritoneal lining covering the pancreas and the anterior layer of the transverse mesocolon for preventing peritoneal metastasis had long been controversial. However, a phase III trial (JCOG 1001) failed to demonstrate a significant role of bursectomy in survival of patients with T3/T4 gastric cancer.11

FIGURE 32-2. A. Sagittal transaction near the root of the splenic artery and 3-dimensional scheme of the structures left lateral to the transection. All lymph nodes along the splenic vessels and posterior gastric vessels and in the splenic hilum are included in the dorsal mesogastrium that was expanded into the upper abdomen to form the omental bursa. Numbers in circles indicate lymph node stations according to the Japanese classification. Ao, aorta; LGEA, left gastroepiploic artery; LRV, left renal vein; PEA, posterior epiploic artery; PGA, posterior gastric artery; SPA, splenic artery. B. Sagittal transactional scheme near the origin of the right gastroepiploic vessels. Anatomic structures of the greater omentum, transverse colon and mesocolon, pancreas head, and duodenum are shown with vessels surrounding the organs. The ventral mesoduodenum includes the supraduodenal vessels, and the dorsal mesoduodenum includes infrapyloric vessels. The origins of the dorsal mesoduodenum and mesogastrium share the common root that joins with the right gastroepiploic vein (RGEV), the anterosuperior pancreatoduodenal vein (ASPDV), and the accessory right colic vein (ARCV), making Henle’s common trunk. GDA, gastroduodenal artery; IPA, infrapyloric artery; PV, portal vein; RGEA, right gastroepiploic artery; SDA, supraduodenal artery; SMV, superior mesenteric vein.

The last part of the antrum (4-6 cm) and the first portion the duodenum (duodenal bulb) are dually supplied by the infrapyloric vessels in the dorsal mesoduodenum12 and by the supraduodenal vessels in the ventral mesoduodenum (Fig. 32-2B). To treat an antral cancer, proper dissection of both the mesogastrium and the mesoduodenum is essential. The incidence of metastasis to the infrapyloric node station is nearly 50% for distal cancers of T2 or more, and more than 40% of those having such metastasis will survive more than 5 years after proper D2 dissection.13

THE PLACE OF LAPAROSCOPIC AND ROBOTIC SURGERY Reflecting the result from the JCOG 0703 phase II study that explored the feasibility of the laparoscopic distal gastrectomy for stage I gastric cancer, the Japanese Guidelines for the Treatment of Gastric Cancer revised the position of laparoscopic distal gastrectomy for stage I gastric cancer in 2014 from a promising but experimental treatment to a valid option in daily clinical practice.14 Thereafter, surgeons in East Asia have proceeded to conduct large

randomized controlled trials comparing open versus laparoscopic surgery and have gradually extended the indication to more advanced cancers.15,16 In many respects, however, laparoscopic surgery has limitations, including lack of tactile sensation; difficulty in widely spreading out the membranes, which is essential for proper D2 dissection; and longer learning curve. Considering the high tendency to develop peritoneal metastasis and extranodal metastasis in the adipose tissue,6 application of laparoscopic surgery for T3/4 tumors should be carefully considered until noninferiority of this approach to open surgery is proven. The recent development of surgical robotics represented by the da Vinci System may have overcome several shortcomings inherent to the laparoscopic approach. This system has advantages compared with conventional laparoscopic surgery systems, such as the EndoWrist, including additional degrees of freedom, elimination of the fulcrum effect, and highresolution 3-dimensional images that can be magnified and reduce human tremor. Decrease in the incidence of surgical complications when compared with laparoscopic surgery has been reported from a leading Japanese institution.17 However, a nonrandomized prospective study that compared robotic surgery with laparoscopic surgery in Korea has shown morbidity to be extremely low in both approaches, but the robotic surgery required a longer operating time and was significantly more expensive.18 Another retrospective comparison of robot-assisted and laparoscopy-assisted pyloruspreserving gastrectomy also demonstrated no benefit of robotic over laparoscopic surgery.19 Given the shorter learning curve for acquisition of relevant surgical skills,20 easier access to robotic surgery and more frequent opportunities for training will be indispensable for the future progress of this promising modality.

REFERENCES 1. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1 D2 trial. Lancet Oncol. 2010;19:439-449. 2. Sasako M, Sano T, Yamamoto S, et al. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008;359:453-462. 3. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1:1479-1482. 4. Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation: technical notes and outcome. Colorect Dis. 2009;11:354-364.

5. Shinohara H, Kurahashi Y, Haruta S, et al. Universalization of the operative strategy by systematic mesogastric excision for stomach cancer with that for TME and CME colorectal counterparts. Ann Gastroenterol Surg. Epub [DOI: 10.1002/ags3.12048] 6. Etoh T, Sasako M., Ishikawa K., et al. Extranodal metastasis is an indicator of poor prognosis in patients with gastric cancer. Br J Surg. 2006;93:369-373. 7. Bonenkamp JJ, Hermans J, Sasako M, et al. Extended lymph node dissection for gastric cancer. N Engl J Med. 1999;340:908-914. 8. Sano T, Sasako M, Mizusawa J, et al. Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma (JCOG0110). Ann Surg. 2017;265:277-283. 9. Csendes A, Burdiles P, Rojas J, et al. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 817 patients with gastric carcinoma. Surgery. 2001;131:401-407. 10. Yu WS, Choi GS, Chung HY. Randomized clinical trial of splenectomy versus splenic preservation in patients with proximal gastric cancer. Br J Surg. 2006;93:559-563. 11. Terashima M, Doki Y, Kurokawa Y, et al. Primary results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001). J Clin Oncol. 2017;35(Suppl):5. 12. Sasako M, McCulloch P, Kinoshita T, et al. New method to evaluate the therapeutic value of lymph node dissection for gastric cancer. Br J Surg. 1995;82:346-351. 13. Haruta S, Shinohara H, Ueno M, et al. Anatomical considerations of the infrapyloric artery and its associated lymph nodes during laparoscopic gastric cancer surgery. Gastric Cancer. 2015;18:876880. 14. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113-123. 15. Hur H, Lee HY, Lee HJ, et al. Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized controlled clinical trial. BMC Cancer. 2015;15:335-362. 16. Hu Y, Huang C, Sun Y, et al. Morbidity and mortality of laparoscopic versus open D2 distal gastrectomy for advanced gastric cancer: a randomized controlled trial. J Clin Oncol. 2016;34:1350-1357. 17. Suda K, Man-I M, Ishida Y, Kawamura Y, Satoh S, Uyama I. Potential advantages of robotic radical gastrectomy for gastric adenocarcinoma in comparison with conventional laparoscopic approach: a single institutional retrospective comparative study. Surg Endosc. 2015;29:673-685. 18. Kim HI, Han SU, Yang HK, et al. Multicenter prospective comparative study of robotic versus laparoscopic gastrectomy for gastric adenocarcinoma. Ann Surg. 2016;263:103-109. 19. Han DS, Suh YS, Ahn HS, et al. Comparison of surgical outcomes of robot-assisted and laparoscopy assisted pylorus preserving gastrectomy for gastric cancer: a propensity score matching analysis. Ann Surg Oncol. 2015;22:2323-2328. 20. Zhou J, Shi Y, Qian F, et al. Cumulative summation analysis of learning curve for robot-assisted gastrectomy in gastric cancer. J Surg Oncol. 2015;111:760-767.

GASTROINTESTINAL STROMAL TUMORS Nicole J. Look Hong • Chandrajit P. Raut

INTRODUCTION Gastrointestinal stromal tumors (GISTs) are rare neoplasms. Although they represent only 0.1% to 3% of all gastrointestinal malignancies,1–4 they account for 80% of gastrointestinal mesenchymal neoplasms.5 Approximately 5000 to 6000 new cases are diagnosed per year in the United States, for an annual incidence of 14.5 per million and prevalence of 129 per million.6 In the last 15 years, the understanding and treatment of GIST has witnessed remarkable advances due to two key developments: (1) the identification of constitutively active signals (oncogenic mutation of the c-KIT and plateletderived growth factor alpha [PDGFRA] gene-encoding receptor tyrosine kinases) and (2) the development of therapeutic agents that suppress tumor growth by specifically targeting and inhibiting these signals. These developments in the management of GIST illustrate the principle of translational therapeutics in oncology, confirming that specific inhibition of tumor-associated receptor tyrosine kinase activity is an effective cancer treatment. The advent of effective targeted medical therapy for GIST has

increased the complexity of management and opened new dialogues regarding the need for integrated multimodality therapy. This chapter reviews the biology, treatment, and emerging clinical challenges of these mesenchymal neoplasms.

PATHOLOGIC FEATURES Historical Background The term “GIST” was initially coined in 1983 by Mazur and Clark to describe intra-abdominal nonepithelial neoplasms which lacked the ultrastructural features of smooth muscle cells and the immunohistochemical characteristics of Schwann cells.7 GISTs typically exhibit heterogeneous histologic features. They are most commonly composed of long fascicles of spindle cells with pale to eosinophilic cytoplasm and rare nuclear pleomorphism, but may occasionally exhibit epithelioid characteristics, including sheets of round- to oval-shaped cells with abundant eosinophilic cytoplasm and nuclear atypia (Fig. 33-1). As such, they are typically classified as spindle cell type, epithelioid type, or mixed type. The majority of GISTs are of spindle cell appearance (70%), while epithelioid (20%) and mixed (10%) cell morphology are less common.

FIGURE 33-1 GIST histology. Staining of tumor paraffin sections with hematoxylin and eosin (H&E) reveals three patterns of GIST histology: (A) spindle cell, (B) mixed cell, and (C) epithelioid cell type. In 1995, Miettinen and colleagues discovered that 70% of GISTs were positive for CD34 by immunohistochemistry, a myeloid progenitor cell

antigen also present in endothelial cells and fibroblasts.8 Based upon their histologic features, GISTs are believed to arise from the interstitial cells of Cajal, components of the intestinal autonomic nervous system that serve as intestinal pacemakers and also express CD34.9 Nonetheless, until the late 1990s, there were no objective criteria to classify GISTs. They were frequently misclassified as leiomyomas, leiomyoblastomas, leiomyosarcomas, Schwannomas, gastrointestinal autonomic nerve tumors, or other similar soft tissue histologies.10 Consequently, interpretation of clinical results for reports on “GISTs” published before 2000 is challenging.

Receptor Tyrosine Kinase Mutations In a landmark publication in 1998, Hirota and colleagues reported two critical findings: (1) near-universal expression of the transmembrane receptor tyrosine kinase KIT in GISTs and (2) presence of gain-of-function mutations in the corresponding c-KIT proto-oncogene.11 The KIT receptor is activated by binding its cytokine ligand, known as steel factor or stem cell factor,12 which then causes receptor homodimerization, phosphorylation, and cellular proliferation. KIT plays a critical role in the development and maintenance of components of hematopoiesis, gametogenesis, and intestinal pacemaker cells.13–15 Oncogenic KIT mutations have been identified as molecular drivers of neoplasms corresponding to these functions, including mast cell tumors, myelofibrosis, chronic myelogenous leukemia, germ cell tumors, and GIST.13 Mutated KIT remains constitutively active even in the absence of ligand binding and results in both unregulated cell growth and malignant transformation.11 GISTs are identified by immunohistochemical staining for the CD117 antigen, part of the KIT receptor (Fig. 33-2). CD117 expression is characteristic of most GISTs, but not of other gastrointestinal smooth muscle tumors such as leiomyosarcoma, which are more likely to express high levels of desmin and smooth muscle actin.13–16 Application of CD117 staining as a diagnostic criterion for GIST has heightened understanding of disease prevalence but is an imperfect isolated surrogate for GIST diagnosis. Some GISTs may stain strongly for KIT (CD117) by immunohistochemistry (KITpositive) yet lack KIT mutations,13 while others that do not stain for KIT (KIT-negative) may nevertheless harbor KIT mutations.17

FIGURE 33-2 Immunohistochemistry to detect c-KIT expression. Immunohistochemistry to detect expression of KIT (CD117) is present in approximately 95% of GIST and varies among tumors from predominantly cytoplasmic (left), to perinuclear and dot-like (right). Variable expression within a given tumor also occurs (right). Over 85% of GISTs have activating KIT mutations (Fig. 33-3).13 These mutations commonly occur in exon 11 (in 57% to 71% of cases), exon 9 (10% to 18%), exon 13 (1% to 4%), and exon 17 (1% to 4%).18–21 GISTs with KIT exon 9 mutations predominantly arise in the small intestine, and homozygous mutant GISTs are often associated with recurrent disease. Mutations in exon 11 may include deletions, insertions, single-base substitutions, and various combinations of these and are associated with variable rates of disease recurrence following complete resection.22–25 Deletion mutations in exon 11 are an independent adverse prognostic factor, with worse prognosis than those with point mutations.26–28 Deletions specifically involving codon 557 and 558 are considered mutational “hotspots” and are associated with more aggressive and often metastatic behavior.29–30

FIGURE 33-3 KIT and PDGFRA mutations in GIST. KIT and PDGFRA mutations in GIST produce constitutive ligand-independent receptor activation. Response to tyrosine kinase inhibitors correlates with the location of the activating mutation, with best response in patients whose tumors contain mutations in KIT exon 11. Approximately 35% of neoplasms lacking KIT mutations have activating mutations in a gene encoding a related receptor tyrosine kinase, the plateletderived growth factor receptor alpha (PDGFRA).31–33 PDGFRA mutations have been identified in exon 12 (1% to 2% of GISTs), exon 18 (2% to 6%), and exon 14 (2 cm, irregular extraluminal borders, ulceration, heterogenous echogenic foci, presence of cystic spaces, and/or development of symptoms should prompt reconsideration of the management strategy.96 European Society for Medical Oncology (ESMO) guidelines recommend annual surveillance with EUS for presumed 10/50 HPF, tumor size >5 cm with mitotic rate >5/HPF, or tumor rupture. With a median duration of follow-up of 54 months, patients treated with 36 months of imatinib had a

significantly longer 5-year RFS compared to 12 months of treatment (66% vs 48%, p 27 with related comorbidities and is being increasingly used in patients with inadequate weight loss or weight regain after bariatric surgery. These mediations can help increase compliance with low-calorie diets by suppressing hunger and increasing satiety. Table 36-5 provides a summary of current FDA-approved agents.15,17 Usual practice is to try a medication for 3 months and, if significant weight loss is not seen, discontinue and try an alternative. TABLE 36-5: FDA-APPROVED DRUGS FOR WEIGHT MANAGEMENT

Phentermine was introduced in 1959 and became part of the drug combination “fen-phen” that was ultimately withdrawn from the market in

1997 due to the heart valve disease caused by the fenfluramine component of the formulation. Phentermine is approved for short-term use (3 months), with most weight loss being observed in the first few weeks. Orlistat was the only FDA-approved weight loss medication until 2012, but its gastrointestinal side effects limited tolerability in many patients. However, in patients with obesity and baseline constipation, it can be an attractive option.18 Lorcaserin, at the recommended dose, is a selective 5-HT2c receptor agonist that is thought to reduce food intake and increase satiety by selectively activating these receptors on anorexigenic proopiomelanocortin (POMC) neurons in the hypothalamus. Activation of other serotonin receptors, specially 5-HT2a and 5-HT2B, can lead to the side effects associated with the drug, including hallucinations and possible heart valve disease.19 Phentermine-topiramate is another combination drug containing phentermine. The other ingredient, topiramate, was originally approved for migraine and epilepsy but was also noted to reduce food intake.20 Bupropion slow release (SR)-naltrexone SR is another combination drug containing 2 agents that have been on the market for many years but for different indications: bupropion for depression and naltrexone for opiate dependency and alcohol addiction. The drugs work in a synergistic fashion to release hypothalamic release of α-melanocyte–stimulating hormone, a potent anorectic neuropeptide.21 Liraglutide was approved in 2010 for the treatment of type 2 diabetes but was also found to cause weight loss in a dose-dependent manner. This led to the approval of the drug at a higher dose of 3.0 mg for management of obesity. The drug is administered as a daily subcutaneous injection, starting at a low dose with weekly dose escalation.22

Endoluminal Therapies and Alternative Devices To address the need of many in whom diet, lifestyle modifications, and/or medications have been unsuccessful in achieving meaningful weight loss, gastrointestinal innovators have developed many endoscopic devices with the goal of achieving greater weight loss while avoiding the uneasiness of surgery.

Table 36-6 provides an overview of the FDA-approved endoluminal devices.15 Intragastric balloons, the most commonly used devices, have a long history that dates back to the Garren-Edwards bubble, which was approved by the FDA in 1985 but subsequently withdrawn from the market in 1988 due to increasing rates of complications. Over the subsequent years, balloon designs have evolved with improved safety and efficacy. There are currently 3 different FDA-approved intragastric balloons for patients with BMI of 30 to 40; duration of use is 6 months, after which they need to be removed. The Orbera and ReShape balloons are endoscopically placed and removed, whereas the Obalon system, which consists of 3 smaller balloons placed at 2-week intervals using fluoroscopy, only requires an endoscopy for removal. Main side effects are gastrointestinal related and include nausea, vomiting, abdominal pain, reflux, and burping. Serious adverse events related to the balloon have also been reported. Balloons, especially those not removed on time, can rupture with balloon migration and possible bowel obstruction.23,24 With increasing utilization of the balloons, cases of spontaneous overdistention and acute pancreatitis have also been reported, and an FDA warning was recently issued. Regaining of lost weight is a common problem in patients after balloon removal, although some studies have suggested that with continued diet and exercise, some weight loss can be maintained for up to 5 years after removal.25 TABLE 36-6: FDA-APPROVED ENDOLUMINAL DEVICES FOR MANAGEMENT OF OBESITY

The Aspire Assist device consists of a gastrostomy tube (A-tube) attached to a port, which is used to aspirate gastric contents 20 to 30 minutes after

eating a meal. The device is approved for patients with BMIs up to 55 and can be used long-term.26 Some believe the device may have a role as a bridge to a more definitive weight loss intervention, by helping patients with high BMI achieve significant preoperative weight loss. Main side effects include abdominal pain, nausea and vomiting, tube blockage, granulation and irritation at the tube site, and risk of gastrocutaneous fistula after tube removal. Endoscopic sleeve gastroplasty is an endoscopic procedure in which a sleeve-like gastric conduit in a created, similar to a sleeve gastrectomy. A series of endoscopic full-thickness sutures are placed endoscopically using a commercially available suturing device (Overstitch; Apollo Endosurgery) to create a narrowed gastric conduit with reduced gastric volume. Several serious adverse events have been reported with this procedure, including perigastric collections requiring interventional radiology drainage and selflimited splenic hemorrhage.15 Another FDA-approved obesity device is the VBLOC system. Unlike the procedures summarized in Table 36-6, this device is placed laparoscopically under general anesthesia as an outpatient surgical procedure. The system consists of a subcutaneously placed neuromodulator, connected via 2 electrodes placed laparoscopically around the anterior and posterior vagal trunks. Several studies have shown an 8% to 10% total body weight loss with this procedure, which was superior to controls.27 The device received FDA approval in 2015 for patients with a BMI of 35 to 45 with at least 1 other obesity-related condition, such as type 2 diabetes. The serious adverse event rate with the device is low and reported at or = 50 kg/m2) compared with gastric bypass. J Gastrointest Surg. 2010;14:211-220. 75. Roslin MS, Oren JH, Polan BN, et al. Abnormal glucose tolerance testing after gastric bypass.

Surg Obes Rel Dis. 2013;9:26-31. 76. Slater G, Ren CJ, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg. 2004;8:48-55. 77. Sethi M, Chau E, Youn A, et al. Long-term outcomes after biliopancreatic diversion with and without duodenal switch: 2-, 5-, and 10-year data. Surg Obes Rel Dis. 2016;12:1697-1705. 78. Rutledge R. The mini-gastric bypass: experience with the first 1,274 cases. Obes Surg. 2001;11:276-280. 79. Johnson WH, Fernandez AZ, Farrell, et al. Surgical revision of loop (“mini”) gastric bypass procedure: multicenter review of complications and conversions to Roux-en-Y gastric bypass. Surg Obes Rel Dis. 2007;3:37-41. 80. Lee WJ, Ser KH, Lee YC, et al. Laparoscopic Roux-en-Y vs. mini-gastric bypass or the treatment of severe obesity: a 10-year experience. Obes Surg. 2012;22:1827-1834. 81. Musella A, Susa A, Greco F, et al. The laparoscopic mini-gastric-bypass: the Italian Rexperience: outcomes from 974 consecutive cases in a multicenter review. Surg Endosc. 2014;28:156-163. 82. Bruzzi M, Rau C, Voron T et al. Single anastomosis or mini-gastric bypass: long-term results and quality of life after a 5-year follow-up. Surg Obes Rel Dis. 2015;11:321-326. 83. Chevalier JM, Arman JM, Guenzi M, et al. One thousand single anastomosis (omega loop) gastric bypasses to treat morbid obesity in a 7-year period: outcomes show few complications and good efficacy. Obes Surg. 2015;25:951-958. 84. Altieri MS, Yang J, Telem DA, et al. Lap band outcomes from 19,221 patients across centers and over a decade within the state of New York Surg Endosc. 2016;30:1725-1732. 85. Schneck AS, Lazzati A, Audureau E, et al. One or two steps for laparoscopic conversion of failed adjustable gastric banding to sleeve gastrectomy: a nationwide French study on 3357 morbidly obese patients. Surg Obes Rel Dis. 2016;12:840-848. 86. Stroh C, Weiner R, Wolff S, et al. Revisional surgery and reoperations in obesity and metabolic surgery: data analysis of the German bariatric surgery registry 2005-2012. Chirurg. 2015;86:346554. 87. Aminian A, Shoar S, Khorgami Z, et al. Safety of one-step conversion of gastric band to sleeve: a comparative analysis of ACS-NSQIP data. Surg Obes Rel Dis. 2015;11:386-391. 88. Worni M, Ostbye T, Shah A, et al. High risks for adverse outcomes after gastric bypass surgery following failed gastric banding: a population-based trend analysis of the United States. Ann Surg. 2013;257:279-86. 89. Elnahas A, Graybiel K, Farrokhyar F, et al. Revisional surgery after failed laparoscopic adjustable gastric banding: a systematic review. Surg Endosc. 2013;27:740-745. 90. Kellum JM, Chikunguwo SM, Maher JW, et al. Long-term results of malabsorptive distal Rouxen-Y gastric bypass in superobese patients. Surg Obes Rel Dis. 2011;7:189-193. 91. Thompson CC, Slattery J, Bundga ME, et al. Peroral endoscopic reduction of gastrojejunal anastomosis after Roux-en-Y gastric bypass: a possible new option for patients with weight regain. Surg Endosc. 2006;20:1744-1748. 92. Thompson CC, Chand B, Chen YK, et al. Endoscopic suturing for transoral outlet reduction increases weight loss after Roux-en-Y gastric bypass surgery. Gastroenterology. 2013;145:129137. 93. Kumar N, Thompson CC. Transoral outlet reduction for weight regain after gastric bypass: longterm follow-up. Gastrointest Endosc. 2016;83: 10-17. 94. Mikami D, Needleman B, Narula V, et al. Natural orifice surgery: initial U.S. experience utilizing the StomaphyX to reduce gastric pouches after Roux-en-Y gastric bypass. Surg Endosc. 2010;24:233-238. 95. Heneghan HM, Annaberdyev S, Eldar S, et al. Banded Roux-en-Y gastric bypass for the treatment of morbid obesity. Surg Obes Rel Dis. 2014;10:210-216.

96. Bessler M, Daud A, DiGiorgi MF, et al. Adjustable gastric banding as revisional bariatric procedure after failed gastric bypass—intermediate results. Surg Obes Rel Dis. 2010;6:31-35. 97. Barkin JS, Reiner DK, Goldberg RI, et al. The effects of morbid obesity and the Garren-Edwards gastric bubble on solid phase gastric emptying. Am J Gastroenterol. 1988;83:1364-1367. 98. Hogan RB, Johnston JH, Long BW, et al. A double-blind, randomized, sham-controlled trial of the gastric bubble for obesity. Gastrointest Endosc. 1989;35(3):381-385. 99. Kumar N, Bazerbachi F, Rustagi T, et al. The Influence of the Orbera Intragastric Balloon Filling Volumes on Weight Loss, Tolerability, and Adverse Events: a Systematic Review and MetaAnalysis. Obes Surg. 2017;27:2272-2278. 100. (https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140008b.pdf). 101. (https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140012b.pdf). 102. DePeppo F, Caccamo R, Adorisio O, et al. The Obalon swallowable intragastric balloon in pediatric and adolescent morbid obesity. Endosc Int Open. 2017;5:E59-63. 103. Kotzampassi K, Grosomanidis V, Papakostis P, et al. 500 intragastric balloons: what happens five years thereafter? Obes Surg. 2012;22:896-903. 104. Bazerbachi F, Vargas Valls EJ, Abu Dayyeh BK. Recent clinical results of endoscopic bariatric therapies as an obesity intervention. Clin Endosc. 2017;50(1):42-50. 105. ASGE Endoscopy Bariatric Task Force; ASGE Technology Committee Abu Dayyeh, BK, Edmundowicz SA, Jonnalagada S, et al. Endoscopic bariatric therapies. Gastrointest Endosc. 2015;81(5):1073-1086. 106. “Smart pill” reduces weight in overweight and obese subjects. ScienceDaily 2014. http://www.sciencedaily.com/releases/2014/06/140623141859.htm (accessed July 13, 2015). 107. Patel SR, Hakim D, Mason J, Hakim N. The duodenal-jejunal bypass sleeve (EndoBarrier Gastrointestinal Liner) for weight loss and treatment of type 2 diabetes. Surg Obes Rel Dis. 2013;9:482-484. 108. Thompson CC, Abu Dayyeh BK, Kushner R, et al. Percutaneous gastrostomy device for the treatment of class II and class III obesity: results of a randomized controlled trial. Am J Gastroenterol. 2017;112:447-457. 109. Lopez Nava G, Sharaiha RZ, Vargas EJ, et al. Endoscopic sleeve gastroplasty for obesity: a multicenter study of 248 patients with 24 months follow-up. Obes Surg. 2017;27:2649-2655. 110. Hamad GG, Ikramuddin S, Gourash WF, et al. Elective cholecystectomy during laparoscopic Roux-en-Y gastric bypass: is it worth the wait? Obes Surg. 2003;13:76-81. 111. Sharaf RN, Weinshel EH, Bini EJ, et al. Endoscopy plays an important preoperative role in bariatric surgery. Obes Surg. 2004;14:1367-1372. 112. Wolter S, Dupree A, Miro J, et al. Upper gastrointestinal endoscopy prior to bariatric surgery mandatory or expendable? An analysis of 801 cases. Obes Surg. 2017;27:938-943. 113. Parikh M, Liu J, Vieira D, et al. Preoperative endoscopy prior to bariatric surgery: a systematic review and meta-analysis of the literature. Obes Surg. 2016;26:2961-2966. 114. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222:339-352. 115. Sugerman HJ. Roux-en-Y gastric bypass. J Am Coll Surg. 2005;201: 824-825. 116. Evers SS, Sandoval DA, Seeley RJ. The physiology and molecular underpinnings of the effects of bariatric surgery on obesity and diabetes. Ann Rev Physiol. 2017;79:313-334. 117. O’Connor EA, Carlin AM. Lack of correlation between variation in small-volume gastric pouch size and weight loss after laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2008;4:399-403. 118. Rubino Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a nonobese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239:1-11.

119. Holst JJ. Postprandial insulin secretion after gastric bypass surgery: the role of glucagon-like peptide 1. Diabetes. 2011;60:2203-2205. 120. Ye J, Hao Z, Mumphrey MB, Townsend RL, et al. GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents. Am J Physiol Regul Integr Comp Physiol. 2014;306:R352-362. 121. Manning S, Pucci A, Batterham RL. GLP-1: a mediator of the beneficial metabolic effects of bariatric surgery? Physiology. 2015;30:50-62. 122. Gault VA, Kerr BD, Harriott P, Flatt PR. Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with type 2 diabetes and obesity. Clin Sci. 2011;121:107-117. 123. Challis BG, Pinnock SB, Coll AP, et al. Acute effects of PYY3–36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun. 2003;311:915-919. 124. Boey D, Lin S, Enriquez RF, et al. PYY transgenic mice are protected against diet-induced and genetic obesity. Neuropeptides. 2008;42:19-30. 125. Wynne K, Park AJ, Small CJ, et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes. 2005;54:2390-2395. 126. Bhutta HY, Deelman TE, Le Roux CW, et al. Intestinal sweetsensing pathways and metabolic changes after Roux-en-Y gastric bypass surgery. Am J Physiol Gastrointest Liver Physiol. 2014;307:G588-593. 127. Chambers AP, Jessen L, Ryan KK, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology. 2011;141:950-958. 128. Bojsen-Møller KN, Dirksen C, Jorgensen NB, et al. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass. Diabetes. 2014;63:1725-1737. 129. Zhou X, Qian B, Ji N, et al. Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes. J Endocrinol. 2016;228:13-23. 130. Li JV, Ashrafian H, Bueter M, et al. Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Gut. 2011;60:1214-1223. 131. Sweeney TE, Morton JM. The human gut microbiome: a review of the effect of obesity and surgically induced weight loss. JAMA Surg. 2013;148:563-569. 132. Liou AP, Paziuk M, Luevano JM Jr, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178ra41. 133. Tremaroli V, Karlsson F, Werling M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228-238. 134. Flynn CR, Albaugh VL, Cai S, et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun. 2015;6:7715. 135. Myronovych A, Kirby M, Ryan KK, et al. Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner. Obesity. 2014;22:390-400. 136. Kohli R, Myronovych A, Tan BK, et al. Bile acid signaling: mechanism for bariatric surgery, cure for NASH? Dig Dis. 2015;33:440-446.

INTESTINE AND COLON

SMALL BOWEL OBSTRUCTION Kristina L. Go • Janeen R. Jordan • George A. Sarosi, Jr. • Kevin E. Behrns

Bowel obstruction vexed medical practitioners as long ago as 350 BC, and it continues to do so today.1 The management of patients with bowel obstruction is challenging because decision-making is complicated in many patient care scenarios. First, the diagnosis of bowel obstruction may be difficult in a patient who recently underwent surgery. That is, does this lack of gastrointestinal function represent an ileus or a true bowel obstruction? Second, the timing of surgical intervention may not be obvious. When is an operation appropriate in a patient who underwent recent surgery? Finally, what is the appropriate operation in patients who have had multiple, chronic intestinal obstructions? All of these scenarios represent high-risk decisions, and thus management of bowel obstruction requires critical analysis and decision-making. The goal of this review is to provide a contemporary summary of the epidemiology, diagnosis, and management of bowel obstruction in a broad context of impaired gastrointestinal function.

DEFINITION

Bowel obstruction is defined by the lack of aborad transit of intestinal contents, regardless of etiology. Bowel obstruction may involve only the small intestine (small bowel obstruction), the large intestine (large bowel obstruction), or both via systemic alterations in metabolism, electrolyte balance, or neuroregulatory mechanisms (generalized ileus). Traditionally, the surgeon’s perspective of a bowel obstruction represents a mechanical obstruction that is due to physical stenosis or occlusion of the intestinal lumen. In the broader context, however, ineffective motility, without any physical obstruction, causes a functional obstruction or ileus of the intestine. Furthermore, intestinal obstruction can be classified based on duration of presence (acute vs chronic obstruction), extent (partial vs complete), type of obstruction (simple vs closed-loop), and risk of bowel compromise (incarcerated vs strangulated). Bowel obstruction continues to be one of the most common intraabdominal problems faced by general surgeons. In a 2010 global burden of disease study, bowel obstruction and ileus were responsible for 2.1 deaths, 54 years of life lost, and 54 disability-adjusted life-years per 100,000 population, respectively, second only to peptic ulcer disease for all abdominal conditions for each of these parameters.2 Independent of the underlying etiology, bowel obstruction remains a major cause of morbidity and mortality. Early recognition and aggressive treatment are crucial in preventing irreversible ischemia and transmural necrosis, thereby decreasing mortality and long-term morbidity. Despite multiple recent advances in diagnostic imaging and marked advances in our treatment armamentarium, intestinal obstruction will remain a significant surgical problem given the lack of treatment options to manage adhesions, hernias, and malignancies.

Mechanical Bowel Obstruction Mechanical bowel obstruction is defined as a physical narrowing or occlusion of the intestinal lumen. This blockage may be intrinsic or extrinsic to the wall of the intestine or secondary to luminal obstruction arising from intraluminal contents (eg, an intraluminal gallstone or other foreign body) (Table 38-1). Partial obstruction implies that the intestinal lumen is narrowed, and some intestinal content can transit distally. In the presence of a complete obstruction, the lumen is obliterated, and no intestinal content can pass beyond the point of obstruction. The risk of strangulation, that is, vascular

compromise of the intestine, increases markedly in the presence of a complete obstruction, especially when caused by an extraluminal etiology such as a hernia defect or an adhesive band compressing the small bowel mesentery. Accordingly, complete obstruction can be categorized further as simple, closed-loop, and strangulated obstruction. A simple obstruction has no associated vascular compromise, and the intestine can be decompressed proximally. Closed-loop obstruction occurs when both ends of the involved intestinal segment are obstructed (eg, volvulus or compressive adhesive bands), and results in increased intraluminal pressure secondary to increased intestinal secretion and accumulation of fluid in the involved intestinal segment. Closed-loop obstruction carries a substantial risk of vascular compromise and irreversible intestinal ischemia of the involved bowel, and thus requires emergent operative attention. Finally, strangulation occurs when the blood supply to the affected intestinal segment is compromised, leading to focal or segmental transmural necrosis. The affected segment may involve only a portion of the bowel wall compressed by a tight adhesive band or an entire intestinal segment as occurs with a strangulated hernia or a closed loop. If viability of the bowel is maintained after relief of the obstruction, strangulation can be reversed (reversible strangulation obstruction). In contrast, irreversible strangulation occurs if the vascular compromise has caused irreversible transmural necrosis whether or not the strangulation is relieved. All irreversible strangulated obstructions start as reversible strangulated obstructions, and thus early diagnosis is paramount to rescuing compromised intestine. TABLE 38-1: MECHANICAL BOWEL OBSTRUCTION

Functional Bowel Obstruction or Ileus Functional obstruction or ileus occurs when the bowel, small or large, fails to propel content distally in the absence of a mechanical obstruction. The pathophysiology of ileus involves electrolyte disturbances, impaired neuroregulatory innervation, imbalanced hormonal input, and other less common causes (Table 38-2). The most common form of functional bowel obstruction is postoperative ileus, because it is present to some extent after nearly all intra-abdominal operative procedures. Various types of extraabdominal medical and surgical conditions may also cause a transient functional ileus. Besides these more frequent forms of functional bowel obstruction caused by a response to local or systemic stimuli, there is a group of rare, chronic, progressive, gastrointestinal (GI) “pseudo-obstructions.” These rare forms of functional obstruction are related either to hereditary or acquired visceral myopathies, visceral neuropathies, or a poorly understood disruption of myoneural coordination of organized contractile activity. TABLE 38-2: FUNCTIONAL BOWEL OBSTRUCTION, ILEUS, AND PSEUDOOBSTRUCTION

Postoperative ileus represents the most common cause of delayed hospital discharge after abdominal operations. The duration of postoperative ileus may correlate with the degree of surgical trauma or the type of operation, and might even be considered a “physiologic” response. A prolonged “pathophysiologic” postoperative ileus may develop in patients operated on for radiation enteropathy, chronic obstruction, or severe peritonitis. Recovery from ileus after manipulation and local trauma differs among anatomic segments of the gastrointestinal tract. Generally, the small bowel recovers effective motor function within hours after an abdominal operation and, in fact, transient focal intestinal peristalsis is often visualized during an abdominal operation. In contrast, the stomach regains motor function 24 to 48 hours after an operation leading to delayed gastric emptying. The colon exhibits the slowest recovery response and may take 3 to 5 days to recover effective propulsive activity postoperatively.2 Differentiation of postoperative ileus from early postoperative mechanical bowel obstruction is important, because these anomalies are caused by different pathophysiologic mechanisms.3 In ileus, there is a prolonged inhibition of coordinated bowel activity that can take days or even weeks to resolve, depending on the etiology. The process of impaired postoperative peristaltic activity and coordinated aborad propulsion may be improved by the administration of alvimopan, a peripherally acting μ-opioid receptor antagonist, which has been shown to decrease the incidence of ileus and shorten hospital length of stay.3

Early Postoperative (Mechanical) Bowel Obstruction Early postoperative bowel obstruction is defined as bowel obstruction occurring within the first 6 weeks postoperatively. This type of intestinal obstruction represents a distinct clinical entity with a unique pathophysiology, and it should be differentiated from both the classic mechanical bowel obstruction as well as from postoperative ileus. The formation of acute adhesions is the responsible cause in over 90% of early postoperative bowel obstructions necessitating surgical management. Other causes include internal herniation, fascial herniation especially after laparoscopic surgery, intra-abdominal abscess, intramural intestinal hematoma, and anastomotic edema or leak. The differential diagnosis is

difficult as it may not be easy or possible to differentiate early postoperative mechanical obstruction from postoperative ileus. Nausea, vomiting, abdominal distention, and obstipation are themselves relatively common findings in the early postoperative period and are alone not distinguishing features of mechanical obstruction. Because the initial symptoms of early postoperative mechanical obstruction tend to be vague, patients are often considered to have ordinary postoperative ileus. Pain secondary to the recent incision, and masked by the use of narcotic analgesics, makes the physical examination often unreliable as well. Interpretation of imaging studies may be difficult, because early postoperative bowel obstruction and ileus can present with similar findings on plain abdominal radiographs. Computed tomography (CT) and contrast studies can help differentiate patients who can be treated conservatively from those who may need operative intervention, especially those with either a focal site of obstruction or the presence of dilated proximal and decompressed distal small bowel; the latter defines a mechanical etiology.4

EPIDEMIOLOGY In recent decades, the overall incidence of small bowel obstruction has been stable over time as noted by a study that examined the incidence from 1988 to 2007 when it ranged from 579 to 654 diagnoses for bowel obstruction per 100,000 population.5 The etiology of obstruction has not changed during the study period as adhesions remained the most common etiology.5 The etiology and frequency of obstruction, however, was altered markedly throughout the 20th century when repair of hernias became commonplace, and thus the etiology of bowel obstruction related to incarceration in a hernia defect decreased and was replaced by adhesive obstruction as the most common cause of bowel obstruction. In the underdeveloped world, however, bowel obstruction still manifests with a clinical picture resembling that found in the early 20th century in Western societies, with incarcerated hernias leading the list in frequency. The wider application of minimally invasive surgical procedures with fewer adhesions may decrease the frequency of bowel obstruction secondary to postoperative adhesions,6 particularly in cholecystectomies and hysterectomies. However, a review by Barmparas and colleagues7 concluded that while laparoscopic colectomies lowered incidence

of adhesions, this did not correlate to a lower incidence of adhesive small bowel obstruction. Nonetheless, access to improved surgical care in lower middle−income countries will change the etiology of bowel obstruction and improve care.8 Obstetric, gynecologic, and other pelvic surgical procedures represent important etiologies for the development of postoperative adhesions.9 Therefore, it is not surprising that a slightly greater frequency of bowel obstruction is observed in women. About 80% to 90% of bowel obstructions occur in the small intestine; the other 10% to 20% occur in the colon. Colorectal cancer is responsible for 60% to 70% of all large bowel obstructions, while diverticulitis and volvulus account for the majority of the remaining 30%. In contrast, small bowel obstruction is most commonly attributed to adhesions, abdominal wall hernias, or neoplasms in most advanced Western societies. Resources expended and costs incurred in the treatment of intestinal obstruction represent a substantive burden on the national health care system of any country. Surprisingly few contemporary data exist regarding the burden of costs for bowel obstruction over a large population regardless of etiology. Most studies are small, with less than 200 patients, and examine only one etiology of obstruction in a defined population. One dated study, however, estimated that adhesive bowel obstruction accounted for over 1 million days of inpatient care and $1.33 billion in health care expenditures in the United States in 1994.9 Indeed, it has been estimated that 1% of all hospitalizations, 3% of emergency surgical admissions to general hospitals, and 4% of major celiotomies (about 250,000) are undertaken because of bowel obstruction or procedures necessitating adhesiolysis.9 Another study showed that between 12% and 17% of patients who have undergone a total colectomy are admitted for small bowel obstruction within 2 years of their index operation, while approximately 3% will require an operation to treat an established small bowel obstruction. Bowel obstruction results in substantial overall mortality and morbidity. Depending on the clinical setting and the presence of related or unrelated comorbidities, mortality rates range from up to 3% for simple obstructions to as great as 30% when there is vascular compromise or perforation of the obstructed bowel. Further, bowel obstruction is frequently a recurrent problem, adding to the overall morbidity of an operation or even repetitive

successful nonoperative management. Recurrence rates vary according to method of management (conservative or operative). Intestinal obstruction recurs in about 12% of patients after a successful primary conservative treatment and in 8% to 32% of patients after operative management for adhesive bowel obstruction. Another study showed that while operatively treated patients had a decreased frequency of recurrence and a greater time interval to recurrence, they also had a greater hospital stay than patients treated conservatively. Also, there was no significant difference in incidence, type of treatment, or type of prior operative procedure among patients presenting with early or late small bowel obstruction. In this study, none of the analyzed variables were predictive of success of a particular treatment.10

PATHOPHYSIOLOGY Mechanical bowel obstruction results in numerous alterations of the normal intestinal physiology, including motility and absorption. The pathophysiology of bowel obstruction remains incompletely understood despite numerous investigations both clinically and experimentally. Bowel distension, decreased absorption, intraluminal hypersecretion, and alterations in motility are found universally, but the mechanisms mediating these relatively dramatic pathophysiologic derangements remain unclear. In addition, bowel obstruction is accompanied by considerable disruption of mechanisms of neural and hormonal control, the type and quantity of endogenous bacterial flora, and the innate immunity of the gut. The older, classic literature addressing the pathophysiology of bowel obstruction considered a decrease in blood flow as the sentinel event leading to most of the observed pathophysiologic changes. More recent experimental work, however, suggests that an increase in blood flow in association with an intense intramural inflammatory reaction and subsequent mucosal production of reactive oxygen species mediate many of the pathophysiologic changes observed in the early phase of bowel obstruction.11

Distension, Absorption, and Secretion Bowel distension is a characteristic, fundamental, and constant pathophysiologic response to mechanical bowel obstruction. Accumulation of

swallowed air is responsible for much of the small bowel distention in the early phases of obstruction. As would be expected, intraluminal gas consists of approximately 75% nitrogen in the obstructed bowel. Fermentation of sugars, production of carbon dioxide by interaction of gastric acid and bicarbonates from pancreatic and biliary secretions, and diffusion of oxygen and carbon dioxide from the blood are other sources of gas in early obstruction. Dilation and inflammation of the bowel wall cause accumulation of activated neutrophils and stimulation of resident macrophages within the muscular layer of the bowel wall, impairing secretory and motor processes by release of reactive proteolytic enzymes, cytokines, and other locally active substances. Local release of nitric oxide, a potent inhibitor of smooth muscle tone and contractility by the inflammatory response, aggravates intestinal dilation through inhibition of contractile activity. Notably, a correlation between the amount and activity of nitric oxide synthase, the enzyme responsible for nitric oxide synthesis, and the severity of intestinal dilation observed exists. Furthermore, experimental data demonstrate a relationship between distention and the intramural production of reactive oxygen metabolites. In addition to disrupting gut motility, these metabolites also modulate permeability of the vasculature and the gut mucosa. Along with the intraluminal accumulation of gas, the bowel also has a secondary decrease in net absorption resulting in the addition of water and electrolytes into the lumen during the first 12 hours of small bowel obstruction. By 24 hours, intraluminal water and electrolytes accumulate more rapidly because of a further decrease in absorptive flux; this decrease in net absorptive reflux occurs via stimulation of a concomitant increase in net intestinal secretion (secretory flux). These changes are caused by increased permeability due to secondary mucosal injury resulting in intraluminal leakage of plasma, electrolytes, and extracellular fluid. Whether associated neural or systemic humoral/hormonal mechanisms aggravate this upregulation of unidirectional secretory flux also remains likely but poorly investigated or explained. This net secretion of fluid into the lumen of the obstructed bowel is exacerbated further by the accumulation of intraluminal bacteria−derived toxins, bile acids, prostaglandins, vasoactive intestinal polypeptide, and mucosa-derived oxygen-free radicals. With a more chronic obstruction, bacterial proliferation occurs in the lumen, further disrupting absorption, secretion, and mucosal integrity. The decrease in the absorptive capacity and

increase in secretion lead to important fluid losses (enterosecretion) that may result in profound dehydration. Although the intestinal wall distal to the obstruction maintains relatively normal function, the inability of luminal content to reach the unobstructed small bowel and colonic absorptive surface is an important component of overall dehydration.

Intestinal Motility In an attempt to propel intraluminal contents past the obstruction, intestinal contractile activity increases in the early phase of bowel obstruction, probably in large part related to the intestinal distention. Later in the course of the bowel obstruction, however, contractile activity decreases likely secondary to a relative hypoxia of the intestinal wall and enhanced intramural inflammation. Although the exact mechanisms have not been described adequately, these responses may be similar to the changes found early after an abdominal operation, again related to inflammation of the intestinal wall.12,13 Some investigators14 have suggested that the alterations in intestinal motility are secondary to a disruption of the normal autonomic parasympathetic (vagal) and sympathetic splanchnic innervation, while others relate these changes more to a local effect of inflammation of the intestinal wall. Splanchnic innervation has been the focus of extensive research, and especially so in the pathogenesis of paralytic ileus. Chemical sympathectomy has been successful in ameliorating ileus in several experimental models. Other pharmacologic approaches have focused on blocking the neural inhibitory mechanisms affecting enteric neuromuscular coordination via sympatholytics and cholinergic agonists.15,16 Still other experimental approaches have been designed to prevent or inhibit the inflammatory response that accompanies the “physiologic” response to celiotomy or the abnormal inflammatory response accompanying generalized ileus. More recent investigative attention has been directed to impaired intestinal motility in the face of opioid administration postoperatively.17 The μ-receptor antagonist alvimopan appears to inhibit opioid-induced intestinal impairment and enhance motility.

Circulatory Changes

Bowel wall ischemia may occur through several mechanisms such as extrinsic compression of the mesenteric arcades by adhesions or an axial twist of the mesentery in a hernia defect. Alternatively, progressive distention in the presence of a closed-loop bowel obstruction without mesenteric axial torsion can cause vascular compromise or strangulation. Rarely, extensive mesenteric venous thrombosis leads to compromised arterial inflow and ischemia. During an obstruction, the large bowel obstruction is especially susceptible to vascular compromise and subsequent colonic distention because watershed areas of colonic perfusion represent end organ blood supply. Colonic ischemia is further exacerbated by bacterial proliferation and generation of luminal gas. Progressive distention of the bowel lumen with a concomitant increase in intraluminal pressure results in increased transmural pressure on capillary blood flow within the bowel wall. The possibility of intestinal wall ischemia presents a real concern in a closed-loop small bowel obstruction, especially in large bowel obstruction when the ileocecal valve is competent and the distended colon cannot decompress retrograde into the small bowel. The resultant increase in intraluminal pressure may compromise blood flow by exceeding venous pressure. This scenario occurs most commonly in the ascending colon where the luminal diameter and resulting wall tension are the greatest. This pathophysiology increases the urgency of treatment response for large bowel obstruction since vascular compromise may occur quickly. This type of bowel wall ischemia may lead to further disruption of intestinal absorption, a relative increase in net secretion, an unregulated increase in mucosal permeability, and intramural production of reactive oxygen species by activated resident and recruited leukocytes. These reactive oxygen species cause peroxidation of the lipid components of the cellular membrane, release of cytokines and other inflammatory mediators, and permit systemic toxicity. With strangulation of the blood supply, blood loss is exacerbated by infarcted bowel, which, together with the preexistent fluid loss, leads to more hemodynamic instability.

Microbiology and Bacterial Translocation The resident and transient flora of the upper small intestine consists mainly of gram-positive, facultative, anaerobic organisms in small concentrations, usually less than 106 colonies/mL. The bacterial count increases distally to

about 108 colonies/mL in the distal ileum. In addition to this increase in number of bacteria, a change of flora to primarily coliform and anaerobic organisms is apparent. In the presence of obstruction, however, a rapid proliferation of bacteria occurs proximal to the point of obstruction, consisting predominantly of fecal-type organisms. The proliferation of this fecal flora, proportional to the duration of obstruction, reaches a plateau of 109 to 1010 colonies/mL after 12 to 48 hours of an established obstruction. The bowel distal to the obstruction tends to maintain its usual bacterial flora until the onset of a generalized inflammatory-provoked ileus, resulting only then in bacterial proliferation distal to the point of obstruction. Bacterial toxins play an important role in the mucosal response to bowel obstruction. Experiments in germ-free dogs with mechanical bowel obstruction have shown that net intraluminal accumulation of fluid and electrolytes does not occur, and net absorption continues. Experiments, primarily in rodents, have shown that bacterial translocation occurs secondary to impairment of the barrier function of the intestinal mucosa if bowel obstruction persists. The disruption of the mucosal barrier begins early after the onset of bowel obstruction. The cellular response to obstruction is multifactorial. In the enterocyte, the endoplasmic reticulum dilates as early as 4 hours after onset of bowel obstruction. Mitochondrial swelling, focal epithelial necrosis, intracellular ballooning, and degenerative changes in the nucleus of epithelial cells (apoptosis) have been demonstrated as early as 6 to 12 hours after the onset of obstruction in this experimental model.18 The mucosal defense is compromised further by a decrease in perfusion of the intestinal wall. The loss of mucosal integrity allows luminal bacteria to both translocate as well as to invade the submucosa and enter the systemic circulation via the portal venous and lymphatic systems. Several bacterial substances can be retrieved from peritoneal fluid and lymphatic channels even in the absence of perforation. In the rodent model, bacteria can be cultured from the spleen, liver, and mesenteric lymph nodes, indicating a marked increase in bacterial translocation. Concomitant with bacterial translocation, lymph fluid contains numerous bacterial proteins and lipoproteins that further disrupt normal gut function. The demonstration of bacterial translocation in these elegant studies with rodent models led to the erroneous assumption of the existence of a similar bacterial translocation in humans. Reproducible documentation of true bacterial translocation in man is notably lacking, and existence of a true

bacterial translocation seems unlikely. Several studies have unsuccessfully tried to document the presence of bacteria in intra-abdominal lymph nodes, spleen, liver, and even lymphatics. In contrast, more recent work has shown that lipopolysaccharide and other inflammatory vasoregulatory mediators, but not bacteria, can be recovered from the mesenteric lymphatics. The eventual drainage of these inflammatory substances into the systemic circulation may lead both to the systemic manifestations of sepsis and further disruption of the mucosal barrier function. The change in the intraluminal bacteriology in simple intestinal obstruction is important clinically, because it markedly increases the risk of infectious complications, especially if an intestinal resection is required or if an inadvertent enterotomy occurs with intraperitoneal contaminated of highly inoculated, bacterial-laden enteric contents. In contrast, with irreversible strangulation obstruction, a myriad of local and systemic alterations, such as systemic entry of bacterial products, activation of immunocompetent cells, release of cytokines, and increased formation of reactive oxygen intermediate, can promote the systemic inflammatory response syndrome and progress to multiple organ dysfunction with all its consequences.

ETIOLOGY Adhesions Adhesions are inflammatory-derived, fibrous attachments of connective tissue that adhere to organ surfaces. Adhesions may be congenital or acquired through postinflammatory and/or postoperative processes. Congenital or inflammatory adhesions are less frequent causes of bowel obstruction than postoperative adhesions, except in certain circumstances such as rotational disorders (malrotation) or a persistent urachus. The leading cause of small bowel obstruction in Western societies is postoperative adhesions, which are responsible for 40% to 80% of bowel obstructions in hospitalized patients. This wide variation in incidence of adhesive obstruction varies with referral patterns, community practice settings, racial cultures, and regional preferences. Adhesion formation is nearly universal after celiotomy and starts within hours of an intra-abdominal operation, since the inflammatory phase is the

first requirement for adhesion development.19 While the exact pathogenesis of adhesion formation remains incompletely understood, experts agree that adhesion formation is a surface event associated with peritoneal injury. This inciting trauma triggers a local inflammatory response leading to activation of the complement and coagulation cascades along with exudation of fibrinogen-rich fluid; the full establishment of this fibrinous inflammatory response is present 5 to 7 days after the trauma of a celiotomy.20 Recent findings have identified the presence of sensory nerve fibers in human peritoneal adhesions, suggesting that these structures may be capable of conducting pain or other neural responses.21 Peritoneal healing (mesothelialization) appears to differ from the response in skin, where re-epithelialization occurs from the periphery inward. In the peritoneum, operative or traumatic defects are reperitonealized by implantation of mesothelial cells in multiple areas of the defect. This mesothelialization takes place quite rapidly, and resurfacing is often complete by 2 to 5 days after the injury, depending on local conditions.22 Normal peritoneal healing, however, is a complex, interrelated, programmed inflammatory process. The initial response involves infiltration of the wound area with polymorphonuclear leukocytes and lymphocytes. During the ensuing 24 to 36 hours, circulating and local macrophages are recruited by various chemokines. By 48 hours, a fibrin scaffold overlying the defect has been established, covered by macrophages and a few mesothelial cells. These mesothelial cells then coalesce to fully cover the defect over the next 2 to 5 days. Fibroblasts and other mesenchymal cells populate the underlying fibrin scaffold and begin to lay down a basement membrane. By 8 to 10 days, a single layer of mesothelial cells resting on a continuous basement membrane has been established, and the underlying reactive matrix and inflammatory cells regress. This process describes the simple resurfacing of an uncomplicated peritoneal defect. In comparison to the previously described physiologic process of normal peritoneal healing, adhesion formation is a pathologic process. Studies suggest that adhesions form in response to the initial fibrin gel matrix in response to the local, inflammatory microenvironment. This fibrin gel matrix consists of numerous types of cells, including the initial leukocytes, but also other humorally active cells such as platelets, mast cells, and erythrocytes, in conjunction with surgical debris, nonviable tissue, foreign bodies, and

possibly bacteria. The resultant spectrum of fibro-inflammatory changes between physiologic mesothelial healing versus pathologic adhesion formation varies not only among individuals but is dependent also on many other conditions, such as inflammation, infection, devitalized tissue, and foreign bodies. If the fibrin gel allows apposition of adjacent surfaces, a band or bridge may form (ie, an adhesion). This process of adhesion formation is dynamic, consisting predominantly of macrophages early, but by 2 to 4 days, larger strands of fibrin begin to appear along with fibroblasts. By 5 days, distinct bundles of collagen are apparent, and the fibroblasts begin to form a syncytium within the matrix. These cells predominate thereafter, and eventually the fibrin matrix and cellular elements are replaced by a vascularized, granulation-type tissue containing macrophages, fibroblasts, giant cells, and a rich vascular supply. Eventually, the surface of the adhesions are covered by a mesothelial layer, but only after formation of the underlying fibrous scar leading to surface opposition and transperitoneal fibroinflammatory bands of varying severity and extent. An important factor in the spectrum of adhesion formation that contributes to the risk of future adhesive bowel obstruction is the type of surgical procedure performed. Operations involving structures in the inframesocolic compartment and those in the pelvic region such as colonic, rectal, and gynecologic procedures impart the highest risk. Open procedures, use of gloves containing starch granules, gallstone spillage during cholecystectomy, and separate peritoneal closure were also correlated with adhesive SBO in a review article.10 Adhesive bowel obstruction may occur at any time postoperatively after a celiotomy, with reports ranging as early as within the first postoperative month to more than eight decades after the index operation. A study by Menzies and Ellis23 found that about 20% of adhesive bowel obstructions occur within 30 days after the initial celiotomy, about 20% occur between 1 and 12 months postoperatively, another 20% tend to occur between 1 and 5 years postoperatively, with the remainder (~40%) occurring after 5 years. A Norwegian study of patients requiring an operation for adhesive bowel obstruction found that most episodes of recurrent bowel obstruction occurred within 5 years after the previous episode, but the risk of bowel obstruction persisted for more than 20 years after a prior episode, reaching an incidence as great as 29% at 25 years.24 Therefore, a common predisposition to adhesive obstruction is the presence of a prior episode of

adhesive obstruction. Numerous surgical attempts to decrease or prevent the development of postoperative adhesions have been reported and are discussed subsequently. The literature on pharmacologic prophylaxis against postoperative adhesion formation is extensive and riddled with numerous false claims of benefit. Suffice it to say that no reliable or truly effective pharmacologic agent has been developed to augment mesothelialization and prevent adhesion formation. Several proprietary barrier products of variable efficacy have been developed and will be discussed.

Hernia Hernias are the second most common cause of bowel obstruction in most reported series. Inguinal hernias and hernias acquired postoperatively most frequently lead to intestinal obstruction, but congenital abdominal wall or internal hernias may on occasion cause a bowel obstruction by incarcerating intestinal contents. Hernias as an etiology are more common in males than in females, primarily because of the predominance of inguinal hernias in men. In contrast, incarcerated femoral or obturator hernias are more common in women. Approximately 5% of external hernias will require emergency operation if they are not repaired electively. These hernias are usually incisional hernias, umbilical hernias, and indirect inguinal or femoral hernias. Inguinal hernias rarely incarcerate, which has changed their management from repair of all inguinal hernias to a watchful waiting approach in the asymptomatic or minimally symptomatic patient.25 The presence of acute incarceration should prompt emergent operative management, because 10% to 15% of incarcerated hernias contain necrotic bowel at exploration (Figs 38-1 and 382). Chronically incarcerated hernias can develop strangulation, but most chronically incarcerated hernias can be managed electively.

FIGURE 38-1 Gangrenous bowel from an irreversible, strangulated, incarcerated inguinal hernia.

FIGURE 38-2 Umbilical hernia. Operative en bloc resection of hernia sac, umbilical skin, and irreversible strangulation obstruction.

Internal Hernia after Laparoscopic Gastric Bypass Minimally invasive surgery has brought new etiologies of intestinal obstruction. The reported incidence of internal hernia after laparoscopic

intestinal surgery, and especially after Roux-en-Y gastric bypass (RYGB), is 0.2% to 3%, a significantly increased incidence compared with the open approach.26,27 Factors contributing to the increased risk of internal hernia after a laparoscopic approach include lack of adhesion formation, increased small bowel mobility, marked weight loss−induced increased mesenteric openings, and failure to close all mesenteric defects appropriately. There are two or three mesenteric defects created during laparoscopic RYGB, depending on whether the retrocolic or antecolic technique is used28 (Fig. 383). Petersen’s defect or space is the best-known site of herniation and can arise with either an antecolic or retrocolic position of the alimentary limb.29 It is named after Petersen, who in 1900 described two cases of internal herniation posterior to a loop gastrojejunostomy.30 Internal hernias are often difficult to diagnose; indeed, patients with internal hernias present often with nonspecific or intermittent symptoms (periumbilical pain, nausea, vomiting, anorexia, abdominal distention). Spontaneous reduction in the hernia can occur, and CT, upper GI contrast series, and plain abdominal films may be nondiagnostic.28 Symptoms of intermittent bowel obstruction after laparoscopic gastric bypass should raise suspicion for the presence of an internal hernia, especially after weight loss. The best measure to prevent these hernias is the meticulous closure of the created mesenteric defects, and suspicion of an internal hernia may itself be appropriate justification for operative exploration, especially via a diagnostic laparoscopy.

FIGURE 38-3 Internal hernia defects after Roux-en-Y gastric bypass (RYGB). A. Retrocolic RYGB; B. Antecolic RYGB. R, Roux limb; ST, stomach. Mesenteric defect at enteroenterostomy (solid arrows), transverse mesocolic defect (open arrow), and Peterson’s hernia posterior to Roux limb mesentery (dashed arrows).

Trocar Site Hernia The reported incidence of trocar site herniation is 0.2% to 3%; the true longterm incidence, however, might even be greater.31 Trocar site hernias are observed rarely with 5-mm trocars but more frequently with the use of 10mm, 12-mm, or bigger trocars and especially with the “cutting” or bladed trocars. Closure of the fascial defect and the use of noncutting, radial expanding trocars are recommended to decrease the risk for formation of trocar site hernias.31−33 Trocar site hernias can lead to small bowel obstruction early or late after a minimal access, intra-abdominal procedure.

Following a laparoscopic procedure, patient complaints of pain in the region of a trocar site, nausea, or vomiting should lead to investigation for a bowel obstruction. In these cases, the bowel obstruction may be partial or complete. Commonly, the antimesenteric portion of the bowel wall will be incarcerated in the small fascial defect, resulting in a partial obstruction. These hernias are dangerous, because they may result in strangulation and necrosis in the absence of intestinal obstruction. Reduction of necrotic bowel during hernia repair can result in missed perforation and peritonitis. Although trocarassociated hernias are rare, with the widespread use of laparoscopy, they have become a well-known complication.

Malignant Bowel Obstruction Primary intra-abdominal neoplasms are a common cause of both large and small bowel obstruction. Colorectal, gastric, small bowel, and ovarian neoplasms are the most frequent causes of malignant bowel obstruction, either from the primary lesion (colon and small bowel neoplasms) or from peritoneal metastases (ovarian, colonic, and gastric neoplasms). In many of these patients, bowel obstruction is associated with a high rate of recurrence and morbidity, and may often be a terminal event. Metastatic cancer can also cause bowel obstruction, usually small bowel obstruction. The most common form of obstructing metastatic lesion is peritoneal carcinomatosis related to one of the aforementioned primary, intraabdominal malignancies, but localized hematogenous metastases to the wall of the small intestine from melanoma and carcinoma of the breast, kidney, or lung can also cause intraperitoneal metastases that can obstruct the bowel (Fig. 38-4).

FIGURE 38-4 Renal cell carcinoma metastatic to small intestine.

Crohn’s Disease Crohn’s disease is a chronic, transmural, inflammatory ailment of the gastrointestinal tract that may affect any part of the alimentary tract from the mouth to the anus. Despite often intense involvement of the bowel wall, Crohn’s disease is responsible for fewer than 5% of cases of small bowel obstruction. When true mechanical obstruction is present, the cause is usually secondary to the inflammatory process or to chronic stricture formation. Other granulomatous diseases causing obstruction, such as tuberculosis and actinomycosis, are much less common in Western countries, but in the developing world where acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection are endemic, intra-abdominal tuberculosis must be entertained in the diagnosis of intestinal obstruction.

Intussusception Intussusception is a relatively frequent cause of bowel obstruction in infancy, but it accounts for only 2% of bowel obstruction in the adult population.34 The median age of presentation in adults with intussusception is the sixth to seventh decade. The etiology of intussusception differs greatly between adult

and pediatric patients. In the vast majority of adult intussusceptions, there is a demonstrable inflammatory lesion or a neoplasm that serves as the lead point of the intussusception; however, up to 20% of adult cases are idiopathic.35 Neoplasms causing intussusception in adults are malignant in almost 50% of patients. Although rare in the Western Hemisphere, intussusception is one of the most common causes of bowel obstruction in central Africa, for reasons not yet fully explained.

Volvulus Volvulus represents an axial twist of the bowel and its mesentery. This entity is an infrequent cause of small or large bowel obstruction in the Western Hemisphere (Figs 38-5 and 38-6). Volvulus is encountered more frequently in the geriatric population, in individuals with a long history of constipation, or in institutionalized, neurologically impaired, or psychiatric patients. Colonic volvulus comprises about 1% to 4% of all bowel obstructions and about 10% to 15% of all large bowel obstructions. The volvulated segment must be mobile to allow the degree of freedom necessary to permit an axial twist of the mesentery. The affected segment has either an especially long, narrow mesentery (eg, malrotation or cecal volvulus) and/or a lack of bowel wall fixation (floppy cecum syndrome).

FIGURE 38-5 Sigmoid volvulus. A. Supine abdominal radiograph showing

the dilated, volvulated segment of redundant sigmoid colon pointing toward the right upper quadrant; arrows show the space between the sigmoid and hepatic and splenic flexures. B. Contrast enema in sigmoid volvulus showing cutoff at distal site of volvulated sigmoid having a “bird-beak” appearance.

FIGURE 38-6 Cecal volvulus. Dilated volvulated cecum pointing to left upper quadrant. Arrows indicate the cecal tip. Overall, sigmoid volvulus accounts for 75% of all patients with volvulus. In contrast, cecal volvulus is responsible for the majority of the remaining 25% of bowel volvulus incidences in the United States and is the most common cause of large bowel obstruction in pregnancy. The “cecal bascule” is a unique, though less common, form of cecal volvulus that occurs when the true anatomic cecum (ie, the part of the ascending colon that lies caudal to the

entrance of the ileocecal valve) folds anteriorly over onto the ascending colon, obstructing the lumen. This form of cecal volvulus may be intermittent and recurrent, and is especially difficult to diagnose. Primary volvulus of the small intestine is extremely rare in the United States but is quite prevalent in central Africa, India, and the Middle East. Speculation about etiology has been related to abrupt dietary changes that occur during the religious holiday when the people celebrating Ramadan fast during the day and then consume a large meal after dark. Some investigators, however, maintain that this racial group has an exceedingly long, floppy small bowel mesentery that permits generous mobility of the small bowel.

Other Causes Numerous other causes of bowel obstruction exist, but these are so uncommon that we list them in Table 38-1 for completeness but will not discuss them further other than to highlight two unique causes—radiation changes and radiation enteropathy—with images (Figs 38-7 and 38-8).

FIGURE 38-7 Radiation changes in distal colon/rectum (arrows).

FIGURE 38-8 Radiation enteropathy. Note the narrowed segments of ileum with much thickened bowel walls (separation between adjacent loops).

DIAGNOSIS The diagnosis of bowel obstruction is highly suspected clinically based on careful history-taking and physical examination, and it may be confirmed by imaging, such as abdominal radiography or CT. The etiology of the obstruction can often be determined by astute history-taking complemented with physical examination and imaging studies.

History and Physical Examination

The classic clinical picture of a patient suffering from bowel obstruction includes intermittent crampy abdominal pain, distention, acute obstipation, nausea, and vomiting. Abdominal pain and then distention usually precede the appearance of nausea and vomiting by several hours. The more proximal the obstruction, the earlier and more prominent are the symptoms of nausea and vomiting, while distension is usually less prominent. Conversely, the more distal the obstruction, the more prominent the abdominal distention. Vomiting is relatively uncommon in colonic obstruction until its later stages. The abrupt onset of symptoms makes an acute obstructive cause more likely and may herald the presence of a closed-loop obstruction. The location and character of pain may be helpful in differentiating mechanical bowel obstruction from ileus. Ileus tends to have a more diffuse and mild pain, often without waves of colic, while mechanical bowel obstruction usually presents as severe, truly colicky pain. Recurrent paroxysms occurring in short (10-30 seconds) crescendo-decrescendo episodes is often associated with mechanical small bowel obstruction, while in mechanical large bowel obstruction episodes are usually spaced farther apart and tend to last longer (1-2 minutes). Pain is usually described as visceral and poorly localized. Classically, the presence of constant or localized pain has been regarded as a sign of strangulation. Several studies, however, have shown that these findings are neither sensitive nor specific for the detection of strangulation. Obtaining a complete medical history is of paramount importance to make the diagnosis and determine the etiology. The fundamentals of history-taking, including the type and location of pain, the temporal association of symptoms, associated symptoms, and aggravating and alleviating factors, are all important components in obtaining a thorough history. The past medical history may also be critical in both making the diagnosis and establishing the cause of bowel obstruction. It is especially important to inquire about previous episodes of bowel obstruction, recent and distant abdominal operations, current medications, a history of chronic constipation, recent changes in the caliber of stools, and a history of cancer including its stage at presentation and related treatments (operative therapy, chemotherapy, or radiation therapy). Other causes of chronic intestinal obstruction such as Crohn’s disease or other intra-abdominal inflammatory processes should be discussed. A thorough physical examination is mandatory and should include

assessment of vital signs and hydration status as part of the initial resuscitation. Tachycardia, hypotension, and oliguria are signs of advanced dehydration that mandate aggressive resuscitation. Fever may be associated with an infectious cause or with strangulation. Thereafter, the exam should proceed with abdominal inspection, auscultation, percussion, and palpation. It is important to look closely for potential hernia defects and previous surgical incisions, including inguinal incisions for previous herniorrhaphies. Differential diagnosis should also include the possibility of internal hernias or those “external” hernias not necessarily associated with an obvious bulge, such as obturator, femoral, or intramural Spigelian hernias. Auscultation can determine the presence, frequency, and quality of the “obstructed” bowel sounds. Bowel obstruction may have the metallic tinkling sounds of “water dripping into a large hollow container,” indicative of dilated bowel with an air−fluid interface. Functional obstruction (ileus) may present with an absence of bowel sounds. Mechanical bowel obstruction presents with an increase in the frequency of bowel sounds, but more specifically the high-pitched “rushes” and “groans” followed by the metallic tinkling sounds. In both mechanical and functional bowel obstruction, a succussion splash may be heard in the presence of a dilated stomach or markedly dilated small bowel filled with an air−fluid interface. The presence of a succussion splash is not normal in a patient who has not eaten or ingested liquids in the previous 1 to 2 hours and should be regarded as an important, abnormal, and often underappreciated sign of bowel obstruction. Abdominal palpation should reveal the presence of peritoneal signs, such as rebound, localized tenderness, and involuntary guarding that herald vascular compromise or perforation. The presence of these findings is suggestive of the need for an emergent operation. Abdominal masses should be sought and noted. A meticulous search for hernia defects, especially inguinal and femoral hernias, is essential, because they can easily be overlooked. Rectal examination is required to rule out fecal impaction or locate a low-lying rectal cancer as a cause of obstruction.

Laboratory Laboratory tests are essential in patients with bowel obstruction because they may aid in the diagnosis, and more importantly, any underlying metabolic defects should be corrected prior to operative therapy. While no laboratory

test is sensitive and specific enough to diagnose mesenteric ischemia reliably, a spectrum of laboratory tests may be helpful in determining the condition of the patient and should guide resuscitation. A complete blood cell count and differential, electrolyte panel, blood urea nitrogen, creatinine, and urinalysis should be obtained to evaluate fluid and electrolyte imbalance and to assess the possibility of sepsis. Arterial blood pH, serum lactate concentrations, and amylase and lactic dehydrogenase activity may be useful tests in the evaluation of bowel obstruction, especially when trying to exclude the presence of strangulation or underlying bowel necrosis. An increase in serum lactate concentrations should raise the suspicion of intestinal ischemia; however, it is often a late finding.36,37 D-dimer was proposed as an early marker of acute mesenteric ischemia, but it appears to be insensitive.38,39 Intestinal fatty acid–binding protein (I-FABP) is a highly sensitive marker for extensive mesenteric infarction; however, it does not appear to be sensitive enough to detect more limited intestinal ischemia in strangulated bowel.40,41 Some authors have suggested that serum concentrations of phosphate and isoforms of creatine phosphokinase (isoform B),42,43 plasma level of ischemia-modified albumin,44 gut luminal tyrosine concentrations,45 and αglutathione S transferase (α-GST)46 may identify the presence of intestinal cell necrosis. However, the specificity and especially the sensitivity are not accurate enough to base a management decision solely on these parameters.

Radiologic Findings The management of small bowel obstruction remains heavily reliant on excellent clinical acumen and appropriate imaging. The clinician is faced with answering the critical questions, “is this complete obstruction,” and “is the intestine ischemic?” The literature is replete with clinical studies examining the prognostic value of various forms of imaging in terms of predicting the need for operative management or the presence of intestinal ischemia.47 Most of these series have investigated the role of CT, and we will highlight these findings.

FLAT AND UPRIGHT ABDOMINAL RADIOGRAPHS Plain radiographs, including a chest x-ray and flat and upright films of the

abdomen, remain a valuable initial imaging modality in patients with clinical small bowel obstruction. An initial chest x-ray may reveal extra-abdominal processes such as pneumonia that could be associated with an ileus rather than bowel obstruction. In addition, the presence of free air from a perforated viscus may indicate a diagnosis other than small bowel obstruction or a serious complication of small bowel obstruction requiring emergent treatment. Flat and upright films of the abdomen in patients with a small bowel obstruction characteristically have multiple air−fluid levels in dilated loops of bowel and a paucity of gas in the distal (decompressed) small bowel and colon (Fig. 38-9). The location of the obstruction in the proximal or distal small intestine, however, greatly influences the findings on the plain abdominal films. A very proximal small bowel obstruction may be associated with films that demonstrate few, if any, air−fluid levels, with a relatively small gastric air−fluid level resulting from a fluid-filled stomach. Conversely, a distal small bowel obstruction will likely have multiple air–fluid levels with dilated loops of small bowel stacked on one another (Figs 38-10 and 38-11). Similarly, the pattern of bowel gas may assist in determining whether the obstruction represents a small or large bowel process. On a plain abdominal film, the small bowel lies centrally, and intestinal markings from the valvulae conniventes or plicae circulars encompass the entire diameter of the bowel, whereas the large bowel lies at the periphery of the abdomen, and haustral markings only partially cross the bowel. Furthermore, the appearance of the bowel gas may also give a clue as to the duration of the obstruction. So-called “fecalization” of the small bowel content, whereby the luminal content shows less of an air–fluid level and more of an appearance of semisolid content with pockets of gas, suggests a more chronic obstruction and may be helpful in supporting the need for operative intervention, not because of worry of strangulation but rather a chronic, established, non-resolving process.

FIGURE 38-9 Supine abdominal radiograph showing an incomplete small intestinal obstruction. Note the dilated loops of small bowel.

FIGURE 38-10 Complete small bowel obstruction. A. Supine abdominal radiograph shows multiple loops of dilated small bowel with colonic gas. B. Upright radiograph shows multiple air–fluid levels in the small intestine (arrows).

FIGURE 38-11 Small bowel obstruction with fluid-filled loops of small bowel in left lower quadrant (arrows). Rarely, a plain film of the abdomen will contain a pathognomonic sign of intestinal obstruction from gallstone ileus (a misnomer because it is a true mechanical obstruction), as is the case with pneumobilia in a patient with gallstones and no history of biliary instrumentation. Importantly, plain films of the abdomen are notoriously poor indicators of bowel involved with vascular compromise unless the devastating signs of portal venous gas and intestinal pneumatosis are evident. Closed-loop bowel obstructions are also difficult to diagnose on plain x-rays, because the involved bowel with a

proximal and distal occlusion may be fluid-filled and lack any gas. Thus, additional imaging procedures should be obtained in patients with any suspicion of compromised bowel.

CONTRAST STUDIES Though contrast studies using either dilute barium or hyperosmotic, watersoluble contrast of the small and large bowel have been an integral component of the diagnostic evaluation, enthusiasm for these studies has waned substantially. The radiologic literature and various guidelines developed by the radiologic community support strongly the use of contrastenhanced CT as the diagnostic imaging modality of choice.48 Nonetheless, in specific clinical situations, such as in a patient with an obstructing sigmoid or rectal tumor, a radiograph with rectally administered contrast may provide diagnostic information that is timely, economical, and clinically important (Fig. 38-12). On occasion, a small bowel follow-through series may be helpful in distinguishing between mucosal inflammation and extraluminal compromise from adhesions as the etiology of bowel obstruction in a patient with Crohn’s disease. This diagnostic information may alter the therapeutic approach, but generally small bowel followthrough studies have little if any advantage over CT.

FIGURE 38-12 Barium enema showing complete large bowel obstruction in the ascending colon. When contrast agents are utilized, the risks of each agent must be considered carefully. The primary side effects of barium include inspissation in the obstructed large bowel. Also, barium results in severe intraperitoneal infection/barium peritonitis when extravasated in the face of small intestinal perforation. Gastrografin, if aspirated, can cause a severe pneumonitis; moreover, this contrast agent becomes diluted rapidly with an established

small bowel obstruction, and thereby yields little information in a distal small bowel obstruction. Finally, most surgeons agree that contrast studies are contraindicated in patients with a clear diagnosis of complete bowel obstruction and when strangulation or perforation is suspected.

COMPUTED TOMOGRAPHY In many centers, computed tomography (CT) has become the primary diagnostic imaging modality for the diagnosis of suspected intestinal obstruction, and in fact in some institutions it has replaced plain radiographs as the initial imaging test. The increased use of CT reflects the preference of clinicians for the additional diagnostic information garnered from this examination. CT not only provides information about the presence or absence of a luminal obstruction, but it can also define both the site of obstruction and the existence of extraluminal processes, a small bowel transition point, associated inflammation, fluid collections, masses, abdominal wall or internal hernias, and free intraperitoneal fluid. Further, CT can expedite the diagnosis of strangulation obstruction if findings including mesenteric edema, free peritoneal fluid, intestinal wall thickness, and the absence of fecalization of the small bowel content are present.47 Early detection of bowel ischemia is paramount to successful surgical management of obstruction. Several studies have reported a diagnostic accuracy of greater than 90% with the use of CT in intestinal obstruction.49−51 Other work has attempted to identify radiographic characteristics that accurately detect ischemia. The presence of two or more beak signs, a whirl sign, a C- or U-shaped appearance of the bowel loop, and a high degree of obstruction were associated with nonsurgical treatment failure.52 Among studies utilizing IV contrast, reduced bowel wall enhancement had a 95% specificity in determining ischemia, and absence of mesenteric fluid had an 89% sensitivity in ruling out strangulation.53 O’Daly and colleagues found the association of peritoneal fluid with small bowel obstruction to be a strong predictor for the need for operative treatment.54 In settings where iodinated contrast is contraindicated, the finding of increased bowel-wall attenuation on unenhanced images is concerning for bowel ischemia, with a 100% specificity and 56% sensitivity.55 Further reports evaluating the capability of CT to predict ischemia or strangulation have produced contradictory results. In a systematic review,

Mallo et al. found that the sensitivity, specificity, positive predictive value, and negative predictive value of CT for predicting ischemia were 83%, 92%, 79%, and 93%, respectively.56 Conversely, Sheedy et al. noted that with CT, sensitivity was 15% and specificity 94% for identifying bowel ischemia prospectively in patients with small bowel obstruction.57 A recent study by Zielinski et al. suggested that CT findings of free peritoneal fluid, thickened bowel, and mesenteric edema, combined with vomiting, were predictive of the need for eventual operative management, but though relatively sensitive for ischemia, CT was not very specific.47 Some studies suggest that a CT scoring system may accurately predict the need for operative intervention. Jones et al. found that a scoring system with the criteria of a dilated small bowel, identification of a transition point, ascites, complete obstruction, partial obstruction, evidence of a closed-loop obstruction, and/or free air predicted the need for operative treatment in 75% of patients.58 It is important to remember that CT is better at identifying rather than excluding the presence of ischemia. Although the increased use of CT in patients with bowel obstruction has provided greater diagnostic information, caution must be exercised in the use of this modality in distinguishing mechanical small bowel obstruction versus ileus. In one study, up to 20% of patients with a CT diagnosis of ileus required operative intervention eventually.59 Overall, the current preference for the use of CT is associated with an increased likelihood of operative intervention and decreased mortality; however, whether these associations are causal or coincidental remains unknown.60

ULTRASONOGRAPHY Ultrasonography (US) is used infrequently in the diagnosis of intestinal obstruction. Features concerning for strangulated bowel include akinetic bowel loops, hyperechoic and thickened mesentery, and presence of peritoneal fluid.61 Even though the reported specificity is 82%, sensitivity is 95%, and overall accuracy is 81%, this modality is highly operatordependent, and the results are unlikely to be reproduced consistently in many institutions. US has been reported to be useful for the early recognition of strangulation obstruction in several Japanese and European studies62,63; however, in the absence of an experienced ultrasonographer, the reliability of

US remains questionable. Furthermore, US is difficult to perform in obese patients, and extensive bowel gas may obscure the pattern of intestinal obstruction.

MAGNETIC RESONANCE ENTEROGRAPHY Magnetic resonance enterography (MRE) has not been utilized as frequently as CT, because performance of this examination is more time consuming and requires substantial expertise in interpretation. In addition, in general practice MRE does not have a greater diagnostic accuracy than CT. In contrast, in centers that use MRE frequently, diagnostic accuracy exceeding 90% is achievable.64,65 MRE may have an advantage of distinguishing benign from malignant bowel strictures in patients with suspected malignant bowel obstruction.66

VIDEO CAPSULE ENDOSCOPY Video capsule endoscopy (VCE) may be a valuable diagnostic tool in patients with subacute or chronic intestinal obstruction where other imaging techniques have not revealed an etiology. VCE is particularly helpful in patients with obstruction related to a stricture caused by inflammation or malignancy.67 Overall, VCE may provide a diagnosis in nearly 40% of previously undiagnosed patients.68 A major concern with the use of VCE, however, is retention or impaction of the capsule either at a stricture or in any area of severe kinking related to adhesions in a patient who otherwise may have resolution of the obstruction without an operation. The incidence of this circumstance appears infrequent, but impaction may require celiotomy.

Detection of Ischemia Identification of strangulation obstruction caused by ischemia of the intestine is a critical diagnosis, because the mortality associated with strangulated bowel obstruction is 9% to 40% compared to less than 5% in nonstrangulated intestinal obstruction.69 Unfortunately, clinical and imaging parameters claimed to permit early detection and operative intervention remain unreliable, and in fact do not lead to early diagnosis. As mentioned previously, studies examining the efficacy of CT for diagnosis of

strangulation obstruction have yielded mixed results in the determination of intestinal ischemia. Jancelewicz et al. found that decreased bowel wall enhancement on CT, leukocytosis, and peritoneal signs were the only independent predictors of strangulated obstruction on a multiple logistic regression analysis.69 Historically, acidosis, increased serum amylase activity, and increased serum lactate concentrations were also claimed to be indicators of strangulation. While abnormalities of these parameters may prove to be sensitive markers of strangulation, they generally lack specificity and do not offer useful positive or negative predictive value. Abdominal US and pulsed-Doppler US have been reported to be useful in identifying patients with strangulation. Ogata and associates reported that an akinetic, dilated loop of bowel observed on real-time US had a high sensitivity (90%) and specificity (93%) for the recognition of strangulation; the positive predictive value was 73%. The presence of free peritoneal fluid seen on US was also sensitive for strangulation.70 Given the conflicting evidence, the importance of integrating physical exam, imaging, and other clinical parameters (eg, worsening acidosis) when assessing a patient with bowel obstruction cannot be overemphasized.

MANAGEMENT The initial management of patients with small bowel obstruction should focus on aggressive fluid resuscitation and nasogastric decompression of the stomach to prevent further accumulation of intestinal fluid and air. In addition, nasogastric decompression decreases the potential for aspiration and relieves vomiting. These therapies should be instituted in all patients, whether they are treated operatively or undergo a trial of nonoperative management. Blood should be analyzed for serum electrolyte concentrations, complete blood count, lactate concentration, typed and screened for potential transfusion, and when necessary, arterial blood gases should be analyzed as well. The most important initial step in management is crystalloid fluid resuscitation that aims to replete fluid losses. Patients with small bowel obstruction often present with profound volume depletion and may require several liters of isotonic crystalloid solutions, such as normal saline (0.9% NaCl) or lactated Ringer solution with additional potassium as urine output is

restored. Resuscitation should be guided by urine output, provided the patient is hemodynamically stable and has normal renal function. Patients who are hemodynamically unstable or have impaired cardiac, pulmonary, or renal function may require monitoring of central venous pressure to better evaluate their volume status. Colloid solutions, such as 5% albumin or hetastarch, have little or no role in the resuscitation of patients with a small bowel obstruction. Proper fluid resuscitation includes correction of metabolic or electrolyte imbalances, which may be severe. Specifically, in patients who have experienced prolonged vomiting, potassium and chloride should be measured to diagnose hypokalemic, hypochloremic alkalosis and replacement therapy started after resuscitation with normal saline. Though potassium replacement is a critical component of therapy, replenishment of this electrolyte should begin only after renal function has been established by good urine output. Volume resuscitation, electrolyte replacement, and establishment of adequate urine output are critical before operative therapy is undertaken. Broad-spectrum antibiotics should be given to patients within an hour of the incision as prophylaxis against surgical site infection, but otherwise, antibiotics have no defined role postoperatively or in patients managed nonoperatively. Most surgeons believe that nasogastric decompression is important to prevent further intestinal distention from swallowed air and to limit a broad transit of gastric contents. In addition, nasogastric decompression helps to prevent aspiration during vomiting and on induction of general anesthesia. Symptomatically, gastric decompression helps relieve abdominal distension and can improve respiratory function in patients with respiratory compromise. Historically, long intestinal tubes placed distal to the pylorus were used to relieve small intestinal distention under the assumption that intestinal decompression may be therapeutic if related to adhesions, because the decompressed bowel may detort and thereby relieve the mechanical obstruction (Fig. 38-13). Success rates of up to 90% have been reported in some series of patients treated with a long nasointestinal tube.71 In contrast, however, most prospective and retrospective studies have failed to demonstrate the superiority of nasointestinal versus nasogastric intubation,71,72 making the added expense of fluoroscopic or endoscopic placement of a nasointestinal tube unwarranted. Use of these long intestinal tubes has fallen out of favor, and they are of historic interest only in the

preoperative treatment of small bowel obstruction.

FIGURE 38-13 Abdominal radiograph showing distal passage of a long nasointestinal decompression tube into the small bowel distal to the ligament of Treitz.

Nonoperative Management Nonoperative management of intestinal obstruction should be considered only in patients with uncomplicated intestinal obstruction in the absence of peritonitis, a progressive leukocytosis, or impaired bowel wall perfusion on imaging. When indicated, this approach is reported to be successful in 62% to 85% of patients.73−76 The rate of success of nonoperative management is influenced by patient selection, type of bowel obstruction (complete vs partial), etiology (eg, adhesions, hernia, or neoplasm), and the surgeon’s threshold for conversion to operative management. Patients successfully managed nonoperatively require fewer hospital days73,74 and avoid the morbidity or convalescence necessitated by an operation. Few studies have compared the long-term outcomes of patients with a small bowel obstruction treated nonoperatively versus operatively. One such study with over 4 years of follow-up reported by Landercasper and colleagues77 found a recurrence rate of 29% in patients managed operatively versus a recurrence rate of 53% for patients managed nonoperatively. Even though the recurrence rates may be greater with nonoperative management, the authors point out that about half of the patients managed nonoperatively never developed a recurrent small bowel obstruction. A study by Rocha et al.78 used the radiologist definition of “high-grade” obstruction and reported that in these patients, comparing those treated conservatively versus those treated by operation, the conservatively treated patients had a significantly greater readmission rate at 5 years (24% vs 9%) than those treated operatively. Use of this radiologic finding may potentially extend the “indication” when criteria are met for high grade but not complete obstruction. When patients with a small bowel obstruction are initially managed nonoperatively, vigilant attention must be paid to volume resuscitation, electrolyte homeostasis, and nasogastric decompression. Patients managed nonoperatively require the same aggressive resuscitation and replacement of daily losses with an appropriate crystalloid solution and electrolyte replacement as patients who are managed operatively. Fluid replacement should take into consideration the volume and electrolyte loss in the output of the nasogastric tube, urinary output, and insensible losses. Electrolytes should be monitored frequently and corrected as necessary. Delayed correction of

potassium and magnesium concentrations may lead to delayed return of bowel function and misdiagnosis of obstruction versus ileus. Adequate proximal decompression is important to allow the bowel an opportunity to decompress. This concept is accomplished by maintaining a functioning nasogastric tube. If the patient becomes progressively more distended or develops vomiting, tube placement should be evaluated and tube function confirmed by bedside evaluation. Standard nasogastric tubes should be inserted, such that the second of four marks is evident at the tip of the nares. The first mark is 40 cm from the tip of the tube—that is, the normal distance from the nares to the esophagogastric junction. Thus, if all four marks are outside the nares, the tube most likely is not in the stomach. Likewise, if no marks are visible, the tube is coiled within the stomach or is in the duodenum. On occasion, an abdominal radiograph is necessary to confirm placement. If the tube is noted on a radiograph to be out of position, it should be repositioned and imaged again for proper placement. On evaluation, the tube should be connected to the suction apparatus, sumping properly (if the tube has a sump port), and should be checked for patency by flushing and aspirating water through the suction lumen. Oral intake should be nil in the presence of a nasogastric tube. In addition, the tube should never be “clamped” for prolonged periods of time, because by traversing the esophagogastric junction, the tube will lead to an incompetent lower esophagogastric sphincter and potential aspiration. Connection of the tube to a drainage bag for a brief trial is an appropriate alternative to clamping and may be used as a test to determine patient readiness for nasogastric tube removal. Absolute contraindications to nonoperative management include suspected ischemia, large bowel obstruction, closed-loop obstruction, acutely incarcerated or strangulated hernia, and perforation. In an attempt to define which patients with an uncomplicated small bowel obstruction can be successfully treated nonoperatively, Chen and colleagues79 used an orally administered, water-soluble contrast agent (Urografin) to study 116 patients with small bowel obstruction. The presence of contrast material within the colonic lumen within 8 hours of oral administration had an accuracy of 93% for predicting which patients would benefit from nonoperative therapy. In their study, only 19% of patients with a small bowel transit time of more than 8 hours had resolution of their obstruction with nonoperative treatment. One of the criteria for conversion to operative treatment was the failure of contrast

to reach the colon within 8 hours. Therefore, the 81% failure rate in patients in whom contrast never reached the colon within 8 hours after administration may be artificially high based on study design. A relative contraindication to nonoperative management is complete small bowel obstruction—that is, dilated small intestine with no air in the bowel distally. In a prospective study by Fleshner and associates,74 all patients with an uncomplicated small bowel obstruction underwent an initial trial of nonoperative management. They were able to manage 45% of patients successfully with a complete obstruction (by their definition), while 66% of patients with a partial obstruction were successfully managed nonoperatively, all with no mortality. These investigators, however, did not describe the incidence of intestinal ischemia at operation based on the presence or absence of complete versus partial obstruction. Another study by Fevang and colleagues73 reported a 42% success rate in managing patients with a complete small bowel obstruction nonoperatively. When they compared complete and partial obstructions managed nonoperatively, there was a greater rate of bowel strangulation (10% vs 4%) and need for resection (14% vs 8%) in the group with complete obstruction at the time of operation for treatment failure. This group noted a mortality of 6% in patients with a complete obstruction initially managed nonoperatively versus 0% mortality for patients with a partial obstruction initially managed nonoperatively. Other groups have also noted a greater rate of ischemic bowel coupled with a lesser success rate in those patients with a complete obstruction managed nonoperatively.72,78 These studies and the unreliability of clinical acumen to recognize strangulation obstruction accurately have led many surgeons to favor early operation for all patients with a complete small bowel obstruction,76 leading to the often-quoted phrase “The sun should never rise or set on a (complete) small bowel obstruction.” To better delineate partial and complete obstruction, studies have adopted a protocol-driven approach to utilize water-soluble contrast agents (WSCA) in nonoperative management. Among the protocols described in the literature, patients presenting with signs and symptoms of small bowel obstruction were assessed clinically and on CT imaging. Those demonstrating features concerning for ischemia underwent operative exploration immediately following appropriate resuscitation. The remaining patients receiving nonoperative treatment underwent gastric decompression, fluid resuscitation, urinary catheter placement, and WSCA administration.

Following WSCA, abdominal plain films were taken at 8 hours80,81 after WSCA or 1, 2, 4, and 8 hours82 after administration, depending on the study. Patients passed WSCA challenge if contrast reached the right colon by times ranging from 8 hours80,81 to 24 hours82 after WSCA. Patients who developed worsening signs and symptoms consistent with peritonitis underwent exploratory laparotomy. Among the patients who failed WSCA challenge but did not have a worsening exam, time from WSCA administration to operative management varied from 24 hours82 to 4 to 5 days.80 Success rates using WSCA protocols have ranged from 57%82 to 90.5%.83 Based on a recent meta-analysis of 14 prospective trials, presence of contrast in the colon predicted resolution of obstruction with 96% sensitivity, 98% specificity, 99% positive predictive value, and 90% negative predictive value. The authors supported use of WSCA as both a diagnostic and therapeutic tool and demonstrated a decreased need for surgery and decreased hospital length of stay,52 although results from individual studies remain mixed regarding length of stay and frequency of laparotomy. These studies support use of WSCA protocols in adhesive small bowel obstruction and suggest that protocols decrease use of non-therapeutic laparotomies while diminishing delays in surgical care when indicated (Fig. 38-14).

FIGURE 38-14 Protocol using water-soluble contrast agents in nonoperative management of small bowel obstruction. If nonoperative management is attempted in a patient with complete obstruction, the decision should be made with the understanding that there is a definite risk of overlooking an underlying strangulation obstruction,84 and thus there should be a low threshold for operative intervention in patients with complete obstruction.

When to Convert to Operative Management Prompt operative intervention is mandatory in patients who develop signs and symptoms suggestive of a strangulation obstruction. These parameters include fever, tachycardia, leukocytosis, localized tenderness, continuous abdominal pain, and peritonitis. The presence of any three of these signs has an 82% predictive value for strangulation obstruction.84 Similarly, the presence of any four of the above signs has a near 100% predictive value for strangulation obstruction. Obviously, patients who develop free air, signs of a closed-loop obstruction on abdominal radiograph, or gross peritonitis require

emergent operative exploration. If CT demonstrates evidence of ischemia, such as pneumatosis intestinalis, bowel wall thickening, portal venous gas, generalized ascites, or nonenhancement of the bowel wall, operative intervention should be strongly considered.76 The timing of conversion to operative management in a patient with a small bowel obstruction who is not improving with nonoperative management is more controversial. Some surgeons advocate operative intervention in any patient who fails to show improvement within 48 hours of initiating therapy.72,75 Others advocate a more liberal use of nonoperative therapy, citing a mean time to successful resolution of up to 4.6 days.74 The authors believe that nonoperative management can be continued greater than 48 hours with the understanding that delaying inevitable operative treatment will result in a greater overall hospital stay and increased costs, and may place the patient at increased risk for perioperative morbidity. As mentioned earlier, implementation of a protocol-driven approach with use of watersoluble contrast agents may be of diagnostic benefit in this setting, though further studies are needed to identify the optimal time to pursue operative care. It is important for the surgeon to remember that nonoperative management always carries a calculated risk of overlooking an underlying strangulation obstruction.85

Operative Management Once the decision has been made to pursue operative management, steps should be taken to prevent peri- and postoperative complications. Preoperative preparation includes assessing the medical fitness of the patient, and as time allows, taking steps to optimize the patient’s medical status. Special consideration should be given to ensure that the patient has been resuscitated adequately by establishing adequate urine output, appropriate antibiotics have been administered, and any electrolyte abnormalities have been addressed. Consideration should be given to the administration of βblockers to patients with cardiovascular comorbidities and especially to those who were on β-blockers prior to admission.85 A nasogastric tube should already be in place to decrease the risk of aspiration during the induction of anesthesia; nevertheless, a rapid-sequence anesthetic induction will be necessary to protect the airway during intubation, even in the presence of a

nasogastric tube. Several decisions must be made with regard to operative planning to provide the safest approach that will afford the best outcome for each individual patient. The choice of operative approach and incision is important to allow the surgeon adequate exposure and visibility. A laparoscopic approach should be considered in some patients.86 When an obstruction develops in the early postoperative period, the original incision should be reopened provided extensive adhesions were not present originally. Safe entrance into the peritoneal cavity may be best achieved by approaching this from the extremes of the previous incision rather than going directly through the mid-portion of the incision. In patients without a history of prior abdominal operation or those who are remote from their original operation, a midline celiotomy affords the best exposure to all four quadrants of the abdomen. For example, patients with upper oblique, transverse, or subcostal type incisions may have pelvic adhesions that are difficult to address from the upper abdomen, especially through a high transverse incision. Once within the abdominal cavity, the first step is to identify the site and cause of obstruction. If the point of obstruction is not obvious, decompressed bowel distal to the obstruction can be identified and followed proximally to the point of obstruction. Care should be taken when handling the obstructed bowel at or near the point of obstruction when acutely obstructed, especially if it is fixed at an apparent site of obstruction or if it is ischemic. This region is at high risk for strangulation and infarction, making it more likely to rupture with spillage of bacteria-laden enteric contents into the abdomen. The dilated bowel proximal to the offending obstruction is often thin-walled and at increased risk for perforation if the obstruction is acute. After the offending obstruction has been corrected, a thorough exploration of all four quadrants should always be undertaken to ensure that all intestinal injuries are repaired, nonviable segments are resected, and a second site of obstruction or fixation is not overlooked. This concept is especially true for volvulated segments of small bowel where two points of fixation are often present. Occasionally, obstructing bands traversing a sizeable part of the peritoneum can affect more than one loop of bowel. When a small bowel resection is necessary, intestinal continuity of the small bowel can be accomplished generally with a primary anastomosis unless there is generalized peritonitis and the edges of the remnant bowel are of questionable viability. When an intestinal anastomosis is performed, the surgeon must assess the discrepancy in bowel diameter and

wall thickness between the obstructed proximal bowel and decompressed distal bowel when choosing anastomotic techniques. The surgeon may consider a side-to-side or end-to-side anastomosis in situations where massive dilation of the proximal bowel makes an end-to-end anastomosis difficult technically. In addition, a stapled anastomosis may be less safe in cases where a large discrepancy in bowel wall thickness exists or when there is bowel wall edema, because uniform approximation of the tissue for a given staple height may not be possible. Abdominal closure may be difficult to achieve when the small bowel is massively dilated. In these cases, intraoperative intestinal decompression will facilitate closure. Techniques described for intraoperative decompression include manual retrograde decompression into the stomach (with careful handling of the obstructed bowel), intraoperative passage of a long nasointestinal tube and, rarely, performance of a controlled enterotomy with passage of a decompressing tube. The latter technique is strongly discouraged except under very select circumstances, such as tremendous intestinal distention preventing abdominal closure or distention threatening bowel viability. Manual retrograde decompression of luminal contents around the ligament of Treitz, through the pylorus, and into the stomach allows for aspiration through the nasogastric tube by the anesthetist.87 This maneuver is the safest and quickest technique because it allows closure of the abdominal wall while avoiding an enterotomy and excessive manipulation of the bowel. When decompressing the bowel, the inflamed and distended bowel must be handled gently, because experimental studies have demonstrated an increased rate of bacteremia after extensive manipulation of obstructed bowel.88 In addition, the anesthesia team should be alerted to the maneuver to be certain that their nasogastric tube is functioning well. Although intraoperative decompression has not been shown to decrease the rate of postoperative complications or the speed of return of bowel function, it certainly does make abdominal closure easier, faster, and safer. Nonviable bowel needs to be identified and resected. Resection should be undertaken with caution, especially in patients with a limited length of bowel from a previous resection or those with large sections of ischemia. Adjuncts for determining bowel viability include the use of Doppler US and intravenous fluorescein. These tests are relatively subjective, should be used with caution, and are only adjuncts to sound clinical judgment. In patients who would otherwise be left with less than two-thirds of their original bowel

length after resection of all bowel of questionable ischemia, consideration may be given to resecting all the grossly necrotic or obviously nonviable bowel but preserving bowel of questionable viability and performing an end ostomy or a second-look procedure 12 to 24 hours later, particularly if the viability of the ends to be anastomosed is in question.

BYPASS VERSUS RESECTION In patients with an incurable malignant small bowel obstruction, if the offending obstruction is unable to be released or it is deemed unsafe to attempt to dissect out the site of obstruction, intestinal bypass can be performed. Bypass relieves the obstruction while reestablishing intestinal continuity and preventing a closed-loop obstruction; however, the advisability of a bypass procedure should be considered. For instance, in the presence of carcinomatosis, a bypass may prove fastest and safest, because patient survival will be short. In contrast, patients with certain chronic inflammatory diseases will remain at risk for ongoing problems (eg, Crohn’s disease or tuberculosis) related to the inflammation in any “bypassed” segment, and therefore such patients may be served better by resection than simple bypass. The surgeon should at least consider an initial laparoscopic, minimal access approach in patients with uncomplicated small bowel obstruction. Laparoscopy is known to cause fewer adhesions than open laparotomy89 and in that regard may be superior to laparotomy for the treatment of adhesive small bowel obstruction. Several studies have shown laparoscopy to be a safe and effective means of access for the operative treatment of small bowel obstruction.86,90−92 When successful, a laparoscopic approach decreases both the duration of hospital stay86,90−92 and the complication rate.90,92 Patients successfully treated laparoscopically appear to have more rapid return of bowel function.90,92 These reports show a large benefit to laparoscopic treatment for small bowel obstruction, but need to be interpreted carefully. Many series compare patients treated laparoscopically to those who failed initial laparoscopic treatment. Those patients unable to be treated laparoscopically likely had more extensive adhesions or complicated pathology possibly requiring resection. Operative intervention in these patients would be more involved and complex whether done open or laparoscopically. One would expect these patients to have greater hospital

stays, greater complication rates, and slower return of bowel function independent of the method of abdominal access. In addition, the skill and confidence level of the surgeon should weigh in the decision to approach the obstruction laparoscopically. First, if the surgeon lacks skill in using moderately advanced laparoscopic techniques, an open operation may be a better choice. Similarly, if the patient is known to have a frozen abdomen or has either a severely distended, tense abdomen with markedly distended bowel or multiple dense adhesions at the time of insertion of the laparoscope, conversion to an open procedure is wise. Initial access for creating the pneumoperitoneum in a patient with a small bowel obstruction is achieved best by a fully open approach under total visual control, but limited data support this concept.

RECURRENT SMALL BOWEL OBSTRUCTION Although the results of individual studies vary, between 4% and 34% of patients will experience recurrent small bowel obstruction regardless of management modality.9,74,76,77,79,92 This wide range of recurrence rates likely results from variations in both the duration and quality of follow-up between studies as well as the etiology of the original bowel obstruction. Recurrent obstruction is more common in patients with multiple adhesions, matted adhesions, previous admissions for small bowel obstruction, and previous pelvic, colonic, and rectal surgery.9,77 In the past, numerous attempts have been made by surgeons to control the formation of adhesions in an effort to prevent future mechanical obstruction. A simple technique to prevent adherence of the bowel to the undersurface of the fascial incision is to interpose the omentum between the bowel and the incision. Theoretically, when adhesions from the posterior surface of the anterior abdominal wall form after omental interposition, they will involve the omentum and not the underlying bowel. Other more intricate techniques, such as the Noble plication and the Childs−Phillips transmesenteric plication, have been described in the more distant past. These procedures involve the suturing adjacent loops of small bowel into an orderly pattern in an attempt to plicate the bowel permanently in a position that will not allow mechanical obstruction. Although initial reports were encouraging, the Noble and Childs −Phillips procedures have multiple complications and are of historic interest only. The problems associated with plication procedures have included

prolonged operative times and high rates of enterocutaneous and enteroenteric fistula, abdominal abscess, and wound infection; moreover, the rate of recurrent obstruction is as great as 19%, bringing into question their efficacy. Attempts to “plicate” the bowel with a long intestinal tube, so-called intraluminal plication, have not proved effective. In some patients, complete or adequate adhesiolysis is not possible or may risk vascular injury to a substantial segment of bowel because of the acute inflammatory nature or tenacity of the adhesions. This situation is especially common when celiotomy is deemed necessary or performed too soon after a previous intra-abdominal procedure (see the following section on early postoperative small bowel obstruction). This situation is especially common when the previous operation involved an extensive adhesiolysis. In such situations, it may be important to control any bowel injuries present, end any further dissection, and conclude the operation to prevent further bowel injury and its potential sequelae. This “conservative” approach may allow the acute inflammatory process to resolve or regress (often 3-6 months); should the obstruction not resolve by 6 months, the plan should be to reoperate at a time when the adhesions have matured, allowing a more controllable and much safer adhesiolysis. In some situations, the mature decision might be to provide proximal diversion with a proximal enterostomy if the obstruction has no chance for resolution (eg, due to malignancy or radiation) or if a more distal bowel repair is tenuous, or to place a tube gastrostomy for diversion and patient comfort. Pursuing a futile attempt to complete the adhesiolysis puts the patient at risk for serious bowel injury or devascularization injury necessitating resection of otherwise normal bowel with the risk of enterocutaneous fistula or subsequent short bowel syndrome.

ADHESION PREVENTION Over the last 100 years, multiple approaches have been employed in an attempt to prevent the formation of unwanted postoperative adhesions. These attempts include, among others, the use of cow cecum, shark peritoneum, sea snake venom, and fish bladder, as well as multiple fluids, mechanical barriers, and gels.93 The concept of separating injured surfaces mechanically to prevent adhesions is attractive. The formation of fibrin bridges (and thus adhesions) may be preventable by separating injured surfaces in the postoperative interval during the critical period of healing and

mesothelialization by application of an absorbable biofilm. Estimates of the minimum amount of time necessary for an impermeable or semipermeable barrier to prevent adhesion formation appear to be about 36 hours. Some authors have placed a Silastic sheet between two injured peritoneal surfaces and when left in place for 36 hours, no adhesions formed between these surfaces thereafter.22 Others have postulated that separating the surfaces at risk for the first 5 to 7 days until full mesothelialization occurs would seem to be most effective; however, the barrier should not incite its own inflammatory response and should not decrease fibrinolytic activity or suppress access to oxygen. The ideal product, therefore, should be bioabsorbable, last only 5 to 7 days, be easy to apply, be interposed between all injured surfaces, and not itself incite an inflammatory reaction. The most effective method to date has been the application of a sheet of bioresorbable hyaluronate membrane. This approach has been shown to decrease the formation of adhesions at the site of application.93,94 Multiple reviews have supported that use of this product decreased adhesion formation.95−98 Whether hyaluronate application resulted in decreased incidence of reoperation for adhesive small bowel obstruction remains unclear. Reviews by Kumar and Zeng showed no association between hyaluronate use and incidence of postoperative bowel obstruction nor did hyaluronate decrease the need for operative intervention for intestinal obstruction.96,97 Furthermore, if the membrane is wrapped around an intestinal anastomosis, the leak rate is increased. In a study evaluating longterm follow-up of barrier use, van der Wal and colleagues report no decrease in frequency of bowel obstruction, and barrier use failed to improve quality of life as determined on patient survey.99 Initial concerns that were raised over the safety of hyaluronate barriers appear unfounded, with the exception of iron cross-lined hyaluronate that was withdrawn from the market. A prospective, randomized, controlled trial showed that hyaluronate barriers did not increase the risk of intra-abdominal abscess or pulmonary embolism95; however, in a post-hoc subgroup analysis of 289 patients in whom the hyaluronate membrane was wrapped around a fresh anastomosis, the rates of leak, fistula formation, peritonitis, abscess, and sepsis were increased. Based on these studies and assumptions, the use of hyaluronate membranes in elective abdominal surgery does decrease the amount of postoperative adhesions at the site of application but does not

decrease the incidence of intestinal obstruction or the need for future reoperation for obstruction. Use of these products requires careful consideration, because they are expensive and their clinical benefit appears to be relatively low. Other materials or substances are being developed that may someday move to the forefront of adhesion prevention. These include gel and liquid preparations such as hyaluronic acid and carboxymethylcellulose, hydrogel, fibrin sealant, and protein polymers. Other adhesion barriers include oxidized regenerated cellulose (ORC). ORC has been well studied and does help prevent adhesion formation, but its use requires a blood-free field that at times is not practical to achieve. The use of ORC, like hyaluronate membranes, has not been shown to decrease the incidence of subsequent adhesive small bowel obstruction.101 Strategies including use of postoperative hyperbaric oxygen, peritoneal cell transplantation, and use of fetal-liver mesothelial cells have been described in animal models but have yet to be applied in a clinical setting.102,103

EARLY POSTOPERATIVE SMALL BOWEL OBSTRUCTION Early postoperative small bowel obstruction, herein defined as within 6 weeks of the original operation, is a relatively uncommon problem but remains a real dilemma encountered in every practice performing abdominal operations. It is often difficult, if not impossible, to distinguish early obstruction from postoperative ileus, but fortunately the management is usually quite similar. Patients with suspected early mechanical small bowel obstruction should be managed initially by nasogastric decompression, fluid resuscitation, and correction of any electrolyte abnormalities. After a thorough physical examination and the decision that emergent intervention is not indicated, a search for the cause of obstruction should be undertaken. CT can be helpful in determining the etiology of an obstruction but is notoriously unreliable at differentiating ileus versus partial obstruction. Obstructions caused by extrinsic bowel compression amenable to percutaneous correction, including fluid collections, abscesses, and hematomas, may be diagnosed and treated by percutaneous drainage. CT may be able to detect those causes of obstruction that will likely require operative intervention, such as internal hernia, fascial

dehiscence, and uncontrolled anastomotic leak. Early CT may be warranted in patients who had a laparoscopic operation and have signs of early obstruction, because a port site hernia may be evident and would require prompt operation. Generally, two categories of patients with early postoperative small bowel obstruction have been recognized.76 The first category includes those in whom the obstruction becomes evident within 10 days of an abdominal operation. Conservative management is advised usually as long as signs and symptoms of ischemia and strangulation obstruction are not present and other remediable causes have been excluded. Patients within this time frame are not at a substantially increased risk of bowel-related complications after celiotomy, provided there are no internal hernias and, if the original operation was done laparoscopically, that port site hernias can be excluded. It is important to rule out correctable causes of extrinsic compression and reverse any electrolyte abnormalities, especially if ileus is also suspected. Strangulation obstruction, albeit rare, can occur in this group of patients, and thus a high index of suspicion must always be maintained. The etiology of a strangulation obstruction in this group is almost never related to adhesions but rather to some surgical misadventure, such as internal hernia, an overlooked segment of ischemia at the original celiotomy, bowel entrapped in the fascial closure, or an unsuspected abdominal wall hernia. The second category of patients is those presenting between 10 days and 6 weeks after operation.76 Conservative management is advised whenever possible for patients in this category as well. The risk of iatrogenic bowel complications during and after reoperation so early after celiotomy increases dramatically in this group secondary to the dense adhesions often present during this period after abdominal operation. The time period from 7 to 10 days up until 6 to 12 weeks postoperatively represents the window when the greatest inflammatory reaction is present intraperitoneally. The developing adhesions are highly vascular and friable. If the patient had no or very minimal adhesions at the time of celiotomy, reoperation is warranted; however, in a small, unpredictable group of patients without any previous adhesions, and reliably so in those with dense adhesions that had required substantial adhesiolysis at the time of original celiotomy, an acute inflammatory reaction involving the peritoneal surfaces may agglutinate adjacent loops of bowel, often involving the omentum and mesenteric surfaces.

Operations performed during this period have a much greater rate of iatrogenic injury and subsequent fistula formation. Those patients not responding to conservative management during this period are best placed on parenteral nutrition until the obstruction resolves or they are more than 6 to 12 weeks out from their last celiotomy. At this time, the decision to reoperate is made based on several considerations. First, if the patient had relatively few adhesions at the time of celiotomy, reexploration at 6 weeks to 3 months postoperatively may be warranted. In contrast, in those patients who required an extensive adhesiolysis at the time of original celiotomy, many experienced surgeons wait for a full 6 months prior to reoperation for several reasons: (1) by 6 months, the adhesions are reliably less vascular and more mature; (2) reoperation prior to 3 months may reveal a frozen abdomen in which the obstruction may be unable to be dissected free safely; and (3) the obstruction may resolve as the adhesions mature.

BOWEL OBSTRUCTION AFTER ROUX-EN-Y GASTRICBYPASS SURGERY As with all other operations and maybe more so in the current era of laparoscopic Roux-en-Y gastric bypass (RYGB), bowel obstruction is a worrisome complication after bariatric surgery for morbid obesity. Estimates of the rate of bowel obstruction after RYGB vary within a reported range of 0.3% to greater than 9% depending on the technique used to perform the operation. The rate of bowel obstruction appears to be less after open RYGB, but there are no large prospective studies comparing laparoscopic to open procedures at this time. In a large, collected review of more than 9500 patients undergoing laparoscopic RYGB, the rate of bowel obstruction was 3.6%.104 Although some controversy exists, most authors suggest that the rate of bowel obstruction is less with use of an antecolic versus a retrocolic orientation of the Roux limb for the gastric bypass.104−107 Bowel obstruction after RYGB can occur secondary to a variety of etiologies; however, the four most common etiologies, in decreasing order of frequency, are internal hernia, adhesive obstruction, stenosis at the jejunojejunostomy, and incisional hernia. The diagnosis of bowel obstruction after laparoscopic RYGB is more difficult than after other surgical procedures secondary to the altered gastrointestinal anatomy created by the procedure and the often less typical

response of the patient with morbid obesity. After RYGB, the symptoms of bowel obstruction can be vague, and because the most common etiology is internal hernia, the symptoms are often intermittent. Abdominal pain is the most common symptom present in 82% of patients in one large series, and importantly, nausea and vomiting were seen in fewer than 50% of patients in this series. All three symptoms were present in only 28% of patients.106 Unfortunately, imaging studies also have a lesser sensitivity for bowel obstruction in patients after RYGB, with reported sensitivities of 51%, 57%, and 33% for CT, UGI contrast study, and plain abdominal radiography, respectively.106 When patients with unexpected gastrointestinal symptoms after RYGB are assessed, a high index of suspicion for bowel obstruction is warranted. Given the frequency of internal hernia as a cause of postoperative bowel obstruction and the low sensitivity of radiologic evaluation for bowel obstruction in patients after RYGB, a low threshold for laparoscopic exploration is warranted in patients with suspected bowel obstruction. Internal hernia is the most common cause of bowel obstruction after RYGB. Anatomically, there are three different types of internal hernias seen after RYGB. All three types of internal hernias are transmesenteric defects created during the formation of the Roux limb and are illustrated in Fig. 38-3. The so-called Peterson hernia occurs in the infracolic compartment through the potential space between the mesentery of the Roux limb, the transverse mesocolon, and the retroperitoneum, and can be seen with either an antecolic or retrocolic Roux limb. Herniation through the mesenteric defect created by the jejunojejunostomy is the second site of internal hernia observed after RYGB and can occur with both antecolic and retrocolic gastric bypass. Herniation through the mesenteric defect in the transverse mesocolon created by passage of the retrocolic Roux limb is the third type of internal hernia observed in RYGB and is only seen in retrocolic gastric bypass; this type of internal hernia was the most common type before the importance of meticulous closure of this defect was appreciated. Most authors believe that bowel obstruction after RYGB is substantially more common after laparoscopic retrocolic bypass, with reported rates of 3.2% to 5.1% after retrocolic and 0.3% to 1.7% after antecolic bypass reported in the largest series.104,107 Meticulous closure of all potential hernia spaces with nonabsorbable suture at the time of RYGB is the best way to prevent internal hernia; however, care must be taken when closing the mesocolic defect, because obstruction at the mesocolic window from tight scar formation has

also been reported as a cause of bowel obstruction after RYGB.108 When operating on a patient with internal hernia after RYGB, careful closure of the hernia defect with nonabsorbable suture after reduction in the hernia is the treatment of choice.

RADIATION ENTEROPATHY The management of radiation enteropathy is often difficult and frustrating. The clinical presentation can be quite diverse with recurrent intermittent small bowel obstruction, a true, chronic, persistent partial small bowel obstruction, or chronic diarrhea/malabsorption. Operative management is often extremely challenging secondary to the dense adhesions and chronic inflammatory reaction present after radiation. These patients also tend to develop recurrent areas of enteropathy consistent with progression of disease in bowel that appeared normal previously, because this ischemic disease is an ongoing and progressive chronic process. The need for operative correction with a resection and anastomosis has been reported to have a mortality rate as high as 21% in some series.100 Patients with radiation enteropathy also have a high rate of anastomotic leak and fistula formation after operation because of the compromised vascular supply to the bowel. These effects are magnified in patients with atherosclerosis, hyperlipidemia, or type 2 diabetes. For these reasons, a cautious, conservative approach to the patient with radiation enteropathy is warranted whenever possible. When operative management is necessary, the surgeon must decide between resection, bypass of the affected segment, or adhesiolysis. As noted earlier, resection has been reported to have a high mortality rate, with a 36% incidence of leak after primary anastomosis.94 In the same study, bypass of the affected segment had a 10% mortality and 6% leak rate. Surgeons advocating aggressive resection back to healthy bowel, however, have reported leak rates between 0% and 8% when confounding conditions (abscess, fistula, necrosis, or recurrent cancer) were absent; such an aggressive approach may require an extensive resection but often involves resection of nonfunctional bowel anyway. In their retrospective analysis, Li et al. identified American Society of Anesthesiologists (ASA) class of III to IV, intraoperative transfusion, preoperative anemia, thrombocytopenia, and presence of radiation uropathy as independent risk factors to Clavien−Dindo grade III to IV morbidity when ileal or ileocecal resection was undertaken.109

Given the complexities in managing radiation enteropathy, implementation of a scoring system may help direct care and improve outcomes. Short bowel syndrome is always a concern, especially because the involved bowel is usually the distal ileum. Most surgeons approach the treatment of radiation enteropathy cautiously. In those patients with recurrent cancer and radiation enteropathy, treatment should consist of palliative bypass of the diseased segment with creation of an anastomosis in visibly normal tissue. If the obstructive process is localized, wide resection back to healthy, non-irradiated tissue (if possible) with primary anastomosis is acceptable, provided adequate absorptive area is preserved. Usually this involves anastomosis from small bowel to the ascending colon, because the terminal ileum has usually been within the radiation field. While ideally a complete resection of the entire involved small bowel is optimal, the surgeon must consider the extent of the resection necessary as well as the anatomic segment involved. Because the distal ileum is commonly involved, major resection back to reliably normal, nonirradiated small bowel may require a total or subtotal ileal resection that carries its own nutritional complications. Thus, the surgeon is faced with a decision concerning preservation of mildly involved but functional ileum versus complete resection. In contrast, if the bowel is severely involved and nonfunctional, resection, despite its side effects, may be the best option. When the affected area contains dense adhesions or is stuck deep within the pelvis, bypass may be a better choice to avoid the very real concern of potential iatrogenic injury to the bowel, bladder, pelvic organs, and ureters; however, if there is a localized abscess or associated septic process, bypass is not a good option because the ischemic inflammatory process will continue. Attempts at complete lysis of adhesions alone without resection are controversial due to the risk of traumatizing the intestine with potential fistula formation. For the patient with advanced disease who presents years after irradiation, adhesiolysis may not be a good option, especially if the bowel is matted and agglutinated. In contrast, in the case of isolated adhesive bands and the patient being early (3 cm in size have a high rate of associated malignancy and are most appropriately treated with either pancreas-sparing duodenectomy or pancreaticoduodenectomy for larger lesions or periampullary tumors in suitable operative candidates.18 Surgical series of resected ampullary adenoma report in situ or frank adenocarcinoma in 34% to 40% of patients. Local recurrence is common for periampullary adenomas treated with excision only; recurrence rate was 40% at 10 years, 25% of which were malignant, in a retrospective series from the Mayo Clinic. For patients treated with excision only, annual surveillance with endoscopy is appropriate.19

Lipomas Lipomas of the gastrointestinal tract are typically identified as incidental findings on abdominal imaging. They rarely cause symptoms, although as polypoid, compressible intraluminal lesions, they may serve as lead points for intussusception. Lipomas are circumscribed lesions arising in the bowel wall appearing as fat density on CT imaging. Small tumors under 2 cm require no intervention, whereas larger lesions or growing lesions should be resected to rule out malignant liposarcoma.

Hamartomas The hamartoma is the characteristic lesion of Peutz-Jeghers syndrome, an autosomal dominant condition characterized by multiple gastrointestinal hamartomas and mucocutaneous pigmentation. The tumors are widely distributed throughout the bowel in affected individuals and, in rare cases, are

associated with intussusception, bleeding, or obstruction. While malignant transformation has been described, this is a rare event. Given the broad distribution of the tumors, prophylactic excision is not feasible and surgical intervention is appropriate only to treat complications caused by the tumors.12

Hemangiomas Hemangiomas are rare congenital lesions of the small bowel. They appear to grow slowly and may become symptomatic in midlife, when acute or chronic bleeding may develop. Arising from the submucosal vascular plexuses, hemangiomas are usually solitary and not at risk for malignant transformation. Hemangiomas associated with bleeding should be locally excised or resected with a limited small bowel resection. Endoscopic sclerotherapy or angiographic embolization has also been reported as a treatment option depending on the size and position of the tumor.

Leiomyomas Leiomyomas are rare benign tumors arising from the smooth muscle and stromal cells of the small intestine. Comprised of benign-appearing smooth muscle and stromal cells, they are distinguished from GISTs by molecular features, notably the absence of cKit mutations. These benign lesions are typically clinically silent. Often growing as extraluminal pedunculated lesions, they may present with mucosal ulceration, particularly in tumors originating in the duodenum; gastrointestinal hemorrhage; and bleeding. Symptomatic lesions warrant surgical resection (Fig. 39-2C).

FIGURE 39-2 Gross appearance of tumors of the small intestine. A. Primary adenocarcinoma of the ileum demonstrating circumferential, extensively ulcerated, irregular mass on the mucosal surface with transmural tumor invasion showing thickening and retraction of the bowel wall. Diagnosis was established by CT with CT enterography. B. Renal cell carcinoma metastatic to the jejunum. This hemorrhagic focal lesion presented with occult gastrointestinal bleeding. Diagnosis was established by video capsule endoscopy. C. Leiomyoma of the second portion of the duodenum. This pedunculated extraluminal lesion presented in a patient with abdominal pain. A Whipple resection was performed anticipating GIST tumor. Final pathology revealed benign leiomyoma. D. GIST tumor of the ileum. Patient presented with intussusception diagnosed by CT. Surgical resection of nonreduced bowel performed.

MALIGNANT NEOPLASMS The small bowel can give rise to a number of different primary tumors and is also a site for metastasis from tumors of other origins. Primary malignancies include adenocarcinoma, GIST, carcinoid, lymphoma, and leiomyosarcoma, with rare reports of other lesions including liposarcoma, myxoliposarcoma, and lymphangiosarcoma. Metastatic tumors may come from any other cancer, but the most common metastatic lesions are from melanoma and lymphomas. Malignant tumors are much more likely to elicit symptoms than benign tumors, including abdominal pain, weight loss, anorexia, and acute or chronic blood loss. As a group, patients with malignant small bowel tumors present at advanced stages and have a poor prognosis. Up to 30% of patients with small bowel malignancy develop a second primary tumor in another organ. For patients with SI-NET (carcinoid) tumors, the incidence of second primaries is 50%. The second primary cancer may arise in any organ, but the most frequent second primary sites are the colorectum and breast.20,21

Adenocarcinoma EPIDEMIOLOGY Adenocarcinoma accounts for about 35% of small bowel tumors, making it the most common primary malignancy.7 The frequency of small bowel tumors decreases along the length of the small bowel, with 80% located in the duodenum and proximal jejunum. Men are slightly more likely to develop adenocarcinoma than women. Risk factors for development of adenocarcinoma include polyposis syndromes, Crohn’s disease, and celiac disease.

CLINICAL PRESENTATION Clinical presentation is dictated by the size and position of the tumor. Large tumors form the classic circumferential annular “apple core” constriction, leading to obstruction with symptoms of anorexia, vomiting, and crampy pain. Periampullary lesions may cause biliary obstruction with secondary jaundice. Absent advanced or strategically placed lesions with obstruction,

the only complaint may be vague, persistent abdominal pain.

DIAGNOSIS For patients with advanced lesions, plain abdominal films may show gastric distention or proximal small bowel obstruction. For the jaundiced patient, ultrasound or abdominal CT or MR cholangiopancreatography (MRCP) may demonstrate the duodenal mass and site of biliary obstruction. Upper gastrointestinal contrast studies and EGD have equal diagnostic rates of 85% to 90%, but EGD allows diagnostic tissue biopsy. CT reveals approximately 50% of small bowel adenocarcinomas, and the appearance is that of a heterogeneous infiltrating mass. Despite diagnostic strategies, preoperative diagnosis of cancers beyond the duodenum is achieved in only 20% to 50% of cases.

MANAGEMENT Surgical resection offers the only potential cure (Fig. 39-2A). Many patients have intra-abdominal metastases at initial surgery, with R0 resection (ie, no gross or microscopic disease left) achieved in only 50% to 65% of cases. Pancreaticoduodenectomy is appropriate for proximal duodenal tumors. In the third and fourth portions of the duodenum and in the mesenteric small bowel, a segmental resection with lymphadenectomy should be performed. Palliative procedures to relieve obstruction or control hemorrhage should be completed at the time of exploration for patients with metastatic disease. Endoscopic expandable stents may be the best strategy to palliate proximal gastrointestinal obstruction from recurrent or metastatic disease. Gastrojejunal bypass or gastrostomy tubes may be of palliative value for decompression or nutritional support in patients with carcinomatosis or unresectable disease.

STAGING AND PROGNOSIS The American Joint Committee on Cancer staging system applies to small bowel adenocarcinoma.22 The tumor (T) classification describes depth of invasion, with T1 and T2 lesions within the bowel wall and T3 and T4 lesions penetrating the bowel wall. The node (N) classification is defined by the

presence or absence of lymph node metastases, and distant metastases are classified by M. Most patients present with stage III (lymph node involvement) or stage IV disease (distant metastases), which carry a poor prognosis. The most significant prognostic factor is lymph node metastases, with poor survival linked to node-positive disease. Likely due to limited reported experience, the primary tumor features, including the degree of differentiation, do not appear to impact survival. Positive margins, extramural venous spread, positive lymph nodes, and a history of Crohn’s disease are associated with poor prognosis.6 Adjuvant therapies including chemotherapy and/or radiation therapy have not demonstrated efficacy, although clinical trials are ongoing.20 The rare nature of this tumor, with advanced-stage presentation, precludes development of clinical trials.

Non-Hodgkin Lymphoma The gastrointestinal tract is the most common extranodal site for development of NHL, comprising approximately 20% of all cases of NHL. Most gastrointestinal lymphomas arise in the stomach (60%), followed by the small bowel (30%), and then the colon. Small bowel lymphomas are distributed in the jejunum and ileum, reflecting the distribution of lymphoid tissue in the bowel. Diagnostic criteria for primary gastrointestinal NHL include the absence of superficial adenopathy on physical examination, absence of mediastinal adenopathy by chest imaging, normal peripheral blood cell counts, and absence of splenic or hepatic involvement. At surgery, disease must be restricted to the primary tumor with mesenteric lymph node involvement.23 The majority of cases of primary intestinal NHL are B-cell type with Tcell lymphoma composing only 10–25%. Low-grade lymphomas derived from mucosal-associated lymphoid tissue (MALT) typically arise in the stomach in association with Helicobacter pylori infection. These tumors may regress with treatment of this infection.24,25 T-cell lymphomas tend to have a worse prognosis than B-cell tumors.

CLINICAL PRESENTATION

The majority of patients present with nonspecific abdominal complaints. Malabsorption, obstruction, or palpable mass may be present. Although rare, small intestinal lymphomas may present with perforation.

DIAGNOSIS Lymphomas may grow to large size before clinical symptoms present. Most small bowel lymphomas will be demonstrable on CT scan as a mass, bowel wall thickening, displacement of adjacent organs, or luminal obstruction. Multiple lesions are present in 10% to 25% of patients. Tissue diagnosis requires biopsy of the submucosal lesion by endoscopy or CT-guided biopsy.

STAGING AND PROGNOSIS Staging is based on site involvement as outlined in Table 39-1. Like tumors elsewhere in the small intestine, most patients present with stage III or IV disease. Fewer than 30% of patients have surgically resectable tumors, and prognosis is poor.22 TABLE 39-1: STAGING FOR LYMPHOMA

TREATMENT With no randomized series and small series at single institutions, the optimal treatment of gastrointestinal NHL remains controversial. Most agree that surgical resection of isolated small bowel lymphoma for local control and prevention of perforation and bleeding are the cornerstones of treatment. For more extensive gastrointestinal lymphoma, there is no evidence-based consensus on optimal management, although a variety of chemotherapeutic regimens have been used.23,24

SMALL INTESTINAL NEUROENDOCRINE

TUMORS SI-NETs, previously known as carcinoid tumors,26 arise from the enterochromaffin cells at the base of the crypts of Lieberkühn. This redesignation was initiated based on the recognition that these tumors share cellular origin and synthetic capability of NETs originating throughout the mucosal surfaces of the body. Enterochromaffin cells are capable of amine precursor uptake and decarboxylation (APUD), and tumors derived from these can secrete vasoactive peptides responsible for the carcinoid syndrome. Eighty percent of NETs arise in the gastrointestinal tract, 10% in the bronchus or lung, and others in rare sites including the ovaries, testicles, pancreas, and kidneys. The appendix is the most common site in the gastrointestinal tract for primary NET, followed by the small bowel where these tumors are noted as SI-NETs (Table 39-1). Thirty percent of SI-NETs arise in the jejunum or ileum and have the most aggressive clinical features. SI-NETs represent 5% to 35% of small bowel neoplasms; the mean age of presentation is 60 years with a slight male preponderance. Autopsy rates reveal that the incidence of occult tumors is approximately 2000 times that of the annual clinical incidence rate, indicating that the overwhelming majority never develop clinical findings.24,27

CLINICAL PRESENTATION AND DIAGNOSIS Most SI-NETs grow slowly and have insidious clinical manifestations; in hindsight, symptoms may be present for 2 to 20 years before diagnosis. Carcinoid syndrome secondary to metastatic disease is the presenting sign in 40% of patients. Rarely, intestinal necrosis secondary to desmoplastic occlusion of the mesenteric vessels may develop, leading to initial presentation as a surgical emergency. The most common presenting symptom for patients with SI-NET is abdominal pain. The polypoid lesion serves as a lead point for intussusception characterized by intermittent symptoms and signs of obstruction. Abdominal films often demonstrate a distal small bowel obstruction, and the CT findings of intussusception are distinctive, demonstrating a multilayer ringed structure in the ileocolic region (Fig. 39-3).

FIGURE 39-3 Concentric rings in the soft tissue mass in the right lower quadrant reveal an ileocolic intussusception. An ileal carcinoid tumor was the lead point. Appendiceal NETs are typically solitary lesions. However, for carcinoids arising in other areas of the gut, multiple tumors are observed in 3% to 40% of patients.28 In addition, 30% to 50% of SI-NETs are associated with second primary malignancies, most frequently of the breast and colon. SI-NETs have the capacity to elicit a marked desmoplastic reaction in the mesentery of the small bowel. The fibrotic reaction can cause sclerosis of mesenteric vessels, leading to kinking of the bowel or intestinal ischemia and necrosis. The fibrosis affects not only peritumoral tissues but also distant tissues in the heart and lungs and is attributed to the humoral products of the tumors, although the specific factors are unknown.29,30

STAGING AND PROGNOSIS Appendiceal NET, even at a small size, may cause appendicitis due to

luminal compression; hence, early diagnosis of appendiceal carcinoid is common. In contrast, SI-NETs exhibit a more aggressive phenotype and are frequently associated with lymph node spread and hepatic metastasis at initial presentation. Tumor size is proportional to the risk for metastatic spread. For SI-NETs smaller than 1 cm, there is a 20% to 30% incidence of nodal and hepatic spread. Tumors 1 to 2 cm in size have nodal spread in 60% to 80% of cases and hepatic disease in 20% of cases. The rates of nodal and hepatic metastasis for tumors larger than 2 cm is >80% and 40% to 50%, respectively.27 Only very small SI-NETs (ie, 6 mm), thickwalled appendix that does not fill with enteric contrast or air, as well as surrounding fat stranding to suggest inflammation (Fig. 41-4).35 In a metaanalysis of 12 prospective studies, CT demonstrated a sensitivity of 94% and a specificity of 95%.32 Appendicitis is highly unlikely if enteric contrast fills

the lumen of the appendix and no surrounding inflammation is present. However, the clinician must remember that a CT performed early in the course of appendicitis might not show the typical radiographic findings.

FIGURE 41-4 Computed tomography of acute appendicitis. The arrow points to an enlarged, fluid-filled appendix with wall hyperemia that does not fill with oral contrast. The paucity of intra-abdominal fat limits identification of fat stranding. (Used with permission from M. Stephen Ledbetter, MD, MPH, Brigham and Women’s Hospital, Boston, MA.)

While CT imaging may rule out alternative diagnoses or assist in operative planning, it is important to note that CT imaging only reduces the rate of negative appendectomy among certain patients. Wagner and colleagues36 conducted a review of over 1400 patients who underwent appendectomy for suspected acute appendicitis. The authors discovered that preoperative CT was associated with a lower rate of negative appendectomy only for adult female patients, but not for adult male patients or children.36 A number of prospective studies have compared the accuracy of CT and US in imaging the appendix (Table 41-2).33,37,38 Balthazar and colleagues37 performed CT and US on 100 consecutive patients with suspected appendicitis. The sensitivity of CT was considerably higher (96% for CT vs 76% for US), whereas the specificity was comparable (89% for CT vs 91% for US), yielding a higher accuracy for CT (94% for CT vs 83% for US). CT

was also able to provide an alternative diagnosis in more patients and was better able to visualize an abscess or phlegmon (Fig. 41-5). Horton and colleagues38 randomized patients with suspected appendicitis to either CT or US. Their findings echo those of Balthazar, with both CT and US having high specificity (100% for CT vs 90% for US), but CT demonstrating significantly higher sensitivity than US (97% for CT vs 76% for US). Yet another prospective study showed similar results, with CT having higher sensitivity (96% for CT vs 62% for US) and specificity (92% for CT vs 71% for US) than US33 and better ability to visualize other intra-abdominal pathology in the absence of appendicitis.

FIGURE 41-5 Computed tomography of perforated appendix. Note retrocecal abscess (arrows) with enhancing wall and periappendiceal fat stranding and adjacent cecal thickening (arrowhead). (Used with permission from M. Stephen Ledbetter, MD, MPH, Brigham and Women’s Hospital, Boston, MA.)

TABLE 41-2: ACCURACY OF CT AND US FOR THE DIAGNOSIS OF ACUTE APPENDICITIS

Taken together, these studies suggest an algorithm for evaluation of patients with suspected acute appendicitis. Patients with a history, physical examination, and laboratory studies consistent with appendicitis should undergo appendectomy based on clinical judgment. In those with an evaluation suggestive but not convincing for appendicitis, further imaging is warranted. In women of childbearing age, this should begin with a pelvic US to evaluate for ovarian pathology. For other patients, transabdominal US should be considered initially with a subsequent abdominopelvic CT scan if the diagnosis remains questionable or an intra-abdominal abscess/phlegmon requires better evaluation. Rectal contrast CT is rarely needed but can be employed to better visualize the appendix.33,35 Patients with a CT showing nonperforated appendicitis should undergo appendectomy. In many instances, patients with a normal CT do not require hospital admission. If symptoms persist, admission to the hospital for observation is warranted. Imaging modalities that avoid ionizing radiation may be preferentially used among children and pregnant patients, as discussed below.

DIFFERENTIAL DIAGNOSIS Because many of its signs and symptoms are nonspecific, the differential diagnosis of acute appendicitis is extensive and includes both abdominal and nonabdominal sources of pain (Table 41-3). However, some diagnoses are more likely than others in certain settings. Meckel diverticulitis causes similar symptoms with the possible addition of episodic painless hematochezia but is relatively uncommon.39 Gastroenteritis is considerably

more common and should be expected when nausea and vomiting precede the abdominal pain or when diarrhea is a prominent symptom. Crohn’s disease affecting the terminal ileum may resemble appendicitis in its initial presentation, but on further questioning, the patient may describe a subacute course, including fever, weight loss, and pain. TABLE 41-3: DIFFERENTIAL DIAGNOSIS OF ACUTE APPENDICITIS

Gastrointestinal causes Cecal diverticulitis Sigmoid diverticulitis Meckel diverticulitis Epiploic appendicitis Mesenteric adenitis Omental torsion Crohn’s disease Cecal carcinoma Appendiceal neoplasm Lymphoma Typhlitis Small bowel obstruction Perforated duodenal ulcer Internal hernia Intussusception Acute cholecystitis Hepatitis Pancreatitis Infectious causes Infectious terminal ileitis (Yersinia, tuberculosis, or cytomegalovirus) Gastroenteritis Cytomegalovirus colitis Genitourinary causes Pyelonephritis or perinephric abscess

Nephrolithiasis Hydronephrosis Urinary tract infection Nonabdominal causes Streptococcal pharyngitis Lower lobe pneumonia Rectus muscle hematoma In women Ovarian cyst (ruptured or not ruptured) Corpus luteal cyst (ruptured or not ruptured) Ovarian torsion Endometriosis Pelvic inflammatory disease Tubo-ovarian abscess In pregnancy Ectopic pregnancy Round ligament pain Chorioamnionitis Placental abruption Preterm labor In middle-aged and older adults, other inflammatory conditions should be considered, including gastric or duodenal ulcer (with symptoms from fluid tracking into the right paracolic gutter), cholecystitis, and pancreatitis. In addition, the symptoms of cecal or sigmoid diverticulitis overlap with those of acute appendicitis. Cecal diverticula, like the appendix, are true diverticula containing all layers of the intestinal wall. Cecal diverticulitis, intuitively, is similar in pathogenesis and presentation to appendicitis. Because a redundant, floppy sigmoid colon can extend to the right side of the abdomen, patients with sigmoid diverticulitis can sometimes present with RLQ pain. Those patients typically describe a more rapid progression to localized tenderness, as well as a prodrome of alteration in bowel habits. Malignancies can present with acute RLQ pain due to perforation of a cecal carcinoma or appendicitis caused by tumor obstructing the appendiceal orifice. Such patients will also

often have guaiac-positive stools, anemia, and a history of weight loss. In women of childbearing years, diagnosing the underlying cause of RLQ pain can be even more difficult. In addition to the causes of RLQ pain mentioned above, young women can also have pain from obstetric and gynecologic etiologies such as ruptured ovarian cyst or follicle, ovarian torsion, ectopic pregnancy, acute salpingitis, and tubo-ovarian abscess. A complete history including recent menstrual history, as well as pelvic examination, can be helpful in differentiating these causes of pain from acute appendicitis. Nonetheless, appendicitis can be difficult to diagnose in this patient population, and higher rates of misdiagnosis have been described in women of childbearing age.40

SPECIAL CONSIDERATIONS Children In the pediatric population, appendicitis most commonly afflicts children age 10 to 19 years, with an overall incidence of approximately 20 cases per 10,000 person-years.12 By age 20, approximately 4% of children and adolescents will have undergone an appendectomy.41 Among those younger than 20, infants age 0 to 4 have the lowest incidence of appendicitis (2 cases per 10,000 person-years), but up to two-thirds will present with perforation.42 Perforation is disproportionately common because infants often present later in their disease course due to the difficulty inherent in obtaining an accurate history. The diagnosis is further complicated by diseases of childhood that can mimic appendicitis. For instance, mesenteric adenitis, or inflammation of the mesenteric lymph nodes, can present with fever and RLQ pain. Streptococcal pharyngitis and bacterial meningitis can also present with fever, nausea, and abdominal pain. These diagnoses and others including ovarian cysts, ovarian torsion, urinary tract infection, pelvic inflammatory disease, and complications of a Meckel diverticulum should be considered when evaluating children or adolescents for suspected appendicitis. For the many children with an equivocal history, physical examination, and laboratory data, imaging with US is the preferred initial study.43 US lacks ionizing radiation, does not require contrast or sedation, and is relatively

inexpensive. Unfortunately, however, ultrasonography is operator dependent. A meta-analysis by Doria and colleagues44 of over 7000 patients documents a pooled sensitivity and specificity of 88% (95% confidence interval [CI], 86%-90%) and 94% (95% CI, 92%-95%), respectively, for the sonographic diagnosis of appendicitis. An important determinant in the diagnostic success of US is BMI of the child. The sensitivity of US has been reported to be 76% for children with a BMI below 25, but as low as 37% for children with a BMI of greater than 25. US had 82% sensitivity for appendicitis in one study in which the patient population had a mean BMI of 17.45-47 When US results are indeterminate, cross-sectional imaging with MRI or CT can help identify intra-abdominal pathology. MRI warrants consideration as the preferred second-line imaging test among children with suspected appendicitis, provided that the modality and its interpretation are institutionally available, the child is clinically stable, and the child is of old enough age to tolerate lying still for a relatively lengthy study. MRI lacks ionizing radiation and has at least equivalent sensitivity and specificity to CT. In a single-institution study of 510 MRIs, Kulaylat and colleagues48 reported both a sensitivity and specificity of 97% for the diagnosis of acute appendicitis. The median imaging duration was 11 minutes. In comparison, CT has the benefits of nearly universal availability, ease of interpretation, and rapid examination. ++However, ionizing radiation from CT in childhood theoretically causes a small increase in the lifetime risk of certain cancers.49 Based on estimated radiation exposure from a CT scan, studies have hypothesized that a 1-year-old and 15-year-old would theoretically develop a 0.18% and 0.11% lifetime risk, respectively, of fatal radiation-induced malignancy following a CT scan.45 A recent study by Pearce and colleagues50 studied the long-term outcomes of patients under age 22 who underwent CT examination between 1985 and 2002. The authors reported one excess occurrence of leukemia and one excess occurrence of a brain tumor per 10,000 head CTs. Despite this association between ionizing radiation and malignancy, the retrospective nature of the available research and the small magnitude of the absolute risk of malignancy (given the low overall rate) should be emphasized. Therefore, clinicians should consider the risks and benefits of MRI and CT, and efforts should be directed toward reducing radiation dose when imaging children.51 There is substantial variability in usage of imaging modalities. For

example, in a study by Rice-Townsend and colleagues of data from the Pediatric Health Information System database, hospital utilization of preoperative imaging with CT or US ranged from 21% to 73%.52 In efforts to systematically reduce such variation, Rangel and colleagues proposed an algorithm to diminish the utilization of CT imaging for children with suspected appendicitis. Incorporating laboratory tests and US findings, the rate of CT utilization was substantially decreased, from 21% to 4%, with an unchanged rate of negative appendectomy.53

Elderly Although appendicitis is more common in younger age groups, it is an important cause of abdominal pain in the elderly. Perhaps because of a diminished inflammatory response, the elderly can present with less impressive symptoms and physical signs, longer duration of symptoms, and decreased leukocytosis compared to younger patients.54 Perforation is thus more common, occurring in as many as 50% of patients older than 65.12 These patients may have cardiac, pulmonary, renal, and other comorbidities, resulting in considerable potential morbidity and mortality from perforation. In one series, the mortality from perforated appendicitis in patients older than 80 was 21%.55 These factors argue that RLQ pain in elderly patients must be efficiently investigated. Because of the multiple other possible causes of abdominal pain in this patient population (including malignancy, diverticulitis, and perforated peptic ulcer disease), prompt CT scan should be considered when the diagnosis is in question.

Pregnancy The diagnosis of acute appendicitis in the pregnant patient can be particularly challenging, as nausea, anorexia, and abdominal pain may be symptoms of appendicitis, abnormal pregnancy, and normal pregnancy. The differential diagnosis of appendicitis includes not only the conditions possible in nonpregnant women but also certain conditions specific to pregnancy: ectopic pregnancy, chorioamnionitis, preterm labor, placental abruption, and round ligament pain. In addition, the gravid uterus can displace the abdominal viscera, shifting the location of the appendix cephalad from the RLQ.

Appendicitis affects 1 in every 1400 pregnant women.56 It can occur in any trimester, with perhaps a slight increase in frequency during the second trimester.57 Perforation is most common in the third trimester, potentially resulting from a longer duration from the onset of symptoms to operation.57 In the first and early second trimesters, the presentation of appendicitis is similar to that seen in nonpregnant women. In the third trimester, women may not present with RLQ pain due to cephalad displacement of the appendix by the gravid uterus. Baer and colleagues performed barium enemas on normal pregnant women and found the appendix to migrate superiorly toward the RUQ in later stages of pregnancy.58 Their findings suggest that appendicitis may present with RUQ or flank pain in late pregnancy. Two retrospective studies note that symptoms do not always reflect this cephalad displacement, however. Even in the third trimester, pain and tenderness are more common in the right lower quadrant than the RUQ.56 Several studies highlight the difficulty of clinically diagnosing a pregnant patient with appendicitis. Brown and colleagues59 reviewed case-control studies that defined the relationship between preoperative presentation and the postoperative diagnosis of appendicitis in pregnant patients. Although patients presented with RUQ pain, RLQ pain, and fevers, only nausea, vomiting, and peritonitis were found to significantly correlate with the diagnosis of appendicitis. Furthermore, laboratory values are altered in the setting of pregnancy, and leukocytosis (including with a neutrophilic predominance) can be a normal finding.60 Given the challenge of clinically diagnosing appendicitis in pregnancy, imaging is critical. US is accurate in pregnancy61 and is a useful radiologic study because it has no known adverse fetal effects.62 However, nonvisualization of the appendix is a frequent problem, especially in increasingly advanced gestations.63 In the setting of an US equivocal for appendicitis, MRI is an excellent modality. Like US, to date, no adverse effects of MRI on the developing fetus have been reported.64 In a retrospective, multicenter study of 709 pregnant women with abdominal pain who underwent MRI for the evaluation of acute appendicitis, 66 (9%) had MRI findings consistent with appendicitis. The authors report sensitivity and specificity rates of 97% and 99%, respectively.65 Gadolinium should be avoided due to potential for teratogenicity. If MRI is unavailable or will cause an extreme delay in management, CT imaging of pregnant patients

with suspected appendicitis can and should be performed. The risk of radiation should be weighed against the risk of spontaneous abortion from an unnecessary laparotomy or from undiagnosed appendicitis progressing to perforation. Although ionizing radiation has risks to the fetus, the radiation from a typical abdominopelvic CT is below the threshold of 5 rad (50 mGy) at which teratogenic effects are seen.66 Furthermore, CT imaging protocols can be modified to reduce the amount of fetal radiation, without impacting diagnostic value.67 The pregnant patient should proceed directly to appendectomy if appendicitis is suspected. A normal appendix is not an uncommon finding, as negative appendectomy has been reported in approximately one-third of cases due to the difficulty of diagnosis in this population.56 Negative appendectomy should not be considered an error in management, because the risk to the fetus varies directly with the severity and progression of appendicitis. In a large California inpatient database, the fetal loss rate after negative appendectomy was 4%.56,68 However, fetal mortality was 2% to 5% in cases of nonperforated appendicitis and 6% to 35% in cases of perforated appendicitis.59 These data warrant an expedited approach to appendectomy that favors operation. As laparoscopic appendectomy has become increasingly popular, the technique has been adapted to appendectomy in pregnancy.69 Pregnancy can increase the complexity of the procedure, as the gravid uterus can make laparoscopic visualization difficult, particularly if the appendix is located in the pelvis. In addition, carbon dioxide insufflation of the abdomen results in fetal hypercarbia and decreased placental blood flow, the effects of which have not been completely studied.70 A meta-analysis including 11 studies from 1990 to 2011 with 3415 patients estimated a 91% higher relative risk of fetal loss in the laparoscopic group compared with the open appendectomy group.71 However, a more recent retrospective review from 2009 directly comparing laparoscopic to open appendectomy in 42 pregnant women found no intra- or postoperative complications in either group and 1 fetal loss in both groups.72 Given the large time frame and retrospective nature of included studies in the aforementioned meta-analysis, the conclusions drawn from this synthesis are limited. Caution should be exercised when selecting surgical approach to appendectomy during pregnancy. Furthermore, certain risk-minimizing measures should be taken, such as limiting the degree of

pneumoperitoneum. After uncomplicated appendectomy, there do not appear to be any lasting effects on child development. Choi and colleagues prospectively studied pregnant women who underwent appendectomy.73 Of 29 patients who delivered without complication (1 fetal death occurred due to extreme prematurity) and completed a detailed study survey of developmental milestones, none indicated developmental delay for their child, with a mean follow-up time of nearly 4 years.

Immunocompromise The immunocompromised state alters the normal response to acute infection and wound healing. Appendicitis must be considered among those with abdominal pain who have undergone organ transplantation, are receiving chemotherapy, have a hematologic malignancy, or have decreased CD4 cell counts due to infection with the human immunodeficiency virus (HIV). The differential diagnosis of abdominal pain in the immunosuppressed population is broad and includes hepatitis, pancreatitis (from medications or cytomegalovirus infection), acalculous cholecystitis, intra-abdominal opportunistic infections (cytomegalovirus colitis or mycobacterial ileitis), secondary malignancies (lymphoma or Kaposi sarcoma), graft-versus-host disease, and typhlitis. This broad differential diagnosis often results in delay in diagnosis and late presentation to surgical evaluation, at which time perforation may be more likely.74 Appendicitis in patients with HIV and acquired immunodeficiency syndrome (AIDS) presents unique challenges. Abdominal pain is not an uncommon symptom in these patients, making differentiation between surgical and nonsurgical causes difficult. Nonetheless, immunocompromised patients with appendicitis present with symptoms similar to those of the general population, including RLQ pain, nausea, and anorexia. Fever and WBC may not be helpful in this population given the underlying poor immune response. Therefore, imaging studies, particularly CT, have been supported by some authors.74 There is no specific contraindication to operation in immunocompromised patients. Once diagnosed with appendicitis, appendectomy should be performed promptly.

TREATMENT

Nonoperative Management Appendectomy was one of the first intra-abdominal operations performed, and appendicitis has since been a surgically treated disease. Historically, Treves was an advocate of early nonoperative management of acute appendicitis, even prior to the advent of antibiotics.10 In the postantibiotic era, Coldrey75 presented his retrospective series of 471 patients with appendicitis treated with antibiotics. This treatment failed in at least 57 patients, with 48 requiring appendectomy and 9 requiring drainage of an appendiceal abscess. Decades after this 1959 study, interest in nonoperative management (NOM) has reemerged, based on the results of several randomized controlled trials. NOM is currently a topic of controversy in the contemporary management of acute appendicitis. Recent data suggest that NOM with intravenous antibiotics may present an alternative to appendectomy. This management strategy parallels the treatment of sigmoid diverticulitis and is based on work suggesting that nonperforated and perforated appendicitis are distinct diseases.22 Potential benefits of NOM derive from the upfront avoidance of an invasive procedure, which must be weighed against the risk of immediate progression of disease as well as the long-term risk of recurrent appendicitis. Given the association between appendicolith and complicated appendicitis, patients with this imaging finding should not undergo NOM.76,77 Similarly, these data on NOM do not necessarily apply to other high-risk patients, such as pregnant patients, the immunosuppressed, and the elderly. On the other hand, antibiotic treatment is a useful temporizing measure in environments with no surgical capabilities such as in space flight and submarine travel.78 Of note, early data suggest feasibility of NOM among children with acute appendicitis. A recent prospective, nonrandomized cohort study was conducted of 102 children 7 to 17 years of age with suspected uncomplicated acute appendicitis who were offered the choice of NOM and appendectomy. Among children who underwent NOM, the 1-year rate of appendectomy (ie, 1-year failure rate of NOM) was 24%.79 Potential benefits of NOM in the pediatric population were found to be fewer disability days and lower health care costs related to treatment of appendicitis at 1 year after diagnosis, despite longer initial length of hospital stay.79,80 There are several important issues to highlight when considering NOM.

First, laparoscopic (or open) appendectomy for uncomplicated acute appendicitis is a safe procedure, performed with very low levels of complication. Second, recurrence rates after NOM can be as high as 35%.81 In the recent Appendicitis Acuta (APPAC) study (described below), the recurrence rate of 27% exceeded the predefined threshold of an unacceptably high rate of recurrent appendicitis.82 In addition, imaging alone has a substantial false-negative rate for diagnosing perforated appendicitis.77 For example, in a 2011 trial by Vons and colleagues,77 18% of patients who underwent appendectomy were unexpectedly found to have perforated appendicitis and peritonitis at the time of operation. Finally, NOM does not assess the presence of appendiceal neoplasm, which is discovered in as many as 1.5% of appendectomy specimens.82 An early randomized controlled trial, performed by Eriksson and associates,81 first sought to evaluate the comparative effectiveness of NOM and appendectomy in 1995. The authors randomized 40 adults with presumed appendicitis to appendectomy or 10 days of intravenous and oral antibiotics. The results included a high rate of recurrent appendicitis after NOM. Eight (40%) of the 20 patients in the antibiotic group required appendectomy within 1 year: 1 patient for perforation within 12 hours of randomization and another 7 for recurrent appendicitis (1 of whom had perforation). Since then, several other randomized controlled trials have addressed this same question. Table 41-4 displays the characteristics of 6 important randomized trials comparing the effectiveness of appendectomy and NOM.8186 These data generally suggest fewer workdays lost with NOM and decreased duration and severity of abdominal pain. Initial cost may also be decreased with NOM, although long-term cost in the setting of recurrence and the need for close follow-up is challenging to define. In contradistinction, length of hospital stay tended to be lower with appendectomy. Neoplasm was detected after 0.5% to 1.5% of appendectomies. Recurrence rates after NOM ranged from 8% to 32%. This is consistent with a recent meta-analysis, in which the likelihood of failure was 23%.83 TABLE 41-4: STUDIES COMPARING NONOPERATIVE AND OPERATIVE MANAGEMENT OF ACUTE APPENDICITIS

The most recent and largest to date randomized controlled trial was a noninferiority study by Salminen and colleagues.82 The APPAC trial was performed in 6 Finnish hospitals between 2009 and 2012. The researchers evaluated the effectiveness of antibiotic therapy (intravenous ertapenem for 3 days followed by oral levofloxacin and metronidazole for 7 days) versus open appendectomy (laparoscopic appendectomy was performed only 5% of the time) as the primary treatment for uncomplicated acute appendicitis among nonpregnant patients age 18 to 60 years. Patients with evidence of fecaliths, perforation, abscess, or tumor on CT imaging were excluded. Among patients randomized to NOM, the primary end point was need for appendectomy and recurrent appendicitis during 1-year of follow-up. Based on existing literature, the threshold for noninferiority was set at 24%. There were 273 and 257 patients randomized to appendectomy and NOM, respectively.82 Appendectomy was a successful management strategy 99.6% of the time. In the NOM cohort, 27.3% of patients required an appendectomy within the first year of follow-up, exceeding the a priori threshold for noninferiority. Those with recurrent appendicitis underwent appendectomy at a median of 102 days after initial treatment. The complication rate after appendectomy for recurrent appendicitis in the NOM cohort was relatively low at 7%, compared to a complication rate of 20% in the appendectomy cohort. While this difference was statistically significant, many complications were minor, including superficial surgical site infection and pain-related symptoms. Appendiceal neoplasms were intraoperatively discovered in 1.5% of patients in the appendectomy cohort. In summary, currently available data show a moderately high rate of

recurrence of appendicitis with NOM and a small but important risk of malignancy. As such, for the majority of patients with uncomplicated acute appendicitis, laparoscopic (or open) appendectomy should be considered the gold standard treatment, while NOM may be offered on a case-by-case basis in certain circumstances.

Preoperative Preparation When the decision is made to perform an appendectomy for acute appendicitis, the patient should proceed to the operating room with little delay to minimize the chance of progression to perforation. While in-hospital progression to perforation is rare and most cases of appendiceal perforation occur prior to surgical evaluation, the operation should nevertheless be expedited.20,21 Patients with appendicitis may be dehydrated from fever and poor oral intake. Intravenous fluids should be infused, and vital signs including urine output should be closely monitored. Markedly dehydrated patients may require a Foley catheter to ensure accurate urine output monitoring. Severe electrolyte abnormalities are uncommon with nonperforated appendicitis, as vomiting and fever have typically been present for 24 hours or less but may be significant in cases of perforation. Any electrolyte derangements should be corrected prior to the induction of general anesthesia. Intravenous broad-spectrum antibiotics have been shown to significantly reduce the incidence of postoperative wound infection and intra-abdominal abscess, including after negative appendectomy.41 Antibiotics should be administered at the time of diagnosis and re-dosed appropriately. The typical flora of the appendix resembles that of the colon and includes gram-negative aerobes (primarily Escherichia coli) and anaerobes (Bacteroides species). No standardized antibiotic regimen exists. Acceptable options include a secondgeneration cephalosporin or a combination of antibiotics directed at gramnegative bacteria and anaerobes, tailored to institutional antibiogram. In nonperforated appendicitis, a single preoperative dose of cefoxitin suffices.87 In cases of perforation, an antibiotic course of at least 4 days after source control is obtained is advocated, in accordance with recent findings from the randomized controlled Study to Optimize Peritoneal Infection Therapy (STOP-IT).88

Laparoscopic Versus Open Appendectomy Open appendectomy (OA) has been the standard of care for the surgical management of acute appendicitis since Amyand performed the first appendectomy in 1736. Little changed in the surgical management of this disease until Semm developed the laparoscopic appendectomy (LA) in 1980. Over the ensuing decades, laparoscopy has increasingly taken hold as the preferred approach to appendectomy. In an analysis of the Nationwide Inpatient Sample, Masoomi and colleagues89 documented an increase in the use of laparoscopy for appendectomy over the past decade, from 43% in 2004 to 75% in 2011. Numerous randomized controlled trials have compared these 2 surgical approaches, sometimes with conflicting results.90,91 Meta-analyses and systematic reviews have combined these studies to address the controversy (Table 41-5).92-94 These meta-analyses have similar findings, which can be summarized as follows: (1) OA can be performed more quickly; (2) LA patients have less postoperative pain and reduced narcotic requirements; (3) there is a trend toward reduced length of stay with LA; (4) LA patients have fewer wound infections; (5) OA patients develop fewer intra-abdominal abscesses; (6) LA patients return to work more quickly; (7) operating room and hospital costs are decreased with OA; and (8) societal costs may be decreased with LA.92-94 Based on the available data, one cannot definitively recommend either OA or LA over the other. TABLE 41-5: LAPAROSCOPIC VERSUS OPEN APPENDECTOMY

Laparoscopic appendectomy may be especially advisable for certain patient populations, including for women of childbearing age, obese patients, and the elderly. Among women of childbearing age, obstetric and gynecologic pathology may be clinically indistinguishable from appendicitis, and a normal appendix is found in more than 40% of patients with suspected appendicitis.95 However, when a normal appendix was discovered, gynecologic pathology was found in 73% of women explored laparoscopically but only 17% of women who had an OA.96 Among such patients with uncertain diagnosis, laparoscopy can thus be both diagnostic and therapeutic, avoiding a laparotomy if nonappendiceal pathology is found. Additionally, laparoscopy warrants consideration among obese patients, for whom open dissection is more technically challenging. In a National Surgical Quality Improvement Program (NSQIP) study of obese patients undergoing appendectomy, Mason and colleagues97 reported a 57% reduction in morbidity with laparoscopy, compared to the open approach, after adjusting for preoperative risk factors. For the elderly, LA was found to confer lower mortality (0.4% vs 2.1%) for uncomplicated appendicitis and a less complicated postoperative course (shorter length of hospital stay and higher rate of discharge home) for perforated appendicitis.98 Finally, among children, Esposito and colleagues99 conducted a literature review, which

revealed a lower incidence of surgical site infection, lower analgesic use, and more rapid recovery with laparoscopic, compared to open, appendectomy. Operative time was longer with laparoscopy than laparotomy for complicated appendicitis, but not for uncomplicated appendicitis. Ultimately, the decision of surgical approach to appendectomy should depend on patient factors and surgeon comfort with the technique.

Laparoscopic Appendectomy Multiple port placements for LA exist. The authors use a three-port technique, with an umbilical port, a suprapubic port, and a left lower quadrant port (alternatively, an RLQ port could be used in the place of the latter). Although the third port can be placed in either the left lower quadrant or RLQ, we prefer the left lower quadrant. This follows the laparoscopic principle of triangulation, such that the port locations direct the camera and instruments toward the RLQ for optimal visualization of the appendix. The patient is positioned supine on the operating room table with the left arm tucked to allow room for both the surgeon and assistant (Fig. 41-6). The video monitor is placed at the patient’s right side and, once pneumoperitoneum is performed, the surgeon and assistant both stand on the patient’s left. Prior to incision, a nasogastric tube and a Foley catheter can be placed to decompress the stomach and urinary bladder. A Foley catheter can be avoided if a reliable patient urinates immediately prior to entering the operating room. A 1- to 2-cm vertical or transverse incision is made just inferior to the umbilicus and carried down to the midline fascia. A 12-mm trocar is placed using either Hasson or Veress technique, depending on surgeon preference. After insufflation of the abdomen and inspection through the umbilical port, a 5-mm suprapubic port is placed in the midline, taking care to avoid injury to the bladder. Next, a 5-mm port is placed in the left lower quadrant. These port sites typically provide excellent cosmesis postoperatively due to their small size and peripheral location on the abdomen.

FIGURE 41-6 Laparoscopic appendectomy technique. A. Patient positioning, B. Port placement, C. Creation of mesoappendix window, and D. Transection of the appendix. A 5-mm, 30-degree laparoscope is inserted through the left lower quadrant trocar. Placing the laparoscope in the left lower quadrant allows triangulation of the appendix in the RLQ by instruments placed through the 2 midline trocars. The surgeon operates the 2 dissecting instruments and the assistant operates the laparoscope. The appendix is identified at the base of the cecum at the confluence of the teniae coli. Any adhesions to surrounding structures can be lysed with a combination of blunt and sharp dissection supplemented with electrosurgery. If a retrocecal appendix is encountered, division of the

lateral peritoneal attachments of the cecum to the abdominal wall often improves visualization. Care must be taken to avoid injury to underlying retroperitoneal structures, specifically the right ureter and iliac vessels. The appendix or mesoappendix can be gently grasped with a Babcock clamp placed through the suprapubic port and retracted anteriorly. A dissecting forceps placed through the umbilical port creates a window in the mesoappendix at the appendiceal base. Caution should be taken not to injure the appendiceal artery during this maneuver, the risk of which can be reduced by dissecting close to the appendiceal base and out of the mesoappendix. The base of the appendix should be adequately dissected so that it can be divided without leaving a significant stump.25 The appendix should be divided at the confluence of the appendix and cecum, or just onto the cecal wall, to avoid the possibility of stump appendicitis or mucocele (see Fig. 41-6). The appendix can be removed in a retrograde fashion, first dividing the appendix, followed by division of the mesoappendix. A laparoscopic gastrointestinal anastomosis stapler is placed through the umbilical port and fired across the appendiceal base. After reloading, the stapler is again inserted through the umbilical port and placed across the mesoappendix, which is also divided with firing of the stapler. Alternatively, the appendix can be secured using an Endoloop100 (Ethicon, Endo-Surgery, Cincinnati, OH) and the mesoappendix secured with Endoloop, clips or an electrosurgery device. If desired, the appendix can be removed antegrade by first dividing the mesoappendix prior to directing attention to the base. The appendix should be placed in a retrieval bag and removed through the umbilical port site to minimize the risk of wound infection. The operative field is inspected for hemostasis and can be irrigated with saline, although irrigation is typically not necessary. Finally, the fascial defect at the umbilicus is closed with absorbable 0 suture, and all skin incisions are closed with fine subcuticular absorbable suture. For nonperforated appendicitis, no further antibiotics are required.

Open Appendectomy If OA is chosen, the surgeon must then decide on the location and type of incision. The patient should be reexamined after the induction of general anesthesia, which enables deep palpation of the abdomen. If a mass representing the inflamed appendix can be palpated, the incision can be

centered at that location. If no appendiceal mass is detected, the incision should be centered over McBurney’s point, one-third of the distance from the anterior superior iliac spine to the umbilicus. A curvilinear McBurney’s incision is made in a natural skin fold to avoid tension on the closure. It is important not to make the incision too medial or too lateral. An incision placed too medial opens onto the anterior rectus sheath, rather than the desired oblique muscles, while an incision placed too lateral may be lateral to the peritoneal cavity. The operation proceeds as McBurney first described it in 1894.101 The incision extends through the subcutaneous tissue, exposing the aponeurosis of the external oblique muscle, which is divided, either sharply or with electrosurgery, in the direction of its fibers (Fig. 41-7). A muscle-splitting technique is typically used, in which the external oblique, internal oblique, and transversus abdominis muscles are separated along the orientation of their muscle fibers. The peritoneum is thus exposed, grasped with forceps, and opened sharply along the orientation of the incision, taking care not to injure the underlying abdominal contents. Hemostat clamps can be placed on the peritoneum to facilitate its identification at the time of wound closure. Cloudy fluid may be encountered on entering the peritoneum. Although some advocate bacterial culture of the peritoneal fluid, studies show that this superfluous practice neither helps direct the antibiotic regimen102 nor reduces infectious complications.103

FIGURE 41-7 Open appendectomy technique. With a correctly placed incision, the cecum will be visible at the base of the wound. The incision should be explored with a finger in an attempt to locate the appendix. If the appendix is palpable and free from surrounding structures, it can be delivered through the incision. Frequently, the appendix is palpable, but adherent to surrounding structures. Filmy adhesions can be divided using blunt dissection, but thicker adhesions should be divided under direct vision. The cecum can be partially delivered through the incision to provide better exposure of the appendix. If necessary to further improve exposure, the incision can be extended medially by partially dividing the rectus muscle or laterally by further dividing the oblique and transversus

abdominis muscles. If the nonpalpable appendix cannot be visualized, it can be located by following the teniae coli of the cecum to the cecal base, from which the appendix invariably originates. Once located, the appendix is delivered through the incision. Grasping the mesoappendix with a Babcock clamp can sometimes facilitate this maneuver. The arterial supply to the appendix, which runs in the mesoappendix, is now clamped, ligated with 3-0 silk suture, and divided. This is usually performed in an antegrade fashion, from the appendiceal tip toward the base. As in the laparoscopic approach, adequate dissection is necessary to ensure that the entire appendix can be removed without leaving an excessively long appendiceal stump, thereby allowing the potential for stump appendicitis. In excising the appendix, the surgeon must decide whether or not to invert the appendiceal stump. Traditionally, the appendix had been ligated and divided and its stump inverted with a purse-string suture for the theoretical purpose of avoiding bacterial contamination of the peritoneum and subsequent adhesion formation.104 However, prospective studies show no advantage to appendiceal stump inversion.105 In one such study, 735 appendectomy patients were randomly assigned to ligation plus inversion or simple ligation of the appendiceal stump. There was no difference between the 2 groups in the incidence of wound infection or adhesion formation, and operating time was shorter in the simple ligation group. Inversion may also have the deleterious effect of deforming the cecal wall, which could be misinterpreted as a cecal mass on future contrast radiographs.105 Furthermore, the long-standing notion that stump inversion reduces postoperative adhesions was discredited by Street and colleagues.106 In their analysis, postoperative adhesions requiring operation were significantly increased in the inversion group. To divide the appendix, the surgeon can use either suture ligation or a gastrointestinal stapler. For ligation, 2 hemostat clamps are placed at the base of the appendix. The clamp closest to the cecum is removed, having crushed the appendix at that site. Two heavy, absorbable sutures such as 0 chromic gut are used to doubly ligate the appendix, and the appendix is subsequently divided proximal to the second clamp. The exposed mucosa of the appendiceal stump can be cauterized to minimize the theoretical risk of postoperative mucocele, although no data exist to support this. If appendiceal stump inversion is chosen, a seromuscular purse-string 3-0 silk suture is

placed in the cecum around the appendiceal base after ligation but prior to division of the appendix. The purse-string suture should be placed approximately 1 cm from the base of the appendix, as placing it too close to the appendix makes stump inversion difficult. After the appendix is divided, the purse-string suture is tightened and tied while the assistant uses forceps to invaginate the appendiceal stump. Alternatively, the appendix can be divided at its base using a TA-30 stapler. Again, the stump need not be inverted, but can be if desired, using interrupted Lembert sutures with 3-0 silk suture. No matter how the appendix is divided, the residual appendiceal stump should be no longer than 3 mm to minimize the possibility of stump appendicitis in the future.25 Occasionally, inflammation at the tip of the appendix makes antegrade removal of the appendix difficult. In such cases, the appendix can be removed in a retrograde fashion. In so doing, the appendix is divided at its base using one of the methods described previously. The mesoappendix is then divided between clamps, starting at the appendiceal base and progressing toward the tip (Fig. 41-8).

FIGURE 41-8 Retrograde dissection of the appendix. The base of the appendix is secured with a pursestring suture, transected, and dissected off the cecum. In certain cases, the appendiceal inflammation extends to the base of the appendix or beyond to the cecum. Division of the appendix through inflamed, infected tissue leaves the potential for leakage of cecal contents with a resultant abscess or fistula. Ensuring that the resection margin is grossly free of active inflammation minimizes this risk. If the base of the cecum is also inflamed but there is sufficient noninflamed cecum between the appendix and

the ileocecal valve, an appendectomy with partial cecectomy can be performed using a stapling device.107 Care should be taken to avoid narrowing the cecum at the ileocecal valve. If the inflammation extends to the ileocecal junction, an ileocecectomy with primary anastomosis may be necessary. After the appendix is removed, hemostasis is achieved and the RLQ and pelvis are irrigated with warm saline. The peritoneum is closed with a continuous 0 absorbable suture. This layer provides no strength but helps to contain the abdominal contents during abdominal wall closure. The internal and external oblique muscles are then closed in succession using continuous 0 absorbable suture. To decrease postoperative narcotic requirements, the external oblique fascia can be infused with local anesthetic. Interrupted absorbable sutures are typically placed in Scarpa’s fascia, and the skin can be closed with a subcuticular absorbable suture. With a preoperative dose of intravenous antibiotics and primary closure of the skin, fewer than 5% of patients with nonperforated appendicitis can be expected to develop a wound infection.108

Postoperative Care Postoperative care is similar after laparoscopic and open approaches. Patients with nonperforated appendicitis typically require a 24- to 48-hour hospital stay. Patients can be started on a clear liquid diet immediately, which can be advanced to their preoperative baseline diet as tolerated. No postoperative antibiotics are required for nonperforated appendicitis. Patients can be discharged when they tolerate a regular diet and pain is controlled on oral agents.

PERFORATED APPENDICITIS When appendicitis progresses to perforation, management depends on the nature of the perforation. If the perforation is contained, a solid or semisolid periappendiceal mass of inflammatory tissue can form, referred to as a phlegmon. In other cases, contained perforation may result in a pus-filled abscess cavity. Finally, free perforation can occur, causing intraperitoneal dissemination of purulent fluid and fecal material. In the case of free

perforation, the patient is typically quite ill and perhaps septic. Urgent laparotomy or laparoscopy, as described above, is necessary for appendectomy and irrigation and drainage of the peritoneal cavity. Sometimes patients with free perforation present with an acute abdomen and generalized peritonitis, and the decision to operate is made without a definitive diagnosis. Depending on the clinical stability of the patient, a diagnostic laparoscopy or exploratory laparotomy through a midline incision is performed. Once perforated appendicitis is confirmed, appendectomy again proceeds as described previously. Peritoneal drains are not necessary, as they do not reduce the incidence of wound infection or abscess after appendectomy for perforated appendicitis.109,110 The final operative decision is whether or not to close the surgical site. Because of wound infection rates ranging from 30 to 50% with primary closure of grossly contaminated wounds, many advocate delayed primary or secondary closure.111 However, a cost-utility analysis of contaminated appendectomy wounds showed primary closure to be the most cost-effective method of wound management.112 Our technique of skin closure is interrupted permanent sutures or staples every 2 cm with loose wound packing in between. Removal of the packing in 48 hours often leaves an excellent cosmetic result with an acceptable incidence of wound infection. Patients continue to receive treatment with broadspectrum antibiotics for at least 4 days after source control and should remain in the hospital until afebrile and tolerating a regular diet.88 If the patient does not have signs of generalized peritonitis but an abscess or phlegmon is suspected by history and physical exam, a CT scan can be particularly helpful to confirm the diagnosis. A solid, inflammatory mass in the RLQ without evidence of a fluid-filled abscess cavity suggests a phlegmon. In such instances, appendectomy can be difficult due to dense adhesions and inflammation. Ileocecectomy may be necessary if the inflammation extends to the wall of the cecum. Complications such as inadvertent enterotomy, postoperative abscess, or enterocutaneous fistula may ensue. Because of these potential complications, many support an initially nonoperative approach.113 Such an approach is only advisable if the patient is not clinically ill. Nonoperative management includes intravenous antibiotics and fluids as well as bowel rest. Patients should be closely monitored in the hospital during this time. If fever, tenderness, and leukocytosis improve, diet can be slowly advanced, usually within 3 to 5 days. Patients are discharged home when clinical parameters have

normalized. Using this approach, many patients can be spared an appendectomy at the time of initial presentation. If imaging studies demonstrate an abscess cavity, CT- or US-guided drainage can often be performed percutaneously or transrectally.113 Studies suggest that this approach to appendiceal abscesses results in fewer complications and shorter overall length of stay.113 Again, following drainage, the patient is closely monitored in the hospital and is placed on bowel rest with intravenous antibiotics and fluids. Advancement of diet and hospital discharge progress as clinically indicated.

INTERVAL APPENDECTOMY Treatment following initial nonoperative management of an appendiceal phlegmon or abscess is controversial. Some recommend interval appendectomy114 (appendectomy performed approximately 6 weeks after inflammation has subsided), while others consider subsequent appendectomy unnecessary.115 Factors to be considered when advising patients on interval appendectomy include a relatively low incidence of future appendicitis (8%-10% and often associated with an appendicolith) and a morbidity associated with an interval appendectomy of approximately 11%.115 Importantly, malignancy was detected in 1.2% of cases, and colonoscopy is recommended after resolution of acute disease.115 These factors must be weighed against the higher morbidity associated with an immediate appendectomy in the setting of acute recurrent appendicitis in the future (as high as 36% when appendicitis is associated with a phlegmon or abscess)115 as well as the possibility of an ongoing appendiceal pathology, including inflammatory bowel disease and cancer.115 Because it can now be performed laparoscopically on an outpatient basis and with low morbidity,116 interval appendectomy should be considered for patients who were initially treated for perforated appendicitis with nonoperative management.

NORMAL APPENDIX Because of the difficulty in diagnosing appendicitis, it is not uncommon for a normal appendix to be found at appendectomy. Misdiagnosis can occur more

than 15% of the time, with considerably higher percentages in infants, the elderly, and young women.40 Negative appendectomy must be avoided when possible, because of the risk of surgical complications and the cost associated with unnecessary surgery.117 Nonetheless, in certain instances, a noninflamed appendix is found at laparotomy or laparoscopy. The surgeon must then decide whether or not to remove the appendix. For multiple reasons, it is generally advisable to remove the grossly normal appendix. First, if the pain recurs and the appendix has been removed, appendicitis will no longer be a possibility and can be removed from the differential diagnosis. If the patient suffers RLQ pain in the future and the appendix has not been removed, but the patient has a classic RLQ scar, a surgeon evaluating the patient may assume a history of appendectomy and erroneously disregard appendicitis as a possible diagnosis. As LA becomes more popular, this may even become true for patients with port site scars suggestive of appendectomy. Finally, there is strong evidence that a surgeon’s gross assessment of the appendix can be inaccurate. In one study, 11 (26%) of 43 appendectomy specimens described as normal by the surgeon showed acute appendicitis on pathologic examination.118 As a result, removal of a grossly normal appendix at the time of the operation for suspected appendicitis is recommended. When a normal appendix is discovered at appendectomy, it is important to search for other possible causes of the patient’s symptoms. The terminal ileum can be inspected for evidence of terminal ileitis, which could be from infectious causes (Yersinia or tuberculosis) or Crohn’s disease. If Crohn’s disease is discovered and the cecum is not inflamed, appendectomy should be performed without an increase in complication rate. In the setting of cecal inflammation, appendectomy should not be performed, and appropriate medical therapy for the treatment of newly diagnosed Crohn’s disease should be initiated postoperatively. The ileum should also be evaluated for an inflamed or perforated Meckel diverticulum, which should be excised. In females, the ovaries, fallopian tubes, and uterus should be examined for pathology as well. Evaluation of the left adnexa can be difficult through an RLQ incision, highlighting the utility of laparoscopy for female patients.

CHRONIC APPENDICITIS Although rare, chronic appendicitis can explain persistent abdominal pain in

some patients. Patients do not present with the typical symptoms of acute appendicitis. Instead, they endorse weeks to years of RLQ pain and may have had multiple medical evaluations in the past. When queried, they may describe an initial episode with more classic symptoms of acute appendicitis, for which no treatment was delivered.119 Diagnosis can be difficult, as laboratory and radiologic studies are typically normal. Because the diagnosis is often uncertain preoperatively, laparoscopy can be a useful tool to allow minimally invasive exploration of the abdomen.120 Pathology evaluation revealing chronic inflammation confirms the diagnosis.

ASYMPTOMATIC APPENDICOLITH As CT imaging becomes more widely used, it is likely that an increasing number of asymptomatic appendicoliths will be discovered. As discussed previously, appendicoliths are not pathognomonic for appendicitis but should be considered in conjunction with the clinical presentation and other diagnostic studies. Lowe and colleagues121 compared CT imaging of children with suspected appendicitis to children with abdominal trauma. Six (14%) of 44 patients with suspected appendicitis had an appendicolith but proved not to have appendicitis. In addition, 2 (3%) of the 74 trauma patients had an appendicolith on CT. These children were not followed to see if appendicitis developed later in life, but the considerable number of asymptomatic appendicoliths seen on adult abdominal radiographs suggests that many patients with an appendicolith will never develop appendicitis.16,31 Based on this, appendectomy for asymptomatic appendicolith cannot be recommended.

NEOPLASMS OF THE APPENDIX Neoplasms of the appendix are rare, discovered in less than 1% of appendectomies. Signs and symptoms of appendicitis prompt appendectomy in up to 50% of patients with appendiceal neoplasms, and it is not uncommon for such patients to develop acute appendicitis.122 Patients may also present with a palpable mass, intussusception, urologic symptoms, or an incidentally discovered mass on abdominal imaging or at laparotomy for another purpose. Typically, the diagnosis is not known until the time of operation or pathologic evaluation of the appendectomy specimen. However, preoperative

diagnosis may become more common as imaging techniques improve and become more widely used. Because of their common embryologic origin, the appendix and colon are susceptible to many of the same neoplastic growths. The most common appendiceal tumors include cystic neoplasms, neuroendocrine (carcinoid) tumors, adenocarcinoma, and metastases. Other tumors have been reported but are extremely rare, such as lymphoma, stromal tumors (leiomyoma and leiomyosarcoma), and Kaposi sarcoma.123

Cystic Neoplasms and Pseudomyxoma Peritonei Sometimes referred to as mucoceles, mucinous neoplasms of the appendix include a spectrum of benign and malignant diseases, including simple cyst, mucinous cystadenoma, mucinous cystadenocarcinoma, and pseudomyxoma peritonei. Mucocele is not a true pathologic diagnosis and instead refers to the macroscopic appearance of an appendix distended with mucus. Any of the above conditions can grossly form a mucocele, but the more specific diagnostic term is more precise.124 The term low-grade appendiceal mucinous neoplasm (LAMN) can be used to refer to mucinous tumors with low-grade cytology, whereas tumors with high-grade cytology are classified as mucinous cystadenocarcinoma.125 The pathway from mucinous cystadenoma to cystadenocarcinoma is postulated to be akin to that of progression from colonic polyps to adenocarcinoma. A simple cyst results from nonneoplastic occlusion of the appendiceal lumen, is usually less than 2 cm in diameter, and is often an incidental finding at appendectomy. In contrast, mucinous cystadenomas, benign tumors that represent the majority of “mucoceles,” can grow to 8 cm or larger (Fig. 41-9).126 Patients typically remain asymptomatic due to slow-growing distension of the appendix and instead present incidentally with a mass on physical examination or abdominal imaging (Fig. 41-10). On plain radiograph or CT, wall calcification is characteristic.124 Ten-year disease-free survival progresses from 100% in low-grade mucinous neoplasms confined to the appendix, to 88% in low-grade mucinous neoplasms with extra-appendiceal acellular mucin, to 9% in low-grade mucinous neoplasms with extra-appendiceal neoplastic epithelium, to 0% in appendiceal mucinous neoplasms with poor prognostic markers of invasion, complex architecture, or high-grade cytology.127

FIGURE 41-9 A 14-cm mucinous cystadenoma of the appendix. The appendiceal tip is to the left, and the base is to the right. (Used with permission from Jacqueline M. Wilson, MD, PhD, Brigham and Women’s Hospital, Boston, MA.)

FIGURE 41-10 Computed tomography axial image at the level of the terminal ileum shows a fluid-filled mass (arrowhead) corresponding to the mucinous cystadenoma seen in Figure 41-9. The more proximal appendix (arrow) is seen between the mass and cecum. (Used with permission from M. Stephen Ledbetter, MD, MPH, Brigham and Women’s Hospital, Boston, MA.)

Mucinous appendiceal masses should be surgically removed because of the potential for underlying malignancy.126 In one study of 129 patients who underwent resection of appendiceal mucoceles, Stocchi and colleagues noted that tumor size was not statistically related to risk of malignancy.126 For mucinous cystadenoma, appendectomy is sufficient if the lesion does not involve the appendiceal base. Occasionally, the mass will rupture prior to or at the time of removal, but this rupture is typically contained to the RLQ and is considered localized pseudomyxoma peritonei (see below). If the mass is benign, appendectomy and removal of any residual mucin are curative.126 Mucinous cystadenocarcinoma represents the malignant form of cystic neoplasms of the appendix. In contrast to cystadenoma, patients are more likely to be symptomatic with abdominal pain, weight loss, an abdominal mass, or signs of acute appendicitis. Right hemicolectomy should be performed in the setting of any indication of malignancy in an appendiceal mass with the possibility of cure.126 The laparoscopic approach is not generally recommended because of the possibility of malignancy and the risk of spillage of mucin-secreting cells throughout the abdomen. Because of an association with colon and rectal carcinoma, a screening colonoscopy is recommended postoperatively.126 It is not uncommon, however, for the malignant diagnosis to be unknown until the pathologic evaluation of the appendectomy specimen indicates incidental appendiceal mucinous cystadenocarcinoma. In such cases, reoperation with right hemicolectomy is recommended, as 5-year survival for mucinous cystadenocarcinoma is 75% after hemicolectomy and less than 50% after appendectomy alone.128 Some referral centers advocate extensive initial resections including omentectomy, as well as repeated debulking procedures for recurrent disease.129 Pseudomyxoma peritonei is a condition in which tumor perforation has seeded the peritoneum with mucinous tumor cells. On physical exam, increasing abdominal girth may also be present, suggesting perforation and peritoneal dissemination of mucin-secreting cells characteristic of

pseudomyxoma peritonei. Diffuse pseudomyxoma peritonei is highly predictive of malignancy; in one series, 95% of patients with pseudomyxoma had an associated mucinous cystadenocarcinoma.126 The recommended treatment consists of a minimum of a right hemicolectomy with debulking of any gross spread of disease and removal of all mucin. Recently, hyperthermic intraoperative chemotherapy (HIPEC) is increasingly being used. Chua and colleagues130 report results from a large multicenter study of 2298 patients with pseudomyxoma peritonei from appendiceal origin who were treated with cytoreductive surgery and HIPEC. The authors document a median survival and progression-free survival of greater than 16 and 8 years, respectively. Outcomes were significantly worse for those with gross residual disease after debulking surgery. Data from a French multicenter study indicate that patients with pseudomyxoma peritonei should be referred to centers with experience in their treatment, as higher center volume was significantly associated with improved disease-free survival.130 Long-term management involves debulking for symptomatic disease, with a high likelihood of repeated surgery.

Adenocarcinoma Primary adenocarcinoma of the appendix is classified into 3 types: mucinous (discussed previously), colonic, and signet-ring cell. The colonic type is least common, least likely to secrete mucin, and most likely to present with acute appendicitis due to obstruction of the appendiceal lumen.124 Staging is distinguished from that of colonic adenocarcinoma in the American Joint Committee on Cancer staging manual.131 The colonic type has a less favorable prognosis, with only 41% 5-year survival after treatment, compared to 71% for the mucinous type. The optimal treatment is right hemicolectomy, and reoperation should be recommended if the diagnosis is made on pathologic evaluation of an appendectomy specimen.128 Signet-ring cell type confers the poorest prognosis. The effectiveness of adjuvant chemotherapy or radiotherapy on primary appendiceal adenocarcinoma is unknown. HIPEC may be considered for patients with disseminated appendiceal adenocarcinoma, with promising results from a series of 46 consecutive patients with median overall survival and disease-free survival of 56.4 months and 20.5 months, respectively.132

Carcinoid Tumors The most common neoplasm of the appendix, carcinoid tumors, compose more than 50% of all appendiceal tumors.122 Among malignant tumors of the appendix, carcinoids are less aggressive and carry a much more favorable prognosis than adenocarcinomas, with 5-year survival approaching 90%.133 Most appendiceal carcinoids are found incidentally at the time of appendectomy for appendicitis. However, perhaps because the majority of appendiceal carcinoids are located at the tip of the appendix, the carcinoid mass is the cause of appendicitis only 25% of the time.123 Tumor size, extent of disease, and histology are the primary determinants of malignant potential. Approximately 75% of carcinoids are less than 1 cm in size and only 5% to 10% are over 2 cm. Lymph node invasion and distant metastases are rare except in tumors over 2 cm.134 In a pooled summary of 517 patients, nodal metastasis were found in 0%, 7.5%, and 33% of patients with tumors ≤1 cm, 1.1 to 1.9 cm, and ≥2 cm, respectively.135 Goblet cell carcinomas were previously categorized as a subtype of carcinoid but have characteristics of both carcinoid and adenocarcinoma.136 Goblet carcinoma behaves more aggressively than classic carcinoid but still has a better prognosis than adenocarcinoma.133 Reflecting this in a study of 2812 patients with appendiceal neuroendocrine tumors in the National Cancer Database, Hsu and colleagues reported a 5-year overall survival rate of 86% for malignant carcinoid tumor, 78% for goblet cell carcinoid, and 56% for composite goblet cell carcinoid-adenocarcinoma.137 Treatment of appendiceal carcinoid is dictated primarily by tumor size. Regardless of the operation, it is important to visually inspect and palpate the bowel to investigate the possibility of multifocal disease. Simple appendectomy is sufficient for tumors less than 1 cm in diameter because of the low likelihood of lymph node involvement. Among patients with tumors of 1 to 2 cm in diameter, right hemicolectomy is reserved for patients with positive margins or deep mesoappendiceal invasion, higher proliferation rate (grade 2), or angioinvasion.138 For masses larger than 2 cm, right hemicolectomy is recommended. Because of a concern for increased metastatic potential, some authors also advocate right hemicolectomy regardless of tumor size in the setting of young patients; carcinoids at the appendiceal base; and/or histopathologic evidence of lymphatic invasion,

lymph node involvement, spread to the mesoappendix, tumor-positive resection margins, or cellular pleomorphism with a high mitotic index.139

SMALL BOWEL DIVERTICULA Small bowel diverticula can be characterized according to their anatomic location (duodenal, jejunoileal, and distal ileal diverticula) or the type of diverticula (false or true diverticula). Small bowel diverticula are typically false diverticula, which by definition do not contain all the layers of the bowel wall and involve herniated mucosa and submucosa. They occur at points of weakness, where blood vessels enter the mesenteric border of the small bowel. In contradistinction, intraluminal diverticula occur from congenital abnormalities. Finally, a distal ileal (Meckel) diverticulum is a true diverticulum containing all of the layers of the small bowel. It is a congenital anomaly resulting from the failure of the vitelline duct to obliterate and is located along the antimesenteric border of the distal ileum. Although the presence of small bowel diverticula is not uncommon, most are asymptomatic and thus never appreciated. Fewer than 4% of small bowel diverticula cause symptoms, including inflammation, hemorrhage, obstruction, perforation, and malabsorption.

Duodenal Diverticula Duodenal diverticula (DD) account for approximately 45% of small bowel diverticula and have a reported incidence on radiologic and autopsy studies of 5% to 22%.140 They are rarely multiple (12%), and the vast majority (88%) are located in the medial wall of the second portion of the duodenum.141 When the diverticulum is located adjacent to the ampulla of Vater, as is often the case, it is known as a perivaterian or periampullary diverticulum. DD typically occur in patients age 50 to 65 years and are often asymptomatic at presentation. Less than 5% of patients with DD present with symptoms, including nausea, vomiting, RUQ abdominal pain, fevers, chills, and bleeding. These presentations are often noted in case reports and result from one of many potential complications, including inflammation, obstruction of the duodenum or biliary-pancreatic duct, fistula formation in the bile duct, bezoar formation inside the diverticulum, and perforation. Although it is the

most unusual complication, DD perforation is the most serious and can carry a mortality of up to 20%. Perforation usually results from acute inflammation but may also result from enterolithiasis, ulceration, increased intraluminal pressure (eg, during endoscopy), abdominal trauma, gallstones, or ischemia. Perforation usually occurs posteriorly and thus can result in a retroperitoneal abscess and sepsis. Anterior perforation can also occur, resulting in intraperitoneal spillage or communication with surrounding structures. Of resultant fistulae, including to the pancreas, colon, and gallbladder, the most catastrophic is duodenal perforation into the aorta. The nonspecific nature of the presenting symptoms and their commonality with other gastrointestinal diseases such as pancreatitis, cholecystitis, cholangitis, and peptic ulcer disease highlight the fact that the diagnosis of a complicated DD is often one of exclusion (unless one of the aforementioned unique presentations occurs). Radiologic studies including plain abdominal films and US may be helpful to exclude other etiologies but are not definitive. CT imaging and upper endoscopy are the modalities of choice for evaluation. In the case of an inflamed diverticulum, CT may demonstrate a thickened duodenal wall and surrounding fat inflammation. If perforation has occurred, an extraluminal collection of air and fluid (predominantly retroperitoneal) may be identified. In addition, the administration of oral contrast with a CT scan or an upper gastrointestinal swallow study may define the extent of a leak in the case of a perforation. However, it is rare to identify a DD on CT scan, and additional studies may be required. Sideviewing endoscopy and endoscopic retrograde cholangiopancreatography (ERCP) are valuable in correctly diagnosing the presence of a DD as well as potentially treating some of the associated complications. Successful endoscopic management of hemorrhage, duodenal obstruction, pancreatobiliary obstruction resulting in pancreatitis or cholangitis, and retroperitoneal abscess drainage associated with a DD have been reported.142 The management of DD depends on the presence or absence of symptoms and the clinical stability of the patient. Given the precarious typical location of a DD near the ampulla of Vater and the concomitant morbidity associated with resection, asymptomatic DD discovered on imaging or endoscopy for other reasons should be observed. Symptomatic DD can be managed endoscopically, nonoperatively, or with surgical exploration and resection or bypass. If inflammation with or without perforation is present, nonoperative management, including nasogastric decompression, antibiotics, serial

examinations, and radiologic-guided drainage if an abscess is present, has been reported. This approach can be considered in patients with mild symptoms who are clinically stable or when CT confirms a contained leak.140-142 If the patient is not a candidate for nonoperative management because of hemodynamic instability, generalized peritonitis, or persistent severe symptoms, the choice of surgical intervention depends on such factors as the location of the diverticulum and other intraoperative findings. In the setting of minimal inflammation and favorable diverticular anatomy, a simple closure of the perforated diverticulum or diverticulectomy with single- or double-layer duodenal closure after Kocherization of the duodenum is the treatment of choice. After repair, appropriate drainage tubes should be placed and the greater omentum can be used to reinforce the repair. It is imperative to avoid damaging the pancreatic and distal common bile ducts during the repair, so cannulation of the ampulla of Vater (either retrograde or antegrade through the cystic duct with subsequent cholecystectomy) can be performed to help visualize the ampulla prior to dissecting the diverticulum. At times, diverticular anatomy is unfavorable with significant inflammation at the site of the diverticulum, the diverticulum buried in the pancreatic head, or the papilla located deep in the diverticulum. In such cases, a diversion should be performed by either a distal gastrectomy with a Billroth II reconstruction or a Roux-en-Y gastrojejunostomy. Again, appropriate drainage tubes are typically placed to decompress the affected areas. In addition to diversion and diverticulectomy, segmental duodenal resection for a perforated DD has also been reported for the rare case of a DD located in segment III or IV of the duodenum. A pancreaticoduodenectomy may also be necessary if the DD lies in close proximity to the common bile and pancreatic ducts and the inflammation is thought to be too severe for safe diversion or drainage.140,142 If symptoms derive from obstruction of the pancreaticobiliary system, causing cholangitis or pancreatitis, resection of the duodenum may not be required. In such cases, treatment may consist of diversion of bile flow with a Roux-en-Y choledochojejunostomy and duodenojejnuostomy.142

Jejunoileal Diverticula The least common of the small bowel diverticula, jejunoileal diverticula (JID) have a rare prevalence of 0.002% to 5% based on postmortem and enteroclysis studies. The risk of diagnosis increases with age and peaks in the

sixth and seventh decades of life. JID are acquired pseudodiverticula believed to result from a jejunoileal dyskinesia causing increased intraluminal pressures and ultimately herniation of the mucosa and submucosa through the weakest site of the muscularis propria of the bowel wall (ie, the mesenteric border where paired blood vessels enter the bowel wall). They can be single (33%) or multiple (66%) and located in the jejunum (55%-80%), ileum (15%-38%), or both (5%-7%).143 Interestingly, patients with JID also frequently have other coexisting gastrointestinal diverticula, including those found in the colon (20%-70%), duodenum (10%-40%), esophagus, and stomach (2%), highlighting a potential common etiology.144 Most patients with JID are asymptomatic (up to 70%). When symptomatic, the diagnosis of a JID is often challenging because patients often present with vague abdominal symptoms. There is no gold standard imaging technique used to diagnose a JID. Upper gastrointestinal studies with small bowel follow-through as well as traditional enteroclysis and CT enteroclysis studies are beneficial. CT, tagged red blood cell scan, or angiogram may demonstrate findings consistent with a complication of a JID such as inflammation, perforation, or bleeding. Capsule endoscopy and double-balloon endoscopy are useful in diagnosing small bowel disorders and may be of benefit in identifying JID in a nonacute setting.144 Ultimately, JID are often identified on exploratory laparotomy or laparoscopy for other indications or for the evaluation of chronic or acute symptoms.144 Asymptomatic, incidentally discovered JID need not be resected. When symptomatic, patients with JID can be divided into those with acute or chronic symptoms. Forty to 60% of patients with a known diagnosis of JID present with chronic symptoms. These symptoms are often nonspecific and include nausea, vomiting, postprandial bloating, recurrent abdominal pain, cramping, weight loss, fatigue, and failure to thrive. Because of the vague nature of the presenting symptoms, these patients often go undiagnosed or misdiagnosed for several months (average 22 months) prior to being correctly diagnosed.143 The underlying pathophysiology of the chronic symptoms is believed to be related to either intestinal dyskinesia or bacterial overgrowth from blind loop syndrome due to stasis in the diverticular lumen. When bacterial overgrowth and a blind loop syndrome are present, the patient may develop malabsorption, steatorrhea, and megaloblastic anemia resulting from vitamin B12 deficiency. Frequently, chronic symptoms from JID can be

successfully managed medically. Medical management consists of a lowresidue diet, antispasmodics, antacids, analgesics, and vitamin B12 supplementation. Bacterial overgrowth and blind loop syndrome can be initially managed with antibiotics. In the rare case in which medical management fails, patients may require resection of the segment of bowel containing the diverticulum with subsequent primary anastomosis. Approximately 10% to 19% of patients with JID present with acute, often emergent, symptoms resulting from a complication of the diverticulum, including gastrointestinal hemorrhage, diverticulitis, obstruction, fistula formation, and perforation. The presentation and management of a patient with an acute complication of a JID depend on the complication. Inflammation resulting in diverticulitis occurs in 2.3% to 6.4% of patients with JID and can present as mild abdominal pain or diffuse peritonitis associated with free perforation.143 If perforation occurs in the setting of fullthickness necrosis, it can be associated with a mortality of up to 40%.143 Traumatic and foreign body perforations of JID have also been described. If the perforation is contained within the mesentery, nonoperative management with bowel rest and antibiotics with or without percutaneous drainage can be attempted. Similarly, in a clinically well patient, asymptomatic pneumoperitoneum in the setting of a known JID is not an absolute indication for surgery and this scenario may be managed nonoperatively.143 Lack of clinical improvement after a period of nonoperative management, however, mandates resection of the affected segment of bowel with a primary anastomosis. Similarly, patients presenting with more significant findings of fever, elevated WBC, peritonitis, and septic physiology require immediate laparotomy with resection of the affected segment of bowel.143 Of patients with JID, 2% to 4.6% present with obstruction related to adhesions, intussusception, volvulus, and extrinsic compression from a fluidfilled diverticulum or, rarely, from an enterolith formed in the diverticulum causing obstruction at the diverticulum or at the ileocecal valve. Obstruction believed to be secondary to adhesions can initially be managed conservatively. However, if nonoperative management fails, lysis of adhesions and segmental bowel resection of the JID with a primary anastomosis are required. Similarly, surgical resection is indicated for the management of obstruction resulting from intussusception, volvulus, or extrinsic compression.144 Enterolith ileus associated with a JID is best

managed by an initial attempt at manual lysis of the stone without an enterotomy. If not possible, the stone can be retrieved, advanced into the colon, and/or mechanically fractured through an enterotomy performed in a nonedematous segment of bowel.145 If 1 or multiple diverticula appear inflamed or scarred, segmental resection of the involved bowel with a primary anastomosis is mandated. However, many patients often have multiple diverticula over a long stretch of bowel, and thus, if no evidence of inflammation or scarring is present, avoiding resection is indicated.143 Approximately 3% to 8% of patients with JID present with bleeding complications. Hemorrhage from a JID can be slow and chronic in nature or acute and massive presenting with hemorrhagic shock. Upper and lower endoscopies are often negative, and the diagnosis is made with angiographic and radioactive red blood cell studies. Although successful intervention with angiographic embolization has been documented, segmental bowel resection is frequently the required treatment.143,146

Meckel Diverticula Meckel diverticula are the most common congenital malformations of the gastrointestinal tract, occurring in 1% to 3% of the population.147 A Meckel diverticulum is a true diverticulum containing all 3 layers of the intestinal wall. The structure results from the failure of the obliteration of the vitelline (omphalomesenteric) duct, which normally occurs during the fifth to seventh weeks of fetal life. Blood supply derives from the vitelline artery, a branch of the superior mesenteric artery. It is typically located on the antimesenteric border of the small bowel within 100 cm of the ileocecal valve. Although Meckel diverticula are often lined with ileal mucosa, they may also contain ectopic gastric, duodenal, colonic, and endometrial mucosa as well as pancreatic tissue, carcinoid tissue, Brunner’s glands, and hepatobiliary tissue.148 Gastric mucosa, followed by pancreatic tissue, is the most commonly occurring heterotopic tissue. Similar to other small bowel diverticula, the majority of Meckel diverticula are asymptomatic and discovered incidentally at the time of an operation for other indications. Recent reviews indicate that up to 84% of Meckel diverticula found at operation were asymptomatic. A symptomatic Meckel diverticulum can present in both the pediatric and adult population.

However, the frequency of presentation decreases with increasing age. There is a male predominance (3:1) of both symptomatic and asymptomatic Meckel diverticula in both pediatric and adult populations.147 Symptomatic presentation results from one of many potential complications, including bleeding, obstruction, diverticulitis, perforation, intussusception, ulceration, and, rarely, the presence of malignancy within the Meckel diverticulum. In the adult population, the most common presentations are bleeding (38%), obstruction (34%), and diverticulitis (28%). In the pediatric population the most common presentations are obstruction (40%), bleeding (31%), and diverticulitis (29%).147,148 Obstruction may result from the Meckel diverticulum serving as a lead point for intussusception, a point of fixation for volvulus, or as a result of an adhesive band to the diverticulum. Bleeding in the setting of a Meckel diverticulum is believed to result from acid secretion from ectopic gastric mucosa, leading to ulceration of and subsequent bleeding from ileal mucosa. The typical presentation is episodic, painless gastrointestinal hemorrhage. The most common sites of ulceration are the base of the diverticulum at the juncture between ectopic gastric and ileal mucosa, followed by the mesenteric ileal mucosa. Among patients who develop malignancy in the Meckel diverticulum, carcinoid predominates. Finally, just as an Amyand hernia contains the appendix, a Littre hernia contains a Meckel diverticulum. The most common type of Littre hernia is inguinal in adults and umbilical in children.149 Preoperative diagnosis of a symptomatic Meckel diverticulum can be difficult. A technetium-99m pertechnetate scan is the most accurate noninvasive study used to interrogate the presence of a Meckel diverticulum. The tracer used in this study is specific for ectopic gastric mucosa, and thus false-positive results may occur when a duplication cyst containing gastric mucosa is present. A false-negative result occurs if the Meckel diverticulum does not contain ectopic gastric mucosa. During the study, a bladder catheter can be used to avoid accumulation of contrast media obscuring the area of interest. Despite these limitations, studies have found technetium-99m pertechnetate scans to be highly sensitive and specific in both the pediatric and adult populations.147 In cases of a suspected bleeding Meckel diverticulum, angiography, and a tagged red blood cell scan may be of diagnostic value. If suspicion is high, other etiologies have been ruled out, and noninvasive diagnostic tools exhausted, exploratory laparoscopy may be used to diagnose and treat a complicated Meckel diverticulum.

Surgical resection is indicated for symptomatic Meckel diverticula. Options for resection include a diverticulectomy or a segmental bowel resection with a primary anastomosis. Indications for segmental bowel resection include damage to the normal ileal mucosa due to ulceration or bleeding as well as the presence of diverticulitis or palpable ectopic tissue at the diverticular-intestinal junction.148 In other circumstances, a diverticulectomy can be performed if amputating the diverticulum at its base will not compromise the ileal lumen. If diverticulitis is present, the line of resection should be free of inflammation. Amputation should be performed in a transverse orientation and can use a surgical stapling device. The staple line can then be oversewn with interrupted 3-0 silk Lembert sutures. Alternatively, the diverticulum can be resected between bowel clamps and the defect sutured closed transversely in 2 layers, using a continuous inner layer of 3-0 Vicryl or chromic suture followed by an outer layer of 3-0 silk Lembert sutures. In either case, the surgeon should identify and ligate the artery perfusing the Meckel diverticulum. For an asymptomatic Meckel diverticulum incidentally discovered on imaging study, we recommend nonoperative management. The potential benefit of an operation is outweighed by the high number needed to treat (n = 758) and the risk of complications with diverticulectomy or bowel resection.150 For an asymptomatic Meckel diverticulum incidentally discovered during an operation, the appropriate action is slightly less clear and likely depends on patient selection. In a meta-analysis that includes nearly 3000 patients, Zani and colleagues150 report that the postoperative complication rate was significantly higher among patients who underwent incidental diverticulectomy (5.3%) compared to those with the Meckel diverticulum left in situ (1.3%). Furthermore, of the 64 patients included in the systematic review who did not undergo resection of their asymptomatic Meckel diverticulum, none developed complications with long-term followup. Caution should be used when interpreting these data, which incorporate the findings of dated and retrospective studies.150 The authors proceed to argue that appendicitis is 50-fold more likely to occur than symptomaticity from a Meckel diverticulum.150 While incidental appendectomy has become an obsolete practice, incidental diverticulectomy may have even less utility. Despite this, the risk of developing symptoms was estimated to be as high as 6%, and selected asymptomatic patients may be at higher risk than others.

As such, some authors support incidental diverticulectomy for any patient who fulfills any of the following criteria: (1) younger than 50 years, (2) male sex, (3) diverticulum greater than 2 cm in length, and (4) ectopic or abnormal features within a diverticulum. These criteria are based on a review of 1476 patients who underwent incidental diverticulectomy at a single institution between 1950 and 2002.148 Of those, 1238 patients were asymptomatic and 238 were symptomatic. The aforementioned criteria were significantly associated with symptomaticity in multivariable analysis. The decision to resect an asymptomatic Meckel diverticulum should be made on a case-bycase basis, based on these patient factors.

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104. Kingsley DP. Some observations on appendicectomy with particular reference to technique. Br J Surg. 1969;56(7):491-496. 105. Engström L, Fenyö G. Appendicectomy: assessment of stump invagination versus simple ligation: a prospective, randomized trial. Br J Surg. 1985;72(12):971-972. 106. Street D, Bodai BI, Owens LJ, et al. Simple ligation vs stump inversion in appendectomy. Arch Surg Chic Ill 1960. 1988;123(6):689-690. 107. Poole GV. Management of the difficult appendiceal stump: how I do it. Am Surg. 1993;59(9):624625. 108. Lemieur TP, Rodriguez JL, Jacobs DM, Bennett ME, West MA. Wound management in perforated appendicitis. Am Surg. 1999;65(5):439-443. 109. Greenall MJ, Evans M, Pollock AV. Should you drain a perforated appendix? Br J Surg. 1978;65(12):880-882. 110. Petrowsky H, Demartines N, Rousson V, Clavien P-A. Evidence-based value of prophylactic drainage in gastrointestinal surgery: a systematic review and meta-analyses. Ann Surg. 2004;240(6):1074-1084; discussion 1084-1085. 111. Cohn SM, Giannotti G, Ong AW, et al. Prospective randomized trial of two wound management strategies for dirty abdominal wounds. Ann Surg. 2001;233(3):409-413. 112. Brasel KJ, Borgstrom DC, Weigelt JA. Cost-utility analysis of contaminated appendectomy wounds. J Am Coll Surg. 1997;184(1):23-30. 113. Oliak D, Yamini D, Udani VM, et al. Initial nonoperative management for periappendiceal abscess. Dis Colon Rectum. 2001;44(7):936-941. 114. Lugo JZ, Avgerinos DV, Lefkowitz AJ, et al. Can interval appendectomy be justified following conservative treatment of perforated acute appendicitis? J Surg Res. 2010;164(1):91-94. 115. Andersson RE, Petzold MG. Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis. Ann Surg. 2007;246(5):741-748. 116. Freitas MS, Glick PL. Interval appendectomy for acute appendicitis. J Pediatr Surg. 2009;44(5):1056-1058. 117. Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide analysis. Arch Surg Chic Ill 1960. 2002;137(7):799-804; discussion 804. 118. Grunewald B, Keating J. Should the “normal” appendix be removed at operation for appendicitis? J R Coll Surg Edinb. 1993;38(3):158-160. 119. Mattei P, Sola JE, Yeo CJ. Chronic and recurrent appendicitis are uncommon entities often misdiagnosed. J Am Coll Surg. 1994;178(4):385-389. 120. Klingensmith ME, Soybel DI, Brooks DC. Laparoscopy for chronic abdominal pain. Surg Endosc. 1996;10(11):1085-1087. 121. Lowe LH, Penney MW, Scheker LE, et al. Appendicolith revealed on CT in children with suspected appendicitis: how specific is it in the diagnosis of appendicitis? AJR Am J Roentgenol. 2000;175(4):981-984. 122. Connor SJ, Hanna GB, Frizelle FA. Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomies. Dis Colon Rectum. 1998;41(1):75-80. 123. Deans GT, Spence RA. Neoplastic lesions of the appendix. Br J Surg. 1995;82(3):299-306. 124. Pickhardt PJ, Levy AD, Rohrmann CA, Kende AI. Primary neoplasms of the appendix: radiologic spectrum of disease with pathologic correlation. Radiogr Rev Publ Radiol Soc N Am Inc. 2003;23(3):645-662. 125. Misdraji J. Appendiceal mucinous neoplasms: controversial issues. Arch Pathol Lab Med. 2010;134(6):864-870. 126. Stocchi L, Wolff BG, Larson DR, Harrington JR. Surgical treatment of appendiceal mucocele. Arch Surg Chic Ill 1960. 2003;138(6):585-589; discussion 589-590.

127. Pai RK, Beck AH, Norton JA, Longacre TA. Appendiceal mucinous neoplasms: clinicopathologic study of 116 cases with analysis of factors predicting recurrence. Am J Surg Pathol. 2009;33(10):1425-1439. 128. Nitecki SS, Wolff BG, Schlinkert R, Sarr MG. The natural history of surgically treated primary adenocarcinoma of the appendix. Ann Surg. 1994;219(1):51-57. 129. Smith JW, Kemeny N, Caldwell C, et al. Pseudomyxoma peritonei of appendiceal origin. The Memorial Sloan-Kettering Cancer Center experience. Cancer. 1992;70(2):396-401. 130. Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(20):2449-2456. 131. Overman MJ, Fournier K, Hu C-Y, et al. Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade. Ann Surg. 2013;257(6):1072-1078. 132. Chua TC, Al-Alem I, Saxena A, Liauw W, Morris DL. Surgical cytoreduction and survival in appendiceal cancer peritoneal carcinomatosis: an evaluation of 46 consecutive patients. Ann Surg Oncol. 2011;18(6):1540-1546. 133. McCusker ME, Coté TR, Clegg LX, Sobin LH. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973-1998. Cancer. 2002;94(12):3307-3312. 134. Roggo A, Wood WC, Ottinger LW. Carcinoid tumors of the appendix. Ann Surg. 1993;217(4):385-390. 135. Rorstad O. Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol. 2005;89(3):151-160. 136. Tang LH, Shia J, Soslow RA, et al. Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. Am J Surg Pathol. 2008;32(10):1429-1443. 137. Hsu C, Rashid A, Xing Y, et al. Varying malignant potential of appendiceal neuroendocrine tumors: importance of histologic subtype. J Surg Oncol. 2013;107(2):136-143. 138. Pape U-F, Perren A, Niederle B, et al. ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology. 2012;95(2):135-156. 139. Goede AC, Caplin ME, Winslet MC. Carcinoid tumour of the appendix. Br J Surg. 2003;90(11):1317-1322. 140. Martinez-Cecilia D, Arjona-Sanchez A, Gomez-Alvarez M, et al. Conservative management of perforated duodenal diverticulum: a case report and review of the literature. World J Gastroenterol. 2008;14(12):1949-1951. 141. Jang LC, Kim SW, Park YH, Kim JP. Symptomatic duodenal diverticulum. World J Surg. 1995;19(5):729-733. 142. Schnueriger B, Vorburger SA, Banz VM, Schoepfer AM, Candinas D. Diagnosis and management of the symptomatic duodenal diverticulum: a case series and a short review of the literature. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2008;12(9):1571-1576. 143. Woods K, Williams E, Melvin W, Sharp K. Acquired jejunoileal diverticulosis and its complications: a review of the literature. Am Surg. 2008;74(9):849-854. 144. Kassahun WT, Fangmann J, Harms J, Bartels M, Hauss J. Complicated small-bowel diverticulosis: a case report and review of the literature. World J Gastroenterol. 2007;13(15):2240-2242. 145. Harris LM, Volpe CM, Doerr RJ. Small bowel obstruction secondary to enterolith impaction complicating jejunal diverticulitis. Am J Gastroenterol. 1997;92(9):1538-1540. 146. El-Haddawi F, Civil ID. Acquired jejuno-ileal diverticular disease: a diagnostic and management challenge. ANZ J Surg. 2003;73(8):584-589.

147. Sagar J, Kumar V, Shah DK. Meckel’s diverticulum: a systematic review. J R Soc Med. 2006;99(10):501-505. 148. Park JJ, Wolff BG, Tollefson MK, Walsh EE, Larson DR. Meckel diverticulum: the Mayo Clinic experience with 1476 patients (1950-2002). Ann Surg. 2005;241(3):529-533. 149. Skandalakis PN, Zoras O, Skandalakis JE, Mirilas P. Littre hernia: surgical anatomy, embryology, and technique of repair. Am Surg. 2006;72(3):238-243. 150. Zani A, Eaton S, Rees CM, Pierro A. Incidentally detected Meckel diverticulum: to resect or not to resect? Ann Surg. 2008;247(2):276-281.

SHORT BOWEL SYNDROME AND INTESTINAL TRANSPLANTATION Diego C. Reino • Douglas G. Farmer

INTRODUCTION Intestinal failure (IF), including surgical short bowel syndrome (SBS), is a life-threatening condition that is associated with several major medical complications as well as limitations in quality of life. The evolution of treatment strategies for IF/SBS has seen significant changes in the past 30 years. Like several major advances in surgery, the discovery of anastomotic techniques by Alexis Carrel in the early 1900s paved the way for intestinal transplantation (ITx). As a parallel to surgical discoveries, the development and implementation of parenteral nutrition (PN) and hormonal analogs has allowed clinicians to support IF patients and bridge them toward the ultimate therapy of ITx. The purpose of this chapter is to provide an overview of the causes and medical management of IF/SBS, indications for and various

surgical techniques within ITx. The chapter reviews the landmark developments in surgical therapy techniques and provides an outline for the different technical variations within ITx.

BACKGROUND/HISTORY The evolution in the medical management of IF/SBS has relied heavily on the advent of PN. Prior to 1968, patients who suffered a massive infarction of their small intestine were often left unresected at the time of laparotomy due to the lack of intravenous nutritional support in the perioperative setting.1 This often led to consecutive operations for resections of necrotic bowel and patients would ultimately succumb to sepsis and multiorgan failure. The first major breakthrough for PN was ushered in as an alternative therapy for the IF patient in 1968. Wilmore and colleagues were able to demonstrate that the infusion of a hypertonic nutrient solution through a dedicated central venous catheter (CVC) could deliver all of the necessary nutrients to sustain growth and development in an infant with intestinal atresia and IF/SBS.2 This development was a major stepping stone that paved the way for the surgical developments that followed. Richard Lillehei and Thomas Starzl established the early techniques of ITx in canine models in the 1950-1960s.3,4 However, the first reports of ITx came in the mid-1980s when Williams, Starzl, and others documented the first successful isolated intestine, multivisceral, and liver-intestine transplants in humans.5−8 Together, these landmark medical and surgical establishments set the groundwork for the modern era of ITx.

PATHOPHYSIOLOGY OF INTESTINAL FAILURE AND ADAPTATION The complex mechanisms and relationships of the neurohormonal, enteric nervous, and immune systems of the intestine are beyond the scope of this chapter. However, it must be noted that IF/SGS results from an inadequate delivery of micronutrients, fluid, and electrolytes via the gastrointestinal tract. In the IF/SBS patient, compensatory mechanisms of adaptation can be achieved in the remnant bowel in an attempt to restore the threshold for

nutrient delivery.9−11 Clinically, the cornerstone of successful adaptation relies upon enterocyte mass. Likewise, patients with a greater length of functional bowel and the presence of an ileocecal valve (ICV) are likely to succeed at achieving an adapted state. The functional response of the remnant gut in the IF/SBS patient is primarily to modify sodium, water, and glucose absorption. Enterocyte hyperplasia contributes to increasing enterocyte mass; however, modifications in enterocyte-specific gene expression that leads to improved nutrient trafficking also adds a functional increase to the enterocyte mass, thus rendering an adapted state.9−11 These molecular mechanisms have been the foundation that have led to the surgical concepts which focus on bowel lengthening procedures. The techniques such as the Bianchi and the serial transverse enteroplasty (STEP) procedures strive to increase overall enterocyte mass, and these are discussed in further detail later in this chapter.

INTESTINAL FAILURE: DEFINITIONS AND CLASSIFICATIONS Historically, “short bowel syndrome” was a blanket term that had been used for patients who suffered a catastrophic loss of bowel length that rendered them incapable of maintaining enteral nutrition. These patients were all managed with total parenteral nutrition (TPN), and thus there was no need to further stratify the definition or causes of IF. Advances in prenatal and neonatal intensive care along with more recent developments in medical therapies such as recombinant growth hormone, somatostatin, and glucagonlike peptide-2 (GLP-2) analogs have forced us to further classify the definition of IF. In 2006, a group of experts developed a consensus definition whereby “Intestinal failure results from obstruction, dysmotility, surgical resection, congenital defect, or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte or micronutrient balance.”12 With a well classified definition, we are now better able to evaluate the relative efficacy of these therapies and thus offer some patients the opportunity to regain nutritional autonomy free of PN or intravenous fluids.12 Thus, it is important to recognize that while IF can occur as a result of surgical resection of the gut (“short bowel syndrome”) it can also result from conditions that disrupt gastrointestinal motility or enterocyte function. In these latter cases, the length of remnant intestine is irrelevant and

usually normal.

PEDIATRIC CAUSES OF INTESTINAL FAILURE The pathogenesis of IF in the pediatric population can be classified into (1) anatomic/surgical reductions of bowel (necrotizing enterocolitis, intestinal atresia, gastroschisis, and midgut volvulus), (2) neuromuscular diseases of the gut (intestinal aganglionosis or Hirschsprung disease), chronic intestinal pseudoobstruction, and (3) congenital diseases of the intestinal epithelium (microvillous atrophy, tufting enteropathy, intestinal epithelial dysplasia). In some cases, overlap can occur as in a pseudo-obstruction patient with multiple small bowel resections. The details of the complex medical management and maintenance of nutrition in this patient population is beyond the scope of this chapter. However, it must be noted that growth can be achieved on long-term PN, and the aim of appropriate medical management should be to prevent complications of PN such as catheterrelated sepsis and vascular thrombosis. Moreover, a combined use of early enteral feeding with supplemental PN can help prevent intestinal failure −associated liver disease (IFALD) as the ultimate complication of PN use.

ADULT CAUSES OF INTESTINAL FAILURE IF within the adult population is largely attributable to massive resection of bowel following a catastrophic event suffered by the patient. Generally, it is the result of a surgical complication from a previous procedure.13 However, adult causes of IF can be categorized into iatrogenic complications, ischemic complications, infiltrative disease processes, obstruction related, and functional problems (see Table 42-1). TABLE 42.1: ETIOLOGIES OF INTESTINAL FAILURE

When referring to iatrogenic complications, we will focus on how IF/SBS can occur as a result of bariatric surgery for example. These patients are at risk of developing postoperative adhesions, incisional hernias, mesenteric ischemia, and internal hernias that can occur after a mesenteric defect is created during Roux-en-Y gastric bypass (RYGB) surgery. Internal hernias can develop through this defect that result in an obstruction and ultimately infarction of significant segments of bowel. The incidence of internal hernias is approximately 5% in patients who have undergone RYGB.14 The three main locations where internal hernias can develop are posterior to the roux limb mesentery known as the Petersen hernia, through the mesenteric defect created for the jejunojejunostomy, or through the transverse mesocolic defect created for a retrocolic roux limb (Fig. 42-1).15 Although the incidence of internal hernias is low, the treatment of this complication is highly timesensitive and if left unexplored, catastrophic loss of bowel can occur that renders the patient with SBS if they are even able to survive the initial insult.

FIGURE 42-1 Three potential sites for internal herniation after Roux Y gastric bypass. (Reproduced with permission from Huang, CK. Essentials and controversies in bariatric surgery. London, UK: IntechOpen Limited; 2014.)

Ischemic events can be classified based on the distribution of blood supply to the bowel; namely, the celiac axis, the superior mesenteric artery (SMA), and the inferior mesenteric artery (IMA). The celiac trunk supplies blood to the liver, stomach, duodenum, and the foregut up to the proximal jejunum. The SMA takes over and perfuses the remainder of the small bowel and the colon up to the splenic flexure. Finally, the IMA supplies blood to the remainder of the colon and rectum. Ischemia to these segments of bowel can occur as a result of direct trauma from penetrating missile/stab injuries or blunt trauma, as described by Asensio in his multi-institutional, retrospective series.16 In this review, the authors highlighted that although the incidence of these injuries is minimal, at approximately 1%, they are often lethal and the patients who survive are often left with a short segment of bowel. More commonly, embolic events from atrial fibrillation and severe atherosclerotic vascular disease results in perfusion defects, with the most devastating being to the SMA.17 These patients can often present with the sine qua non of “pain out of proportion to physical exam”; however, the onset of symptoms can be insidious, and late intervention is often fatal. After diagnosis with helical CT

scan, angiographic or open embolectomy is often undertaken with the hopes of instituting thrombolytic therapy and reconstituting blood flow. The advantage of open procedures in this scenario is the ability to inspect the bowel and thus facilitate a second-look laparotomy if needed. Mesenteric venous thrombosis is another type of vascular insult that can occur, although less commonly. The most common clinical scenario is that of a chronically ill or institutionalized patient who becomes progressively dehydrated, resulting in venous thrombosis. Without sufficient outflow, the bowel becomes progressively engorged, ultimately restricting arterial inflow resulting in ischemia. In previously healthy individuals, mesenteric venous thrombosis can often occur after routine laparoscopic surgery as a result of pressure effects from pneumoperitoneum. These clinical scenarios often coincide with an underlying hypercoagulable disorder such as Protein S or C deficiency that contributes to the mesenteric venous thrombosis.18 The infiltrative processes that lead to IF/SBS are from small bowel amyloidosis or desmoid, carcinoid, and other metastatic tumors that not only invade the bowel wall but can often infiltrate the vasculature at the mesenteric root, compromising long segments of bowel. Desmoid tumors are often associated with Gardner syndrome, and these tumors create a desmoplastic reaction with a subsequent area of dense fibrosis that cause local obstructions and enterocutaneous fistulae formation.19 Carcinoid tumors (see Chapter 40) are similar to desmoids; however, they are also notorious for mesenteric involvement, with a dense desmoplastic reaction that results in much wider areas of bowel resection.19 Finally, metastatic cancers that infiltrate the small bowel or retroperitoneum such as gynecologic tumors, colon cancers, and retroperitoneal sarcomas can all cause the same degree of local destruction as primary bowel tumors. Functional causes of IF/SBS are largely due to pseudo-obstruction, Hirschsprung disease, or scleroderma, which were briefly mentioned in the “Pediatric Causes of Intestinal Failure” section. These are pure motility disorders that affect the transit and ultimate absorption of nutrients. The functional causes of IF/SBS are generally diagnosed at a young age, although they can progress into adolescence and even early adult years if patients can be maintained on effective PN. Crohn’s disease is mainly classified as a mucosal etiology of IF/SBS (see Chapter 46 ). Although SBS is classically defined by having less than 200 cm

of bowel, Crohn’s results in SBS due to the malabsorption that occurs at the mucosal surface, rendering patients with normal bowel length functionally with SBS. The severe forms of Crohn’s disease result in IF/SBS through the development of fistulae, bowel perforations, and abscesses which frequently necessitate surgical resection and subsequent gradual shortening of bowel.20 The cornerstone of treatment for Crohn’s disease are the aminosalicylates, antibiotics, corticosteroids, and immunosuppressants such as Azathioprine and 6-mercaptopurine. However, newer therapies such as anti-TNF drugs (infliximab, adalimumab) are being used with the intention to reduce morbidity and the amount of bowel resections that are associated with moderate to severe Crohn’s disease.21 In an effort to ward off the need for ITx, bowel lengthening procedures such as the STEP procedure and stricturoplasty are often being employed in order to preserve bowel length in Crohn’s patients.22,23 Intractable diarrhea of infancy comprises a spectrum of disorders that includes microvillous atrophy or microvillous inclusion disease, tufting enteropathy, and autoimmune enteropathy. The general features of these congenital enteropathies are that they affect the development of the intestinal mucosa that leads to intractable diarrhea during infancy and is not related to a bacterial or viral pathogen. The clinical features of these disorders are large volume diarrhea associated with electrolyte abnormalities and the ultimate need for PN. Although the clinical features are distinct, diagnosis is most commonly achieved with histopathological analysis.

ASSESSMENT OF SBS-ASSOCIATED INTESTINAL FAILURE Patients with SBS and IF/SBS often have very complex past medical histories and the approach to their care can be overwhelming. When evaluating these patients, it is of paramount importance to approach the evaluation in a consistent, systems-based manner. Langnas et al. best described the components of the history and physical evaluation as follows: 1. A thorough review and summary of the past medical record. This is extremely important and painstaking. Every effort should be made to review appropriate surgical and pathological documentation to confirm

the preexisting diagnoses. 2. The cause of SBS, the anatomy and length of the intestine, including a detailed review of prior surgical procedures and any related complications. Upper GI small bowel series, barium enema, and endoscopic studies should be reviewed to determine the anatomy of the remnant bowel and anastomotic locations. 3. The number of central lines and the reasons they were changed. 4. Causal microorganisms for central line infections. 5. Nutritional assessment including parenteral and enteral intake, daily caloric requirements, and macro- and micronutrient components of PN. 6. Laboratory evaluation including serum electrolytes, liver function tests, glomerular filtration rate (GFR), albumin/prealbumin, prothrombin time, vitamin B12, fat-soluble vitamins, serum citrulline, and stool calprotectin levels. 7. Detailed vaccination status. 8. Complete physical exam with focus on hydration status, nutritional status (height, weight, basal metabolic index), type of central line, and inspection for signs of nutritional deficiencies and complications from PN such as dermatitis or signs of chronic liver disease.24

PARENTERAL NUTRITION IN THE INTESTINAL FAILURE PATIENT Prognostic factors for adaptation include length of remnant bowel, location (ileum>jejunum), presence of ICV, absence of stoma, presence of colon in continuity, absence of liver disease, age of patient, time since onset, and the absence of an underlying GI disease/disorder. Of the aforementioned factors, the length and function of a patient’s remnant bowel are the main parameters that determine the need for PN dependence. In all cases of IF/SBS, it is critical to first assess the ability to maintain at least partial enteral nutrition, as it has been shown that partial feeding via the enteral route is associated with a better prognosis than a nonfunctioning gut.25 Thus, exclusive use of PN should be avoided because this population of patients has the highest incidence of vascular, infectious, and metabolic complications including IFALD.26−30 To that end, a thorough assessment to determine the ability to

establish intestinal/colonic continuity and to surgically correct any forms of obstruction in order to restore intestinal continuity should be carried out prior to initiating PN. The typical PN formula contains macronutrients (in the form of hypertonic dextrose up to 70%), lipids, amino acids, vitamins, minerals, electrolytes, and fluid. Conceptually, the dextrose is included as a source of carbohydrate delivery, protein as crystalline amino acids, lipids provide essential fatty acids, and sterile water helps meet the patient’s fluid requirements.1 It should also be noted that all of the components of PN including electrolytes, vitamins, and trace elements play a collaborative role in nutritional efficiency, and along with energy, in maintaining a positive nitrogen balance. Thus, when instituting a home PN plan, it is important to ensure that the patient and caregivers are properly trained and capable of executing the plan at home.

COMPLICATIONS OF PARENTERAL NUTRITION Problems related to PN can be broken down into three categories: catheterrelated, metabolic, and organ dysfunction.31 Catheter-related problems are the most demanding components of caring for IF/SBS patients; however, it must be recognized that these catheters and maintenance of vascular access are literally the lifelines for these patients. Ideally, CVCs should be tunneled and placed in the superior vena cava (SVC) with the tip outside of the heart borderline on the post-procedure chest x-ray. These catheters should ideally be reserved for PN only and should be single lumen, although patients who are chronically requiring other intravenous solutions such as IV antibiotics or frequent replacement fluids may benefit from a dual-lumen catheter. CVC thrombosis and occlusion are the most common complications associated with the use of these catheters, having been reported in up to 60% of patients.31 However, CVC-related infections carry a very high morbidity and if not recognized early can be fatal. The single most common organism that is being isolated in patients receiving home PN is coagulase-negative Staphylococcus (CONS), accounting for up to 60% of home PN bacteremias. This is followed by Enterococcus, S. aureus, and Candida sp. Gram-negative bacteria account for 14% to 25% of infections.32−34 It is important to

recognize that the management of CVC infections in this patient population is different from most patients. Typically, a suspected CVC infection mandates removal of the catheter, particularly in the inpatient setting. In IF/SBS patients, however, a trial of broad-spectrum antibiotics while leaving the suspected catheter in situ is important in order to preserve as many future access sites as possible. If 48 hours of antibiotics has not demonstrated clinical improvement or if the patient is clinically worsening during the trial period, then removal of the tunneled catheter is warranted. If the suspected organism causing the sepsis is a fungus, earlier removal is recommended. Metabolic complications generally are related to fluid/electrolyte disturbances and macro- or micronutrient delivery problems. The complexities of management of hyper- and hypoglycemia are beyond the scope of this chapter. However, it is critical to acknowledge that IF/SBS patients often have high-output ostomies or enterocutaneous fistulae, both of which require higher additional water and electrolyte replacements and vigilant attention to the patient’s hydration status. It is known that these patients live in a chronically dehydrated state, and this contributes to a silent renal insufficiency that is not always readily apparent. Blood urea nitrogen (BUN) and creatinine are not reliable indicators of renal function in these patients, as they are often sarcopenic, and these variables will often underestimate the degree of renal impairment. Ament and others at UCLA have previously demonstrated that children with IF who were on TPN had a reduction in yearly GFR that was inversely correlated with chromium concentration in TPN as well as the duration of TPN use.35 Thus, we have made it our practice to follow the GFR closely for these patients in the outpatient setting, and our intestinal transplant evaluation process includes a nuclear medicine GFR study to accurately determine the patient’s renal function. Organ dysfunction is the final stage of PN-related complications. In addition to the renal insufficiency discussed above, other organ systems that can be injured with PN include the skeletal system (osteomalacia, osteopenia, osteoporosis), intestine (bacterial overgrowth, increased permeability, and bacterial translocation), neurologic (memory disturbance), gallbladder (sludge/cholelithiasis/dyskinesia) and liver (steatosis, cholestasis, fibrosis, cirrhosis, and portal hypertension). IFALD is a well-recognized complication of PN for both children and adults. It is commonly identified by the presence of jaundice, although that

represents an advanced stage of liver disease. More conventional practice has focused on using liver function tests at 1.5 times the upper limit of the reference range, for at least 2 weeks, and in the absence of another cause to define the presence of IFALD.35,36 Given the large variation in defining IFALD, incidence estimates are often difficult to obtain. It has been consistently reported, however, that approximately 50% of children on PN for 4 to 12 weeks have cholestasis, but in adults there is a much wider variation in frequency of IFALD, with around 30% to 50% having a mild disturbance of liver function tests and between 2% and 30% becoming cholestatic after a median of 6 months of PN.26,37−40 Nonetheless, it is important to recognize that a large proportion of patients on PN will suffer from some form of liver injury, and the early signs of IFALD must be recognized and treated with adjustment of PN formulas that reduce total calories and increase the carbohydrate:lipid ratios. If allowed to progress, decompensated IFALD can occur very rapidly, and this accounts for the high mortality rate of patients awaiting combined liver and intestine transplants.

EMERGING PHARMACOLOGIC OPTIONS FOR INTESTINAL FAILURE The period of adaptation following the onset of SBS-associated intestinal failure is believed to last approximately 24 months. The process of adaptation occurs through both structural (villous cell hyperplasia, increased crypt depth, and intestinal dilatation) and functional (increased mucosal enzyme activity and reduction of intestinal transit) mechanisms leading to a gradual increase in absorptive capacity. Nutritional (eg, glutamine) and non-nutritional (eg, growth factors) substances have been implicated in promoting this adaptive response. In the last decade, most intestinal failure research has been focused on exploring the potential of these substances as supportive intestinal failure treatment. However, clinical trials so far have not demonstrated reproducible or meaningful clinical benefits with the use of glutamine or growth hormone.41 GLP-2 is a 33-amino acid peptide that has shown great promise in helping intestinal failure patients achieve PN independence. Human and animal studies have revealed that dietary fiber and short-chain fatty acids, carbohydrates, and fats are potent stimulators of GLP-2 secretion.41 GLP-2

exerts a wide variety of effects on the gastrointestinal tract and is a key mediator of intestinal adaptation. In animal studies, GLP-2 treatment induces mucosal growth in the small and large intestine through an increase in crypt cell proliferation and a reduction of villous cell apoptosis. This increase in mucosal mass is accompanied by enhanced functional absorptive capacity. Recent multicenter, placebo-controlled studies of GLP-2 in SBS patients demonstrated meaningful reduction of up to 20% less PN use in patients who received GLP-2.42 Future studies using GLP-2 in combination with other growth hormones could potentially pave the path toward PN independence for many intestinal failure patients.

AUTOLOGOUS LENGTHENING TECHNIQUES OF THE GI TRACT The basic principles behind surgical adaptation are to recruit and optimize the surface area of unused intestine in order to improve intestinal function and achieve enteral nutrition. First and foremost, fistulae and ostomies must be closed and bowel obstructions must be surgically relieved. Once this has been achieved, bowel tapering and lengthening procedures can be performed. Prior to embarking on these often-treacherous surgical explorations, it must be deemed that the patient has a reasonable chance to achieve independence from PN and that the remaining bowel length and function will not be better served by transplantation. Several surgical options exist, such as reversed segments, colonic interposition, and nipple valve construction. These techniques have not been widely used or commonly successful. We will primarily focus on the more commonly used non-transplant surgical options including the Bianchi procedure (longitudinal lengthening) and the STEP procedures.

Bianchi Procedure The Bianchi procedure was first described in 1980 in a pig model.43 It was then applied to humans, and several published reports became available in the 1990s depicting their results. In brief, the technical conduct of the procedure intends to achieve longitudinal length by dividing the small bowel at either end of a dilated loop. The plane between both leaves of the mesentery is then

developed so as to maintain the blood supply to both of the stapled ends of bowel. A GI stapling device is then passed between both leaves of mesentery and applied to the single, dilated loop of bowel. Once the stapler is fired, the single loop of bowel then becomes two parallel loops of normal caliber bowel, each with its own mesentery. The two new loops of bowel are then sewed to each other in an antegrade, end-to-end fashion forming a “lazy S” configuration (see Fig. 42-2).44 Several published series of Bianchi longitudinal lengthening procedures have been published and many of the authors were able to reproducibly double the lengths of bowel in their series of patients. With the increased length, patients were able to achieve improved intestinal motility and prolonged transit times. Although most series of patients were small, Weber and others were able to demonstrate complete parenteral independence in many patients along with improved carbohydrate and fat absorption.45−47 Although the early results of this procedure were promising, it largely has become of historical value due to complexity of the procedure, the difficulty in predicting which patients would become enterally independent, and the advent of intestinal transplantation.

FIGURE 42-2 Longitudinal intestinal lengthening. (A) The small bowel is divided at either end of a dilated loop. The mesentery is dissected to create a

plane along the axis of the intestine between branches of mesenteric blood vessels. (B) The mesentery has two leaves. Arterial and venous branches of mesenteric vessels alternate from one leaf of the mesentery to the other. (C) A gastrointestinal stapling device can be passed between the leaves of the mesentery. (D) When the stapler is fired, the single loop of dilated intestine is divided into two parallel loops. (E) The parallel loops can then be turned in a “lazy S” fashion to approximate the distal end of one loop to the proximal end of the second loop. In this way, the parallel loops are anastomosed endto-end to reestablish continuity and double the length of the small bowel. In addition, the lengthened segment is then reanastomosed to the normal small bowel or colon proximally and distally (not shown).

Serial Transverse Enteroplasty In 2003, Kim and others introduced a novel technique for bowel lengthening.48 Once again, the general concept was to introduce overall surface area in order to increase mucosal contact with nutrients. With the STEP procedure, however, this was achieved by narrowing the luminal diameter that would result in increased bowel distances between areas of undivided bowel, thus leading to increased transit times. In brief, the dilated segment of small bowel is narrowed by alternate firings of the GI stapling device from the mesenteric and antimesenteric borders of the bowel. This would result in luminal diameters between 1 cm and 2.5 cm and a resultant increase in bowel length (see Fig. 42-3A-C).48 In 2013, Kim and others published their results from the STEP registry data which included 111 patients in 50 centers worldwide. They were able to demonstrate that 47% of patients who were on PN pre-STEP were able to achieve complete enteral nutrition after their STEP procedure.49 The overall mortality in this study was 11%, but it likely reflected the high acuity of the patients who were undergoing surgery as the two main risk factors for death on multivariate analysis were higher direct bilirubin and shorter bowel length.49 Intestinal lengthening procedures have a clear role in patients with intestinal failure. The basic premise is that patient selection is of paramount importance because patients who are jaundiced should likely be considered for transplantation, and lengthening procedures are likely contraindicated.

FIGURE 42-3 The STEP procedure is shown here. A. The dilated intestine is divided from alternating sides using a stapling device thus creating a zigzag pattern, B. the resultant intestine is shown intra-operatively, and C. the simple calculation of the new functional lenght of the intestine after STEP is shown as initial length plus the product of the length of each staple cut times the number of cuts. (Reproduced with permission from Kim H, Fauza D, Garza J, et al. Serial transverse enteroplasty (STEP): A novel bowel lengthening procedure, J Pediatr Surg 2003 Mar;38(3):425-429.)

INTESTINAL TRANSPLANTATION ITx marks the final available therapy for patients with IF/SGS who in general have failed PN therapy. The indications are: 1. Patients with permanent/irreversible IF/SBS with one or more lifethreatening PN-related complications such as loss of central venous access, recurrent catheter-related bloodstream infections, and/or IFALD. 2. Patients with a poor prognosis for enteral adaptation, such as those with complete loss of midgut, should also be considered early in their onset of IF/SGS for ITx. 3. Patients with poor quality of life, uncontrollable fluid and electrolyte disorders, and chronic abdominal pain while on PN should be considered. 4. Patients with low-grade unresectable malignancies such as gastrointestinal stromal tumors (GISTs) or desmoids may benefit. Likewise, patients with polyposis syndromes may benefit from subtotal enterectomy and transplantation. 5. Lastly, patients with pan portosplenomesenteric venous thrombosis not amendable to shunting or isolated liver transplantation should be considered. Once patients have been deemed candidates for ITx, a complete multidisciplinary evaluation at a transplant center is carried out to determine eligibility. Specifications for this process vary from center to center and have been outlined in “Assessment of SBS-Associated Intestinal Failure”. Once accepted for transplantation, the patients are listed for the intestinal type of allograft deemed necessary. In general, diseased organs are replaced while functional ones should be retained.

Donor Selection In general, cadaveric donors of intestinal grafts are often young, healthy individuals who have suffered a catastrophic brain trauma or anoxic brain injury. These donors are a highly selected subset of patients mainly because of the sensitivity of the intestine to ischemic injury. Thus, many of the events surrounding brain death (down time, length of cardiac arrest/cardiopulmonary resuscitation) and peri-donation management (vasopressor requirements) of the donor will often exclude these patients as donors for intestinal grafts.

Donor/Graft Techniques The donor operation for multiorgan procurements is employed when the team is planning to procure multivisceral grafts. Within the abdominal compartment, preparation for rapid aortic cross-clamp is performed by first cannulating the inferior mesenteric vein for infusion of portal cooling flush both prior to aortic cross-clamp and after cross-clamping/exsanguination has occurred. The infrarenal aorta is encircled and cannulated and the supraceliac aorta is also encircled in preparation for placement of a vascular clamp just prior to exsanguination and cooling with University of Wisconsin solution (ViaSpan®, Barr Laboratories). After these steps and in coordination with the chest teams, the liver, pancreas, and small intestine can be procured either separately or in combination, depending on the recipient’s needs (see Fig. 424).50

FIGURE 42-4 Diagram demonstrating the graft options resulting from a multiorgan procurement. Divisions at duodenum and jejunum indicate potential levels of transection, both vascular and gastrointestinal. Thus, all organs can be procured either separately or in any combination.

Intestinal Type of Grafts In general, there is little consensus on the terminology regarding allograft type. This chapter utilizes the intestinal graft types as described by the

program at UCLA.51 The graft types are (1) isolated intestinal allograft, (2) liver-intestine allograft, (3) multivisceral allograft, and (4) modified multivisceral allograft. Of note, accessory organs can be easily added to most of the graft types. Accessory organs are the stomach, colon, and kidney. These are discussed separately.

ISOLATED INTESTINE GRAFTS Isolated intestine (I-ITx) grafts contain all or part of the donor jejunoileum. The jejunum is stapled past the ligament of Treitz, and the small mesenteric vessels connecting the proximal mesentery are ligated. In this scenario, the SMA and SMV are used as the vascular pedicles at the root of the mesentery in the recipient operation. If the pancreas is not being procured, the SMA can be lengthened to include a cuff of aorta and the SMV can go up as far as the portal vein (PV) (see Fig. 42-5a).50 This graft type is indicated for patients with IF/SBS only who have normal foregut and liver function.

FIGURE 42-5 (A) Demonstrates a jejunoileal graft procured with its vascular pedicle consisting of the SMA and SMV. (B) Demonstrates a liverintestine (L-ITx) graft procured using the traditional technique; the entire liver and jejunoileal segment is present. The vascular inflow is shown off a cuff of donor aorta. (C) Demonstrates multivisceral (MVTx) allograft. ([A,C]: Reproduced with permission from Moon JI, Tzakis AG: Intestinal and multivisceral transplantation, Yonsei Med J 2004 Dec 31;45(6):1101-1106.)

LIVER-INTESTINE GRAFTS The original description of this technique was by Grant et al.,8 where this graft included an en bloc liver and intestine only, while the donor pancreas was removed. Today, the most commonly used method for procurement of the liver-intestine (L-ITx) graft is the “Omaha technique.”52,53 With this technique, the liver is mobilized using standard techniques. The duodenum is stapled off distal to the pylorus, the pancreas is left wholly intact for biliary drainage, and the entire jejunoileum is mobilized and controlled. At completion, the L-ITx graft consists of liver, duodenum, pancreas, spleen, and jejunoileum with the vascular pedicles of a common aorta/celiac/SMA trunk and an intact donor PV and bile duct (see Fig. 42-5b).52 Liver-inclusive grafts are used in the clinical scenarios where patients have experienced liver failure, as in IFALD coupled with IF/SBS.

MULTIVISCERAL GRAFTS The multivisceral (MVTx) graft is very similar to the L-ITx graft described above. The stomach is most commonly included in this allograft type. During the procurement operation, rather than dividing at the level of the pylorus, the esophagus is transected above the GE junction. At completion, the organ complex consists of liver, duodenum, pancreas, spleen, and jejunoileum with or without the stomach. Vascular inflow is the same as described above for the L-ITx graft (see Fig. 42-5c).52 This allograft is used in patients with disease of both the foregut and midgut who also have irreversible IFALD.

MODIFIED MULTIVISCERAL GRAFTS Modified multivisceral MMVTx grafts are basically the same as the MVT except that the liver is not included in the complex. This allograft is used in patients with disease of both the foregut and midgut but where native liver function is preserved or salvageable.

Accessory Organs As noted above, the stomach can be added onto the MVT or MMVTx allografts largely in patients who have motility disorders involving the

stomach. Of note, due the fact that a vagotomy is performed in the donor, a pyloroplasty is required in this scenario. Alternatively, the stomach transplant can be omitted and thus a partial or subtotal gastrectomy is performed with the use of a Roux-en-Y gastrojejunostomy for final GI reconstruction. Colon-inclusive transplantation was initially deemed to be higher risk with worse outcomes.54 However, subsequent experiences demonstrated that colon inclusion can be accomplished without a higher rate of sepsis or graft loss.55 In the donor, rather than transect the intestine at the terminal ileum, the line of transection can occur in the mid-transverse colon (beyond middle colic vessels) or more distal. Inclusion of the colon is indicated for patients without significant remnant native colon, as it has been shown to improve fluid management post transplant. Concomitant kidney transplantation can also occur in patients with poor chronic renal function deemed candidates for such a transplant. The kidney allograft can be included en bloc with the visceral organs. We most commonly keep the right kidney intact, with the renal artery included in the aortic cuff and the renal vein included in the inferior vena cava (IVC). In this manner, only ureteral reimplantation is required in the recipient.

Recipient Operation The recipient operation can vary considerably between patients; thus, we briefly touch upon the major components of the recipient operation. As we have noted throughout this chapter, vascular access is of paramount importance with these patients. Preoperative mapping with a magnetic resonance venogram (MRV) is usually performed during the initial evaluation, and this is often necessary to help guide the anesthesiologist during CVC placement. Central access above the diaphragm is usually necessary both because of substantial blood loss encountered during the organectomy in a hostile abdomen and also because large-bore peripheral IV access is generally not possible in these patients. Exposure is the key to any operation. In a hostile abdomen, achieving exposure is often treacherous, and an adequate incision followed by extensive adhesiolysis is generally necessary before organectomy can proceed. For liver-inclusive grafts, a bilateral subcostal and vertical incision is necessary with extension of the midline incision to below the umbilicus. For patients

who are not receiving the liver as part of their grafts, a midline laparotomy incision is sufficient. With these incisions, optimal exposure to achieve venous outflow into the portomesenteric circulation and also to restore gastrointestinal continuity can be established. Recipient organectomy is variable depending upon the organ(s) being transplanted. In general, the I-ITx recipient undergoes mobilization of the remnant jejunoileum. This is resected while leaving behind a suitable length of jejunum to perform jejunojejunostomy between donor and recipient jejunum as well as distal colon to perform jejunocolostomy between donor jejunum and recipient colon. Vascular inflow and outflow was discussed for each type of grafts above. However, it should be mentioned that during the recipient operation liberal use of aortic conduits should be used. Generally, donor iliac or donor aorta can be used to create a conduit at the recipient infrarenal aorta that will be then be sewn to the allograft during implantation. When en bloc organs are procured, the suprahepatic IVC of the donor graft serves as the venous outflow. Biliary reconstruction requirements are variable depending on the graft used. In liver-inclusive grafts procured using the Omaha technique or as MVTx grafts, biliary anastomosis is not needed. This is followed by restoration of intestinal continuity. Again, the grafts being used as detailed previously will dictate the targets for intestinal anastomosis. Of importance, however, is the critical step of creating intestinal continuity along with an ileostomy to allow for allograft surveillance with biopsies in the perioperative period. Enteral feeding tube placement is the next surgical step, and this can be in the form of a Stamm gastrostomy in patients who do not receive a stomach, or as a jejunostomy tube into the transplanted intestine. Finally, abdominal wall closure is often complex, since these patients have had multiple previous operations and primary fascial closure is often difficult to achieve. In order to provide a tension-free closure, the liberal use of prosthetic materials as a temporary closure device while abdominal wall and bowel edema subsides is often the best strategy. A second-look laparotomy can then be performed and a definitive closure can be performed at that time either primarily or with permanent mesh (see Fig. 42-6).50

FIGURE 42-6 Diagrams demonstrating an isolated intestinal graft after implantation (A), and liver-intestinal graft with inclusion of the whole pancreas (B) and a multivisceral graft (C). The vascular anastomoses are indicated. Abbreviations: SMV, superior mesenteric vein; PV, portal vein; SMA, superior mesenteric artery; IVC, inferior vena cava.

COMPLICATIONS OF INTESTINAL TRANSPLANTATION Surgical complications after ITx can be broken down into postoperative-, endoscopic-, or vascular access−related. The postoperative complications have evolved over time. Biliary complications are no longer a major problem given that we no longer perform a complete hilar dissection as was originally described by Grant et al.8 Thus, this has left us mainly with intestinal perforation, mechanical obstructions, anastomotic leaks, intra-abdominal abscesses, chylous ascites, ostomy-related complications, and vascular complications.50 These complications are all life-threatening in an immunosuppressed patient, and a low threshold for reexploration should be maintained as the clinical presentation can often be insidious. Endoscopic complications are not uncommon in the intestinal transplant patient. These patients are regularly monitored for rejection in the postoperative period and they are thus at risk for bleeding, hematoma causing obstruction of the bowel lumen, perforation, and stomal disruption.24 In a

recent review of 1770 endoscopic procedures in intestinal transplant recipients, the rate of procedural complications, including but not limited to bleeding and perforation, was 1.8%.56 Similarly, vascular complications often persist in the post-transplant period. This often presents a challenge since most patients who have a functional graft have not completely weaned off of PN in the postoperative period. Some groups have reported up to a 15% incidence of patients experiencing thrombosis of their central veins that have required balloon angioplasty to maintain access following transplantation.57 Medical complications after ITx are largely related to infectious and immunosuppression-related issues. Recipients of intestinal transplants are at major risk for infections because the transplanted organ represents a reservoir of pathogens. In the immediate perioperative period, the source of infection is often from catheter-related bacteremia, anastomotic dehiscence, or intraabdominal fluid collections. In long-term patients, urinary tract infections, pneumonia, and catheter infections predominate as the causes for infections. However, it should be noted that patients with marginal graft function often are subject to bacterial translocation with resultant bacteremia. Thus, prevention of bacterial overgrowth with scheduled administration of oral antibiotics can often be useful to prevent recurrence of bacteremia. Immunosuppression-related complications are vast in number and beyond the scope of this chapter. However, it is important to recognize that there is a broad spectrum of complications that occur as a result of over- or underimmunosuppression.58 On the one hand, acute rejection is almost invariable for most intestinal transplant recipients, especially in young patients or those who are noncompliant with their immunosuppression regimen. At the opposite end of the spectrum, infectious complications and post-transplant lymphoproliferative disorder (PTLD) can occur in patients who are overimmunosuppressed or have received induction agents at the time of transplant such as antithymocyte globulin (ATG) or lymphocyte-depleting agents. Given the presence of lymphoid-rich tissue in intestinal grafts, graft-versushost disease (GVHD) can occur in up to 5% of patients and is clinically marked by diarrhea, ulceration of oral mucosa, and skin rash.24 It is this balancing act of over- versus under-immunosuppression that calls for very close monitoring, even when patients are remote from their operations, as these complications can arise over the entire course of a transplant recipient’s life.

SUMMARY AND FUTURE DIRECTIONS ITx has evolved since the initial attempts in the 1960s. Our knowledge of immunology, experience with surgical techniques, and perioperative care has improved substantially and this has afforded a 1-year graft survival of approximately 80%.54 The field of ITx depends on the contributions from a multidisciplinary team and strong support from an intestinal rehabilitation program that can bridge IF/SBS patients toward transplant. Aggressive rehabilitation programs that focus on minimizing complications from PN, reestablishing GI continuity, maximizing enterocyte mass via STEP procedures, and optimizing macro- and micronutrient delivery all contribute to successful patient outcomes. Future directions that will focus on tolerance induction, prevention of PTLD, and tissue engineering will help pave the path for intestinal transplantation and hopefully minimize the morbidity associated with immunosuppression.

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12. O’Keefe SJD, Buchman AL, Fishbein TM et al. Short bowel syndrome and intestinal failure: consensus definitions and overview. Clin Gastroenterol Hepatol. 2006;4(1):6-10. 13. Thompson JS, Rochling FA, Weseman RA, et al. Current management of short bowel syndrome. Curr Probl Surg. 2012;49(2):52-115. 14. Carmody B, Demaria EJ, Jamal M, et al. Internal hernia after laparoscopic roux en Y gastric bypass. Surg Obes Relat Disease. 2005;1:543-548. 15. Huang, CK. Essentials and controversies in bariatric surgery. InTech. 2014; 1-152. 16. Asensio JA, Britt LD, Borzotta A, et al. Multi-institutional experience with the management of superior mesenteric artery injuries. JACS. 2001; 193(4):354-365. 17. Greenwald DA, Brandt LJ, Reinus JF. Ischemic bowel disease in the elderly. Gastroenterol Clin North Am. 2001;6:445-473. 18. Aaolu N, Mustafa NA, Turkyilmaz S. Prothrombotic disorders in patients with mesenteric vein thrombosis. J Invest Surg. 2003;16:299-304. 19. Fishbein T, Schiano T, Jaffe D, et al. Isolated intestinal transplantation in adults with nonreconstructible GI tracts. Transplant Proc. 2000;32: 1231-1232. 20. Agwunobi AO, Carlson GL, Anderson ID, et al. Mechanisms of intestinal failure in Crohn’s disease. Dis Colon Rectum. 2001;44:1834-1837. 21. Krupnick AS, Morris JB. The long-term results of resection and multiple resections in Crohn’s disease. Semin Gastrointest Dis. 2000;11:41-51. 22. Sampietro GM, Cristaldi M, Maconi G, et al. A prospective, longitudinal study of nonconventional stricturoplasty in Crohn’s disease. J Am Coll Surg. 2004;199:8-20; discussion, 2. 23. Sampietro GM, Cristaldi M, Porretta T, et al. Early perioperative results and surgical recurrence after strictureplasty and miniresection for complicated Crohn’s disease. Dig Surg. 2000;17:261267. 24. Langnas AN, et al. Intestinal Failure: Diagnosis, Management and Transplantation. Malden: Blackwell; 2008:1-390. 25. Messing B, Lemann M, Landais P, et al. Prognosis of patients with nonmalignant chronic intestinal failure receiving long-term home parenteral nutrition. Gastroenterology. 1995;108:10051010. 26. Cavicchi M, Beau P, Crenn P, et al. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med. 2000;132:525-532. 27. Stanko RT, Nathan G, Mendelow H, et al. Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. Gastroenterology. 1987;92:197-202. 28. Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome. J Pediatr Surg. 1997;32:473-475. 29. Kaufman SS. Prevention of parenteral nutrition-associated liver disease in children. Pediatr Transplantation. 2002;6:37-42. 30. Colomb V, Jobert-Giraud A, Lacaille F, et al. Role of lipid emulsions in cholestasis associated to long-term parenteral nutrition in children. J Parenter Enteral Nutr. 2000;24:345-350. 31. Buchman AL, Complications of long-term home total parenteral nutrition: their identification, prevention and treatment. Dig Dis Sci 2001;46:1-18. 32. O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Pediatrics. 2002;110:1-24. 33. de Jonge RCJ, Polderman KH, Gemke RJBJ. Central venous catheter use in the pediatric patient: mechanical and infectious complications. Pediatr Crit Care Med. 2005;6:329-339. 34. Fletcher SJ, Bodeham AR. Safe placement of central venous catheters: where should the tip of the

catheter lie? Br J Anaesth. 2000;85:188-191. 35. Moukarzel AA, Song MK, Buchman AL, et al. Excessive chromium intake in children receiving total parenteral nutrition. Lancet. 1992;339:385-388. 36. Buchman AL, Iyer K, Fryer J. Parenteral nutrition-associated liver disease and the role of isolated intestine and intestine/liver transplantation. Hepatology. 2006;43:9-19. 37. Nightingale JM. Hepatobiliary, renal and bone complications of intestinal failure. Best Pract Res Clin Gastroenterol. 2003;17:907-929. 38. Sondheimer JM, Asturias E, Cadnapaphornchai M. Infection and cholestasis in neonates with intestinal resection and long-term parenteral nutrition. J Pediatr Gastroenterol Nutr. 1998;6:131137. 39. Beath SV, Davies P, Papadopoulou A, et al. Parenteral nutrition related cholestasis in post-surgical neonates: multivariate analysis of risk factors. J Pediatr Surg. 1996;31:604-606. 40. Kelly DA. Liver complications of pediatric parenteral nutrition-epidemiology. Nutrition. 1998;14:153-157. 41. Lumen W, Shaffer JL. Prevalence, outcome and associated factors of deranged liver function tests in patients on home parenteral nutrition. Clin Nutr. 2002;21:337-343. 42. Tee CT, Wallis K, Gabe SM. Emerging treatment options for short bowel syndrome: potential role of teduglutide. Clin Exper Gastroenterol. 2011;4:189-196. 43. Bianchi A. Intestinal loop lengthening—a technique for increasing small intestinal length. J Pediatr Surg. 1980;15:145-151. 44. Bianchi A. Intestinal lengthening: an experimental and clinical review. J R Soc Med. 1984;77(suppl):35-41. 45. Boeckman CR, Traylor R. Bowel lengthening for short gut syndrome. J Pediatr Surg. 1981;16:996-997. 46. Chang RW, Javid PJ, Oh JT, et al. Serial transverse enteroplasty enhances intestinal function in a model of short bowel syndrome. Ann Surg. 2006;243:223-228. 47. Weber T, Powell M. Early improvement in intestinal function after isoperistaltic bowel lengthening. J Pediatr Surg. 1996;31:61-64. 48. Kim H, Fauza D, Garza J, et al. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg. 2003;38:425-429. 49. Modi BP, Javid PJ, Jaksic T, et al. First report of the international Serial Transverse Enteroplasty registry: indications, efficacy, and complications. J Am Coll Surg. 2007;204(3):365-371. 50. Abu-Elmagd K, Fung J, Bueno J, et al. Logistics and technique for procurement of intestinal, pancreatic, and hepatic grafts from the same donor. Ann Surg. 2000;232:680-687. 51. Farmer DG, Venick RS, Colangelo J, et al. Pretransplant predictors of survival after intestinal transplantation: analysis of a single-center experience of more than 100 transplants. Transplantation 2010;90:1574-1580. 52. Moon JI, Tzakis AG. Intestinal and multivisceral transplantation. Yonsei Med J. 2004;31:11011106. 53. Sudan D, Iyer K, Deroover A, et al. A new technique for combined liver-intestine transplantation. Transplantation. 2001;72:1846-1849. 54. Todo, S., Reyes, J., Furukawa, H., et al. Outcome analysis of 71 clinical intestinal transplantations. Annals of Surgery. 1995;222: 270-282. 55. Kato T, Selvaggi G, Gaynor JJ, et al. Inclusion of the donor colon and ileoceccal valve in intestinal transplantation. Transplantation. 2008;86: 293-297. 56. Yeh J. Ngo KD, Wazniak LJ, et al. Endoscopy following peditric intestinal transplant. JPGN. 2015;61:636-640. 57. Selvaggi G, Gyamfi A, Kato T, et al. Analysis of vascular access in intestinal transplant recipients

using the Miami classification from the 8th international small bowel transplant symposium. Transplantation. 2005; 79:1639-1643. 58. Reyes J, Mazariegos GV, Bond GM, et al. Pediatrical intestinal transplantation: historical notes, principles and controversies. Pediatric Transplant. 2002;6:193-207.

DIVERTICULAR DISEASE AND COLONIC VOLVULUS Timothy Eglinton • Frank A. Frizelle

Diverticular disease and colonic volvulus are common benign colonic conditions that can cause patients significant symptoms, impair of quality of life, and on occasion lead to fatal outcomes without treatment. Management at times can be challenging as decisions for surgical intervention must be carefully balanced against the patient’s relative procedural risks and comorbidities, which also can be significant. In this chapter, we discuss the current understanding of these 2 pathologies.

DIVERTICULAR DISEASE Colonic diverticula are the most common structural abnormality of the bowel and constitute the fifth most costly gastrointestinal disorder in Western society.1,2 An acquired condition, diverticula usually affect the sigmoid colon in Western societies, but they are also found on the right colon in countries with diets rich in fiber, especially in Asia. The prevalence of clinically apparent diverticular disease has increased over the past century,3 which probably reflects both an increase in detection and an aging population. Until 30 years ago, the proportion of patients requiring surgery or dying from

diverticular disease was decreasing4; however, over the past 20 years, the rates of hospital admission and surgical intervention have increased, while inpatient and population mortality rates from diverticular disease have remained unchanged.5 Colonic diverticulum is an acquired condition with increased prevalence with increasing age. It affects fewer than 10% of people in their fifth decade of life, increasing to around 50% to 66% in their ninth decade.6 Most patients with diverticulosis do not require surgery; however, complications of diverticular disease may require surgery. Such surgery can be challenging, and good outcomes rely on timely and appropriate intervention. The terms used include diverticulum (diverticula—plural); diverticulosis, which indicates asymptomatic diverticula; diverticulitis (simple or complicated), or diverticula with inflammation; and diverticular disease, which is diverticula with or without inflammation.

History Diverticular disease was initially described by Littré in 1700 as saccular outpouchings of the colon.7 Cruveilhier is credited with the first clear and detailed description of the pathogenesis of diverticulitis and complicated diverticular disease.8 In 1899, Graser introduced the term “peridiverticulitis” and suggested that diverticula were caused by herniation of colonic mucosa through areas of penetration of the vasa recta. This is now well established as the pathogenesis of colonic diverticulosis.9 In contrast, the mechanism for diverticulitis was not identified until 1904 by Edwin Beer.10 This seminal work on the pathophysiology of diverticular disease reviews the medical literature on diverticular disease at the turn of the 19th century. Beer summarized the use of cadaveric and animal experiments to identify diverticula associated with colonic wall blood vessels and ascribes the cause of diverticulitis to hard fecal matter lodged within the diverticulum.11 He described the ensuing pathologic processes of mucosal ulceration, acute inflammation, abscess formation, colonic perforation, and fistulation. Beer also describes the process of cicatricial contraction caused by marked “connective tissue growth.” Beer also succinctly summarizes 18 case reports into 6 clinical scenarios, including diverticula that produce stenosis of the sigmoid or upper rectum, diverticula that lead to perforation into the

peritoneum, diverticula that lead to abscesses or localized peritonitis in the left iliac fossa, diverticula that lead to perforation into the urinary bladder, diverticula that are densely adherent to the bladder, and diverticula and carcinoma. He proposed that impacted fecal matter at the neck of the diverticulum caused inflammation and subsequent abscess and fistula formation. Moynihan12 reported a case of peridiverticulitis in 1907 and underlined the difficulties in distinguishing diverticular disease from malignancy. Telling and Gruner’s classic paper describing complex diverticular disease was not published until 1917.13 At this time, the prevalence and pathophysiology of diverticular disease were well recognized, as were the complications, including acute diverticulitis, abscess, fistula, perforation, and obstruction. The development of radiologic imaging of the large intestine was important in establishing a diagnosis and documenting the extent of diverticular disease.14 In 1914, De Quervain and Case were the first to demonstrate colonic diverticula with x-rays.15,16

Etiology Diverticular disease is a disease of Western populations. A number of studies have shown an increase in incidence over the past 30 years.3,5 Migrant studies likewise confirm an increase in incidence when populations move to a Western country. There is a widely held view that fiber content of food is important and that the high intraluminal pressure associated with low-fiber diets precipitated by colonic compartmentalization causes an unsustainable increase in tension within the bowel wall. This is compounded by the hyperelastosis and altered collagen structure seen in the colon due to aging.17,18 Both mechanisms ultimately lead to a loss of bowel wall integrity and the formation of diverticula. Exercise and a reduction in the intraluminal pressure associated with a high-fiber diet may be protective.19 High intraluminal pressures are generated because of colonic motility. Colonic motility is complex and not easily studied. The most common motor patterns are tonic segmenting and rhythmic contraction. Tonic segmentation creates stationary narrow rings that appear as haustral markings. Their purpose is to slow the fecal stream and to permit water absorption and

electrolyte exchange. Infrequent propulsive peristaltic contractions move fecal matter in a caudal direction; these occur around 6 times a day.20 The alteration in pressure caused by these movements has been implicated in the pathogenesis of colonic diverticulosis. Several groups have studied colonic motility with intraluminal manometry in humans and animals. Most studies agree that there is increased phasic pressure activity, but this relates more to the presence of symptoms rather than diverticula. The results, however, are heterogeneous, principally because of methodologic differences, in particular relating to bowel preparation and pressure sensors.21 It may therefore be unreasonable to draw firm conclusions from these investigations.22 More generalized alterations in colonic motility have been implicated in the pathogenesis of colonic diverticular disease. In vitro and in vivo studies, however, are conflicting. Some demonstrate an absence of slow-wave activity (favoring nonpropagating contractile activity), and some demonstrate unimpaired or increased slow-wave activity.23,24 Others have demonstrated an increase in fast-wave activity, which persists after resectional surgery.25 The exact relevance of these myoelectric changes remains uncertain. Diverticulosis is a Western disease that has a striking geographic distribution. The disease is rare in rural Africa and Asia with the highest prevalence seen in the United States, Europe, and Australia.26 Within a single country, the disease incidence can vary depending on ethnicity.27 Urbanization can also increase diverticular disease incidence, possibly attributable to a dietary change.28,29 The incidence of complicated diverticular disease also seems to be increasing.30 Diverticular disease in Asian patients is often right-sided with manifestations early in life and is often multiple. The reasons for this variation are unknown; however, it has been suggested that both diet and elastin/collagen differences may play a role.31

Morphologic Features Colonic diverticula are false diverticula most commonly found in the sigmoid colon (95%). The sigmoid colon is the exclusive site in about 50%, and the entire colon is involved in just 5%. The muscular colonic wall is composed of both longitudinal and circular layers. The circular layer of the muscularis

propria forms a continuous sheet of muscle throughout the large bowel. The longitudinal layer forms 3 discrete condensations called taeniae; 1 of these is adjacent to the mesentery while the other 2 are antimesenteric. The taeniae coalesce to form an enveloping muscular layer in the rectum. Much of the colonic wall is therefore devoid of longitudinal muscle, and it is in these areas that diverticula form. Herniations of muscularis mucosa occur between the taeniae along the arteries (vasa recta) that penetrate the muscle wall en route to the submucosa and mucosa (Figs 43-1 and 43-2).

FIGURE 43-1 Relationship of diverticulum and vasa recta.

FIGURE 43-2 Cross section through the sigmoid colon containing diverticula (arrows). Many studies have demonstrated a change in the histologic structure of the muscularis propria in diverticular disease. In a classic study, Whiteway and Morson17 found the muscle cells to be normal with no evidence of hyperplasia or hypertrophy, but both layers were thickened. They demonstrated excessive amounts of elastin in the taeniae but not in the circular muscle.17 Repeated intermittent distension of the colon can result in increased synthesis of connective tissue components.32 It may be that the Western diet with its lower fecal load only intermittently distends the bowel wall and encourages elastin deposition. The importance of collagen and elastin types in the colonic wall is increasingly being recognized. Elastin deposition, termed “elastosis,” explains the contracted and thickened appearance of the diverticulumaffected colon. The taeniae shorten, and because of fascial linkage between the longitudinal and circular muscles, the colonic wall looks like a concertina. Thickened circular muscle folds project into the lumen, causing a decrease in caliber. The mesocolon is also foreshortened, possibly as a result of chronic inflammation. Other studies have suggested that the type of collagen may be

important.33 One study has shown that in the bowel sections of patients with diverticulitis, there were decreased levels of mature collagen type I and increased levels of collagen type III with a resulting lower collagen I:III ratio. The expression of matrix metalloproteinase 1 was reduced significantly in the diverticulitis group.33 These findings support the theory of structural changes in the colonic wall as one of the predisposing pathogenic factors for the development of diverticula (Fig. 43-3A and 43-3B).33 In those with certain connective tissue diseases, such as Marfan and Ehlers-Danlos syndromes, diverticular disease is a common association.

FIGURE 43-3 A. Sigmoid colon with diverticula. B. Mucosal view of colonic diverticula.

Diverticulitis always starts with a microperforation, leading to peridiverticulitis. This is instigated by either a rise in intraluminal pressure and/or erosion by inspissated feces. Nonresolution of this initial injury leads to complications of diverticulitis.

Presentation Given the high incidence of diverticulosis, it is surprising that clinical manifestations are relatively infrequent. Many patients are unaware that they have colonic diverticula until they develop acute symptoms or when diverticulosis is found incidentally during colonic investigations. Typically an acute attack of diverticulitis begins with lower abdominal pain that then localizes to the left iliac fossa. An inflamed sigmoid colon can lie against the dome of the bladder or the cecum, mimicking a urinary tract infection or appendicitis. Fever, tachycardia, and a leukocytosis accompany the acute attack. The inflammatory response starts at the site of a blocked diverticulum, and bacterial proliferation eventually leads to abscess formation. Minor episodes may be self-limiting, but an abscess can develop and then rupture into the abdomen causing a purulent peritonitis. More rarely, feculent peritonitis occurs when a diverticulum ruptures freely into the peritoneum.3441

Physical examination will often reveal peritonitis localized to the left iliac fossa or suprapubic area; a palpable mass is not uncommon. The differential diagnosis includes appendicitis, segmental ischemic colitis, colorectal cancer, inflammatory bowel disease, gastroenteritis, and irritable bowel disease. In the absence of complications, patients with acute diverticulitis are best managed conservatively with antibiotics. Generalized rigidity suggests purulent or fecal peritonitis, and early surgery is required in this situation. Once fluid and electrolyte resuscitation has begun, an emergency laparotomy or laparoscopy with an appropriate colonic resection should be performed. Often, diverticular disease presents in a more indolent manner with nagging left iliac fossa pain, abdominal distension, and a change in bowel habit. In the course of investigations to exclude colon cancer, diverticular disease may be discovered by computed tomography (CT) colonography, or colonoscopy (Figs 43-4, 43-5A, and 5B). In the majority of these patients,

education about the natural history of the disease with advice on dietary modification and supplementary written information will suffice. A very limited number of patients who continue to have symptoms despite long periods of medical management may benefit from surgery in the absence of other specific complications of the disease; however, determining the contribution of symptoms from diverticular disease and associated conditions such as irritable bowel syndrome can be difficult. These patients often have persisting symptoms following surgery.

FIGURE 43-4 Left colonic diverticula on double-contrast barium enema (arrows).

FIGURE 43-5 CT axial view of sigmoid diverticula.

COMPLICATIONS

Free Perforation. Feculent peritonitis is usually associated with toxemia and signs of generalized peritonitis. These patients will require an immediate laparotomy, resection, and diversion. Mortality rates for emergency operations have remained unchanged at 12% to 36% for the past 20 years and are most often affected by the patient’s underlying fitness for surgery. Fistula. An inflamed segment of sigmoid colon can adhere to a number of intra-abdominal structures or to the abdominal wall. A fistula may arise spontaneously as a result of the inflammatory condition itself or as a result of surgical intervention. It is more common in males, in those with previous abdominal surgery, and in immunocompromised patients. Diverticular fistulas can drain either internally or externally. Often, these fistulas are single tracts, but in about 8% of patients, they are multiple. Rare sites of fistulous involvement include the ureters, other colonic segments, and stomach. Colocutaneous. Occasionally, a paracolic diverticular abscess will discharge spontaneously through the abdominal wall, causing a colocutaneous fistula. More often, a fistula will result from incision and drainage of a pointing paracolic abscess or from a drain placed under radiologic control. A fistula can arise from a leaking colonic anastomosis in patients who have undergone resection for diverticular disease. Colovesical. This is the most common fistula, accounting for about twothirds of diverticular fistulae. It is more common in men because in women the uterus is interposed between the bladder and the colon. A relatively mobile sigmoid colon becomes adherent to the dome of the bladder and a communication develops. Patients present with recurrent urinary sepsis, urgency, frequency, and pneumaturia. Fecaluria is uncommon. Cystoscopy sometimes identifies an area of inflamed transitional epithelium but is more useful to exclude bladder cancer. A double-contrast enema or CT colonography provides a useful map of the anatomy and in some cases can confirm the presence of a fistula. Caution should be exercised when using barium in an acute situation to avoid peritoneal contamination. Coloenteric. Small bowel can become adherent to an inflamed diverticulumaffected colon. Fistulas form when an abscess discharges through the small bowel wall. This may be asymptomatic.

Colovaginal. This is a particularly debilitating fistula. The patient may pass flatus and feces through the vagina and suffer recurrent vaginal infections. Colovaginal fistulas usually only occur if a previous hysterectomy has been performed. Barium studies of both the bowel and the vagina or pelvic magnetic resonance imaging (MRI) usually can confirm the diagnosis. They are also helpful to exclude colonic malignancy as a cause; however, an examination of the vagina may also be required to exclude the rare possibility of a gynecologic malignancy. Single-stage operative resection with primary anastomosis and repair of the contiguous organ can be performed in most circumstances.42 Interposition of the pedicalized greater omentum between the anastomosis and the site of the fistula is a useful adjunct in preventing recurrent fistula formation. Bleeding. Severe hemorrhage from diverticular disease is rare (5%).43,44 However, distinguishing diverticular bleeding from other causes can be a diagnostic challenge, particularly because diverticular disease is so prevalent.45,46 In elderly patients, angiodysplasia is the most common colonic cause of rectal bleeding. Taken together, bleeding from angiodysplasia and diverticula account for 90% of cases of severe lower intestinal hemorrhage. In diverticular bleeding, the penetrating vasa recta that has led to the development of the diverticulum is easily eroded as it is only separated from the bowel lumen and its contents by a thin layer of mucosa. On histology, there is thinning of the media and thickening of the intima of the vasa recta with rupture of the vessel usually at the dome of the diverticulum. There usually is no inflammation associated with the bleeding diverticulum.47,48 Diverticular hemorrhage presents with abrupt passage of large-volume bright or dark red blood per rectum and may be associated with lower abdominal pain probably related to colonic distension. Most diverticular bleeding occurs from left-sided diverticula except in patients of Asian ethnic origin, in whom it is more common to find the bleeding occurring on the right side.31 Diverticular bleeding is more common in those on nonsteroidal antiinflammatory drugs (NSAIDs). Colonoscopy in situations of large-volume bleeding is considered futile if not dangerous. CT angiography is now considered the most useful diagnostic test as it more readily localizes the site of bleeding should the bleeding rate exceed 0.5 mL/min. Formal mesenteric angiography to embolize the segmental vessel is then undertaken with good bleeding control and low associated complications (Fig. 43-6).49,50 Failing

this, other techniques to control or localize the bleeding site include vasopressin injection or methylene blue. A more sensitive test for colonic bleeding is a radiolabeled red blood cell scan or technetium-99m–labeled sulfur colloid (>0.1 mL/min), but accuracy in localizing the bleeding site is not as good.51 Colonoscopy can be used before a laparotomy or as an adjunct with the abdomen open if all else fails in a patient who continues to bleed. It is useful in an attempt to localize and control the bleeding or to minimize the amount of colonic resection. It is also important to note that in these situations a preoperative gastroscopy is mandatory to exclude an upper gastrointestinal tract source of bleeding. Most diverticular hemorrhage ceases spontaneously (70%-80%), with rebleeding rates of 22% to 38%.44,45,52 High-dose barium impaction therapy has been suggested to reduce the risk of rebleeding, and a recent randomized controlled trial with medium-term follow-up supported its efficacy.53 CT colonography or colonoscopy in patients who have stopped bleeding is useful to exclude malignancy, particularly in those with smaller volume bleeding, with associated suspicious symptoms, or with a significant personal or family history of cancer.

FIGURE 43-6 Formal angiography demonstrating “contrast blush”—active bleeding from sigmoid colon. Obstruction. Obstruction due to diverticular disease accounts for 10% to 20% of large bowel obstructions (LBOs) in Western society. Diverticular disease causes colonic obstruction through either luminal stenosis as a result of wall edema on top of the already thick-walled, fibrotic colon or extrinsic compression from an abscess (Fig. 43-7). Often the obstruction is incomplete. Small bowel obstruction can occur if a loop of small bowel becomes adherent to the inflamed sigmoid colon. The diagnosis is usually apparent from the patient’s history. Radiologic confirmation either by contrast enema or by CT with oral and rectal contrast should be obtained. Caution is wise in those with questionable underlying active diverticulitis particularly if complicated by localized perforation. Direct visualization and histologic exclusion of malignancy are mandatory but at times difficult.

FIGURE 43-7 CT scan of active diverticulitis with occlusion of colonic lumen secondary to inflammation (arrow). Differential diagnosis is a sigmoid colon malignancy.

Management of colonic obstruction in this setting depends on the mode of presentation and the medical fitness of the patient. An insidious onset is characterized by pain, increasing constipation, and the passage of ribbon-like stools. The majority of patients, however, will present acutely with a classic LBO. The surgical options include a Hartmann resection and resection with primary anastomosis or rarely with a diverting loop ostomy. In patients deemed unfit for surgery, the endoscopic or fluoroscopic deployment of a colon stent is a useful alternative procedure with a high clinical success rate.54 Abscess. Abscess formation is the most common complication of acute diverticulitis. It occurs when the center of the inflammatory mass or phlegmon becomes necrotic. The patient presents with worsening abdominal pain, undulating fever, leukocytosis, and raised inflammatory markers. A mass is often palpable in the left iliac fossa or suprapubic region. It may also be felt transvaginally or transrectally. The most common site for a diverticular abscess is in the sigmoid mesocolon, although a variety of unusual presentations have been described.55 A significant number of abscesses are detected radiologically on CT or ultrasound scanning. Most small (60 years, and metastatic cancer best predicted mortality following resection. Notably, in both groups, anastomotic complications occurred in over 15% of patients. In a similar study using the California Inpatient Database, Kasten et al. reported a 21% mortality over 3 years in patients requiring total colectomy for the treatment of their volvulus.18 In contrast, patients treated with detorsion and fixation, but no bowel resection, had the lowest morbidity and mortality but were found to have a re-intervention rate of over 25% within an approximately 2-year follow up period.18 The significant mortality and morbidity associated with colonic volvulus is likely a reflection of both the severity of the disease process as well as the baseline comorbidity and poor functional status of patients that tend to be affected.

OTHER FORMS OF VOLVULUS Cecal bascule is a variant of cecal volvulus in which the cecum folds anteriorly and superiorly on top of itself toward the fixed ascending colon,

creating an organoaxial rotation, rather than a true mesenteroaxial volvulus. This process occurs less frequently than true cecal volvulus,7 and is thought to be associated with less vascular compromise.19 In addition, cecal bascule may be more likely to spontaneously reduce, resulting in intermittent symptoms of cecal obstruction. Nonetheless, if unrecognized and persistent, cecal bascule can progress to ischemia, necrosis, perforation, and sepsis.7,20 Therefore, it is generally recommended to proceed with resective therapy for patients with acute, persistent cecal bascule, or those felt to have symptoms referable to intermittent, recurring cecal bascule. Volvulus of the transverse colon has been described, but it occurs very infrequently. This process appears to be most similar to that of sigmoid volvulus, with chronic constipation acting as one of the major risk factors. Radiographically, it most closely resembles sigmoid volvulus, but can be differentiated by the more proximal site of obstruction demonstrated on contrast enema. As in the treatment of sigmoid volvulus, detorsion may be attempted in the appropriate setting via an endoscopic approach; however, there is a lower success rate, and the patient often ultimately requires surgical intervention. Even less common than transverse colon volvulus is volvulus of the splenic flexure, which has been described in the literature as scattered case reports.21 Like sigmoid volvulus, chronic constipation is a common complaint among patients developing splenic flexure volvulus.21 The underlying pathophysiology of this condition appears to involve non-fixation of the splenic flexure, which may occur in the setting of prior mobilization of the splenic flexure or adhesion formation from prior abdominal surgery. Alternatively, it has been described in association with a congenital abnormality of the gastrocolic, splenocolic, or phrenocolic ligaments or lateral peritoneal attachments. Management of this problem is guided by the same principles used for sigmoid volvulus. Devitalized colon must be resected emergently, and partial colectomy should be considered to prevent recurrence. Finally, a type of volvulus termed the ileal-sigmoid knot is a relatively well-described entity in regions where colonic volvulus is more common.22,23 Also known as “compound volvulus” or “double volvulus,” this condition is a variant of sigmoid volvulus. As its name implies, ileal-sigmoid knotting occurs when the ileum wraps around the base of the sigmoid colon, resulting

in two closed-loop obstructions. It occurs predominantly in men and has a mean age of diagnosis around 40 years. This form of volvulus is associated with more profound and early malperfusion of the bowel. Importantly, endoscopic detorsion is often futile in the setting of ileosigmoid knotting, and therefore it is crucial to differentiate this process from isolated sigmoid volvulus.22 Emergent laparotomy should not be delayed. It is recommended that sigmoid resection be performed regardless of bowel viability, and that the decision to resect the involved portion of ileum be guided primarily by evidence of gangrene.

SPECIAL POPULATIONS There are several unique populations of patients worth noting in relation to colonic volvulus. Sigmoid volvulus is reportedly one of the most common, albeit still rare, causes of large bowel obstruction in pregnant women.1,24–26 It is hypothesized that the gravid uterus displaces the sigmoid colon out of the pelvis and thereby predisposes it to twisting at its point of mesenteric fixation.27,28 This complication of pregnancy occurs most frequently in multiparous women, and during the third trimester.25 It can be diagnosed using MRI in non-emergent settings in order to avoid ionizing radiation exposure to the fetus.27 If possible, endoscopic detorsion is favored over operative treatment in these patients. Regardless, rates of maternal and fetal mortality associated with the diagnosis of sigmoid volvulus are reportedly as high as 14% and 28%, respectively.26 Although rare, colonic volvulus has also been reported in children. It seems to occur most commonly in males and has an association with Hirschsprung disease. Indeed, nearly 20% of children presenting with sigmoid volvulus are found to have comorbid Hirschsprung disease, which likely increases one’s risk of volvulus due to chronic constipation and bowel distention.29 Mortality is significant in this population, with reported rates ranging from 11% to 22%.29,30

CONCLUSIONS Colonic volvulus is a rare but potentially life-threatening cause of large

bowel obstruction. It most commonly involves either the sigmoid colon or the cecum, and results in obstruction and strangulation, which can progress to gangrene and perforation. Sigmoid volvulus occurs in the setting of a large redundant colon in combination with a long, narrow mesentery, which is often the result of longstanding chronic constipation, while cecal volvulus is associated with congenital non-fixation of the cecum. Sigmoid volvulus can often be managed initially with endoscopic detorsion, followed semielectively by sigmoid resection, while the management of cecal volvulus almost universally requires early cecal resection.

REFERENCES 1. Ballantyne GH. Review of sigmoid volvulus. Clinical patterns and pathogenesis. Dis Colon Rectum. 1982;25(8):823-830. 2. Jones IT, Fazio VW. Colonic volvulus. Etiology and management. Dig Dis. 1989;7(4):203-209. 3. Lal SK, Morgenstern R, Vinjirayer EP, Matin A. Sigmoid volvulus: an update. Gastrointest Endosc Clin N Am. 2006;16:175-187. 4. Halabi WJ, Jafari MD, Kang CY, et al. Colonic volvulus in the United States: trends, outcomes, and predictors of mortality. Ann Surg. 2014;259(2):293-301. 5. Ballantyne GH, Brandner MD, Beart RW Jr, Ilstrup DM. Volvulus of the colon. Incidence and mortality. Ann Surg. 1985;202(1):83-92. 6. Feldman D. The coffee bean sign. Radiology. 2000;216(1):178-179. 7. Rabinovici R, Simansky DA, Kaplan O, Mavor E, Manny J. Cecal volvulus. Dis Colon Rectum. 1990;33(9):765-769. 8. Rosenblat JM, Rozenblit AM, Wolf EL, DuBrow RA, Den EI, Levsky JM. Findings of cecal volvulus at CT. Radiology. 2010;256:169-175. 9. Macari M, Spieler B, Babb J, Pachter HL. Can the location of the CT whirl sign assist in differentiating sigmoid from caecal volvulus? Clin Radiol. 2011;66:112-117. 10. Grossmann EM, Longo WE, Stratton MD, Virgo KS, Johnson FE. Sigmoid volvulus in Department of Veterans Affairs Medical Centers. Dis Colon Rectum. 2000;43(3):414-418. 11. Bak MP, Boley SJ. Sigmoid volvulus in elderly patients. Am J Surg. 1986;151(1):71-75. 12. Tan KK, Chong CS, Sim R. Management of acute sigmoid volvulus: an institution’s experience over 9 years. World J Surg. 2010;34(8):1943-1948. 13. Larkin JO, Thekiso TB, Waldron R, Barry K, Eustace PW. Recurrent sigmoid volvulus - early resection may obviate later emergency surgery and reduce morbidity and mortality. Ann R Coll Surg Engl. 2009;91(3):205-209. 14. Turan M, Sen M, Karadayi K, et al. Our sigmoid colon volvulus experience and benefits of colonoscope in detortion process. Rev Esp Enferm Dig. 2004;96(1):32-35. 15. Maddah G, Kazemzadeh GH, Abdollahi A, Bahar MM, Tavassoli A, Shabahang H. Management of sigmoid volvulus: options and prognosis. J Coll Physicians Surg Pak. 2014;24(1):13-17. 16. Madiba TE, Thomson SR. The management of cecal volvulus. Dis Colon Rectum. 2002;45(2):264-267. 17. Benacci JC, Wolff BG. Cecostomy. Therapeutic indications and results. Dis Colon Rectum. 1995;38(5):530-534.

18. Kasten KR, Marcello PW, Roberts PL, et al. What are the results of colonic volvulus surgery? Dis Colon Rectum. 2015;58:502-507. 19. Fry RD, Mahmoud NN, Maron DJ, Bleier JIS. Colon and rectum. In: Townsend CM, Beauchamp D, Evers M, Mattox KL (eds). Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Saunders; 2012:1294-1380. 20. Pousada L. Cecal bascule: an overlooked diagnosis in the elderly. J Am Geriatr Soc. 1992;40(1):65-67. 21. Ballantyne GH. Volvulus of the splenic flexure: report of a case and review of the literature. Dis Colon Rectum. 1981;24(8):630-632. 22. Machado NO. Ileosigmoid knot: a case report and literature review of 280 cases. Ann Saudi Med. 2009;29:402-406. 23. Selcuk Atamanalp S. Treatment for ileosigmoid knotting: a single-center experience of 74 patients. Tech Coloproctol. 2014;18(3):233-237. 24. Hellinger MD, Steinhagen RM. Colonic Volvulus. In: Wolff BG, Fleshman JW, Beck DE, Pemberton JH, Wexner SD (eds). The ASCRS Textbook of Colon and Rectal Surgery. 1st ed. New York, NY: Springer Science+Business Media; 2007:286-298. 25. Atamanalp SS, Kisaoglu A, Ozogul B, et al. Sigmoid volvulus complicating pregnancy: a case report. Eurasian J Med. 2015;47:75-76. 26. Perdue PW, Johnson HW Jr, Stafford PW. Intestinal obstruction complicating pregnancy. Am J Surg. 1992;164(4):384-388. 27. Palmucci S, Lanza ML, Gulino F, Scilletta B, Ettorre GC. Diagnosis of a sigmoid volvulus in pregnancy: ultrasonography and magnetic resonance imaging findings. J Radiol Case Rep. 2014;8:54-62. 28. Alshawi JS. Recurrent sigmoid volvulus in pregnancy: report of a case and review of the literature. Dis Colon Rectum. 2005;48(9):1811-1813. 29. Zeng M, Amodio J, Schwarz S, Garrow E, Xu J, Rabinowitz SS. Hirschsprung disease presenting as sigmoid volvulus: a case report and review of the literature. J Pediatr Surg. 2013;48(1):243246. 30. Atamanalp SS, Yildirgan MI, Basoglu M, Kantarci M, Yilmaz I. Sigmoid colon volvulus in children: review of 19 cases. Pediatr Surg Int. 2004;20(7):492-495.

CROHN’S DISEASE Heather Yeo • Alessandro Fichera • Roger D. Hurst • Fabrizio Michelassi

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal (GI) tract that can give rise to strictures, inflammatory masses, fistulas, abscesses, hemorrhage, and cancer. This disease commonly affects the small bowel, colon, rectum, or anus. Less commonly, it can also involve the stomach, esophagus, and mouth. Often, the disease will simultaneously affect multiple areas of the GI tract. The etiology of Crohn’s disease is not known and there is no curative treatment. Current medical and surgical treatment is effective at controlling the disease, but even with optimal treatment, recurrences and relapses are frequent. The combined approach of optimal medical treatment with timely and strategic surgical intervention offers the most effective management to patients affected by Crohn’s disease. Care of patients with Crohn’s disease, however, can be particularly challenging, as it has a myriad of manifestations and potential complications. Additionally, its course and response to therapy can be difficult to predict. To add to the overall complexity, there are many therapeutic options that must be tailored to each individual patient and to each site of involvement to achieve optimal outcomes.

HISTORY Crohn’s disease became recognized as a specific pathologic entity in 1932 when Crohn and colleagues first identified regional enteritis as a unique clinical entity.1 In retrospect, case descriptions of what appeared to be Crohn’s disease date back to at least 1612, when Fabry reported on the death of a boy experiencing severe abdominal pain.2 Autopsy revealed a contracted ulcerated cecum and ileum with complete bowel obstruction. In 1761, Morgagni described a case of an inflamed ileum with perforation and thickened mesentery in a young man with a history of diarrhea and fever.3,4 It is unclear how common Crohn’s disease might have been before 1932, as it is likely that cases of this disease occurring in an era of limited abdominal surgery may have been mistaken for other processes such as tumor or intestinal tuberculosis. In 1913, Sir Dalziel of Glasgow, Scotland, reported in the British Medical Journal on 13 patients and provided what is now recognized as a classic clinical and pathologic description of Crohn’s disease.5 Although not often cited, Dalziel’s description predates the one by Crohn and colleagues, and some have argued that the disease should be known by the eponym “Dalziel-Crohn disease.” After the report by Crohn and colleagues, increased awareness of the disease led to a marked increase in reported cases in the 1930s through the 1950s. The general public’s awareness of the disease increased when, in 1956, one of the most famous figures of the 20th century, President Dwight Eisenhower, was diagnosed with Crohn’s disease of his terminal ileum. That same year, President Eisenhower underwent intestinal bypass surgery with the small intestine proximal to the area of disease anastomosed to the transverse colon.6 Following this operation, he remained relatively free of symptoms for the remainder of his life.7 Early in the history of Crohn’s disease, optimal surgical management remained disputed. Initially, many thought that the disease was one of both the bowel and the mesentery, and similar to malignancies, wide excision with radical dissection of the mesentery was believed to be the best way to provide for the optimal long-term outcome.8 It was also appreciated that diversion of the fecal stream was effective at decreasing active inflammation and ameliorating symptoms. Frequently performed in the 1940s and 1950s, bypass operations are now only rarely undertaken for Crohn’s disease, given

the risk of malignancy in the excluded segment.9-11 Additionally, a greater understanding of the clinical course of Crohn’s disease has led to more conservative resections, as it is appreciated that wide surgical margins of normal tissue and radical resection of the mesentery do not affect early recurrence of disease. Despite the increased attention given to Crohn’s disease of the small intestine, Crohn’s colitis was not widely recognized as a form of Crohn’s disease until 1960 when Lockhart-Mummery and Morson firmly established the pathologic criteria for distinguishing Crohn’s disease from idiopathic ulcerative colitis.12

EPIDEMIOLOGY Since the original description of Crohn’s disease in 1932, the number of reported cases has increased greatly. Today, it is estimated that the incidence of Crohn’s disease in the United States is approximately 4 new cases per year for every 100,000 persons. Because this disease is chronic and patients live for many years with the ailment, the prevalence is much higher and is reported to be between 80 and 150 cases per 100,000 persons.13,14 The incidence of Crohn’s disease increased rapidly from 1930 to at least the 1980s, but more recently, the incidence of new cases now appears to have stabilized. The United States, Canada, and Europe have the highest incidence of Crohn’s disease. It is much less common in Asia, South America, and Japan. Crohn’s disease is believed to be uncommon in Africa, but accurate data regarding the incidence of inflammatory bowel disease in this region of the world are lacking. The peak age of presentation for Crohn’s disease is between 15 and 25 years old. As such, Crohn’s disease typically affects young adults, yet the disease can occur at almost any age. It should be noted, however, that Crohn’s disease is very rare in children younger than 6 years.15 In the United States, the incidence of Crohn’s disease is highest among Caucasians, low among blacks, and lowest among Hispanics and Asians. It is 3 to 4 times more common among ethnic Jews than non-Jewish whites. It also appears to be slightly more common in women than in men, although a slight male predominance has been reported in some populations.16 Familial clusters of Crohn’s disease are not uncommon, with a 6- to 10-

fold increase in the risk of this disease in first-degree relatives of those affected by this disease or its sister ailment, ulcerative colitis. Although familial aggregations are common, the distribution within families does not indicate a pattern of simple Mendelian inheritance.

ETIOLOGY The etiology of Crohn’s disease is not known. Many possible causes have been the subject of both speculation and investigation.4 Basic science research into the molecular biology of Crohn’s disease has begun to give some better insight into the genetics of this condition, but much regarding its ultimate causes remains unclear. It is known that Crohn’s disease is an altered immune response that results in inflammation and destruction of intestinal tissues. It is not clear if this altered immune response is the result of a primary dysfunction in the gutrelated immune system or whether an unknown pathologic trigger induces an otherwise normal immune system to overreact. Most believe that Crohn’s disease occurs in individuals with a genetic predisposition and that development of the disease is dependent on exposure to environmental triggers that start the pathologic sequence that ultimately manifests as Crohn’s disease. To date, no specific primary defect in the systemic or mucosal immune system has been identified. Studies of intestinal transport mechanisms have demonstrated an increase in intestinal permeability in both Crohn’s disease patients and their symptom-free first-degree relatives.17-21 This has led some to speculate that Crohn’s disease is the result of an altered mucosal barrier function that allows abnormal interactions to take place between the multitude of antigenic substrates normally found in the gut lumen and the immunocompetent tissue of the submucosa. As indicated by the observed familial aggregations and variability of risks among differing ethnic and racial groups, a genetic predisposition is likely to have a major role in the etiology of Crohn’s disease. The distribution of Crohn’s disease within family aggregates is complex and defies classification with simple Mendelian transmission of disease. Genetic linkage studies have identified susceptibility to Crohn’s disease to the CARD15/NOD2 gene mapped to chromosome 16q12.22,23 CARD15 is a gene product related to

innate immunity, and it is preferentially expressed to Paneth’s cells of the ileum.24,25 While the CARD15/NOD2 gene has been linked to susceptibility to Crohn’s disease, the known mutations of CARD15 are neither necessary nor sufficient to contract this disease. Hence, it appears that the genetic relationship of CARD15/NOD2 to Crohn’s disease is complex and still poorly understood. The suspicion that infectious agents may play a role, either directly as a primary cause of Crohn’s disease or indirectly as a trigger to stimulate a defective immune system, has generated much attention. This hypothesis has always found strength in the identification of noncaseating granulomas as the characteristic histopathologic lesion found in Crohn’s specimens and in the isolation of Mycobacterium paratuberculosis from resected Crohn’s disease specimens. This finding has been far from consistent, and even sensitive polymerase chain reaction studies have been unable to provide definitive evidence for the presence of M paratuberculosis–specific DNA in Crohn’s disease–affected segments of the bowel. Other infectious agents have been studied and shown not to be causative agents for Crohn’s disease. These include measles virus, non-pylori Helicobacter species, Pseudomonas, and Listeria monocytogenes.26 To date, no single infectious agent has been consistently associated with Crohn’s disease. Although diet modification can ameliorate the symptoms of Crohn’s disease, no dietary factor has been identified as its cause. Smoking, however, has been associated with the development of Crohn’s disease, with smokers having a substantially higher risk for contracting this disease than nonsmokers.27-30 Additionally, smoking is known to exacerbate existing Crohn’s disease and can accelerate its recurrence after resection.31,32 The component of cigarette smoke that is responsible for these deleterious effects on the clinical course of Crohn’s disease is not known.

PATHOLOGY The earliest gross manifestations of Crohn’s disease are the development of small mucosal ulcerations called aphthous ulcers.33 Aphthous ulcers appear as red spots or focal mucosal depressions and typically occur directly over submucosal lymphoid aggregates. As the inflammation progresses, the ulcers enlarge and become stellate. The enlarging ulcerations then coalesce to form

longitudinal mucosal ulcerations. In Crohn’s disease of the small bowel, these linear ulcerations almost always occur along the mesenteric aspect of the bowel lumen. Further progression leads to a serpiginous network of linear ulcerations that surround islands of edematous mucosa producing the classic “cobblestone” appearance. Mucosal ulcerations may penetrate through the submucosa to form intramural channels that can bore deeply into the bowel wall and create sinuses, abscesses, or fistulas. The inflammation process progresses to extend through all layers of the bowel wall. The inflammation of Crohn’s disease also involves the mesentery and regional lymph nodes such that the mesentery may become massively thickened. With early acute intestinal inflammation, the bowel wall is hyperemic and boggy. As the inflammation becomes chronic, fibrotic scarring develops and the bowel wall becomes thickened and leathery in texture. Histopathologic examination of Crohn’s disease typically demonstrates transmural inflammation characterized by multiple lymphoid aggregates in a thickened submucosa. Lymphoid aggregates may extend beyond the mucosa and can be found within the muscularis propria.33 The presence of wellformed lymphoid aggregates in an edematous fibrotic submucosa is a classic histologic feature of the disease. Another sentinel microscopic feature of Crohn’s disease is the presence of noncaseating granulomas. Noncaseating granulomas are a valuable diagnostic feature of Crohn’s disease, but they are seen in only 50% of resected specimens and are rarely seen on endoscopic biopsies. Additionally, the presence of granulomas does not correlate with disease activity, as areas of active inflammation are no more likely to contain granulomas than areas of quiescent disease.34

CLINICAL PRESENTATION The clinical presentation and symptoms of Crohn’s disease vary greatly depending on the segment of intestine involved35 and the predominant features of the disease: stricturing, perforating, or inflammatory. While the next few paragraphs discuss the influence of disease patterns and locations, there are additional more complex classifications that are used to subcategorize disease. The most common of these are the Rome, Montreal, and Vienna classifications (Table 45-1). These classifications are used help to

guide clinical decisions and frame medical and surgical management.36,37 TABLE 45-1: COMPARISON OF ROME, VIENNA, AND MONTREAL CLASSIFICATION SYSTEMS FOR CROHN’S DISEASE

Patterns of Disease Crohn’s disease can be categorized into 3 general manifestations: stricturing disease, perforating disease, and inflammatory disease.38 These 3 classes do not represent truly distinct forms of the disease; rather, they are terms that are used to describe the predominant gross manifestation of the disease.39 It is typical for more than 1 pattern to occur in the same patient or even the same segment of intestine; even so, 1 pattern tends to predominate in most cases. It is generally the predominant pattern of disease that determines the clinical presentation and affects the therapeutic options.

STRICTURING PATTERN Chronic inflammation of Crohn’s disease results in the development of fibrotic scar tissue that constricts the intestinal lumen with cicatricial

strictures, often referred to as “fibrostenotic lesions.” Patients with a stricturing pattern of this disease generally develop partial or complete intestinal obstruction, and hence their symptoms are primarily obstructive in nature. Being the result of submucosal deposition of connective tissue, fibrostenotic strictures are not reversible with medical therapy. Once fibrostenotic areas become symptomatic, significant improvement rarely occurs and surgical intervention is often required. While surgery is clearly the standard of care for these patients, there are data on successful treatment with endoscopic balloon dilation and stenting in selected patients with strictures refractory to medical therapy.40

PERFORATING PATTERN Perforating Crohn’s disease is characterized by the development of sinus tracts, fistulas, and abscesses. Penetrating sinus tracts develop from deep mucosal ulcerations. These sinus tracts penetrate through the muscularis propria and give rise to abscesses or to fistulas if they penetrate into surrounding structures. The term “perforating” disease can be misleading, as free perforation with spillage of intestinal contents into the abdominal cavity is not a common phenomenon with Crohn’s disease. Inflammatory response around the advancing sinus tract typically results in adhesion to surrounding structures. The sinus usually bores through the area of adhesion such that abscess formation or fistulization to other structures occurs much more often than free perforation into the abdominal cavity. Typically, perforating disease is accompanied by a degree of stricture formation, but the fistula or abscess generated by the perforating component of the disease dominates the clinical picture.

INFLAMMATORY PATTERN The inflammatory pattern of Crohn’s disease is characterized by mucosal ulceration and bowel wall thickening. The edema that results from inflammation can lead to an adynamic segment of intestine and luminal narrowing. This pattern often gives rise to obstructive symptoms in the small intestine and diarrhea in the colon. Of the 3 patterns of Crohn’s disease, the inflammatory pattern is much more likely to respond to medical therapy.

Location of Disease Crohn’s disease is a panintestinal condition that may affect any area from the mouth to the anus. The most commonly affected location is the terminal ileum, and one-fifth of all patients have more than 1 intestinal segment affected simultaneously.

CROHN’S DISEASE OF THE FOREGUT Crohn’s disease of the upper GI tract gives rise to symptoms of nausea, vomiting, dysphagia, or odynophagia.41 Oral Crohn’s disease usually manifests with aphthous ulcers in the hard palate that may cause discomfort, especially during mastication and deglutition. Esophageal Crohn’s disease is uncommon, but it is believed to be more frequent in children than in adults.42 Esophageal involvement in Crohn’s disease may be asymptomatic or may give rise to dysphagia or odynophagia. Esophageal Crohn’s disease is associated with Crohn’s disease elsewhere within the GI tract, as disease isolated to the esophagus is extremely rare. Symptomatic Crohn’s disease of the stomach and duodenum is more common than disease of the esophagus, yet both locations are the least frequently involved by Crohn’s disease. The symptoms are usually related to the obstructive nature of the disease with delayed gastric emptying, a sense of postprandial gastric fullness, nausea, and vomiting.

CROHN’S DISEASE OF THE SMALL INTESTINE Abdominal pain is the predominant symptom of small bowel Crohn’s disease, as it occurs in 90% of cases.35 Abdominal pain may be the result of obstructive or septic complications. Pain related to partial obstruction is mostly postprandial and crampy in nature; pain from septic complications is typically steady and associated with fevers. Other common symptoms and findings include anorexia and weight loss. Weight loss is usually related to food avoidance, but in severe cases, it may be the result of malabsorption. With disease of the small intestine, patients may develop a palpable mass, usually located in the right lower quadrant, related to an abscess or phlegmon in perforating disease or a thickened loop of intestine in obstructive disease. Evidence of fistulization to the skin, urinary bladder, or vagina may also be

elicited with an accurate history and physical examination.

CROHN’S COLITIS Crohn’s involvement of the colon typically results in diarrhea that may or may not be bloody. Acute flares of Crohn’s colitis are often associated with fever and abdominal pain that is often exacerbated by bowel movements. Stricturing of the colon with more advanced disease can give rise to colonic obstruction. Like Crohn’s disease of the small intestine, Crohn’s colitis can give rise to abscess formation and fistulas. Toxic megacolon can occur with Crohn’s disease, but this severe complication is rare and less frequently seen than in ulcerative colitis.43

PERINEAL CROHN’S DISEASE Crohn’s disease frequently affects the anal crypts and gives rise to perianal fistulas, abscesses, and anal strictures. Perineal Crohn’s disease is also associated with hypertrophic perianal skin tags, fissures, and perineal scarring. Approximately 40% of patients with Crohn’s will develop perineal manifestations.44,45 Anal Crohn’s disease is almost always associated with Crohn’s disease present elsewhere in the GI tract, although perianal disease can be the initial symptomatic manifestation of Crohn’s disease.

EXTRAINTESTINAL CROHN’S DISEASE In addition to the inflammation of the GI tract, a variety of extraintestinal manifestations can occur in Crohn’s disease. These include ocular, dermatologic, hepatobiliary, and joint disorders.46,47 Such extraintestinal manifestations occur in a minority of patients, but, when present, they produce symptoms that can be more severe than those of the primary intestinal disease. Ocular manifestations of Crohn’s disease include uveitis and episcleritis.48 Cutaneous manifestations of Crohn’s disease include erythema nodosum and pyoderma gangrenosum. Joint disorders such as ankylosing spondylitis, sacroiliitis, and seronegative polyarteritis can occur. Patients with Crohn’s disease are also at risk for the development of primary sclerosing cholangitis. However, the risk for primary sclerosing cholangitis is much less in Crohn’s disease patients than in patients who suffer from

ulcerative colitis. Peripheral polyarteritis, episcleritis, uveitis, and erythema nodosum typically correlate with the activity of intestinal Crohn’s disease. These particular extraintestinal manifestations usually regress with complete surgical resection of the affected segment of intestine or with successful medical control of the intestinal inflammation. Pyoderma gangrenosum may also improve with treatment of primary intestinal disease, but available clinical data on this particular issue have not always been consistent. The clinical course of ankylosing spondylitis and primary sclerosing cholangitis tends to be independent of the level of disease activity within the intestine. Ankylosing spondylitis and primary sclerosing cholangitis do not improve with surgical resection of the Crohn’s disease–affected bowel.

DIAGNOSIS The onset of Crohn’s disease is often insidious, and many patients will experience some symptoms for months or even years before the diagnosis is made. The diagnosis of Crohn’s disease is typically made by a thorough history and physical examination along with intestinal radiography, endoscopy, and pathologic confirmation. There is no specific laboratory test that is diagnostic for Crohn’s disease, although serologic and inflammatory markers are typically elevated and correlate with disease activity (eg, calprotectin and C-reactive protein). Advanced imaging studies such as computed tomography (CT) scan or magnetic resonance imaging (MRI) can assess or detect some of the complications and manifestations of Crohn’s disease49 but do not replace endoscopic and pathologic confirmation.50

History and Physical Examination The symptoms of Crohn’s disease are dependent on the location of the involved segment, the pattern and the severity of disease, and the associated complications. As noted previously, in most cases, the onset of disease is gradual, with the most common complaints being intermittent abdominal pain, bloating, diarrhea, nausea, vomiting, weight loss, and fever.51 Patients may also have symptoms related to complications of the disease, including abdominal masses, pneumaturia, perianal pain and swelling, or skin rash. In

some cases, the onset of symptoms can be more sudden, with patients relating a history reminiscent of acute appendicitis. In these cases, pain in the right lower quadrant may have been present only for a few hours or days. However, a brief history of symptoms such as these is atypical. In patients suspected of having Crohn’s disease, a complete physical examination should include a thorough abdominal assessment and digital rectal exam. In cases of ileal Crohn’s disease, tenderness is typically present in the right lower quadrant, and occasionally a palpable mass is present. The oral cavity should be examined for the presence of aphthous ulcers. The perianal area should be examined for the presence of fistulas, abscesses, or enlarged skin tags. A digital rectal examination should assess for the presence of anal strictures, fissures, and rectal mucosal ulcerations. The skin in the extremities should be examined for erythema nodosum and pyoderma gangrenosum.

Imaging SMALL BOWEL RADIOGRAPHY Upper intestinal contrast studies, either small bowel follow-through or enteroclysis, are the best means for assessing the small bowel for Crohn’s disease.52-55 The radiographic abnormalities of small bowel Crohn’s disease are often distinctive56 (Fig. 45-1). With early Crohn’s disease, mucosal granulations with ulceration and nodularity can be identified. Thickening of the mucosal folds and edema of the bowel wall itself can be demonstrated as the disease progresses. With more advanced disease, cobble stoning becomes radiographically apparent. Small bowel contrast studies can also provide information regarding enlargement of the mesentery, as well as formation of an inflammatory mass or abscess. Such findings are demonstrated by a general mass effect separating and displacing contrast-filled loops of small intestine (see Fig. 45-1; Fig. 45-2). Small bowel contrast studies can demonstrate some of the complications of Crohn’s disease, including highgrade strictures and fistulas. It is important to note, however, that small bowel radiography may not identify all such lesions. For instance, many enteric fistulas including ileosigmoid and ileovesical fistulas are not typically demonstrated on contrast radiography.57,58 Thus, the absence of radiographic evidence for fistulization does not exclude this possibility. Additionally,

small bowel studies may not demonstrate all the areas of disease with significant strictures.59 While small bowel radiographs may underestimate the extent of complicated Crohn’s disease, small bowel studies performed by an experienced GI radiologist are very effective as a diagnostic tool for this disease. Besides their diagnostic utility, small bowel radiographs can also help in assessing the extent of the disease by identifying the location and length of involved and uninvolved intestine and by recognizing whether the disease is continuous or discontinuous with skip lesions separated by areas of normal intestine (Fig. 45-3). Experienced radiologists can also assess areas of luminal narrowing and determine if they are the result of acute inflammatory swelling or are the result of fibrostenotic scar tissue. Such a distinction provides valuable information regarding the value of medical therapy versus early surgical intervention, as inflammatory stenoses are likely to respond to medical therapy whereas fibrotic strictures are best treated with surgery.

FIGURE 45-1 Small bowel radiograph demonstrating Crohn’s disease of the terminal ileum. (Reproduced with permission from the University of Chicago General Surgery Archives.)

FIGURE 45-2 Small bowel radiograph demonstrating Crohn’s disease of the terminal ileum with high-grade strictures and ulcerations. (Reproduced with permission from the University of Chicago General Surgery Archives.)

FIGURE 45-3 Small bowel radiograph demonstrating Crohn’s disease with strictures in the jejunum. (Reproduced with permission from the University of Chicago General Surgery Archives.)

ENDOSCOPY Upper and lower endoscopies allow for inspection of mucosal disease and provide an opportunity for a biopsy for histologic evaluation. Upper endoscopy is useful in the diagnosis of mucosal lesions of the esophagus, stomach, and duodenum; it also easily identifies strictures and grades their severity. Characteristic colonoscopic features of Crohn’s disease include aphthous ulcers, longitudinal ulcerations, skip lesions often with rectal sparing, pseudopolyps, and strictures.53 In many cases, the terminal ileum can be entered and evaluated.

CAPSULE ENDOSCOPY Capsule endoscopy is a new tool in the diagnosis and evaluation of Crohn’s disease.60,61 With this study, a small camera embedded within a capsule-size casing is swallowed, and images from the camera are transmitted to a small electronic receiver worn by the patient. Images from the capsule endoscopy can detect subtle mucosal lesions that may not be apparent on small bowel xrays. Prior to the capsule endoscopy, patients with suspected Crohn’s disease should undergo a small bowel contrast study to exclude stricture formation, as the capsule may fail to pass through areas of narrowing and result in intestinal obstruction. The value of capsule endoscopy in the diagnosis of Crohn’s disease has been recently evaluated in a prospective study from the Mayo Clinic.62 This study compared capsule endoscopy, CT enterography (CTE), ileocolonoscopy, and small bowel follow-through in the diagnosis of small bowel Crohn’s disease in a prospective blinded trial and found that the sensitivity of capsule endoscopy was not significantly different from that of the other tests. A meta-analysis of capsule endoscopy studies comparing it to CTE suggested that the prevalence of abnormalities detected on capsule endoscopy was 38% higher than that of CTE.63 However, this value was significantly higher than CTE only for the subgroup of patients with known Crohn’s disease. The need for a preliminary small bowel contrast study to detect asymptomatic partial small bowel obstruction before the capsule endoscopy can be safely performed and the lack of a clear advantage over other imaging studies limit the utility of capsule endoscopy as a first-line test in Crohn’s disease and perhaps reserves this study for those cases in which there is a substantial diagnostic uncertainty.

COMPUTED TOMOGRAPHY CT findings of uncomplicated Crohn’s disease are nonspecific, and routine CT is not necessary for the diagnosis of Crohn’s disease. CT, however, is very useful in identifying enteric involvement (>90%) and complications associated with Crohn’s disease.64-66 Specifically, CT can readily identify thickened and dilated intestinal loops, inflammatory masses, abscesses, and hydronephrosis resulting from retroperitoneal fibrosis and ureteral narrowing. CT scans may also raise suspicion for an enterovesical fistula as suggested by the presence of air within the urinary bladder. More recently, cross-sectional

imaging techniques have assumed an increasing role in the imaging of patients with Crohn’s disease. Using ileoscopy and biopsy of the terminal ileum as reference to evaluate the performance characteristics of crosssectional enterography,67 CTE has been shown to have a higher sensitivity than barium small bowel follow-through.62 These findings have convinced many to use CTE combined with ileocolonoscopy as a first-line test for the diagnosis and staging of Crohn’s disease.62 CTE exploits the high spatial resolution and speed of modern CT, using large volumes of neutral oral contrast agents to generate detailed images of the small bowel wall, lumen, and mesentery.68 In addition, CTE has several potential advantages over barium studies in the identification of fistulizing disease. Unlike traditional fistulography, CTE does not suffer from superimposition of bowel loops and displays the mesentery, retroperitoneal, and abdominal wall musculature, typically involved by fistulas. Sinus tracts and abscesses can also be readily characterized by CTE.68 Widespread access and rapid scan time make CT useful and convenient; however, recent concerns about radiation-induced cancer arising from medically related CT69 have stimulated a reassessment of the role of CTE in young Crohn’s disease patients70 and have prompted many to encourage the use of magnetic resonance enterography (MRE).

MAGNETIC RESONANCE ENTEROGRAPHY MRE has similar advantages to CTE, such as the ability to evaluate the entire small bowel, detect transmural inflammation, grade the severity of inflammation, and detect extracolonic inflammation, without the requirement of ionizing radiation. In fact, in a recent study, MRE was shown to have almost identical sensitivities to CTE for detecting active small bowel inflammation, although image quality across the study cohort appeared to be better with CTE.71 Improved soft tissue contrast with MRI provided by the combination of T2/T1 postcontrast and diffusion-weighted images has the potential to allow a better assessment of the relative inflammation versus fibrosis burden in stricturing Crohn’s disease, although the utility of this characterization is still being studied.66 MRI is also able to provide functional motility information, which may have a role in surgical planning. Although imaging modalities are evolving, currently, MRE appears to be a comparable alternative to CTE, in particular when radiation exposure is a concern, and

provide complementary information to ileocolonoscopy in the diagnosis of Crohn’s disease.

DIFFERENTIAL DIAGNOSIS The differential diagnosis for small bowel Crohn’s disease includes irritable bowel syndrome, acute appendicitis, intestinal ischemia, pelvic inflammatory disease, endometriosis, and gynecologic malignancies. Other disorders that are within the differential diagnosis include radiation enteritis, Yersinia infections, intestinal injury from nonsteroidal anti-inflammatory agents, intestinal tuberculosis, and small bowel tumors. Among the most important ailments to consider are small bowel malignancy and intestinal tuberculosis. In patients in whom small bowel malignancy is suspected, resection should be undertaken to make certain the diagnosis. The exclusion of intestinal tuberculosis can be difficult, as the inflammation and stricturing of the terminal ileum can occur in a manner that closely mimics Crohn’s disease. The patient should be assessed for exposure to tuberculosis and screened for tuberculosis with a purified protein derivative skin test. Chest radiography should also be considered. Even when the diagnosis of Crohn’s disease is certain, patients who coincidentally are found to also have latent tuberculosis should be treated in accordance with American Thoracic Society guidelines prior to the initiation of immunosuppressive therapy for management of their Crohn’s disease.72 Intestinal injury from nonsteroidal anti-inflammatory drugs (NSAIDs) can result in focal enteritis with ulceration and stricture formation.73,74 These manifestations can be very difficult to distinguish from Crohn’s disease of the small bowel. This rare side effect from the commonly used NSAIDs often requires resection or biopsy to confirm the diagnosis. For Crohn’s disease of the colon, the differential diagnosis includes ulcerative colitis, infectious colitis, collagenous colitis, ischemic colitis, diverticular disease, Behçet disease, colonic neoplasm, solitary rectal ulcer syndrome, and NSAID colopathy. The entity that is most difficult to distinguish from Crohn’s colitis is ulcerative colitis. The diagnosis of ulcerative colitis cannot be made with absolute certainty, as it is possible for Crohn’s disease of the colon to reproduce all the features of ulcerative colitis. It is only when features appear

that are unique to Crohn’s disease that the diagnosis of Crohn’s disease can be made. Such distinguishing features of Crohn’s disease include small bowel involvement, perianal disease, skip lesions, transmural inflammation, fistulas, abscesses, and noncaseating granulomas. After a complete history and physical examination complemented by appropriate radiologic, endoscopic, and humoral studies, Crohn’s disease and ulcerative colitis can be distinguished with a high degree of confidence in as many as 85% to 90% of cases, yet in the remaining 10% to 15% of cases, the differential diagnosis will remain indeterminate.

MEDICAL MANAGEMENT The goal of medical treatment of Crohn’s disease is to provide long-lasting symptomatic relief while avoiding excessive morbidity. Crohn’s disease cannot be cured by medical treatment, but it may afford long periods of disease control and avoidance of surgical intervention. Thus, it is important that the surgeon have an understanding of the basics of medical therapy for Crohn’s disease. Selecting the optimal medical treatment for each individual requires experience and special expertise because of the variable course of the disease, the myriad of different clinical presentations and associated complications, and the desire to optimize medical treatment for each clinical situation. Multiple different medical therapies are used for the treatment of Crohn’s disease and depend on the location and severity of the disease as well as goals of treatment (induction vs maintenance of remission).

5-Aminosalicylic Acid The aminosalicylates as a group of medications include sulfasalazine and 5aminosalicylic acid (5-ASA) derivatives. The exact mechanism of action for these agents is not clear, but 5-ASA is thought to function through various pathways.75 5-ASA compounds inhibit leukotriene production by inhibition of 5-lipooxygenase activity. 5-ASA also inhibits the production of interleukin-1 and tumor necrosis factor (TNF). 5-ASA compounds are weak inhibitors of cyclooxygenase (COX) activity, and it is unlikely that they act through the inhibition of prostaglandin production. Aminosalicylates are effective in the treatment of mild to moderate Crohn’s disease. 5-ASA given

in a controlled-release preparation is also effective as maintenance therapy to prevent recurrence after a flare of disease has been effectively managed either medically or surgically.76-79 Aminosalicylates come in a variety of preparations, each designed to deliver the drug in a topical fashion to the affected segments of intestine.80 For instance, Asacol (mesalamine) is 5-ASA contained within a pHdependent resin designed to release the drug in the terminal ileum and colon where the pH is typically greater than 7.0. Pentasa (mesalamine) is 5-ASA contained within ethylcellulose-coated microgranules designed to slowly release the active compound throughout the entire small bowel and colon. Colazal (balsalazide) is 5-ASA bound to an inert carrier by an AZO bond. This bond is broken by bacterial enzymes found within the colon, releasing the active 5-ASA compound to the colonic mucosa. The most common side effects are headache, fever, rash, and reversible infertility in men; a rarer complication is pancreatitis. It is important to emphasize that mesalamine and its derivatives should not be confused with acetylsalicylic acid (aspirin) and other NSAIDs. Unlike 5ASA compounds, classic NSAIDs are powerful inhibitors of COX-1 and COX-2. Many clinicians have had concerns that NSAIDs may exacerbate Crohn’s disease.81-83 Although the basis of these concerns has been challenged,84,85 it is recommended that patients with Crohn’s disease avoid NSAIDs and use alternative medications when appropriate.

Antibiotics (Ciprofloxacin/Metronidazole) Antibiotics have a well-established role in the management of septic complications of inflammatory bowel disease such as abscesses or wound infections. They may be used in the maintenance therapy of chronic perineal septic complications and in the treatment of bacterial overgrowth associated with chronic obstructive disease of the small bowel. Their benefit in primary treatment of Crohn’s disease is not well established, although they are commonly used in clinical practice.86

Corticosteroids Corticosteroids are the most effective agents for controlling acute

exacerbations of Crohn’s disease, but their use is limited due to the risk of serious side effects. The majority of patients with active small bowel Crohn’s disease will experience clinical remission with a short course of oral prednisone given in a dose between 0.25 and 0.5 mg/kg/d.87 For patients unable to take oral medications, methylprednisolone can be administered in the adult at doses of 40 to 60 mg given as a daily infusion.88 Common side effects from corticosteroids include diabetes, osteoporosis, cataracts, osteonecrosis, myopathy, psychosis, opportunistic infections, and adrenal suppression. The risks for these side effects are related to both the dose and the duration of steroid therapy.

Immunomodulators (Azathioprine and 6Mercaptopurine) Azathioprine and 6-mercaptopurine (6-MP) are immunosuppressive agents that inhibit cytotoxic T-cell and natural killer cell function. These agents have been shown to be effective in treating mild to moderate Crohn’s disease.88,89 Azathioprine given at 2.0 to 2.5 mg/kg/d or 6-MP in doses of 1.0 to 1.5 mg/kg/d will result in a 50% to 60% response rate in patients with active Crohn’s disease.88,90 Both 6-MP and azathioprine are also effective in maintaining remission following surgery or successful medical management.77

Biologic Therapies (Anti-TNF Therapies and AntiIntegrin Antibodies) Three anti-TNF therapies are approved for treatment of Crohn’s disease in adults in the United States, and all have been shown to be effective for treatment of GI manifestations of Crohn’s disease. Indirect evidence suggests that there are no significant differences in efficacy between these 3 anti-TNF therapies; however, no randomized controlled trials have directly compared them.91 Infliximab, the best studied, is a chimeric mouse-human monoclonal antibody to TNF. TNF is a proinflammatory cytokine that is believed to be important in the pathophysiology of Crohn’s disease. Infliximab binds to both

free and membrane-bound TNF and prevents TNF from binding to its cell surface receptors.75 Clinical trials have demonstrated an 80% response rate with a single dose of infliximab.92,93 It is important to note that the doses and dosing intervals of infliximab must be individualized, but a typical regimen would include 5 mg/kg of infliximab given intravenously at weeks 0, 2, and 6, with a dose of 5 mg/kg every 8 weeks thereafter. Because anti-TNF drugs are potent immunosuppressive agents, concerns have been raised about the risk for poor wound healing and postoperative septic complications. Current available data on the perioperative risks are somewhat conflicting. Early studies have suggested that preoperative antiTNF drug use does not appear to increase the risk for postoperative complications following abdominal surgery for Crohn’s disease.94-96 More recently, however, a study from the Cleveland Clinic demonstrated an increased risk for infectious complications and intra-abdominal abscesses in Crohn’s disease patients undergoing surgery who received infliximab.97 This study also found that the presence of a diverting stoma significantly decreased the risk for septic complications in patients who had been treated with anti-TNF drugs. Although experience with anti-integrin therapies is still slight, there are several promising drugs on the horizon. Natalizumab is an anti-alpha-4 integrin and blocks leukocyte migration to areas of inflammation. The effectiveness of natalizumab was confirmed in the Encore trial, in which 509 patients with moderate to severe active Crohn’s disease were randomized (1:1) to receive natalizumab 300 mg versus placebo. An improved response was seen in 48% of the natalizumab-treated patients compared to 32% of the patients receiving placebo (P = .001) Vedolizumab is a humanized anti-α4-β7 integrin monoclonal antibody that may help in moderated to severe Crohn’s disease98 and was recently approved by the US Food and Drug Administration. Ustekinumab is a human IgG monoclonal antibody that blocks the activity of interleukin (IL)-12 and IL-23 and has shown benefit in patients resistant to TNF antagonists. Additional monoclonal antibodies are being investigated and show promise.

Other Medical Therapies Other agents that are used with varying success in the treatment of Crohn’s

disease include methotrexate, cyclosporine, tacrolimus, and thalidomide. Each of these agents requires a complete and sophisticated knowledge of appropriate dosing, side effects, therapeutic efficacy, and toxicities, which is beyond the scope of this chapter. These medications are often used in conjunction with the more standard medications.

SURGICAL TREATMENT Similar to medical treatment, the goal of surgical treatment of Crohn’s disease is to provide long-lasting symptomatic relief while avoiding excessive morbidity. Crohn’s disease cannot be cured by surgical therapy, and thus surgery, like medical treatment, should be considered palliative. Complete extirpation of disease should not be the primary goal of surgery, as this does not produce cure and is frequently counterproductive. Rather, treatment of complications and palliation of symptoms while avoiding excessive loss of intestine should be the main aims of surgical treatment. To avoid excessive loss of intestine, nonresectional techniques such as strictureplasty may be required. Additionally, optimal surgical therapy may require leaving behind segments of the intestinal tract affected by mild but asymptomatic disease with resection of only the areas of severe and symptomatic Crohn’s disease. The best surgical strategy for each patient with Crohn’s disease takes into account the indications for surgical treatment and the natural history of the disease, with its high risk for recurrence and the need for repeated surgeries.

Indications for Surgery FAILURE OF MEDICAL TREATMENT The failure to respond to medical treatment and the inability to tolerate effective therapy are the most common indications for surgical treatment of Crohn’s disease.99 Some patients may respond to the initial medical therapy only to rapidly relapse with tapering of the medical treatment. For example, some patients respond well to steroid therapy but become steroid dependent as tapering of the steroid dose results in recurrent symptoms. Because of the severe complications that are virtually inevitable with prolonged steroid treatment, surgery is warranted if the patient cannot be weaned from systemic

steroids within 3 to 6 months. The occurrence of complications related to the medical treatment or the progression of disease while on maximal medical treatment represent additional indications for surgical treatment.

INTESTINAL OBSTRUCTION Partial or complete intestinal obstruction is a common indication for operation for Crohn’s disease.100 The clinical presentation of chronic partial small bowel obstruction is much more typical than complete obstruction. Patients with chronic partial small bowel obstruction due to Crohn’s disease may experience postprandial cramps, abdominal distension, borborygmi, and weight loss. To avoid symptoms, many patients will restrict their diets to soft foods or even liquids. If partial obstruction from Crohn’s disease is primarily due to acute inflammation and bowel wall thickening, initial medical therapy is warranted. If, however, the obstructive symptoms are due to high-grade fibrostenotic lesions, medical treatment will not reverse these lesions and surgery is indicated. When complete intestinal obstruction occurs, initial conservative treatment with nasogastric decompression and intravenous hydration is warranted.34,101 Intravenous steroids are also administered. This allows for decompression of acutely distended and edematous bowel and, in most cases, for resolution of the complete obstruction. Resolution of the complete obstruction should not lead the physician to attempt treating the patient with continuing medical therapy. Patients with complete obstruction who respond well to initial conservative therapy are at high risk for persistent or recurrent symptoms of obstruction and are best managed with surgery once adequate decompression is achieved. The surgery can be performed under elective and safer conditions after appropriate bowel preparation.

FISTULAS Intestinal fistulas occur in one-third of Crohn’s disease patients.57 Intestinal fistulas, however, are the primary indication for surgery in only a minority of patients. Thus, the presence of an intestinal fistula is not in and of itself an indication for surgery.102,103 In general, intestinal fistulas are the primary indication for surgical treatment if they connect with the genitourinary tract, if their drainage is cause for personal embarrassment and discomfort

(enterocutaneous and enterovaginal fistulas), or if they create a bypass of such magnitude as to cause intestinal malabsorption. Fistulas between the ileum and the urinary bladder often result in recurrent urinary tract infections, including pyelonephritis. While it is not mandatory to operate on all cases of enterovesical fistulas, surgery is warranted to avoid deterioration of renal function with recurrent infections or if symptoms persist despite appropriate medical therapy. Enterocutaneous fistulas and enterovaginal fistulas often cause physical discomfort and personal embarrassment. A trial of medical therapy may be elected for enterocutaneous and enterovaginal fistulas, but most such cases will require surgery.104,105 Occasionally, an enteroenteric fistula can result in significant symptoms. Fistulas that result in functional bypass of a major intestinal segment can result in malabsorption or diarrhea. These fistulas need to be addressed surgically.

ABSCESSES AND INFLAMMATORY MASSES Intra-abdominal abscesses and inflammatory masses occur less frequently than fistulas but are more often an indication for operative intervention.106 Small abscesses seen on CT may warrant a trial of treatment with antibiotics, but almost all intra-abdominal abscesses will require drainage. In a vast majority of cases, Crohn’s abscesses can be drained percutaneously with CT or ultrasound guidance.107-109 The rare large intraloop abscesses may require open surgical drainage. Often, in such cases, the abscess can be completely extirpated with the resection of the diseased segment of intestine. Crohn’s abscesses usually originate from a severely diseased segment of bowel. A Crohn’s abscess that has been drained percutaneously is very likely to recur or result in an enterocutaneous fistula, and surgical resection is often advised even after successful drainage.109 Inflammatory masses indicate severe disease and often harbor an unrecognized abscess.106 Thus, inflammatory masses that do not readily respond to antibiotic treatment should be considered for surgical treatment.

PERFORATION Free perforation is a rare complication of Crohn’s disease, occurring in fewer

than 1% of cases.110 When this complication occurs, it is an obvious indication for urgent operation. The diagnosis of free perforation is made by detecting a sudden change in the patient’s symptoms along with the development of the physical findings of peritonitis or the identification of free intraperitoneal air as demonstrated on plain x-rays or CT scans. The use of immunosuppressants and glucocorticosteroids can blunt many of the physical findings of acute perforation; therefore, the index of suspicion for perforation must be higher in immunocompromised patients who complain of worsening symptoms or show early signs of sepsis. Most patients, however, will demonstrate classic signs of peritonitis with rebound, rigidity, guarding, and loss of bowel sounds.

HEMORRHAGE Hemorrhage is an uncommon complication from Crohn’s disease. Massive GI hemorrhage is rare and occurs more frequently from Crohn’s colitis than in small bowel Crohn’s disease.111 Hemorrhage from small bowel Crohn’s disease tends to be indolent with episodic or chronic bleeding requiring intermittent transfusions, but it rarely requires emergent surgery. Localization of the site of bleeding is accomplished by angiography in the presence of brisk bleeding; otherwise, colonoscopy can be attempted preoperatively to localize a source of lower GI hemorrhage. Intraoperative localization can be aided by enteroscopy or colonoscopy. When severe hemorrhage occurs in Crohn’s disease, it is usually due to erosion of a single vessel by a deep ulcer or fissure. Recurrent bleeding in an area of small bowel disease is a common phenomenon, and it has been argued that even after control of hemorrhage from small bowel Crohn’s disease with conservative management, elective resection of the areas of Crohn’s disease should be undertaken to prevent recurrent bleeding. Patients with Crohn’s disease are also at risk for bleeding from peptic ulcer disease. This is particularly true for patients receiving corticosteroid therapy. For this reason, Crohn’s disease patients who develop GI bleeding should undergo an upper endoscopy to rule out gastric or duodenal ulcers.

CANCER OR SUSPICION OF CANCER The presence of Crohn’s disease increases the risk of adenocarcinoma of the

colon and small intestine.112 The diagnosis of adenocarcinoma of the small bowel is difficult because symptoms and radiographic findings of small bowel malignancy can be similar to those of the underlying Crohn’s disease. Male patients and patients with long-standing disease appear to be at increased risk for small bowel adenocarcinoma.112 Defunctionalized segments of bowel also seem to be at particular risk for malignancy.113 For this reason, bypass surgery should be avoided for Crohn’s disease of the small intestine, and defunctionalized rectal stumps should either be restored to their function or excised. Adenocarcinoma of the small intestine should be suspected in any patient with long-standing disease whose symptoms of obstruction progress after a lengthy quiescent period. Surveillance for colonic malignancies can be undertaken by colonoscopy with random mucosal biopsy. If dysplasia is encountered, resection of the areas of Crohn’s disease should be considered.114,115 Areas of stricture formation within the colon should be closely examined and biopsied. Strictures that are too narrow to allow passage of the colonoscope or cannot be adequately assessed colonoscopically should be resected or biopsied if a stricturoplasty is performed.

GROWTH RETARDATION Growth retardation occurs in a quarter of children affected by Crohn’s disease. Although steroid treatment may delay growth in children, the major cause of growth retardation in Crohn’s disease patients is the malnutrition associated with active intestinal disease.116,117

Preoperative Preparation and Evaluation A complete assessment of the GI tract is required prior to surgery. Full delineation of the extent of disease and associated complications is necessary to plan for the optimal surgical strategies. Assessment of the small intestine can be performed with a small bowel follow-through, an enteroclysis study, MRE, or CTE. The colon and rectum are best evaluated by colonoscopy. Barium enema studies can also be used to evaluate for colonic disease, particularly in cases in which strictures do not

allow passage of the colonoscope. If the patient has had a previous resection of the ileocecal valve, a contrast enema can be a useful means of evaluating the ileocolonic anastomosis and the preanastomotic segment for recurrent disease. If an abscess, fistula, or inflammatory mass is suspected, a CT scan of the abdomen and pelvis with both oral and intravenous contrast should be obtained. CTE combined with ileocolonoscopy is used by many as a first-line test for the staging of Crohn’s disease.62 In patients in whom urgent surgery is required, a full evaluation of the GI tract prior to surgery may not be feasible. In these cases, evaluation of disease must be accomplished intraoperatively, and both the patient and the surgeon must be prepared for a wide variety of surgical possibilities. As with preparation for any major operation, metabolic derangements must be treated prior to surgery. Fluid and electrolyte abnormalities must be corrected. Patients with profound anemia need to be transfused, and coagulopathies must be addressed. Patients with cardiovascular or pulmonary disease should have the condition stabilized and their functional capacity optimized prior to operation. Most patients with Crohn’s disease will not require preoperative parenteral nutrition, as most suffer from only a minor degree of malnutrition. There are rare cases, however, in which the nutritional status of the patient has been so severely compromised that they benefit from several weeks of bowel rest, parenteral nutrition, and ongoing medical treatment before operation. The absolute need for mechanical bowel preparation is controversial.118120 Traditionally, mechanical bowel preparations have been an unquestioned standard to lessen the risks of sepsis and to allow for a safe anastomosis. Recently, these advantages have been challenged.118,119 Even so, it is common practice for patients undergoing intestinal resection for Crohn’s disease to undergo a complete mechanical bowel preparation with either polyethylene glycol or sodium phosphate. Should the patient be unable to tolerate oral preparations, enemas can be used. Prophylactic broad-spectrum antibiotics are administered perioperatively,121 and stress dose steroids must be given to patients suspected of hypothalamic-pituitary-adrenal suppression. If feasible, well-contained intra-abdominal abscesses should be drained percutaneously prior to surgery. If an abdominal stoma is contemplated, the optimal site for the stoma location should be marked preoperatively. In patients in whom preoperative CT scan suggests significant inflammation in

proximity to the ureters, preoperative ureteral stenting can be helpful. Some have suggested that, to improve the safety of surgery for Crohn’s disease, anti-inflammatory Crohn’s medication should be either lowered or discontinued prior to elective surgery. Recent studies, however, have shown that preoperative use of steroids and antimetabolites does not appear to affect the perioperative morbidity, and hence, discontinuation of these medications is not likely to result in significant benefit. Methotrexate and infliximab, on the other hand, are 2 medications that may be worth discontinuing at least 2 weeks and 2 to 3 months, respectively, prior to surgery. Laboratory studies have shown decreased wound healing with methotrexate,122 and clinical data to evaluate the safety of methotrexate in patients undergoing bowel resection with anastomosis are lacking. A recent study from the Cleveland Clinic has demonstrated an increased risk for infectious complications and intraabdominal abscesses after recent treatment with infliximab.97

Surgical Options INTESTINAL RESECTION Intestinal resection with anastomosis or stoma formation is the most common surgical procedure performed for the treatment of Crohn’s disease. Most cases of Crohn’s disease require only limited resections that are generally well tolerated and do not place these patients at risk for short bowel syndrome. Cumulative clinical data including randomized studies have indicated that resection of Crohn’s disease need only encompass the grossly apparent disease, as wider resections do not improve the outcome after surgery.97,123-126 Microscopic resection margins that are grossly normal but demonstrate microscopic evidence for Crohn’s activity do not result in early recurrence or other complications. Hence, intraoperative frozen section of the resection margins is not necessary.127 The extent of mesenteric dissection does not affect the long-term results either; hence, the mesentery can be divided at the most advantageous level. Division of the thickened mesentery of small bowel Crohn’s disease can be the most challenging aspect of the procedure. Identification and isolation of individual mesenteric vessels are not feasible with a thickened Crohn’s mesentery. Although many approaches to this problem have been described, a common technique is to apply overlapping clamps on either side of the

intended line of transection. The mesentery is then divided between the clamps, and the tissue contained within the clamps is suture-ligated (Fig. 454). In severe cases, a vascular clamp may be used at the root of the small bowel mesentery to obtain proximal control: mattress sutures may then need to be applied to the cut edge of the mesentery to control bleeding. The use of tissue welding devices can be useful for sealing vessels within the thickened mesentery. Even with these devices, mattress sutures in the mesentery are commonly needed for complete hemostasis. Despite the difficulty dealing with the thickened and often hyperemic mesentery, resection can be performed with a low risk for postoperative hemorrhage, and the risk for postoperative hemoperitoneum requiring reexploration has been reported to be less than 0.5%.99

FIGURE 45-4 Technique for division of thickened Crohn’s mesentery.

ANASTOMOSIS There is no overriding consensus regarding the optimal technique for intestinal anastomosis in Crohn’s disease.76,128-132 It is well established that recurrent Crohn’s disease after resection of terminal ileal disease is most

likely to occur at the ileocolonic anastomosis or at the preanastomotic ileum. It has been proposed that large-caliber anastomoses require a longer period to stricture down to a critical diameter that becomes symptomatic. The argument is made that a longer side-to-side anastomosis may be beneficial over an end-to-end or end-to-side anastomosis.131 To date, however, clinical data do not indicate a benefit for one particular intestinal configuration over another.130 Intestinal anastomosis for Crohn’s disease cases can be fashioned with a stapling device or may be hand-sutured. When performed under selective conditions, resection with primary anastomosis for Crohn’s disease can be performed with a high degree of safety, and small bowel anastomotic dehiscence rates can be kept under 1%.99 In the presence of sepsis, severe scarring, malnutrition, or recent use of methotrexate or infliximab, it may be wise to protect the anastomosis with a proximal loop stoma or to forego the anastomosis altogether and bring out an end stoma at the point of resection.

STOMA FORMATION Permanent stomas are required for the surgical treatment of Crohn’s proctitis and occasionally required for the management of severe, unrelenting perianal disease. Temporary stomas are much more common and typically used as a means of protecting a distal anastomosis or when an anastomosis is not advisable. If an ileostomy or colostomy is contemplated, selection of the optimal placement of the stoma should be determined preoperatively.133 Proper stoma location is critical to achieve a satisfactory stoma. It is preferable to locate the ileostomy over the left or right rectus abdominis muscle on a flat area away from deep skin folds and bony prominences.134 The surface of the abdomen must be evaluated in both the sitting and standing positions, as this will often demonstrate skin folds and creases not evident in the supine position. Attention must be paid to determining the level of the patient’s belt line, and every effort is made to place the stoma below it. Once the optimal position of the stoma has been identified, it is marked in a manner that will remain visible at the time of surgery. Complications related to intestinal stomas are common. They include peristomal hernia, prolapse, and stricture. Peristomal hernia is the most common ostomy-related complication. It can be anticipated that approximately 25% of patients with a permanent stoma will require surgical

revision of their ostomy to deal with 1 or more of these complications.135

BYPASS PROCEDURES Bypass procedures became popular in the 1940s and 1950s once physicians and surgeons realized that aggressive enterectomies did not reduce the incidence of recurrence and were fraught with the development of short gut syndrome. Initially conceived to bypass an area of stricture or obstruction, the use of bypass procedures was eventually extended to Crohn’s disease complicated by septic complications. Increased experience with bypass procedures revealed that persistence of disease put patients at risk of persistent sepsis and eventually neoplastic transformation. Because of these complications, bypass procedures were supplanted by limited intestinal resection as the main surgical option in the late 1960s in all intestinal districts except the duodenum, where a simple side-to-side retrocolic gastrojejunostomy adequately relieves the obstructive symptoms. With increased experience and confidence in the performance of strictureplasty, duodenal disease is now more often managed using strictureplasties.

STRICTUREPLASTY Strictureplasty techniques have gained popularity as a safe and effective means of treating stricturing Crohn’s disease of the small intestine without resorting to lengthy resections. Strictureplasties are best used when resection would otherwise result in loss of a lengthy segment of bowel and thus place the patient at risk for short bowel syndrome. This would include cases with long segments of stricturing disease and patients with multiple prior resections. They are also indicated when they offer a simpler alternative to resection, such as in short recurrent disease at a previous ileocolic or enteroenteric anastomosis. It is generally accepted that the advantage conferred by a strictureplasty over a resection in the preservation of intestinal absorptive capacity is mainly due to the sparing of normal areas in between strictures that would be otherwise sacrificed. Although this is true, there is increased evidence that the acuity of the disease decreases at the site of the strictureplasty and the disease becomes quiescent and may have a lower rate of recurrence of disease.136 Whether this correlates with a simultaneous restoration of absorptive function

has not yet been established. The most commonly performed strictureplasty is the Heinecke-Mikulicz strictureplasty.137-139 The Heinecke-Mikulicz is named after the pyloroplasty technique from which this procedure is derived. With the Heinecke-Mikulicz strictureplasty, a longitudinal incision is made along the antimesenteric border of the stricture (Fig. 45-5). This incision should extend for 1 to 2 cm into the normal elastic bowel on either side of the stricture. Once the enterotomy is made, the area of the stricture should be closely examined. If there is any concern that the stricture may harbor a malignancy, a biopsy with frozen section must be obtained. Complete hemostasis should be obtained with precise application of electrocautery. The longitudinal enterotomy of the Heinecke-Mikulicz strictureplasty is then closed in a transverse fashion. The closure can be accomplished with either single- or double-layered sutures. The Heinecke-Mikulicz stricture technique is appropriate for short-segment strictures of 2 to 5 cm in length.

FIGURE 45-5 Heineke-Mikulicz strictureplasty. The Finney strictureplasty, also named for the pyloroplasty technique from which this approach is derived, can be used for strictures up to 15 cm in length.137 With the Finney strictureplasty technique, the strictured segment is folded onto itself in a U-shape140 (Fig. 45-6). A row of seromuscular sutures is placed between the 2 arms of the U, and a longitudinal U-shaped enterotomy is then made paralleling the row of sutures. The mucosal surface is examined, and biopsies are taken as necessary. Homeostasis is obtained with electrocautery. Full-thickness sutures are then placed beginning at the posterior wall of the apex of the strictureplasty and then continued down to

approximate the proximal and distal ends of the enterotomy. This fullthickness suture line is then continued anteriorly to close the strictureplasty. To complete the procedure, a row of seromuscular Lembert sutures is placed anteriorly. In essence, the Finney is a short side-to-side functional anastomosis. A very long Finney strictureplasty may result in a functional bypass with a large lateral diverticulum. This diverticulum, in theory, could be at risk for bacterial overgrowth and the blind loop syndrome. Fortunately, this theoretical concern has not been observed in clinical practice.

FIGURE 45-6 Finney strictureplasty. The purpose of the strictureplasty is to preserve intestinal length that otherwise would be sacrificed with resection. Those cases with long segments of stricturing disease are the ones in which nonresectional methods should be aggressively pursued. To manage such cases, multiple strictureplasties are typically required. In general, however, repeated Heinecke-Mikulicz or Finney strictureplasties should be separated from each other by at least 5 cm. Otherwise, the result can be a bulky and relatively unyielding segment of intestine with considerable tension placed on each suture line. Patients with multiple strictures grouped close together are best managed with a side-to-side isoperistaltic strictureplasty, also called Michelassi strictureplasty.141 With this technique, the segment of stricturing disease is divided at its midpoint. The proximal and distal ends are then drawn onto

each other in a side-to-side fashion (Fig. 45-7). Division of some of the mesenteric vascular arcades facilitates the positioning of the 2 limbs over each other. The proximal and distal loops are then sutured together with a layer of interrupted seromuscular sutures. A longitudinal enterotomy is then made along both of the loops (Fig. 45-8). The intestinal ends are spatulated to provide a smoothly tailored fit to the ultimate closure of the strictureplasty. Again, this is the time to examine the mucosal surface of the intestine to detect potential areas of neoplastic transformation and control bleeding. The outer suture line is reinforced with an interior row of either interrupted or running full-thickness sutures. This inner suture line is continued anteriorly. The anterior closure is then reinforced with an outer layer of interrupted seromuscular sutures to complete the strictureplasty (Fig. 45-9).

FIGURE 45-7 Isoperistaltic side-to-side strictureplasty. The segment of intestine affected by Crohn’s strictures is divided, and the 2 limbs are drawn onto each other.

FIGURE 45-8 Isoperistaltic side-to-side strictureplasty. Longitudinal enterotomies are made along the antimesenteric borders of the 2 limbs.

FIGURE 45-9 Isoperistaltic side-to-side strictureplasty. The 2 limbs are anastomosed together in a lengthy side-to-side fashion. Originally described in 1996, this procedure has been used with increasing frequency. The isoperistaltic side-to-side strictureplasty is recognized as an effective means of treating extensive small bowel Crohn’s disease and provides the best option for those cases that would otherwise require extensive intestinal resection with loss of significant length of small bowel.136,139,142,143 Unlike resection, diseased segments are retained with strictureplasty, and suture lines are placed in Crohn’s disease–affected tissue. This has been a cause of concern regarding the risk of intestinal suture line dehiscence, longterm recurrences, and risk for malignancy. The ongoing and now substantial clinical experience with these techniques has allayed these concerns.144 In appropriately selected patients, perioperative morbidity from strictureplasty appears to be similar to that of resection and primary anastomosis. Specifically, intestinal suture line dehiscence appears to be uncommon with any of the described strictureplasty techniques.145,146 The most common postoperative complication directly related to strictureplasty is hemorrhage

from the strictureplasty site. This has been reported to occur in up to 9% of cases. Fortunately, the GI hemorrhage following strictureplasty is typically minor and can be managed conservatively with transfusions alone. Rarely, more persistent bleeding may require intra-arterial infusion of vasopressin, but the need for reoperation to control hemorrhage after strictureplasty is very rare. It is by now also well established that strictureplasty techniques provide excellent long-term symptomatic relief that is comparable to resections with anastomosis. Although there are no controlled studies directly comparing strictureplasty to resection, multiple reports of the observed symptomatic recurrence rates after strictureplasty compare well with published recurrence rates after resection and anastomosis.139,146,147 Epidemiologic studies have shown an increased risk for small bowel adenocarcinoma in Crohn’s disease patients.114 This risk is increased in patients with long-standing disease. It is not known if strictureplasty by virtue of its retention of diseased tissue increases this risk. At the time of the writing of this chapter, there have been only 2 reported cases of an adenocarcinoma developing at a site of previous small bowel strictureplasty, and thus, it is believed that the risk of malignancy after strictureplasty is low.148,149

Laparoscopy Over the past 2 decades, laparoscopy has been dramatically changing all aspects of GI surgery. Specifically in colon and rectal surgery, laparoscopy has been widely used in benign disease,150,151 including inflammatory bowel disease, and more recently in colon cancer.152 Several single-institution small reports suggest that not only is laparoscopic surgery for Crohn’s disease feasible and safe but also it reduces length of hospitalization and recovery and allows for a smaller wound, with an overall reduction in morbidity.153-166 Most patients with Crohn’s disease are well suited for laparoscopy. They are usually young, otherwise healthy, and interested in undergoing an operation that involves minimal scarring, because they face the risk of multiple major abdominal operations in their lifetime. On the other hand, Crohn’s disease represents a difficult arena even for the experienced open colorectal surgeon. Many of the unique features of Crohn’s disease, such as the intense inflammation and thickened mesentery, enteric fistula, inflammatory masses or abscesses, and multiplicity of areas of intestinal

involvement, have deterred many surgeons from even considering a laparoscopic approach. Two prospective controlled studies have shown several advantages of the laparoscopic-assisted approach over the conventional approach.153,155 Bemelman and colleagues155 compared 48 open ileocolic resections with 30 laparoscopic-assisted resections. This study showed similarly low morbidity rates in both groups but a shorter hospital stay and improved cosmetic results in favor of the laparoscopic group.155 Alabaz and associates153 compared 48 open ileocolic resections with 26 laparoscopic-assisted resections. The patients in the laparoscopic group returned to work more quickly, had better cosmetic results, and were more likely to have improved postoperative quality of life.153 A prospective randomized trial comparing open and laparoscopic-assisted resections in 60 patients undergoing elective ileocecectomy for Crohn’s disease not complicated by abscess formation or complex fistula showed a faster postoperative recovery of respiratory function (measured as recovery of 80% of forced respiratory volume and forced vital capacity), shorter abdominal incisions, and longer performance time in the laparoscopic-assisted group. These differences were all statistically significant. With limited follow-up, there was no difference in recurrence rate.160 This study demonstrated that in experienced hands, morbidity from the laparoscopic approach compares favorably with that of a conventional open approach. Obviously these results need to be confirmed by larger series with longer follow-up. The indications for laparoscopic surgery for Crohn’s disease should not differ from conventional open surgery, as described previously. Contraindications to a laparoscopic approach include patients who are critically ill and unable to tolerate the pneumoperitoneum due to hypotension or hypercarbia, patients with extensive intra-abdominal sepsis (abscess, free perforation, or complex fistula), and difficulty in identifying the anatomy (previous surgery, obesity, or adhesions). The same variety of surgical procedures described previously can be performed laparoscopically. After induction of general anesthesia, the patient is placed on the operating table supine or in the modified lithotomy position. Rectal irrigation with diluted iodine solution is performed, especially in patients with involvement of the rectum and sigmoid colon. An epidural catheter is usually inserted at the time of surgery. The sympathetic blockade achieved with epidural

administration of local anesthetics and opioids prevents bowel distension, hence facilitating exploration of the GI tract and handling of the bowel. Depending on the procedure planned, 4 or 5 trocars are used, with the camera placed at the level of the umbilicus. Every operation for Crohn’s disease, whether open or laparoscopic, should start with a complete examination of the entire GI tract starting from the ligament of Treitz. The patient is placed in the reverse Trendelenburg position and right lateral decubitus with the assistant standing on the patient’s left side retracting the transverse colon into the upper quadrants and the surgeon at the right of the patient or in between the patient’s legs, tracing the intestine from the ligament of Treitz all the way to the ileocolic pedicle. This maneuver is facilitated by progressively rotating the patient from the reverse Trendelenburg to a full Trendelenburg position and left lateral decubitus. In the presence of skip areas of involvement from Crohn’s disease, these are marked intracorporeally with sutures in order to facilitate retrieval of the diseased segments when the specimen is exteriorized. Laparoscopic-assisted ileocolic resection is the most commonly performed laparoscopic procedure for Crohn’s disease. For laparoscopic ileocolectomy, a 4-trocar technique is used (Fig. 45-10). Trocars of 5 mm can be used exclusively, as a 5-mm, 30-degree camera offers the same resolution as larger ones and the vascular pedicles can be divided intracorporeally with 5-mm instruments. After the bowel has been evaluated in its entirety as previously described, the assistant, standing on the right of the patient or in between the patient’s legs, places the ileocolic pedicle under tension with an intestinal grasper placed through the right lower quadrant trocar (Fig. 45-11). The surgeon on the patient’s left side dissects and divides it (Fig. 45-12). Once this is accomplished, a medial-to-lateral submesenteric mobilization of the ascending colon all the way to the hepatic flexure is completed (Fig. 45-13). When the submesenteric mobilization is completed, the lateral colonic peritoneal reflection is divided all the way to the hepatic flexure (Fig. 45-14). The terminal ileum is completely mobilized by dividing the peritoneum at the level of the pelvic rim to allow a tension-free anastomosis through a small incision. It is often necessary to completely mobilize the hepatic flexure without dividing the right branch of the ileocolic vessels in order to facilitate exteriorization of the specimen (Fig. 45-15). It is imperative to make sure that the mobilization is adequate before evacuating the pneumoperitoneum and making an incision to avoid a difficult anastomosis through a small incision

or the need for a larger incision to exteriorize the specimen. Should this occur, a gel port can be applied through the abdominal incision to allow for creation of the pneumoperitoneum again and further intra-abdominal dissection.

FIGURE 45-10 Port site locations for laparoscopic ileocecectomy.

FIGURE 45-11 Optimal position of the surgeons and assistants for laparoscopic ileocecectomy.

FIGURE 45-12 Laparoscopic isolation of the ileocolic vessels. (Reproduced with permission from the University of Chicago General Surgery Archives.)

FIGURE 45-13 Submesenteric mobilization of the ascending colon and

hepatic flexure with exposure of the duodenum. (Reproduced with permission from the University of Chicago General Surgery Archives.)

FIGURE 45-14 Division of the lateral peritoneal attachments to the ascending colon. (Reproduced with permission from the University of Chicago General Surgery Archives.)

FIGURE 45-15 Final mobilization of the hepatic flexure. (Reproduced with permission from the University of Chicago General Surgery Archives.)

Once the ileum, cecum, and ascending colon are fully mobilized, the instruments are removed. With the pneumoperitoneum still in place, the umbilical port site or the right lower quadrant port site is enlarged. The pneumoperitoneum is evacuated, and the specimen is exteriorized. The ileocolonic resection is then completed by dividing the remainder of the mesentery and the bowel extracorporeally. An anastomosis is then constructed in a standard fashion.

MANAGEMENT OF COMPLICATED CROHN’S DISEASE Crohn’s Disease of the Duodenum Primary Crohn’s disease of the duodenum almost always manifests with stricturing disease that can be managed by strictureplasty or with bypass procedures (Fig. 45-16). Fortunately, resection of the duodenum for Crohn’s disease is almost never required.167-169 Perforating Crohn’s disease almost never affects the duodenum. When the duodenum is involved with Crohn’s fistulas, it is always the result of disease within a distal segment (typically the terminal ileum or neoterminal ileum) that fistulizes into an otherwise normal duodenum.170 Yet, Crohn’s disease of the duodenum can offer a particularly challenging problem due to the retroperitoneal location of the organ and its intimate proximity to the pancreas.

FIGURE 45-16 Upper GI study demonstrating Crohn’s strictures of the duodenum. Contrast seen within the biliary ducts is due to deformity and incompetence of the ampullary sphincter secondary to the Crohn’s disease. (Reproduced with permission from the University of Chicago General Surgery Archives.)

Stricturing disease of the duodenum is often focal, and many cases can be managed with a strictureplasty.171 To safely accomplish a strictureplasty, the duodenum must be fully mobilized with a generous Kocher maneuver. Heinecke-Mikulicz strictureplasties can be safely performed in the first, second, and proximal third portion of the duodenum. Strictures of the last portion of the duodenum are better handled with a Finney strictureplasty constructed by creating an enteroenterostomy between the fourth portion of the duodenum and the first loop of the jejunum. If the duodenal stricture is lengthy or the tissues around the stricture are

too rigid or unyielding, a strictureplasty should not be performed and an intestinal bypass procedure should be undertaken. The most common bypass procedure performed for duodenal Crohn’s disease is a simple side-to-side retrocolic gastrojejunostomy.127 This procedure effectively relieves the symptoms of duodenal obstruction related to Crohn’s strictures but carries a high risk for stomal ulcerations. To lessen the likelihood of ulcerations forming at the anastomosis, it has been recommended that a vagotomy be performed along with the gastrojejunostomy.127 Because of the concerns of vagotomy-related diarrhea, a highly selective vagotomy is preferred to a truncal vagotomy. If the stricturing Crohn’s disease is limited to the third or fourth portions of the duodenum, a Roux-en-Y duodenojejunostomy to the proximal duodenum is preferred to a gastrojejunostomy.170 The Roux-en-Y duodenojejunostomy has the advantage of bypassing strictures and eliminates the concern regarding acid-induced marginal ulceration and the need for vagotomy. As noted previously, when the duodenum is involved with a Crohn’s fistula, it is almost always the case that the diseased segment is located distal in the GI tract, and the duodenum itself is otherwise free of active Crohn’s disease.170 Most of these duodenal fistulas are small in caliber and asymptomatic, but larger fistulas may shunt the duodenal contents to the distal small bowel such that malabsorption and diarrhea result. In the majority of cases, duodenoenteric fistulas are identified with preoperative small bowel radiography; however, many are discovered only at the time of surgery.172 With complex fistulizing disease involving an inflammatory mass, great care at the time of surgery should be undertaken to limit the size of the duodenal defect resulting from the resection of the fistula. Most duodenal fistulas are located away from the pancreaticoduodenal margin, and thus, these fistulas can be managed by resection of the primary Crohn’s disease with primary closure of the duodenal defect. Larger fistulas or fistulas that are involved with a large degree of inflammation may result in a sizable duodenal defect. Such large defects may require closure with a Roux-en-Y duodenojejunostomy or with a jejunal serosal patch.172,173 As noted previously, duodenal resections are almost never necessary for Crohn’s disease, and they should be considered the surgical option of last resort.

Crohn’s Disease of the Small Bowel

COMPLETE INTESTINAL OBSTRUCTION Complete small intestinal obstruction resulting from Crohn’s disease only rarely requires urgent surgical intervention, as the vascular supply to the intestinal loop is never compromised and almost all cases of complete or high-grade partial small bowel obstruction from Crohn’s disease respond to conservative management. Such patients should be treated with nasogastric decompression, intravenous hydration, and steroid therapy.127 This approach allows for resolution of the acute episode of obstruction in a vast majority of cases. Unfortunately, most patients whose Crohn’s disease is severe enough to experience an episode of complete or high-grade partial obstruction are at high risk for recurrent episodes and persistent symptoms. For this reason, elective surgery should be considered once the episode of complete obstruction has resolved. The advantage of this approach is that surgery can be performed under safer conditions when the obstruction has resolved, the bowel is not distended or edematous, and an appropriate bowel preparation has been performed. If the obstruction fails to respond to appropriate conservative treatment, surgery is required. In these situations, the surgeon needs to have a high index of suspicion for small bowel cancer as the cause of the obstruction, as obstructions from cancers do not respond to bowel decompression and steroid treatment.

ILEOSIGMOID FISTULAS Ileosigmoid fistula is a common complication of perforating Crohn’s disease of the terminal ileum. Typically, the inflamed terminal ileum adheres to the sigmoid colon that is otherwise normal and free of primary involvement of Crohn’s disease. Most ileosigmoid fistulas are small and do not produce any symptoms. Asymptomatic ileosigmoid fistulas do not in and of themselves require operative management. On the other hand, large ileosigmoid fistulas can result in bypass of the intestinal contents from the terminal ileum to the distal colon and thus give rise to debilitating diarrhea (Fig. 45-17). Such symptomatic fistulas often fail to respond to medical therapy and should be managed surgically.

FIGURE 45-17 Contrast enema demonstrating large ileosigmoid fistula. (Reproduced with permission from the University of Chicago General Surgery Archives.)

More than half of the ileosigmoid fistulas from Crohn’s disease are not recognized prior to surgery.174 For this reason, the surgeon should be prepared to deal with this complication in any case of Crohn’s disease that involves the terminal ileum. Ileosigmoid fistulas can be managed by simple division of the fistulous adhesion and resection of the ileal disease. The defect in the sigmoid colon is then debrided, and simple closure is undertaken. In this manner, 75% of ileosigmoid fistulas can be managed.58,174 The remainder requires resection of the sigmoid colon. Sigmoid colon resection is necessary when primary closure of the fistula is at risk for poor healing. This is the case either when the sigmoid is also involved in Crohn’s disease, when the fistulous opening is particularly large, or when there is extensive fibrosis extending along the sigmoid colon. In addition, fistulous tracts that enter the sigmoid colon in proximity to the

mesentery can be difficult to close and often require resection and primary anastomosis.

ILEOVESICAL FISTULA Ileovesical fistulas occur in approximately 5% of Crohn’s disease patients.99 Hematuria and fecaluria are virtually diagnostic of ileovesical fistula, but these symptoms are absent in one-third of cases.175 Small bowel x-rays, cystograms, and cystoscopy often do not detect the fistula. Air within the bladder, as noted on CT scan, is often the best indirect evidence for the presence of an enterovesical fistula. An ileovesical fistula is an indicator of complex fistulizing disease, as most ileovesical fistulas occur along with other enteric fistulas. For example, as many as 60% of patients with an ileovesical fistula will also have an ileosigmoid fistula.58 The necessity for surgery for ileovesical fistula is controversial. Many patients with ileovesical fistulas can be managed medically for extended periods of time without significant complications. Healing rates with medical treatment are not clearly defined, but they are probably low, and most patients with ileovesical fistulas will ultimately undergo surgery. Surgery is indicated when recurring urinary infections occur, particularly pyelonephritis, with concomitant potential for worsening of renal function. Surgical treatment of ileovesical fistulas requires resection of the ileal disease with closure of the bladder defect. Most ileovesical fistulas involve the dome of the bladder, and thus debridement and primary closure can be accomplished without risk of injury to the trigone. Decompression of the bladder with an indwelling Foley catheter should be continued postoperatively until the bladder is confidently healed without leaks. A cystogram taken on postoperative day 5 is a convenient means for confirming the seal of the bladder repair and the safety of removing the Foley catheter.

ENTEROVAGINAL AND ENTEROCUTANEOUS FISTULAS These are rare fistulas caused by perforating small bowel disease draining through the vaginal stump in a female who has previously undergone a hysterectomy or through the abdominal wall, usually at the site of a previous scar. These fistulas often require surgical intervention because they cause

physical discomfort and personal embarrassment. Surgical treatment requires resection of the small bowel disease. The vaginal cuff does not need to be closed; the chronic infection along the abdominal wall fistulous tract requires debridement and wide drainage to allow healing by secondary intention.

ABSCESS Intra-abdominal abscesses that result from Crohn’s disease tend to follow an indolent course with modest fever, abdominal pain, and leukocytosis. Rapidly progressive and overwhelming sepsis is not typical for the clinical course of Crohn’s disease–related abscesses. In fact, in up to one-third of intraabdominal Crohn’s abscesses, preoperative clinical signs of localized infection are absent and the abscesses are discovered only at the time of operation. When an abscess is suspected or an abdominal mass is palpated, a CT scan should be obtained, as 50% of tender intra-abdominal masses will harbor an abscess collection within.106 The CT scan can detect most chronic abscesses and can also delineate the size and location of the abscess as well as the relationship of the abscess to critical structures such as the ureters, duodenum, and the inferior vena cava (Fig. 45-18).

FIGURE 45-18 CT scan of the pelvis demonstrating large Crohn’s abscess. (Reproduced with permission from the University of Chicago General Surgery Archives.)

Most abscesses with Crohn’s disease are in fact very small collections that are contained within the area of diseased intestine and its mesentery. In the case of small intraloop or intramesenteric abscesses, resection of the defective segment and its mesentery often extirpates the abscess such that drains are not necessary and primary anastomosis can be performed without risk. Large abscesses related to Crohn’s disease are best managed with CTguided percutaneous drainage.108 Percutaneous drainage is often very effective at controlling the sepsis and healing the abscess cavity.107 With percutaneous drainage of a Crohn’s disease abscess, an enterocutaneous fistula often occurs as the abscess typically connects to a deeply penetrating sinus emanating from a segment of Crohn’s disease–affected intestine. Percutaneous drainage then completes the fistulous tract from the intestine through the sinus to the abscess cavity and out the drain. Such a fistula may spontaneously close or it may persist, and the intestine may continue to be a source of sepsis. With successful drainage of the abscess, the sepsis often clears well enough that it can be tempting to try to manage the disease without subsequent surgery. Published clinical data on the optimal approach to such patients are unfortunately lacking. Even so, in the absence of Crohn’s symptoms, initial nonoperative management after successful percutaneous drainage can be undertaken in carefully selected patients.109 On the other hand, if drainage through the fistula continues, surgical resection of the affected segment of intestine becomes necessary.

PERFORATION Free perforation is a surprisingly uncommon phenomenon because the chronic progressive inflammation of Crohn’s disease normally leads to adhesions with adjacent structures. Most perforations from Crohn’s disease occur in the ileum and are usually proximal to a stenotic lesion.110,127 The diagnosis of free perforation is made by detecting a sudden change in the patient’s symptoms along with the development of the physical findings of peritonitis or the identification of free intraperitoneal air as demonstrated on plain x-rays or CT scans. Free perforation is an absolute indication for emergent laparotomy with resection of the diseased segment and exteriorization of the proximal bowel as an end ileostomy. The distal bowel end can be exteriorized as a mucous fistula or closed as a defunctionalized

pouch, depending on the degree of peritoneal contamination. Creation of a primary anastomosis even with a proximal protecting loop ileostomy carries a high risk of anastomotic breakdown and should be avoided. Primary closure of the perforation should never be attempted, as sutures will not be able to approximate the edges of the perforated, edematous, and diseased bowel in a satisfactory and tension-free way and the presence of a distal intestinal stenosis or partial obstruction will cause an increase in the intraluminal pressure at the level of the local repair with subsequent dehiscence.

HEMORRHAGE Hemorrhage from small bowel Crohn’s disease is managed by resection of the diseased portion of intestine. For patients with multiple skip areas of Crohn’s disease, small bowel angiography may be attempted to localize the exact site of bleeding.111 Localization with angiography may be unsuccessful if the bleeding is episodic or insufficiently brisk to be identified with angiography. In patients in whom small bowel hemorrhage stops spontaneously, the risk for rebleeding is high. Thus elective resection of active Crohn’s disease after the first episode of hemorrhage should be considered.

Crohn’s Disease of the Colon The optimal management of Crohn’s disease of the colon is dependent on the distribution and the location of the disease (Fig. 45-19).

FIGURE 45-19 Contrast enema demonstrating severe Crohn’s colitis with multiple high-grade strictures. (Reproduced with permission from the University of Chicago General Surgery Archives.)

CECAL DISEASE Colonic disease limited to the cecum is almost always associated with terminal ileal disease. The terminal ileitis is the predominant component of the ileocecal disease. Terminal ileal disease with extension into the cecum behaves much like disease limited to the terminal ileum. For this pattern of disease, surgical resection should encompass the margins of gross disease with an anastomosis between the neoterminal ileum and the proximal ascending colon. Recurrence of disease at the anastomosis or at the preanastomotic ileum is common, but the risk for recurrent disease within the distal colon or the rectum is low. This pattern of disease does not imply a

predisposition to more extensive colonic disease.

RIGHT-SIDED COLITIS Disease involving the entire right colon can occur alone but more typically occurs along with disease of the terminal ileum. Extensive involvement of the right colon as a form of ileocolonic disease is less common than the ileocecal pattern. Surgical treatment involves a standard right hemicolectomy to encompass the gross limits of the disease. An anastomosis between the ileum and the transverse colon is then fashioned. With a standard right hemicolectomy, the anastomosis may rest in proximity to the duodenum. Recurrent disease at the preanastomotic ileum may thus secondarily involve the duodenum. This phenomenon can place the patient at risk for substantial morbidity should inflammatory encasement of the duodenum or fistulization into the duodenum occur. For this reason, it is advantageous to protect the duodenum by interposing omentum between the duodenum and the ileocolonic anastomosis.

EXTENSIVE COLITIS WITH RECTAL SPARING Extensive colitis with sparing of the rectum occurs in approximately 20% of individuals suffering from Crohn’s colitis. In such cases, the rectum should be closely examined endoscopically, and, should the rectum be truly free of disease, a total abdominal colectomy with ileorectal anastomosis can be performed when fecal continence is adequate and the patient does not have extensive perineal septic complications. This procedure often results in good long-term function and enables many patients to avoid an ileostomy. Older patients or patients who have undergone an extensive small bowel resection may experience frequent and loose stools to the point that incontinence may develop after an ileorectal anastomosis. Additionally, recurrent disease within the rectum can result in significant deterioration of bowel function requiring further medical or even surgical intervention. Up to 50% of patients who undergo an ileorectal anastomosis for colonic Crohn’s disease will ultimately require a proctectomy with permanent ileostomy because of poor bowel function with incontinence or recurrence of disease in the rectum.176

PROCTOCOLITIS

Surgical management of extensive involvement of the colon and rectum requires total proctocolectomy with permanent ileostomy in almost all cases. In most instances, a total proctocolectomy can be performed in a single step. The presence of severe perianal disease, however, may require that the procedure be performed in 2 stages. At the first stage, the intra-abdominal colon and majority of the rectum are removed and a short rectal stump is created at the level of the levator muscles. At the same time, perineal abscesses are drained and fistulas are laid open. This first step removes the diseased colon and rectum without creating a perineal wound that may be difficult to heal in the presence of active perineal sepsis. Once the perineal sepsis is cleared and the perineum is healed, the short anorectal stump can be removed through a perineal approach. At the second stage, primary closure of the perineum can be accomplished without the high risk of persistent perineal wounds. Restorative procedures such as an ileal pouch–anal anastomosis or continent ileostomy have traditionally not been offered to patients who have Crohn’s colitis because of the recurrent nature of the disease. Even so, some of these procedures have been performed in patients whose diagnosis of Crohn’s disease was not known or suspected at the time of surgery. Various reports indicate that recurrence of Crohn’s disease within the pouch is common and removal of the pouch is often necessary. On the other hand, patients who do not suffer from recurrent disease generally do well and typically experience good pouch function. While it is commonly accepted that restorative proctocolectomy with Jpouch ileoanal anastomosis should not be undertaken for Crohn’s colitis, there is a specific pattern of Crohn’s disease that appears to be at low risk for problems with recurrence after an ileoanal anastomosis.177,178 In cases in which Crohn’s disease is limited to the colon and rectum without any history of small bowel involvement and without any perineal manifestations, the risk for pouch failure after ileoanal anastomosis appears to be low, and such patients can be considered for the ileoanal procedure. This particular pattern of Crohn’s disease, however, is rare, as most patients with Crohn’s proctocolitis will have some degree of small bowel involvement or perineal manifestations and thus would not be considered candidates for the ileoanal procedure.

PROCTITIS Crohn’s inflammation limited to the rectum is unusual. Surgical management of Crohn’s proctitis mandates proctectomy with permanent stoma. The need for resection of the normal proximal colon is controversial. Abdominoperineal resection with end sigmoid colostomy has been associated in some reports with a high risk for stomal complications and recurrent disease in the proximal intestine when compared to total proctocolectomy with end ileostomy. For these reasons, total proctocolectomy with ileostomy has been recommended for Crohn’s disease limited to the rectum and distal colon. This more extensive resection may be of greater value in younger patients who have no history of small bowel Crohn’s disease, as it appears that colorectal Crohn’s disease without small bowel involvement is unlikely to result in recurrence within the small bowel once a proctocolectomy is performed.43 If the patient has undergone a prior resection for small bowel Crohn’s disease, they may be at risk for high output from the ileostomy and therefore may benefit from the preservation of colonic absorptive capacity. Preservation of the colonic absorptive capacity may be beneficial also in the elderly patient. Thus, these patients may be better managed with a proctectomy and end sigmoid colostomy. Proctectomy for Crohn’s disease does not require a wide excision of perirectal tissue. To avoid injury to pelvic sympathetic and parasympathetic nerves, the dissection should be undertaken close to the rectal wall. This is sometimes challenging in the presence of severe rectal mesenteric inflammatory reaction. In the absence of significant perianal disease, the perineal dissection is best carried out along the plane between the internal and external sphincters.179 This intersphincteric dissection allows for a perineal closure that is associated with fewer complications and better healing than wider dissections that encompass the entire sphincter mechanism. In some patients, fistula from the perianal Crohn’s disease can traverse the intersphincteric plane and a wider dissection is required in order to encompass the diseased tissue. In the presence of significant perianal disease, a staged approach, as described previously, can be used as an option. Occasionally, however, because of extensive rectal disease, closure of the rectal stump may be technically challenging or not feasible, forcing the surgeon to proceed with a proctectomy in the face of perianal sepsis. These dissections may need to be carried out widely, and extensive loss of perianal

skin and subcutaneous tissue may occur. The resultant defects are often too large for primary closure, and closure may require advanced tissue transfer techniques such as gluteal flaps, gracilis flaps, or myocutaneous rectus abdominis pedicle flaps. These closures may have to be staged as well in the presence of perineal sepsis. Large open perineal wounds may be managed temporarily or definitively with the assistance of the vacuum-assisted closure device. This device allows for rapid contracture of the wound and facilitates healing.

SEGMENTAL COLITIS The optimal management of segmental colitis is dependent primarily on the location of the disease and secondarily on the presence and severity of concurrent perineal complications, the degree of fecal continence, and the natural history of the disease in the residual colon. Segmental involvement of the right colon should be managed by simple right hemicolectomy with ileotransverse anastomosis. For segmental disease involving the transverse colon, an extended right hemicolectomy is generally preferred to a segmental transverse colectomy. Such an approach may have a lower risk of recurrence compared to a segmental resection of the transverse colon. In addition, the extended right hemicolectomy avoids a colocolonic anastomosis that is associated with a higher risk for anastomotic dehiscences and strictures. For disease in the descending or sigmoid colon, the appropriate surgery is more controversial. Presence and severity of concurrent perineal complications, the degree of fecal continence, and the natural history of the disease in the residual colon all play a role in deciding on the approach for each individual patient. Studies have indicated that segmental colonic resection with colocolonic anastomosis or rarely colonic strictureplasty can be performed with overall good results.180,181 However, such a strategy may be at risk for early disease recurrence within the colon.43 Even if the risk for recurrence is higher with segmental resection, the benefits of preserving the absorptive capacity in appropriately selected cases may outweigh the higher risk of recurrence.

PERIANAL DISEASE The perianal manifestations of Crohn’s disease include abscesses, fistulas,

fissures, anal stenosis, and hypertrophic skin tags.182,183 Perianal Crohn’s disease originates from inflammation within the anal crypts. This inflammation gives rise to sepsis and to fistulization (Fig. 45-20). Perianal Crohn’s disease is common and occurs in one-third of the patients who suffer from intestinal Crohn’s disease.45 Perianal Crohn’s disease is usually associated with active or quiescent disease elsewhere within the GI tract. It is controversial as to whether the activity of perianal Crohn’s disease parallels that of the intestinal disease. There is also controversy over whether medical or surgical control of the intestinal disease can ameliorate the perianal manifestations. Unlike idiopathic perianal abscesses and fistula-in-ano that occur in patients without Crohn’s disease, perianal Crohn’s disease tends to be recurrent, complex, and sometimes progressive.

FIGURE 45-20 Dynamic proctogram demonstrating Crohn’s fistula-in-ano. (Reproduced with permission from the University of Chicago General Surgery Archives.)

Surgical incision and drainage are required to manage perianal abscesses (Fig. 45-21). Attempts at treating purulent collections with antibiotics alone are invariably unsuccessful. With surgical drainage of the abscess, the incision should be placed close to the anal margin. The cavity may be packed with ribbon gauze or drained with a 10- to 16-Fr mushroom catheter. If a fistula tract can be identified at the time of drainage of the suppuration, a loose seton may be placed to ensure adequate drainage.

FIGURE 45-21 CT scan demonstrating a large perirectal abscess secondary to Crohn’s disease. (Reproduced with permission from the University of Chicago General Surgery Archives.)

Uncomplicated submucosal or intersphincteric fistulas are best treated with an initial trial of either metronidazole or ciprofloxacin. These antibiotics are moderately effective in promoting healing of Crohn’s fistulas and are associated with a low risk of complication.184,185 If a low-lying submucosal or intersphincteric fistula fails to heal with antibiotic treatment, a surgical fistulotomy can be performed. These low-lying fistulas typically heal well after fistulotomy, and the risk of incontinence is low. Surgical fistulotomies and cutting setons should not be used for suprasphincteric fistulas and should also be avoided for most transsphincteric

fistulas. For complex fistulas, the risk for surgical complications is higher, and more aggressive medical therapy is warranted before surgery is recommended. Medical treatment for extensive Crohn’s fistulas includes the use of 6-MP, azathioprine, and cyclosporine. Probably the most effective agent at promoting healing of perianal fistulas related to Crohn’s disease is infliximab. With infliximab treatment, healing of complex perianal fistulas is seen in 60% of cases.186,187 Recurrence of the fistula after infliximab is discontinued, however, may be high. Additionally, persistent stasis or sepsis within the fistula tract can impede effective healing with medical treatment. To provide for adequate drainage throughout the fistula tract, many patients may benefit from placement of setons. The use of setons with infliximab therapy can improve the overall effectiveness of infliximab.188 Typically the seton is placed prior to the initiation of infliximab therapy and then is removed after the second or third dose. Fibrin glue has been used for the treatment of Crohn’s disease–related fistulas, but reported experience is limited. Success rates with this approach are low, but given the low risk of complications, an attempt at fibrin glue may be worthwhile in selected cases.189,190 Closure of the internal opening of the fistula with a rectal advancement flap can be considered in cases of Crohn’s disease.191 With this approach, an incision is made at the dentate line, and a flap of mucosa and muscularis is undermined and advanced down over the internal opening of the fistula. The advancement flap is then sutured into position with absorbable sutures. Rectal advancement flaps for Crohn’s disease have a low risk for anal incontinence but are associated with a high failure rate. Rectal advancement flaps are not appropriate in patients in whom the rectal mucosa is involved with Crohn’s disease. In severe cases of perianal disease that do not respond to aggressive medical and surgical therapy, fecal diversion with a stoma may be necessary. Diversion of the fecal stream typically results in significant relief of local inflammation and can assist in the healing of perianal fistulas. Proctectomy is indicated when perianal disease is unrelenting or when damage to the sphincters results in debilitating incontinence.

POSTOPERATIVE RECURRENT DISEASE Crohn’s disease carries a high risk for recurrence after surgery. The actual

incidence of recurrent disease depends on the defining parameters of recurrence. For example, histologic evidence for recurrence can be seen in many patients within days of surgical resection.192 Endoscopic evidence for recurrent Crohn’s disease can be seen in over 80% of patients within 3 years.193 Most cases of histologic or endoscopically detected recurrences, however, do not go on to produce symptoms of Crohn’s disease. For this reason, histologic or endoscopic evidence of recurrent disease may be used as an end point in investigative studies but is not typically used as a guide for clinical management.194 The development of symptoms related to recurrent Crohn’s disease activity is the most commonly applied definition of disease recurrence, as it is the recurrence of symptoms that has the most relevance to the patient. The onset of symptoms of recurrent Crohn’s disease is often insidious, and the severity of symptoms varies greatly. To create a reproducible standard for recurrence of Crohn’s disease symptoms, the Crohn’s Disease Activity Index (CDAI) can be applied as a means of measuring recurrent disease.195,196 A CDAI of greater than 150 is generally accepted as defining clinical recurrence. Once symptoms suggestive of recurrent disease occur, it is still necessary to carry out radiologic and endoscopic tests to confirm that the symptoms are in fact related to Crohn’s disease. The clearest end point as a definition of recurrence is the need for reoperation. Dates of surgery are readily documented even in a retrospective fashion. While reoperation is the most precise definition of recurrence, even this standard does not allow for accurate and reproducible comparisons between series as some centers may submit patients to surgery earlier than other centers. Reported crude and cumulative recurrence rates vary greatly. Symptomatic or clinical recurrence occurs in about 60% of patients at 5 years, and recurrences increase with time such that at 20 years clinical recurrence can occur in between 75% and 95% of cases.35,197,198 Reports of surgical recurrence rates range from 10% to 30% at 5 years, 20% to 45% at 10 years, and 50% to 70% at 20 years.74,100,197-201 While many factors that may influence the risk of recurrence have been studied, the cumulative literature has validated very few as true risk factors. The data are conflicting for most of the proposed predictors of recurrent Crohn’s disease. Much of the clinical data examining potential risk factors

are confounded by poorly defined end points and improper study design. There is, however, general consensus that cigarette smoking has a significant effect on the clinical course of Crohn’s disease.30 Smoking not only exacerbates existing Crohn’s disease but also has been identified as a risk factor for the development of recurrent Crohn’s.27,28,30 What is so striking about the effect of cigarettes on Crohn’s disease is that smoking has the opposite effect on what is thought to be a very similar disease, ulcerative colitis.29 While smoking exacerbates Crohn’s disease, it seems to lessen the activity of ulcerative colitis. The mechanism by which smoking results in exacerbation of Crohn’s disease is not known. Smoking is an independent risk factor for endoscopic, symptomatic, and surgical recurrence.31,32 The risk from smoking appears to be dose-related, with heavy smokers being at higher risk. This effect is reversible, as smokers who quit smoking prior to surgery can lower their risk of recurrence to a level similar to that of nonsmokers. Because of the harmful effects on the clinical course of Crohn’s disease combined with the many other clearly established health hazards caused by cigarette smoking, all patients with Crohn’s disease should be strongly counseled to quit smoking. There is concern that NSAIDs may exacerbate the activity of both ulcerative colitis and Crohn’s disease.74,82 Although there are no studies that have examined the specific issue of NSAIDs and the risks for postoperative recurrence of Crohn’s disease, the currently available data certainly warrant some caution, and patients with Crohn’s disease should be advised to avoid NSAIDs.

POSTOPERATIVE PREVENTION AND MAINTENANCE THERAPY Medical Prevention/Maintenance The risk for recurrent disease can be lessened with postoperative maintenance therapy. Traditionally the most common agents used for postoperative suppression of disease were controlled-release 5-ASA (Pentasa) and 6-MP.7779 Maintenance with 5-ASA is associated with few side effects, but up to 16 pills have to be taken daily. 6-MP is less expensive and is taken on a once-

daily basis. Additionally, 6-MP may be more effective in diminishing the risk of recurrence.77 6-MP, however, is associated with potential bone marrow suppression, so that patients on 6-MP maintenance must be followed with periodic blood cell counts. The effect of these agents on the natural course of Crohn’s disease is not dramatic, and many patients will go on to develop recurrence while on maintenance therapy. The largest benefit demonstrated with 6-MP in a multicenter trial showed a decrease of symptomatic recurrence from 77% with placebo to 50% with 6-MP.77 Recently, anti-TNF agents have shown efficacy in the prevention of Crohn’s disease after resection. Most studies of anti-TNF agents have focused on 1-year clinical and endoscopic outcomes. A more recent randomized controlled trial by Regueiro et al202 followed patients for 5 years after their initial surgery and showed a decreased recurrence rate and longer time to recurrence in patients being treated with anti-TNF medications. The options for maintenance therapy should be considered for most patients with Crohn’s after operative intervention, but the decision for such therapy must be individualized for each patient.203-205

Surgical Prevention Recurrent Crohn’s disease is most likely to occur in proximity to the location of the previously resected intestinal segment, typically at the anastomosis and preanastomotic bowel.100 This is particularly true for terminal ileal disease. Additionally, the length of small bowel involved with recurrent disease parallels the length of disease originally resected.206,207 Short-segment disease tends to recur over a short segment of the preanastomotic bowel, and lengthy disease typically is followed by lengthy recurrence. In addition, stenotic disease tends to recur as stenotic disease, and perforating disease tends to recur as perforating disease.197 There are mixed data on the role of surgical technique and procedure type in minimizing postoperative recurrence. Guo et al208 performed a metaanalysis in 2013 evaluating side-to-side anastomoses in comparison to handsewn end-to-end anastomoses for small bowel disease and were unable to demonstrate a reduction in postoperative recurrence with side-to-side anastomoses. The difference between a side-to-side or end-to-end anastomosis for an ileocolic resection was evaluated by Mcleod et al209 in a

randomized controlled trial, and no difference was found between the 2 anastomotic types. Interestingly, however, Yamamoto et al210 had previously demonstrated that in patients who underwent strictureplasty at a diseased segment there seemed to be a protective effect of the strictureplasty as these patients have lower recurrence than those undergoing segmental resection. More recently, Japanese surgeon Toru Kono has described a new antimesenteric functional end-to-end hand-sewn anastomosis (Kono-S) (Fig. 45-22). Initial results from this author have been very encouraging, showing lower rates of recurrence compared to historical controls (0% vs 15%; P = .0013) at 5 years. A multicenter randomized trial is under way in the United States to evaluate the Kono-S anastomosis compared with a standard anastomosis.211

FIGURE 45-22 Antimesenteric functional end-to-end hand-sewn (Kono-S) anastomosis.

The Kono-S anastomosis is performed by first identifying and mobilizing the segment of bowel to be resected. Control of the lumen of the bowel proximal and distal to the disease segment is obtained by firing a linear GIA stapler with 4.8 staples placed perpendicular to the mesentery. The intervening mesentery is divided very close to the bowel to preserve innervation and vascularization. The GI continuity is then reestablished with a side-to-side antimesenteric enteroenteric anastomosis. Specifically, the 2 stapled suture lines are brought together with interrupted 3-0 silk sutures to serve as a support structure for the anastomosis. A 7- to 8-cm enterotomy is then created, starting 0.7 cm proximal to the stapled suture line on the antimesenteric side of the afferent intestinal loop in a distal to proximal direction; a similar length enterotomy is then created on the antimesenteric portion of the efferent intestinal loop, starting at 0.7 cm from the stapled suture line in a proximal-to-distal direction. The anastomosis is then performed in a side-to-side transverse direction between the 2 enterotomies with an internal layer of running 3-0 Vicryl. The anastomosis is then reinforced with an outer layer of interrupted 3-0 silk Lembert stitches. While preliminary results of the Kono-S are encouraging, the debate over surgical and anastomotic technique in Crohn’s is far from over, and more research is needed.

CONCLUSIONS Management of Crohn’s disease is complex and requires a multidisciplinary team approach. Diagnosis involves a focus on patient clinical exam, supplemented by radiology and confirmed by pathology. Initial management is typically medical and has had several advances over the past few years. Surgical intervention is typically reserved for refractory disease or complications of the disease and should be managed by surgeons with significant clinical expertise in inflammatory bowel disease working closely with their GI colleagues. While significant progress has been made over the past 30 years and new medications are changing the course of treatment, much more work remains to be done, including understanding how these medications will shift surgical treatment and whether specific surgical techniques lower the risk of recurrent disease.

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172. Lee KKW. Diagnosis and treatment of duodenoenteric fistulas complicating Crohn’s disease. Arch Surg. 1989;124(6):712. 173. Pichney LS, Fantry GT, Graham SM. Gastrocolic and duodenocolic fistulas in Crohn’s disease. J Clin Gastroenterol. 1992;15(3):205-211. 174. Block GE, Schraut WH. The operative treatment of Crohn’s enteritis complicated by ileosigmoid fistula. Ann Surg. 1982;196(3):356-360. 175. Gruner JS, Sehon JK, Johnson LW. Diagnosis and management of enterovesical fistulas in patients with Crohn’s disease. Am Surg. 2002; 68(8):714-719. 176. Lefton HB, Farmer RG, Fazio V. Ileorectal anastomosis for Crohn’s disease of the colon. Gastroenterology. 1975;69(3):612-617. 177. Panis Y, Poupard B, Hautefeuille P, Valleur P, Nemeth J, Lavergne A. Ileal pouch/anal anastomosis for Crohn’s disease. Lancet. 1996; 347(9005):854-857. 178. Regimbeau JM, Panis Y, Pocard M, et al. Long-term results of ileal pouch-anal anastomosis for colorectal Crohn’s disease. Dis Colon Rectum. 2001;44(6):769-776. 179. Berry AR, De Campos R, Lee ECG. Perineal and pelvic morbidity following perimuscular excision of the rectum for inflammatory bowel disease. Br J Surg. 1986;73(8):675-677. 180. Allan A, Andrews H, Hilton CJ, Keighley MRB, Allan RN, Alexander-Williams J. Segmental colonic resection is an appropriate operation for short skip lesions due to Crohn’s disease in the colon. World J Surg. 1989;13(5):611-614. 181. Sanfey H, Bayless TM, Cameron JL. Crohn’s disease of the colon: is there a role for limited resection? Am J Surg. 1984;147(1):38-42. 182. Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB. AGA technical review on perianal Crohn’s disease. Gastroenterology. 2003;125(5):1508-1530. 183. Homan WP. Anal lesions complicating Crohn disease. Arch Surg. 1976;111(12):1333. 184. Bernstein LH, Frank MS, Brandt LJ, Boley SJ. Healing of perineal Crohn’s disease with metronidazole. Gastroenterology. 1980;79(3):599. 185. Turunen U, Färkkilä M, Valtonen V. Long-term treatment of ulcerative colitis with ciprofloxacin. Gastroenterology. 1999;117(1):282-283. 186. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999; 340(18):1398-1405. 187. Ardizzone S, Maconi G, Colombo E, Manzionna G, Bollani S, Porro GB. Perianal fistulae following infliximab treatment: clinical and endosono-graphic outcome. Inflamm Bowel Dis. 2004;10(2):91-96. 188. Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis. 2003;9(2):98103. 189. Loungnarath R, Dietz DW, Mutch MG, Birnbaum EH, Kodner IJ, Fleshman JW. Fibrin glue treatment of complex anal fistulas has low success rate. Dis Colon Rectum. 2004;47(4):432-436. 190. Zmora O, Mizrahi N, Rotholtz N, et al. Fibrin glue sealing in the treatment of perineal fistulas. Dis Colon Rectum. 2003;46(5):584-589. 191. Kodner IJ, Mazor A, Shemesh EI, Fry RD, Fleshman JW, Birnbaum EH. Endorectal advancement flap repair of rectovaginal and other complicated anorectal fistulas. Surgery. 1993;114(4):682-689; discussion 689-690. 192. D’Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114(2):262-267. 193. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99(4):956-963.

194. McLeod RS, Wolff BG, Steinhart AH, et al. Risk and significance of endoscopic/radiological evidence of recurrent Crohn’s disease. Gastroenterology. 1997;113(6):1823-1827. 195. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70(3):439-444. 196. Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn’s Disease Activity Index (CDAI). Gastroenterology. 1979;77(4 Pt 2):843-846. 197. Greenstein AJ, Sachar DB, Pasternack BS, Janowitz HD. Reoperation and recurrence in Crohn’s colitis and ileocolitis. N Engl J Med. 1975;293(14):685-690. 198. Mekhjian HS, Switz DM, Watts HD, Deren JJ, Katon RM, Beman FM. National Cooperative Crohn’s Disease Study: factors determining recurrence of Crohn’s disease after surgery. Gastroenterology. 1979;77(4 Pt 2):907-913. 199. Borley NR, Mortensen NJ, Jewell DP. Preventing postoperative recurrence of Crohn’s disease. Br J Surg. 1997;84(11):1493-1502. 200. Post S, Herfarth C, Böhm E, et al. The impact of disease pattern, surgical management, and individual surgeons on the risk for relaparotomy for recurrent Crohn’s disease. Ann Surg. 1996;223(3):253-260. 201. Chardavoyne C, Flint GW, Pollack S, Wise L. Factors affecting recurrence following resection for Crohn’s disease. Dis Colon Rectum. 1986; 29(8):495-502. 202. Regueiro M, Kip KE, Baidoo L, Swoger JM, Schraut W. Postoperative therapy with infliximab prevents long-term Crohn’s disease recurrence. Clin Gastroenterol Hepatol. 2014;12(9):14941502.e1491. 203. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Ann Surg. 2000;231(1):38-45. 204. Regueiro M, Schraut W, Baidoo L, et al. Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology. 2009;136(2):441-450.e441. 205. Doherty G, Bennett G, Patil S, Cheifetz A, Moss AC. Interventions for prevention of postoperative recurrence of Crohn’s disease. Cochrane Database Syst Rev. 2009;4:Cd006873. 206. D’Haens G, Baert F, Gasparaitis A, Hanauer S. Length and type of recurrent ileitis after ileal resection correlate with presurgical features in Crohn’s disease. Inflamm Bowel Dis. 1997;3(4):249-253. 207. D’Haens GR, Gasparaitis AE, Hanauer SB. Duration of recurrent ileitis after ileocolonic resection correlates with presurgical extent of Crohn’s disease. Gut. 1995;36(5):715-717. 208. Guo Z, Li Y, Zhu W, Gong J, Li N, Li J. Comparing outcomes between side-to-side anastomosis and other anastomotic configurations after intestinal resection for patients with Crohn’s disease: a meta-analysis. World J Surg. 2013;37(4):893-901. 209. McLeod RS, Wolff BG, Ross S, Parkes R, McKenzie M. Recurrence of Crohn’s disease after ileocolic resection is not affected by anastomotic type: results of a multicenter, randomized, controlled trial. Dis Colon Rectum. 2009;52(5):919-927. 210. Yamamoto T, Fazio VW, Tekkis PP. Safety and efficacy of strictureplasty for Crohn’s disease: a systematic review and meta-analysis. Dis Colon Rectum. 2007;50(11):1968-1986. 211. Kono T, Ashida T, Ebisawa Y, et al. A new antimesenteric functional end-to-end handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn’s disease. Dis Colon Rectum. 2011;54(5):586-592.

ULCERATIVE COLITIS Christina W. Lee • Freddy Caldera • Tiffany Zens • Gregory D. Kennedy

INTRODUCTION Ulcerative colitis (UC) is a chronic relapsing and remitting intestinal disorder plagued by diffuse and continuous mucosal inflammation involving the rectum, and extending proximally throughout the colon. As one of two wellknown disease types grouped under the umbrella of inflammatory bowel diseases (IBDs), the inflammatory hallmark in UC is limited to the mucosa. The etiology of UC is not yet completely understood; however, research over the last several decades has led to a better understanding of cellular, immunological, and molecular mechanisms involved in its pathogenesis. Scientists continue to discover new and innovative approaches in the development of potential biomarkers, diagnostic tools, and treatment options for patients with this disease. In this chapter, the authors present a broad overview of disease epidemiology, presentation and diagnosis, and current options for medical management with a focus on the surgical approaches to treatment of UC.

EPIDEMIOLOGY Over 1.5 million Americans and 2.2 million Europeans are currently estimated to be afflicted with UC.1 The incidence of UC in the United States and Northern Europe is 9 to 20 cases per 100,000 patients per year.2 Its prevalence ranges from 156 to 291 cases per 100,000 people.2 UC is less common in Eastern and Southern European countries, specifically among Asian, Hispanic, and African American populations. Ashkenazi Jews have demonstrated some of the highest frequencies of UC, estimated at 3 to 5 times higher than other ethnic groups.2 No significant gender discrepancy has been documented. Disease onset is not targeted to a specific age group and may present at any time. However, the age of onset is bimodal in distribution, wherein the primary peak is typically 15 to 30 years and a second, smaller peak occurs in the sixth to seventh decade of life.

PATHOPHYSIOLOGY Although the exact pathophysiology of UC remains unknown, it is postulated to be the result of a combination of dysregulated interactions between the host’s genetic predisposition, environmental triggers and exposures, and the intestinal microbiome, all of which undoubtedly interact with the innate and adaptive immune systems. The overarching hypotheses suggest that the above-mentioned factors function dependently on one another to establish and maintain intestinal homeostasis, which is altered upon dysregulation of any of the contributing players, presenting a platform upon which UC can develop. Studies in molecular genetics have shed light onto the genetic contribution to the development of UC. Monozygotic twin studies have demonstrated concordance rates of 16% in UC.3 In addition, 8% to 14% of patients with UC were found with a family history of IBD, and a first-degree family member with UC statistically increases a person’s risk of development of IBD by approximately tenfold.3,4 To date, genome-wide association studies have identified 163 loci linked to IBD.3 Although disease-specific genes have not yet been identified, patients with UC are often found with mutations of epithelial barrier function, innate and adaptive immune responses, and response to oxidative stress.

Over the years, it has become clear that the environment plays a pivotal role in the onset and progression of UC. This was first evidenced by epidemiological studies demonstrating an increased incidence of disease from 5.3 to 10 per 100,000 people in second-generation Asian immigrants to the United Kingdom.5 Many modifiable risk factors have been identified in the literature. Western diets high in saturated fats, refined sugars, meats, and milk products are linked to increased risk of developing UC. In contrast to Crohn’s disease, smoking has been found to have a protective effect in UC. Smokers are less likely to develop UC and milder disease.3 Breastfeeding has also shown protective effects against UC if continued for greater than 3 months.1 Some evidence suggests that lifestyle factors such as high stress, poor sleep habits, and decreased exercise can be risk factors for development of UC. Finally, studies have demonstrated patients who have undergone an appendectomy are at decreased risk of developing UC, although the mechanism of this protective effect is not fully understood. Alterations in the gut microbiome have been implicated in the development of UC, generating a greater emphasis in research to understand this complex interaction. To illustrate this, an infection with Salmonella or Campylobacter has been associated with an 8- to 10-fold increased risk of developing of UC the following year.6 Likewise, use of certain medications, such as NSAIDs and antibiotics, which can alter the gut microflora, is linked to an increased risk of IBD development.7

DIAGNOSIS The diagnosis of UC is established through a combination of clinical presentation, laboratory tests, imaging, and endoscopic evaluation. A universal scoring or classification system has yet to be widely accepted. Several parameters have been described, such as disease severity (mild, moderate, severe, or fulminant), age of onset, and extent of disease (proctitis, proctosigmoiditis, left-sided, or pan-colitis). All other forms of colitis including infectious, ischemic, and radiation colitis should be excluded prior to diagnosis of UC in a patient. Typically, patients will present with complaints of hematochezia, abdominal pain, diarrhea, pain with defecation, occult or gross rectal bleeding, and/or tenesmus. Symptoms gradually progress over the course of

several weeks to months. Eventually, the patient may develop systemic symptoms including low-grade temperatures, weight loss, and fatigue. There are no disease-specific laboratory tests to diagnose UC. Nonspecific markers of inflammation are often measured, including elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), iron-deficiency anemia (in the instance of chronic rectal bleeding), thrombocytosis, and hypoalbuminemia. In addition, fecal calprotectin (FC) or stool lactoferrin (SL) is more sensitive (88% for FC, 82% for SL) and specific (79% for FC, 79% for SL) markers of intestinal inflammation, although these biomarkers are also elevated in intestinal inflammation of any etiology.8 Autoantibodies may be helpful in differentiating Crohn’s disease from UC. Antineutrophilcytoplasmic antibodies (ANCA), specifically perinuclear antibodies (pANCA), are found in approximately 60% to 70% of patients with UC, compared to 2% to 28% of patients with Crohn’s.2 In contrast, antiSaccharomyces cerevisiae antibodies (ASCA) are found in 39% to 69% of Crohn’s patients but only 5% to 15% of UC patients.2 Other antibody testing including anti-goblet cell antibodies (GAB) can be used to differentiate UC patients from other forms of colitis. Imaging serves as a useful adjunct to diagnosis since it may demonstrate direct evidence of colonic inflammation. Modalities such as computed tomography, ultrasound, MRI, and endoscopy (Figs 46-1, 46-2, and 46-3) can reveal acute mucosal wall thickening, fat stranding, and perforation. Leukocyte scintigraphy is an uncommon imaging technique used to quantify leukocytes in the intestinal wall. It is particularly useful in ascertaining the distribution (continuous vs discontinuous) of disease and response to treatment. However, endoscopy remains the gold standard for imaging in the diagnosis of UC.

FIGURE 46-1 MRI. Yellow arrows point to segments of visualized colon which are narrowed, ahaustral, and foreshortened.

FIGURE 46-2 CT. This is a representation of the classic lead pipe in both descending and ascending colon (yellow arrows). This effect is less appreciated on the right. The thick red arrow demonstrates post-inflammatory polyps, which are true reparative lesions as opposed to pseudopolyps.

FIGURE 46-3 CT, Pancolitis. A. This cross-section clearly demonstrates pancolitis with a striated wall appearance from mucosal enhancement and

intramural edema (yellow arrows). B. This is a patient with an acute on chronic UC flare. The striated appearance is due to chronic submucosal fat deposition. All patients with presumed UC should undergo both an esophagogastroduodenoscopy (EGD) and colonoscopy with sampling of the ileum, four colonic sites, and the rectum, with a minimum of two biopsies from each site.9 Typically, the bowel of patients with UC demonstrates diffuse continuous mucosal inflammation, characterized by edema and widespread erythema with ulcerations and bleeding starting at the rectum with proximal extension (Fig. 46-4). In addition, there is often loss of vascularity, loss of haustral folds, mucosal erosions, mucosal friability, and evidence of mucopurulent exudates. Pseudopolyps are often observed in longstanding disease. Histologically, the mucosa is infiltrated with inflammatory cells; namely, mononuclear cells with plasmacytosis and lymphocytes, villous atrophy, goblet cell depletion, crypt cell branching and atrophy, Paneth cell metaplasia, and crypt cell abscesses.7

FIGURE 46-4 An endoscopic view of ulcerative colitis. A. Mild ulcerative colitis. B. Moderate ulcerative colitis. C. Severe ulcerative colitis. The mucosa is plagued with white exudative granularities.

MEDICAL MANAGEMENT UC is a chronic medical condition that is not medically curable, but like other chronic health conditions it requires long-term therapy directed at controlling gastrointestinal inflammation. The two main goals of medical treatment for

UC are achieving clinical remission (the absence of symptoms), and once that is accomplished, maintaining remission (prevention of flare-ups). To achieve the goals of therapy, two treatment strategies are used: induction and maintenance therapy. Induction therapy is defined as a treatment that induces a quick treatment response and achieves clinical remission. The initial choice of therapy depends upon the severity of disease and required rapidity of action. For example, a patient who feels well but has a high disease burden may be able to wait the necessary 3 or 4 months for immunomodulators to take effect, whereas a patient who is significantly symptomatic needs an effective agent with immediate action. Maintenance therapy is defined as a treatment that has been proven in clinical studies to prevent relapses and maintains patients in clinical remission. These medications have different onsets of action, and the choice of therapy depends on the severity of disease. Medications that are used as maintenance therapy are called corticosteroid-sparing therapy. Corticosteroids are not effective in the prevention of flare-ups and have many undesirable side effects so are not used as maintenance therapy. Most patients will be managed with medical therapy and kept in clinical remission, as only 10% to 15% of patients will require surgical therapy.10 Surgical management is reserved for patients with severe colitis with or without complications (eg, toxic megacolon), or those with chronic colitis unresponsive to maximal medical management. Prior to proceeding with surgical treatment, consultation with a gastroenterologist should be considered to evaluate that maximal medical therapy has been used and to exclude conditions that may exacerbate disease (eg, Clostridium difficile colitis). In the following sections we review the medical management for outpatient and hospitalized patients with UC.

OUTPATIENT MEDICAL THERAPY Aminosalicylates Aminosalicylates are commonly used to treat mild to moderate UC and can be administered orally or topically. Sulfasalazine consists of an antibacterial component, sulfapyridine, bonded by an azo-bond to a salicylate, 5aminosalicylic acid (5-ASA [mesalamine]). Sulfasalazine is split by bacteria

into active components in the colon. The mesalamine portion is the active portion of the drug and acts by interruption of the lipoxygenase and cyclooxygenase pathways, decreased production of IL-1, IL-2, and tumor necrosis factor (TNF) in the colonic mucosa. 5-ASA has been found to be effective in inducing and maintaining clinical remission in mild to moderate UC and usually improves symptoms by 2 to 4 weeks. Agents with 5-ASA are generally well tolerated, unlike sulfasalazine, in which patients usually experience side effects from the sulfa component. Rarely, 5-ASA can cause a paradoxical reaction leading to worsening diarrhea and should be stopped.

Thiopurines Thiopurines (azathioprine and mercaptopurine) are immunomodulators that downregulate the activity of the immune system, and in turn decrease the gastrointestinal inflammatory response. Azathiopurine and 6-mercaptopurine are inactive prodrugs that require enzymatic conversion to produce active metabolites. These are purine analogs that become incorporated into DNA and inhibit DNA synthesis. They interfere with nucleic acid metabolism and cell growth and exert cytotoxic effects on lymphoid cells. The main limitation of these medications is their slow onset of action, which can be from 2 to 6 months and therefore this is not an effective medication to induce remission. However, they are effective in maintaining clinical remission in moderate to severe UC. A meta-analysis showed that compared to placebo, only five patients needed to be treated to maintain remission.11 Thiopurines are generally well tolerated, but side effects include reversible bone marrow suppression, increased liver function test, pancreatitis, and opportunistic infections.

Biologics Biologics are genetically engineered medications that interfere with the body’s inflammatory response in IBD by targeting specific molecular players in the process such as TNF. Unlike corticosteroids, which tend to suppress the entire immune system and thereby have the potential to produce major systemic side effects, biologics offer a distinct advantage in IBD treatment because they act selectively, with a targeted mechanism of action.

TNF INHIBITORS Infliximab, adalilumab, and golilumab are effective in inducing and maintaining clinical remission in UC.12−15 Infliximab is a chimeric anti-TNF inhibitor and is administered intravenously every 8 weeks after induction dosing. Adalilumab and golilumab are fully humanized anti-TNF inhibitors and are administered by subcutaneous injection every 2 weeks or monthly, respectively. These drugs work by binding to and preventing the activity of a specific protein in the body, tumor necrosis factor-alpha (TNF-α). TNF-α is a cytokine, a specialized protein that promotes inflammation in the intestine and other organs and tissues. The agent binds to soluble and membranebound TNF-α, deactivating it and resulting in reduced inflammation. Use of thiopurines in combination with infliximab was found to be more efficacious in maintaining clinical remission compared to infliximab alone.16 TNF inhibitors can exacerbate latent tuberculosis or hepatitis B, leading to disseminated tuberculosis or fulminant hepatitis B. Therefore, prior to initiating TNF inhibitors patients should be evaluated for these infections. Patients who are using TNF inhibitors also carry an increased risk for opportunistic infections, lymphoma, and non-melanoma skin cancer.

SELECTIVE ADHESION MOLECULE INHIBITORS Vedolizumab is the first selective adhesion molecule inhibitor, and was approved in May 2014. It is a humanized monoclonal antibody that inhibits adhesion molecule α4 β7, which results in blocking leukocyte migration and therefore gut inflammation. It only targets gastrointestinal leukocyte migration and provides selective immunosuppression of the gastrointestinal tract and does not cause systemic immunosuppression like TNF inhibitors. The GEMINI trial found it to be effective in inducing and maintain remission in moderate to severe UC.17 There do not appear any increased risks of adverse events or infections with vedolizumab.

Corticosteroids Corticosteroids are potent nonspecific mediators of the inflammatory response. They can be administered by mouth, intravenously, or by rectum. They are effective in induction therapy but are not effective in maintaining

remission. Corticosteroids decrease inflammation by inhibiting arachidonic acid and cytokine release, and by inhibiting chemotaxis and phagocytosis. Corticosteroids are associated with many significant side effects (eg, osteoporosis, diabetes, cataracts, infections) and should always be used in conjunction with corticosteroid sparing therapy.

INPATIENT MANAGEMENT Patients failing outpatient medical management should be admitted for intravenous corticosteroids, which are essential in the management of severe or fulminant UC; up to 70% of patients will respond to intravenous corticosteroids.18 Patients admitted for acute management of UC should receive 400 mg of hydrocortisone per day or 60 mg of methylprednisolone in divided doses.19 The medication should be administered in bolus injections, since they were no more effective than continuous infusion. While awaiting a response to corticosteroids, a flexible sigmoidoscopy should be performed to confirm the degree of inflammation and exclude infections. C. difficile infections can increase risk for blood transfusion, surgery, and mortality in patients with UC.20 Cytomegalovirus infection can be associated with steroid refractory UC and excluded with colonic biopsies. All patients should receive thromboprophylaxis with subcutaneous heparin or low molecular weight heparin, since patients are at increased risk for deep venous thromboembolism.21 There is no evidence to suggest that empirical treatment with antibiotics in severe colitis is beneficial. Agents that could potentially precipitate the effects of toxic megacolon, such as anticholinergics, antidiarrheals, NSAIDs, and opiates, should be discontinued. A response of corticosteroids should be seen by 3 to 5 days. If a response is not seen, rescue therapy with higher level medications or surgery should be strongly considered, as continuing steroids is unlikely to lead to a clinical benefit.22 Infliximab and cyclosporine have both been shown to be effective rescue therapy; a recent clinical trial demonstrated both to have similar efficacy in inducing clinical remission and preventing colectomy.23 Infliximab is more commonly used due to its better safety profile compared to cyclosporine, which can have serious adverse effects including nephrotoxicity, seizures, and infections. Infliximab in the inpatient setting

can have long-term benefits, with colectomy rates of 50% 3 years after treatment.24

SURGICAL MANAGEMENT Despite the improvements made in medical therapy, the only definitive cure for UC remains surgical resection of the colon and rectum. As mentioned, the majority of patients can be managed adequately with medical treatment; however, when emergencies are included, as many as 45% of patients have been reported to require operative treatment.25,26 The overwhelming benefit is elimination of disease, countered by wide variability in function and reestablishing continence postoperatively. Despite these challenges, most patients report a high quality of life with satisfactory long-term functional outcomes.26

Indication for Surgical Intervention The overarching principle in surgical treatment is to eliminate disease and the risk of colorectal cancer. The main goals of operative intervention include achieving definitive cure by resection of the colon and rectum, reconstructing a route of elimination, and minimizing morbidity and improving quality of life. As with all procedures, risks and complications are true possibilities. Surgery should be considered a therapeutic alternative rather than a failure of medical therapy. Hence, discussions between the patient, gastroenterologist, and colorectal surgeon should be introduced early into the patient’s treatment time course. Given the wide variability in clinical manifestation, disease behavior largely directs the indications for surgical intervention. The first, and invariably the most straightforward, indication includes life-threatening complications such as toxic megacolon, perforation, and uncontrolled hemorrhage. The emergent nature of this approach is associated with higher morbidity and a greater number of subsequent operations.27,28 A second category encompasses cancer-related indications such as proven high-grade dysplasia, multifocal low-grade dysplasia, strictures, or localized cancer. A diagnosis of cancer and dysplasia is an absolute indication for surgery (Fig. 46-5). Patients comprising the largest indication category include those with

chronic, continuous disease and developed unresponsiveness to medical therapy. These patients are largely steroid dependent, have developed adverse effects, and exhibit insufficient responses to other medical therapies.

FIGURE 46-5 Barium enema. A patient with severe ulcerative colitis and a cancerous lesion in the ascending colon shown by a long apple-core segment

(yellow arrow). Note the smooth, ahaustral lead pipe appearance (red arrow) with backwash ileitis (thin yellow arrow). There is no doubt that the degree of ineffectiveness of medical therapies will vary among patients. Therefore it is critical that conversations regarding when the expectation of medical therapies have not been met are introduced to the patient, along with the treatment offered by surgical intervention. Pending no emergencies, the decision to proceed with elective colectomy may be left to the well-informed patient.25 Historically, non-resectional strategies were the mainstay of surgical approaches, comprising segmental resections for limited disease scattered throughout the colon. The following section discusses the surgical options under acute and elective clinical scenarios, as the management of either is indicatively unique.

MANAGEMENT OF ACUTE COLITIS Severe acute colitis presents a potential surgical emergency. Under ideal circumstances, acute colitis may be initially treated with medical therapy and daily re-evaluation. The patient should be informed that colectomy is a very possible alternative in the instance that the colitis is refractory to medical treatment. Deterioration or failure of symptoms to resolve within the first 3 days triggers the need for urgent colectomy.26 The absolute indications for surgery are toxic megacolon, perforation, and severe, unremitting colorectal bleeding (Fig. 46-6).27

FIGURE 46-6 Abdominal plain radiograph, toxic megacolon. Grossly dilated transverse colon with “thumbprinting” due to mucosal edema. If treatment is initiated via medical therapy, the colorectal surgeon must be consulted for early evaluation and daily assessment in the instance of any deterioration during IV steroid therapy or rescue treatment. Response to medical therapy may be objectively monitored by stool frequency, CRP levels, and abdominal imaging.27 Colectomy is recommended by the

European Crohn’s and Colitis Organization (ECCO) guidelines if there is no improvement by days 4 to 7 following initiation of medical therapy under acute circumstances, or if the patient has been taking 20 mg of prednisolone or more daily for over 6 weeks.10 The operation of choice in urgent and emergent situations is total abdominal colectomy (TAC) with end ileostomy, leaving the rectum in situ. This is commonly a staged procedure where the goal is to remove the diseased colon as quickly as possible without distorting anatomic planes. Hence the rectum is not resected until a subsequent procedure may be planned to allow the patient to recover from the initial insult and taper off immunosuppressive medications. Management of the rectal stump remains problematic and can be a source of postoperative complications if it opens up in the postoperative period. Some surgeons opt for high ligation of the rectum at the level of the promontory with transanal rectal drainage. The alternative includes creating a mucous fistula, where the clear advantage lies in the fact that no closed bowel is left within the abdomen. Traditionally, emergent operations are performed in an open approach; however, evidence from specialty centers has recently emerged suggesting laparoscopic subtotal colectomy is not only safe, but demonstrates improved short-term perioperative outcomes.29,30 While clearly adding some benefit to patients in the acute setting, laparoscopy should be undertaken in this setting only by an expert laparoscopist. The colon is often enlarged and quite friable, increasing the technical difficulty of the operation. In addition, laparoscopy is contraindicated in patients who are septic or who have experienced a perforation.

Brief Operative Technique Following induction of general anesthesia with endotracheal intubation, the procedure is begun with the patient in standard Lloyd-Davis position. A urinary catheter is placed and a site demarcating the end ileostomy is made in either the right or left lower quadrant. In the standard open approach, a midline incision provides adequate access into the abdomen with the option of placing the stoma in either lower quadrant. Initial exploration of the abdominal cavity is performed. It is here that the surgeon takes note of tissue integrity and friability in addition to any evidence of disease to the terminal ileum, as this could be suggestive of Crohn’s disease. This is particularly

important in the acute setting, or in a patient with an otherwise unknown diagnosis of UC. The colon is fully mobilized from its peritoneal attachments and both flexures are freed using a combination of cautery and energy devices. The mesentery is ligated and division of the mesenteric vessels is performed. The terminal ileum is then divided immediately proximal to the ileocecal valve. In the total abdominal colectomy, the colon is divided at the level of the mid to distal sigmoid with preservation of the inferior mesenteric artery and superior rectal arteries. In addition to preserving the presacral planes, it is critically important to preserve the ileocolic artery in order to allow for later pouch reconstruction. Preservation of the ileocolic artery prevents foreshortening of the mesentery, which allows the future pouch to easily reach to the anal canal. Management of the rectal stump is largely dependent on the severity of colitis at the time of operation, as well as the friability of the rectosigmoid. The options for handling the rectum include the Hartmann pouch, where a 30 Fr catheter is passed transanally and left in place for decompression, a mucus fistula, or closure of the rectal stump with exteriorization into the subcutaneous tissue. The mucus fistula presents the safest approach in handling the rectum in the instance that tissue is very friable. Closure of the rectum with exteriorization into the subcutaneous tissue has been reported, suggesting outcomes are associated with fewer pelvic septic complications and overall morbidity.31 Regardless of management approach, it is important to recognize that the rectal stump can be a source of postoperative peritonitis if the patient suffers a stump blowout.

MANAGEMENT OF CHRONIC COLITIS Although patients with chronic colitis are in better overall condition than those with acute colitis, healing conditions remain far from ideal. Often, these patients have undergone long-term steroid therapy, which incurs a high risk of septic complications and conditions for poor anastomotic healing. For these reasons, a staged procedure is preferred to allow for reconstruction at a later time. With the benefit of added time, efforts should be made to optimize nutritional status and minimize steroid use. In the following section, we discuss the options available for reconstruction. The best choice is not always obvious and is largely

dependent on patient circumstances of life, gender, occupation, age, and lifestyle. It is therefore critical that all options are discussed with the patient before a final decision is made, as it will drastically impact the patient’s quality of life.

Laparoscopic versus Open Approaches Laparoscopic ileal pouch anal anastomosis (IPAA) was initially described in 1992. Although more recent evidence from several randomized controlled trials suggests elective laparoscopic colectomy fares better in short-term perioperative outcomes compared to the open approach, only a handful of centers have reported outcomes specifically in IBD.30,32 Comparative studies have concluded that laparoscopic IPAA is deemed feasible and a safe approach with significant improvement in perioperative complications.29,30,32−34 Few investigators have examined short-term outcomes and complications after laparoscopic IPAA, such as pouchitis and pouch dysfunctional incontinence, frequency, and sexual function, revealing little difference compared to the open approach.29,32,34 In a study comparing open to laparoscopic IPAA, Fajardo and colleagues did not demonstrate differences in short-term outcomes between groups. However, patients who underwent laparoscopic reconstruction demonstrated a shorter elapsed time to ileostomy closure.35 Currently, there is insufficient data to tout the claim that laparoscopic IPAA leads to faster recovery, as patients who undergo elective restorative proctocolectomy (RPC) are typically younger, healthier, and more motivated. In this era of advancing surgical techniques, laparoscopic surgery has been shown to be a safe and feasible alternative to open surgery in IBD.29,33,36 The outcomes generally studied include operative duration, intraoperative blood loss, time to return of bowel function, length of postoperative stay, and overall pain scores. Studies claim that the laparoscopic approach boasts decreased postoperative narcotic requirements, blood loss, and hospital length of stay, and decreased operative times, although results are inconsistent.29,33,34,37 Other centers report additional reduction in the time to subsequent IPAA.33 This aspect of a laparoscopic approach is particularly difficult to draw conclusions about, considering that the factors that influence delay to IPAA in UC is likely confounded by surgeon comfort and

preference, individual complication rates, and postoperative recovery times. Randomized controlled trials comparing laparoscopic and open approaches have shown lower rates of superficial surgical site infection (SSI) and earlier return of bowel function.38 The majority of reported series describing laparoscopic RPC have utilized the stapled ileal J-pouch configuration. Less commonly, S-pouch techniques are employed. As Harms and colleagues have described, there is additional time required to creating an S- versus a J-pouch in surgery, contributing to the significant increase in intraoperative time to the procedure compared to the open approach. However, the added time provides little difference in the overall costs incurred in a laparoscopic approach, due to shorter hospital stays.37 The greatest advantage to laparoscopic-assisted procedures is improved cosmesis due to reduced incision size. In a Cochrane review by Ahmed and colleagues, various series and clinical trials identified higher cosmesis scores and greater patient preference for laparoscopic approach compared to open.39 As with any laparoscopic approach, conversion to open surgery remains an enduring possibility in each surgeon’s mind. Studies estimate conversion rates ranging widely from 0% to 8%.29 To briefly summarize the laparoscopic technique, the procedure involves a completely laparoscopic, intracorporeal total colectomy followed by either open or laparoscopic proctectomy. In the instance of immediate reconstruction with an open proctectomy, an IPAA is performed with or without mucosectomy.37 Two initial 12-mm ports are placed in the suprapubic and supraumbilical positions, followed by placement of two 5mm ports in both left and right sides, to assume a diamond configuration. The colon is mobilized in a lateral-to-medial fashion and the omentum is preserved during mobilization of the transverse colon. Few series report routine removal of the omentum, with the notion that preserving it may increase the risk of obstruction from adhesion formation; however, there is no clear evidence to support this.40 A bipolar cautery is used to divide the mesocolon, and simultaneous attention is paid to ligating the ileocolic vessels. Following this, colon extraction is accomplished via a 7- to 8-cm extension of the suprapubic incision. Proctectomy and pouch reconstruction are accomplished via placement of a wound retractor into the same extended incision. A handsewn or stapled IPAA is performed. A standard diverting ileostomy is placed in the left lower quadrant for fecal diversion.

Alternatively, the operation can be performed in a completely laparoscopic fashion. In this approach, the abdomen is accessed with three 5-mm trocars in the supraumbilical, suprapubic, and left lower quadrant. A 10/12-mm trocar is placed in the right lower quadrant, completing the diamond configuration. The abdominal colon is mobilized and the mesentery ligated beginning at the distal sigmoid colon, working around to the right side of the abdomen. The most common approach is a lateral-to-medial dissection. However, medial-tolateral dissection of the entire colon can be performed and has been shown to be a very efficient approach.41 In this approach, the mesentery is divided first, followed by complete medicalization of the colon. Once the entire abdominal colon is free from all attachments, attention is turned to the pelvis. The pelvic dissection is carried out under laparoscopic visualization. The proctectomy can be performed as a total mesorectal excision or, in the absence of a concern for malignancy or dysplasia, the dissection can be performed by skeletonizing the rectum and dividing the mesorectum with an energy device. Regardless of technique, the dissection is taken down to the top of the anorectal ring, at which point the rectum is divided with a laparoscopic stapling device. This portion of the procedure can prove to be quite difficult, and great care must be taken to divide the rectum low enough to ensure all disease is removed. Once this is completed, the colon and rectum must be extracted. This can be accomplished through the previously identified ileostomy site or through a suprapubic incision. The authors most commonly extract through the ileostomy site. Once the specimen is extracted, the ileal pouch is created in the standard fashion. The anvil of the circular stapler is inserted into the lumen of the pouch per anus and anvil is wed to the stapler. The ileostomy is then created through the extraction site.

Total Colectomy with Ileorectal Anastomosis In select circumstances, ileorectal anastomosis (IRA) is an appropriate surgical option. Such an indication might be in a patient with chronic quiescent disease with a dysplastic lesion in the right colon. Following standard colectomy, the rectum is left intact, obviating deep pelvic dissection and potential injury to pelvic nerves. The benefits are perceived in the context of less impact on sexual function and fertility, owing to younger patients who have not completed their desires for childbearing. IRA was initially plagued by poor functional results and persistent rectal inflammation; this, however,

has improved over the years. As previously discussed, the rectal remnant requires continued medical therapy and surveillance, as the risks of colitis and later cancer have not been eliminated. The anastomosis is commonly created at the level of the sacral promontory, where the superior hemorrhoidal vessels are left intact. A stapled or handsewn anastomosis can be performed in an end-to-end or endto-side fashion.

Total Proctocolectomy with Ileal Pouch-Anal Anastomosis RPC with IPAA is the elective procedure of choice for UC. Total proctocolectomy (TPC) is carried out as described above. The terminal ileum is reconstructed to recreate a fecal reservoir in order to mimic anorectal continence after colectomy. This can be performed either as a single or staged procedure. Since its introduction in 1978,42 numerous studies have demonstrated low morbidity, high quality of life, patient satisfaction, and good functional outcomes.43 Many variations to the ileal pouch have been described, including the S, J, and W, with the most common being the Jpouch (Fig. 46-7).

FIGURE 46-7 S, J, and W ileal pouch configurations. In the J-pouch reconstruction, an adequate length of the ileocolic pedicle must be confirmed, and the distal ileum is used to construct the J-pouch. There is an inflow and outflow limb of the pouch creating the J-shape. These are typically anastomosed together using a linear stapler. The apex of the pouch is then anastomosed to the rectal cuff, which is performed with a circular stapler, but may also be handsewn to the anal verge.

Ileal Pouch-Anal Anastomosis There are two principle techniques that are currently used in pouch reconstruction, the handsewn and stapled techniques. There are three variations to how this procedure may be performed, separated in terms of the number of stages. A single-stage procedure encompasses removal of the colon and rectum with pouch reconstruction without a diverting ileostomy. The two-stage procedure involves total proctocolectomy with pouch reconstruction and diverting ileostomy, followed by closure of the ileostomy at a later time. The three-stage procedure involves an initial subtotal colectomy, followed by a completion proctectomy and pouch reconstruction with diverting ileostomy, completed by closure of the ileostomy.

A three-stage procedure is preferred when a patient presents with suboptimal conditions such as poor nutritional status, high steroid requirements, and severe colitis. This permits healing between operations so as to optimize the patient’s subsequent preoperative state. The two-stage procedure is most commonly performed in elective scenarios.

HANDSEWN ANASTOMOSIS WITH MUCOSECTOMY OF THE ANAL TRANSITION ZONE Mucosectomy with handsewn anastomosis has long been the technique of choice for IPAA, particularly prior to the introduction of surgical staplers. This technique is more time-consuming and is associated with postoperative functional complications such as incontinence and seepage secondary to manipulation of the anal canal and sphincter stretching.44 Mucosectomy removes the entire rectal mucosa as completely as possible. Although the stapled technique offers various advantages, several surgeons continue to opt for mucosectomy with handsewn anastomosis given the concern over the risk of ongoing inflammation or cancer developing in the rectal remnant. The difficulty with handsewn anastomoses is also perceived in obese patients, where the pouch may be under tension.

DOUBLE-STAPLED TECHNIQUE WITHOUT MUCOSECTOMY The stapled technique has gained much favor as the standard technique for IPAA given good outcomes and ease of approach. A stapled anastomosis is less likely to result in functional problems, however; utilization of the stapler head is introduced transanally, requiring a 1- to 2-cm remnant of rectal cuff, termed the anal transition zone (ATZ), which poses a risk for future development of cuffitis or dysplasia.

Brief Surgical Technique for IPAA It is essential to ensure adequate length of the mesentery to allow mobilization of the small bowel in construction of the pouch. This may be accomplished by ligating the ileocolic vessels as proximal to the level of the takeoff from the superior mesenteric artery (SMA). In the stapled

anastomosis, a transverse linear cutting stapler is used to staple off the rectum at the level of the levators, leaving 1 to 2 cm of rectal mucosa. Pouch reconstruction is initiated by ensuring complete mobilization of the small bowel. This involves taking down inter-loop adhesions and mobilization of the small bowel. A general rule of thumb to ensure adequate length for a stapled anastomosis involves ease with extending the mesentery to the level beyond the pubic symphysis. Constructing a J-pouch involves creating two 15-cm limbs by folding the terminal ileum onto itself. A small enterotomy is created at the apex of the pouch on the antimesenteric side of the bowel. This serves to allow a linear stapler to pass through and create the J conformation of the pouch. Next, a purse-string suture is placed at the enterotomy, which will secure around the endoanal anvil stapler which is passed transanally. This creates the ileoanal anastomosis. The stapler is fired and removed, and inspected for both proximal and distal tissue donuts. A leak test is then performed, followed by creation of a diverting ileostomy. The ileostomy is often found in the right lower quadrant. Figure 46-8 shows an endoscopic view of a normal J-pouch demonstrating the inlet and the blind end of the ileum comprising the tip of the “J”.

FIGURE 46-8 Normal J-pouch appearance. In the handsewn anastomosis, a Lone Star retractor is placed in the patient’s perineum. A solution of dilute epinephrine is injected into the submucosa to gently separate the mucosa away from the underlying tissue planes. The mucosectomy is then performed with electrocautery or via sharp dissection using Metzenbaum scissors, beginning at the level of the dentate line. The pouch is then gently advanced into the pelvis and the anastomosis between the ileal pouch and dentate line can be created using interrupted absorbable suture.

Total Colectomy or Proctocolectomy with End Ileostomy Permanent ileostomy may be a consideration for patients with contraindications to restorative surgery, tolerance, and preference, particular among the elderly. Management of the rectal remnant remains the most burdensome aspect when total abdominal colectomy and end ileostomy is definitive. The rectal stump requires surveillance, continuing to pose cancer risk and unpredictability in symptom control if the patient were to develop extensive proctitis. Patients may also struggle with societal pressures and insecurities with body image on a daily basis as a result of the ileostomy. As a result of the rectal concerns, the vast majority of patients who opt for an end ileostomy as a definitive treatment of their UC should have a total proctocolectomy consisting of removing the abdominal colon in the standard fashion as well as removing the entire rectum via an abdominoperineal approach. This can be performed in the open or laparoscopic fashion. Regardless of approach, the colon is removed in the standard fashion followed by complete rectum and anus removal. Following ligation of the superior hemorrhoidal vessels and inferior mesenteric vessels, the plane between the presacral fascia posterior to the rectum and fascia propria of the rectum is entered. Dissection of the pelvic floor is initiated posteriorly, progressing laterally and lastly, anteriorly. Throughout the dissection, care is taken not to injure the left ureter and sympathetic nerves. The rectum is skeletonized from the mesorectum to reduce the risk of parasympathetic nerve injury. Anteriorly, the dissection is carried out as closely to the

specimen as possible, on the rectal side of Denonvilliers’ fascia, also in avoidance of potential injuries to neighboring structures. Upon completion of the abdominal and pelvic portion of the operations, the surgeon moves to the perineum. Assuming that there is no concern for cancer, an intersphincteric dissection of the anal canal can be performed to maintain pelvic muscular support of the perineal wound closure. In this technique, an incision is made around the anal canal and the intersphincteric space is entered circumferentially. The dissection is taken into the pelvis posteriorly and carried around both sides until the anus is completely free of all attachments in the perineum. The rectal specimen can then be extracted through the perineum. An intersphincteric resection enhances closure of the pelvic floor allowing closure of the healthy muscle. This theoretically decreases wound complications in the short and long term.

Kock Pouch A continent ileostomy was first described by Kock in 1969.45 It was described as a high-volume, low-pressure reservoir maintained by an intussuscepted nipple valve (Fig. 46-9).45 The design of the pouch was to permit fecal material to accumulate and be emptied at the patient’s convenience several times a day. This was accomplished by inserting a tube at the level of the stoma into the reservoir to release its contents.25 Although the concept proved promising, it was idealistic at best given Kock pouches failed to achieve high levels of acceptance due to frequent complications. Currently, the Kock pouch serves as a surgical rescue option following failed IPAA or for those who are not deemed appropriate IPAA candidates. Major complications include valve dysfunction, the most common of which is valve de-intussusception.25

FIGURE 46-9 Kock pouch. A high volume, low-pressure reservoir maintained by an intussuscepted nipple valve. This design permits fecal material to accumulate and be emptied at the patient’s convenience several times a day. This is accomplished by inserting a tube at the level of the stoma into the reservoir to release its contents.

POSTOPERATIVE COMPLICATIONS Pouch-related complications are categorized broadly into those with septic and non-septic sequelae. Septic complications are those characterized by infections originating in the pouch which consequently spread to the pelvic space, and include anastomotic leak, abscess, and fistulas. Non-septic complications present a slightly larger repertoire of clinical events that arise over a longer postoperative time frame. These include obstructions, stricture, cuffitis, and pouchitis. Not uncommonly, septic-related complications present at earlier time courses; however, the majority of early complications are often attributed to predisposing patient factors such as local and general inflammatory changes, hypoalbuminemia, anemia, and prolonged steroid use.46 The J-pouch is created with two ridges corresponding to the anastomosis, creating a posterior appendage called the “J-pouch appendage.” The

appendage consists of the distalmost segment of the terminal ileum that is not incorporated into the reservoir. The length of the appendage is 1 to 2 cm and may potentially dilate over time, lending to downstream complications. Lastly, the definition of pouch failure varies between series and authors. It is often referred to as either the need to remove the pouch and establish a permanent ileostomy or the need for an ileostomy without the anticipation of future closure.28 Here, we discuss an overview of the most commonly encountered immediate and later-stage postoperative complications along with current management strategies.

Immediate Complications ANASTOMOTIC LEAK Anastomotic leak remains a worrisome early postoperative complication following pouch reconstruction. The majority of leaks occur at the pouchanal anastomosis, but may occur at any suture or staple line. Patients often present with early symptoms of abdominal pain, fever, tachycardia, and potentially hypotension, rendering the diagnosis to be made clinically the majority of the time. However, this is often followed up with imaging, such as cross-sectional imaging or Gastrografin enema. The morbidity of anastomotic leaks may be monumental, resulting in sepsis, fistulas, strictures, and potentially pouch failure. Therefore, rapid and early diagnosis and treatment of ensuring pelvic sepsis is critical in order to prevent long-term pouch failure. The overall anastomotic leak rate leading to pelvic sepsis following IPAA has been reported at between 2.9% and 19%.47−50 In severe colitis, leak rates have been reported at 5%.51 Prevention plays a key role in maintaining the standard of improved quality of life. Techniques aimed at reducing leak rates include ensuring adequate blood supply in preventing ischemia and no tension to the anastomosis. Hence, pouch reconstruction is most often reserved as a subsequent surgery following colectomy in the setting of an acute UC flare or high-dose steroid requirements. Treatment for anastomotic leak varies from medical management to percutaneous drainage to operative intervention. The patient is usually started on antibiotic therapy, bowel rest, and intravenous fluid resuscitation. If nonsurgical methods fail, laparotomy for washout with

drain placement and potential primary repair is possible if tissue integrity and the defect are deemed reparable at the time of inspection. The most drastic repair warrants excision of the pouch if there is clear evidence of irreversible ischemia.

ABSCESS Contrary to common belief, pelvic abscess may form without anastomotic leak. The prevalence of abscess formation reported in various series ranges from 5% to 8%.48,49 Diagnosis is achieved via CT imaging and clinical presentation of signs suggestive of sepsis and abdominal pain. In the presence of a sizable pelvic abscess, percutaneous drainage under CT guidance may prevent laparotomy. Antibiotic coverage should also be started, ensuring coverage includes both aerobic Gram-negative and anaerobic organisms. When drain outputs decrease to less than 100 mL over a 24-hour period, a tube or drain contrast study will provide additional information in deciding whether to remove or keep the drain.46 Late complications from pelvic abscess formation include fistula formation, commonly with the urethra in males and the vagina in females. The etiology of abscess formation in the immediate postoperative period is likely attributed to pouch ischemia or leak, in contrast to late-forming abscesses, which may be suggestive of Crohn’s disease.

Late Complications POUCH FISTULA Pouch fistula is considered a late presenting complication, often following abscess or anastomotic leak, and affects upward of 7% of patients.50 The median time of presentation following IPAA has been reported as 10 months, but may occur as early as 3 months. The various types of fistula originate from the appendage, pouch-anal anastomosis, inflow limb, and the pouch reservoir proper. The distal connection can vary from the abdominal wall, bladder, small bowel loops, and vagina in women. The pouch-vaginal fistula is the most common form, affecting upward of 16% of women who develop this complication.52 In order to develop a treatment plan, the origin of the fistula from the pouch must be determined, which can be accomplished by

direct visualization under general anesthesia, pouchoscopy, and via Gastrografin enema. Treatment of pouch-related fistula is complicated by high recurrence rates and imperfect healing, often requiring multiple operations. Repair of pouchvaginal fistulas is approached depending on the location of fistulization along the vaginal canal. A local approach is perineal or transvaginal. If the fistula arises above the ileoanal anastomosis, the abdominal approach includes primary repair of the vaginal defect, resection of the retained rectum, and mucosectomy with a new ileoanal anastomosis. This option offers the best recovery rates, ranging from 67% to 80%.52 Perineal or transvaginal approaches involve full thickness flaps and are associated with lower healing success from 35% to 60%.52,53 Appendage and bladder-associated fistulas are treated by resection of the appendage and restapling the blind end of the ileum. The bladder fistula is resected and primary closure of the pouch and bladder is performed.

SMALL BOWEL OBSTRUCTION Small bowel obstruction (SBO) is a well-known complication following abdominal surgery, and is no exception after IPAA. The two principle causes of SBO in this setting are due to adhesions and a redundant ileal pouch. With adhesive disease, treatment includes bowel rest, decompression, and resuscitation. Adhesiolysis is indicated when bowel rest fails and clinical symptoms worsen, although care must be taken not to damage the pouch intraoperatively. Non-adhesive obstruction is a later manifestation, presenting months following pouch reconstruction. It occurs as a mechanical obstruction secondary to the pouch having stretched out over time, subsequently flipping onto itself. This warrants surgical repair, at which time the redundant pouch may require resection, since a pexy procedure may only serve as temporary relief.

STRICTURE Ileal pouch stricture is another late complication occurring in 10% to 40% of cases due to ischemia, pelvic sepsis, or anastomotic leak.47 The most common locations for stricture formation occur at the pouch-anal anastomosis or proximal to the inflow limb of the pouch. Several series have

evaluated the risk factors for fistula formation, which include pelvic sepsis, handsewn anastomosis, diverting loop ileostomy, mesenteric tension, high body mass index, and NSAID use.54 Treatment modalities include serial dilations, which demonstrate a high success rate.52 In the instance that dilations fail, advancement flap anoplasty serves as the surgical treatment of choice.

MANAGEMENT OF POUCH-RELATED COMPLICATIONS Pouch Dysfunction Pouch dysfunction is an umbrella term used to define any deviation from normal pouch function, or that which imparts negative impact on the patient’s quality of life. Given the broad application of the term, the literature fails to identify a consistent definition of pouch dysfunction; however, the most common complaints include frequency of bowel movements, incontinence of liquid stool, clustering, urgency, and incomplete evacuation. Failure of RPC with IPAA occurs from 3.5% to 15%.55 Salvage surgery exists as a rescue procedure aimed at preserving the existing pouch and anal continence. The majority of patients who undergo salvage surgery often experience severe septic complications that are unamenable to medical therapies. Although surgical repair may successfully save the original pouch, subsequent failure remains an ongoing risk. One Italian series reported higher 5-year failure rates after salvage (28.8%) compared with primary IPAA (5.7%). An overall decrease in bowel frequency and urgency have been reported by patients at 3 years of follow-up.55 There is no doubt that a patient experiences a great deal of discomfort and stress related to pouch complications. Although clinicians encounter this scenario not uncommonly, they may not be fully aware of how pouch dysfunction affects the patient. A study by Brandsborg and colleagues revealed that physicians and patients’ perspective on bowel dysfunction differ on parameters such as urgency, frequency, incontinence, and incomplete evacuation.43 Even expert clinicians overestimated the importance of incontinence and frequency on quality of life and underestimated the impact

of clustering and urgency, compared to how these factors truly mattered to the patient.43

Pouchitis Pouchitis is perhaps the most common long-term complication following IPAA, and significantly impacts the patient’s quality of life and long-term surgical outcome. It represents a spectrum of disease processes with variable risk factors, pathogenic pathways, clinical phenotypes, and prognoses. As a result, an enormous degree of effort and resources have been invested into this complication in hopes of better understanding the root causes of disease and to better prevent it. There exists a wide range of clinical presentations, manifested by crampy abdominal pain, hematochezia, urgency, and frequency of bowel movements and fevers, all of which are not specific to pouchitis alone. Pouchitis has been reported to occur in up to 40% of patients within the first year following ileostomy closure.56 The natural history of disease mimics that of UC, wherein dysregulated acute flares ultimately result in chronic inflammation. It is generally believed that pouchitis results from alterations in the intestinal microbiome, rendering the genetically predisposed host susceptible to developing abnormal immune responses.44 The risk factors associated with pouchitis have been studied extensively. Several authors have identified factors associated with acute or chronic pouchitis, as scientists are beginning to acquire a better understanding that these presentations are likely two different disease processes.57 Smoking has been shown to be associated with acute pouchitis,58 whereas long duration of IPAA, extraintestinal manifestation of UC, preoperative thrombocytosis, and postoperative IPAA complications are all associated with chronic pouchitis.59 Pouch endoscopy offers a highly valuable mode of diagnosing pouch disorders. It reveals the severity and extent of mucosal inflammation under direct visualization with the option of obtaining biopsies for histological assessment. Although histology serves a limited role in diagnosing severity of disease, it allows identification of specific features such as metaplasia, viral inclusion bodies (CMV infection), granulomas, and dysplasia. Treatment is based on the type of pouchitis whether antibiotic-responsive or antibiotic-dependent (those with frequent relapses) to antibiotic refractory

pouchitis. Since the disease is triggered by microbial and immune aberrations, antibiotics serve as mainstream therapy. In antibiotic-responsive cases, first-line therapy includes metronidazole (15-20 mg/kg/d) or ciprofloxacin (1000 mg/d) for 2 weeks’ duration. In the setting of antibioticresistant pouchitis, or chronic pouchitis, various immunologic agents, biologics (infliximab), steroids, and anti-inflammatory agents have been used. Management of chronic pouchitis remains a complex and challenging feat, as it is the most common cause of pouch failure. In the instance of resistance to medical therapy, a temporary diverting loop ileostomy may be warranted, versus pouch excision and end ileostomy.

Cuffitis Cuffitis is defined as chronic inflammation or recurrent disease within the remnant rectal mucosa left within the J-pouch. It has been referred to as a variant form of UC in the rectal cuff among patients with IPAA without mucosectomy (Fig. 46-10). As previously discussed, when IPAA is created, a 1- to 2-cm length segment of rectum resulting from the double-stapled technique in J-pouch reconstruction is retained. Few series have reported the incidence of cuffitis to occur in 4% to 17% of patients, and it is a clinically significant risk factor in the development of pouchitis.46,60 Clinically, cuffitis is very similar to pouchitis, plagued by pain, low-grade fevers, and bloody stools. Diagnosis is made on endoscopy wherein the rectal cuff appears grossly inflamed in contrast to the remainder of the pouch demonstrating normal appearing mucosa. Mucosal biopsy is often performed providing definitive diagnosis, demonstrating inflammatory cell infiltration and ulceration within the rectal mucosa alone. Treatment is achieved by local therapy such as Canasa suppositories. Persistent or recurrent disease warrants further investigation, as Crohn’s disease cannot be ruled out. Surgical intervention entails mucosectomy of the rectal remnant with pouch advancement.

FIGURE 46-10 Pouch endoscopy revealing cuffitis. The mucosa demonstrates diffuse edema, granularity, and exudate.

Cancer and Dysplasia of the Pouch, Rectal Remnant, and Anal Cuff Although proctocolectomy eliminates the source of disease, the presumptive concerns over the inherent risk of cancer in the ATZ remain a source of controversy among surgeons. As discussed, the two techniques for RPC and IPAA are the stapled anastomosis versus a handsewn anastomosis. The debate as to whether the remnant rectal cuff poses a significant cancer risk to the patient post-IPAA has led some surgeons to recommend mucosectomy with handsewn IPAA. Numerous studies sought to identify the incidence of ATZ dysplasia or cancer between the stapled IPAA versus mucosectomy with handsewn IPAA, revealing an extremely low overall incidence of dysplasia and adenocarcinoma.61 Initial studies identified only 19 cases of dysplasia and cancer in the ATZ within the pouch, anal cuff, and ATZ, and interestingly in the majority of

these cases, patients underwent mucosectomy.61 Recent studies have the benefit of longer follow-up duration, upward of 20 years following IPAA. Silva-Velazco and colleagues assessed a single institution experience on the long-term incidence of ATZ dysplasia among patients who had a stapled IPAA for greater than 20 years, revealing the incidence plateaued at 3.4% without any cases of adenocarcinoma.62 In the instance of dysplasia and cancer, TPC should include total mesorectal excision. The circumference margin bears a significant prognostic impact on the rates of local recurrence, distant metastasis, and survival; hence, the circumferential margin serves as a surrogate marker of advanced disease as opposed to an indicator of incomplete excision.63 Neoplastic changes in the columnar cuff are rare, ranging from 0% to 0.03%.28 Various studies have identified a close association of dysplasia or cancer after IPAA to be strongly associated with dysplasia or cancer in the resected proctocolectomy specimen.28 The risk of adenocarcinoma following IPAA in patents with UC is increased with the length of time after surgery, as well the presence of cancer or dysplasia in the original proctocolectomy specimen.61 Increasing evidence suggests that long-term and consistent exposure to fecal material in concert with increased microbial burden in the pouch may result in inflammatory changes leading to colonic metaplasia, effectually mimicking UC. To that end, dysplasia and cancer may develop in the remaining rectal mucosa, anal transition zone, or the pouch itself. A systematic review of the literature revealed the cumulative risk of primary pouch-related cancers arising from the anorectal residual mucosa following IPAA is reported at a maximum of 0.4% at 20 years, with several series revealing 0% incidence.64 It is plausible to venture that IPAA is safe and eliminates an overwhelming cancer risk of colorectal origin. Surgery is warranted with high-grade dysplasia and cancer diagnoses. Mucosectomy with pouch advancement is generally performed. The approach to a stapled ileaoanal anastomosis at the anorectal junction of a stapled IPAA leaves a 1- to 2-cm remnant of rectal mucosa. These patients require continued follow-up for potential neoplastic changes postoperatively. Some authors note that chemotherapy did not negatively influence pouch function, in contrast to radiation therapy, which is associated with poor functional outcomes.28 Multiple series discovered higher pouch failure rates

among cancer patients compared to non-cancer patients; however, results were not statistically different.28,65

CONCLUSION Patients with UC warranting surgical intervention require a well-established relationship with a gastroenterologist and surgeon. The complexities of this disease are best managed within a team of clinicians who are familiar with and experienced in all aspects of the patient’s ongoing battle with UC. Patients are presented with a multitude of options when considering surgery for UC. It is clear that patients can undergo surgery with reconstruction and maintain an excellent quality of life. They should be fully informed and participatory in all decision-making with clinicians, particularly with respect to the risks, benefits, potential complications, and later implications of each procedure. In addition, the surgeon should be well-versed and experienced in the technical demands of the surgery and pre- and postoperative care in management of complications.

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colitis. Aliment Pharmacol Ther. 2009;30(2):126-137. 12. Rutgeerts P, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462-2476. 13. Sandborn WJ, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257-265.e3. 14. Sandborn WJ, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):96-109.e1. 15. Sandborn WJ, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):85-95. 16. Panaccione R, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146(2):392-400. 17. Feagan BG, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699-710. 18. Turner D, et al. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5(1):103-110. 19. Dignass A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis. J Crohns Colitis. 2012;6:965-990. 20. Ananthakrishnan AN, McGinley EL, Binion DG. Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease. Gut. 2008;57(2):205-210. 21. Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol. 2008;103(9):22722280. 22. Ho GT, et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Aliment Pharmacol Therapeut. 2004;19(10):1079-1087. 23. Laharie D, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 380(9857):19091915. 24. Dignass A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management. J Crohns Colitis. 2012;6:991-1030. 25. Devaraj B, Kaiser AM. Surgical management of ulcerative colitis in the era of biologicals. Inflamm Bowel Dis. 2015;21(1):208-220. 26. Bennis M, Tiret E. Surgical management of ulcerative colitis. Langenbecks Arch Surg. 2012;397(1):11-17. 27. Andersson, P, Soderholm JD. Surgery in ulcerative colitis: indication and timing. Dig Dis. 2009;27(3):335-340. 28. Zmora O, et al. Is stapled ileal pouch anal anastomosis a safe option in ulcerative colitis patients with dysplasia or cancer? Int J Colorectal Dis. 2009;24(10):1181-1186. 29. Messenger DE, et al. Subtotal colectomy in severe ulcerative and Crohn’s colitis: what benefit does the laparoscopic approach confer? Dis Colon Rectum. 2014;57(12):1349-1357. 30. Marceau C, et al. Laparoscopic subtotal colectomy for acute or severe colitis complicating inflammatory bowel disease: a case-matched study in 88 patients. Surgery. 2007;141(5):640-644. 31. Carter FM, McLeod RS, Cohen Z. Subtotal colectomy for ulcerative colitis: complications related to the rectal remnant. Dis Colon Rectum. 1991;34(11):1005-1009. 32. Dunker MS, et al. Laparoscopic-assisted vs open colectomy for severe acute colitis in patients with inflammatory bowel disease (IBD): a retrospective study in 42 patients. Surg Endosc. 2000;14(10):911-914. 33. Holder-Murray J, et al. Totally laparoscopic total proctocolectomy: a safe alternative to open

surgery in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(5):863-868. 34. Fleming FJ, et al. A laparoscopic approach does reduce short-term complications in patients undergoing ileal pouch-anal anastomosis. Dis Colon Rectum. 2011;54(2):176-182. 35. Castillo OA, et al. [Laparoscopic treatment of symptomatic simple renal cysts]. Arch Esp Urol. 2008;61(3):397-400. 36. Sica GS, Biancone L. Surgery for inflammatory bowel disease in the era of laparoscopy. World J Gastroenterol. 2013;19(16):2445-2448. 37. Heise CP, et al. Laparoscopic restorative proctocolectomy with ileal S-pouch. Dis Colon Rectum. 2008;51(12):1790-1794. 38. Colon Cancer Laparoscopic or Open Resection Study G, et al. Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial. Lancet Oncol. 2009;10(1):44-52. 39. Ahmed Ali U, et al. Open versus laparoscopic (assisted) ileo pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis. Cochrane Database Syst Rev. 2009;(1):CD006267. 40. Kessler H, Hohenberger W. Multimedia article. Laparoscopic restorative proctocolectomy for ulcerative colitis. Surg Endosc. 2006;20(1):166. 41. McNevin MS, et al. Outcomes of a laparoscopic approach for total abdominal colectomy and proctocolectomy. Am J Surg. 2006;191(5):673-676. 42. Parks AG, Nicholls RJ. Proctocolectomy without ileostomy for ulcerative colitis. Br Med J. 1978;2(6130):85-88. 43. Brandsborg S, et al. Difference between patients’ and clinicians’ perception of pouch dysfunction and its impact on quality of life following restorative proctocolectomy. Colorectal Dis. 2015;17(6):O136-O140. 44. Wu H, Shen B. Pouchitis and pouch dysfunction. Gastroenterol Clin North Am. 2009;38(4):651668. 45. Kock NG. Intra-abdominal “reservoir” in patients with permanent ileostomy. Preliminary observations on a procedure resulting in fecal “continence” in five ileostomy patients. Arch Surg. 1969;99(2):223-231. 46. Gorgun E, Remzi FH. Complications of ileoanal pouches. Clin Colon Rectal Surg. 2004;17(1):4355. 47. Fazio VW, et al. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Ann Surg. 2013;257(4):679-685. 48. Farouk R, et al. Incidence and subsequent impact of pelvic abscess after ileal pouch-anal anastomosis for chronic ulcerative colitis. Dis Colon Rectum. 1998;41(10):1239-1243. 49. Heuschen UA, et al. Risk factors for ileoanal J pouch-related septic complications in ulcerative colitis and familial adenomatous polyposis. Ann Surg. 2002;235(2):207-216. 50. Francone TD, Champagne B. Considerations and complications in patients undergoing ileal pouch anal anastomosis. Surg Clin North Am. 2013;93(1):107-143. 51. Harms BA, et al. Management of fulminant ulcerative colitis by primary restorative proctocolectomy. Dis Colon Rectum. 1994;37(10):971-978. 52. Sherman J, Greenstein AJ, Greenstein AJ. Ileal j pouch complications and surgical solutions: a review. Inflamm Bowel Dis. 2014;20(9):1678-1685. 53. Heriot AG, et al. Management and outcome of pouch-vaginal fistulas following restorative proctocolectomy. Dis Colon Rectum. 2005;48(3): 451-458. 54. Shen B, et al. Efficacy and safety of endoscopic treatment of ileal pouch strictures. Inflamm Bowel Dis. 2011;17(12):2527-2535. 55. Pellino G, Selvaggi F. Outcomes of salvage surgery for ileal pouch complications and dysfunctions. the experience of a referral centre and review of literature. J Crohns Colitis.

2015;9(7):547-557. 56. Gionchetti P, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebocontrolled trial. Gastroenterology. 2003;124(5): 1202-1209. 57. Achkar JP, et al. Differentiating risk factors for acute and chronic pouchitis. Clin Gastroenterol Hepatol. 2005;3(1):60-66. 58. Fleshner P, et al. Both preoperative perinuclear antineutrophil cytoplasmic antibody and antiCBir1 expression in ulcerative colitis patients influence pouchitis development after ileal pouchanal anastomosis. Clin Gastroenterol Hepatol. 2008;6(5):561-568. 59. Hoda KM, et al. Predictors of pouchitis after ileal pouch-anal anastomosis: a retrospective review. Dis Colon Rectum. 2008;51(5):554-560. 60. Shen B, et al. Risk factors for diseases of ileal pouch-anal anastomosis after restorative proctocolectomy for ulcerative colitis. Clin Gastroenterol Hepatol. 2006;4(1):81-89; quiz 2-3. 61. Lee SW, Sonoda T, Milsom JW. Three cases of adenocarcinoma following restorative proctocolectomy with hand-sewn anastomosis for ulcerative colitis: a review of reported cases in the literature. Colorectal Dis. 2005;7(6):591-597. 62. Silva-Velazco J, et al. Twenty-year-old stapled pouches for ulcerative colitis without evidence of rectal cancer: implications for surveillance strategy? Dis Colon Rectum. 2014;57(11):1275-1281. 63. Wibe A, et al. Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer. Br J Surg. 2002;89(3):327-334. 64. Selvaggi F, et al. Systematic review of cuff and pouch cancer in patients with ileal pelvic pouch for ulcerative colitis. Inflamm Bowel Dis. 2014;20(7): 1296-1308. 65. Radice E, et al. Ileal pouch-anal anastomosis in patients with colorectal cancer: long-term functional and oncologic outcomes. Dis Colon Rectum. 1998;41(1):11-17.

PERSPECTIVE ON INFLAMMATORY BOWEL DISEASE Patricia L. Roberts

Ulcerative colitis and Crohn’s disease are gastrointestinal disorders of modern society, and their frequency has increased in developed countries since the mid-20th century. The highest incidence and prevalence of inflammatory bowel disease are seen in North America and Northern Europe, whereas the lowest rates are seen in continental Asia.1 Despite the use of biologics and other advances in medical treatment, up to 15% to 30% of patients with ulcerative colitis and up to 70% of patients with Crohn’s disease will require surgery during the course of their disease. Recent trends in inflammatory bowel disease have included the increased adoption of a laparoscopic or minimally invasive approach to surgery with the advantages of a faster recovery, fewer complications, less intra-abdominal adhesions, better cosmesis, and a shorter hospital stay. Biologics have changed the medical approach to inflammatory bowel disease, particularly in patients with Crohn’s disease, with an increasing usage of a “top down” approach to treatment in an attempt to rapidly induce remission in patients. With increasing usage of biologics for treatment of inflammatory bowel disease,

there is increasing concern about the risk of infectious complications and other complications in patients on biologics who require surgery and the optimal perioperative management of these agents. This perspective reviews trends in surgery for ulcerative colitis, the role and results of ileal pouch anal anastomosis surgery, the use of biologics around the time of surgery, and the management of dysplasia and cancer.

ULCERATIVE COLITIS Since its introduction by Parks and Nicholls in 1978, restorative proctocolectomy with ileal pouch anal anastomosis has become the standard operative approach for the majority of patients who require surgery for ulcerative colitis. Despite over 35 years of experience, the procedure remains technically demanding and is associated with a number of potential complications that are balanced by the patient’s desire to avoid a permanent ileostomy. With appropriate expertise, outcomes are excellent and associated with improved quality of life and high patient satisfaction. The ileoanal pouch procedure is performed in a staged approach, rarely in a single stage without an ileostomy and most commonly as a 2- or 3-stage procedure (Table 47-1). Indications for surgery for patients with ulcerative colitis include failure of medical therapy, intractable fulminant colitis, toxic colitis, perforation, uncontrolled bleeding, intolerable side effects of medications, strictures, growth retardation in children, high-grade or multifocal dysplasia and dysplasia-associated lesions or masses, and cancer. Patients with acute colitis or fulminant colitis and those who require emergency surgery are generally initially treated with total abdominal colectomy, ileostomy, and Hartmann closure of the rectum. In these nonelective situations, pouch construction is generally felt to be contraindicated. TABLE 47-1: RESTORATIVE PROCTOCOLECTOMY: 1-, 2-, AND 3-STAGE PROCEDURES

Review of the Nationwide Inpatient Sample of over 1.5 million patients with ulcerative colitis admitted to a US hospital from 1991 to 2011 has shown an increase of ulcerative colitis–related admissions of 170% and an increase in the number of patients who required total abdominal colectomy of 44%.2 In this time period, total abdominal colectomy increased by 15% (compared to proctocolectomy) and, since 2008, was more frequently performed as the initial operation for surgical intervention for ulcerative colitis. Over the past several decades, there have been a number of refinements in the surgical technique or pouch construction. The ileoanal pouch procedure may be performed as a single stage in carefully selected patients. A number of centers have published series supporting the omission of a diverting ileostomy generally in young, healthy, low body mass index patients who are not anemic, are well nourished, and are not on immunosuppressive medications or biologics.3 The number of patients who undergo the procedure as a single stage omitting a diverting ileostomy remains quite small. Technical aspects of the surgery in patients who are optimal for omitting a diverting ileostomy include no significant blood loss, no tension on the anastomosis, and a technically excellent procedure. These studies have shown similar results in the diverted and nondiverted groups with respect to leak rates and rates of pelvic sepsis but generally have been biased because the decision for an ileostomy was left to the discretion of the surgeon.

Although the use of an ileostomy does not prevent anastomotic leak, the clinically less severe consequences of the leak and pelvic sepsis in diverted patients is generally felt to have a favorable impact on subsequent pouch success and bowel function. Pouch configuration, originally described as an S-pouch, now includes the J-pouch, the H-pouch, the S-pouch, and the W-pouch. Due to the ease and speed of construction, the J-pouch is the most common reservoir performed. A meta-analysis compared W-, J-, and S-pouches, and the functional results are essentially equivalent.4 S-pouches are more likely to require intubation for evacuation, and there was slightly less bowel frequency and need for antidiarrheal medications with W-compared to J-pouches. S-pouches can provide an additional length of several centimeters and may facilitate getting the pouch to reach the anus in cases where a J-pouch will not reach. The efferent limb of the S-pouch, which should be initially constructed to be no longer than 2 cm, may elongate with time and cause obstructed defecation, which may require revision of the limb. Although mucosectomy and double-stapled procedures are both options for the ileoanal anastomosis, the majority of patients undergo the doublestapled technique, which is technically easier to perform. The potential advantages of the technique include less tension on the anastomosis, ease of technical performance, and potentially improved functional results because of less dilatation of the anal canal and the preservation of the transition zone. In small trials, including 3 prospective randomized trials and 1 comparative study, the functional results of a double-stapled technique and mucosectomy have been similar.5-8 Recent studies have looked at the method of closure of the skin of the ileostomy takedown site and have demonstrated a marked reduction in surgical site infection with a purse string closure compared to primary closure in addition to higher satisfaction with the cosmetic outcome.9 A laparoscopic approach is increasingly used for the ileoanal pouch procedure with potential advantages of more rapid recovery and better cosmesis. Most series of laparoscopic pouches are small and avoid patients with a body mass index of greater than 30 kg/m2. A Cochrane review of 11 trials and over 600 patients found similar length of stay, morbidity, reoperation, and readmission with a laparoscopic versus open pouch procedures.10 A laparoscopic approach was associated with longer operating

time, a small incision, and improved cosmesis. An additional advantage of the laparoscopic approach is less intra-abdominal adhesions and less adnexal adhesions, which could result in a decreased risk of infertility and decreased incidence of postoperative bowel obstruction.11 Laparoscopic approaches include laparoscopically assisted, hand-assisted, and single-incision laparoscopic techniques. Pouch failure, defined as the need to return to a permanent ileostomy with or without excision of the pouch, occurs in 5% to 10% of patients and may be due to pouch-related complications including pelvic sepsis, anastomotic leak and the development of fistula, the development of previously unsuspected Crohn’s disease, and poor function. Pouchitis, one of the most common complications, occurs in up to 40% of patients within the first 10 years of pouch construction and up to 70% of patients within 20 years of surgery and is a rare cause of pouch failure.12 The cause of pouchitis remains unknown. The majority of patients respond to antibiotics, whereas a small number of patients have chronic ongoing pouchitis. With increasing years of follow-up, a small cohort of patients may have late pouch failure because of poor bowel function and incontinence as a result of the known decrease in anal sphincter pressures associated with aging and the more liquid frequent bowel movements associated with the pouch. Since its approval by the US Food and Drug Administration (FDA) for use in the United States for patients with ulcerative colitis in September 2005, increasing numbers of patients with ulcerative colitis have been treated with infliximab, an anti-tumor necrosis factor chimeric antibody. Results on the 3year efficacy of infliximab as a rescue therapy in a previous placebocontrolled trial of infliximab used in acute steroid-refractory ulcerative colitis showed that after 3 years, 12 (50%) of 24 patients treated with infliximab and 16 (76%) of 21 of patients treated with placebo had required colectomy. The quality of life of the 2 groups was not different, as measured by the Short Form (SF)-36 and the Short Health Score questionnaire at the time of followup.13 The efficacy of biologic agents needs to be balanced with the morbidity associated with their use, particularly infectious complications. There has been continual debate with respect to the risk of postoperative complications in patients who receive biologics preoperatively. A study from the Mayo Clinic14 advocated a 3-stage versus a 2-stage proctocolectomy in patients

with ulcerative colitis who were managed preoperatively with infliximab. Thus, initial total abdominal colectomy, ileostomy, and Hartmann closure of the rectum would be performed, which would then allow the patient to come off biologics prior to ileoanal pouch construction. A recent systematic review and meta-analysis looked at 7 papers including 162 patients and 468 controls who underwent primary pouch creation.15 Studies included in this review have relatively small sample sizes and include heterogeneous study populations. Confounders such as severity of disease and disease duration are not accounted for. In this review, patients who received infliximab were more likely to have early and postileostomy closure ileoanal anastomosis–related complications. Interestingly, use of biologics was associated with a lower surgical site infection rate. Looking at any type of surgery, biologics were associated with a trend toward higher total and higher infectious complications, but the difference was not statistically significant. With respect to pharmacokinetics, the half-life for elimination of infliximab is between 7 and 18.5 days, and by 12 weeks, the majority of inflammatory bowel disease patients have undetectable levels of infliximab. Should surgery be delayed in such patients for 12 weeks? It is unlikely that this is possible in patients with active ulcerative colitis without resulting in a potential flare of disease. Patients with ulcerative colitis who are on infliximab presumably have more severe disease and should be considered for a 3-stage procedure with initial total abdominal colectomy and ileostomy followed by pouch creation and then ileostomy takedown. Along with patients who are on high-dose steroids, patients with ulcerative colitis on infliximab should be considered for initial colectomy and not ileoanal pouch creation because of the high risk of complications.

CROHN’S DISEASE Infliximab was first approved by the FDA for use in selected patients with Crohn’s disease in 1998. Despite optimal medical therapy, however, approximately 70% of patients with Crohn’s disease will require surgery within 10 years of diagnosis, and a substantial number of patients will require further surgery for recurrent disease. The use of infliximab and other biologic agents and the development of minimally invasive surgical techniques have

substantially changed the medical and surgical approach to such patients. Although biologics were initially felt to decrease the need for surgery, population-based studies have subsequently failed to demonstrate a reduced need for surgery. Tumor necrosis factor (TNF)-α plays a role in the immune response, angiogenesis, and collagen synthesis, so a key concern is the risk of the development of infectious complications in patients with Crohn’s disease who are maintained on biologics who require surgery. The results of a number of retrospective studies have been conflicting. A recent systematic review of 2 prior systematic reviews and 6 meta-analyses was performed.16 This review examined all previous reviews, studies, and meta-analyses and included meta-analyses that included only a large number of patients and applied quality assessment. Patients with Crohn’s disease who were treated with anti-TNF agents had an increased risk of postoperative complications including infectious or anastomotic-related complications after abdominal surgery. Although a preoperative drug-free interval may be considered, there may be an appreciable risk of a flare of disease. My approach to intraoperative management is as follows: for patients who are undergoing total abdominal colectomy for colonic Crohn’s and rectal sparing and who are on biologics with or without steroids, I strongly consider fecal diversion with an ileostomy and perform either a Hartmann closure of the rectum or, depending on specific intraoperative factors, a primary anastomosis with a proximal loop ileostomy. For patients who are not candidates for fecal diversion, such as patients with diffuse jejunoileitis who undergo strictureplasty or patients who undergo ileocolic resection (in whom an ileostomy would be in the proximal ileum), increased vigilance in the perioperative period for prompt recognition and treatment of potential septic complications is warranted. In selected patients, a biologic-free period may be considered but is associated with a risk of flare of disease.

RISK OF CANCER Ulcerative colitis and Crohn’s disease are both associated with an increased risk of colorectal cancer compared to the general population. A populationbased series has reported an annual incidence rate of 0.06% to 0.2%, and a meta-analysis showed rates of 2.1%, 8.5%, and 17.8% at 10, 20, and 30

years, respectively.17-19 Risk factors for the development of colorectal cancer in patients with ulcerative colitis include pancolitis, prolonged disease duration (>8 years), diagnosis at a young age, family history of inflammatory bowel disease, and associated primary sclerosing cholangitis. In patients with Crohn’s disease, the risk factors are similar, although the association of cancer in patients with primary sclerosing cholangitis and Crohn’s does not appear to be as strong. In addition, inflammatory pseudopolyps are also thought to increase the risk of cancer probably from longstanding inflammation, which is believed to be a risk factor for progression to colorectal cancer. Although surveillance colonoscopy is recommended, there is no clear evidence (based on a Cochrane review) that survival is improved in patients with extensive colitis.20 However, cancers that were detected appeared to be detected at an earlier stage. Colonoscopic surveillance includes 2 sets of 4-quadrant biopsies in each segment of the colon (right, transverse, left, and rectum), which yield approximately 32 biopsies. Other groups have shown that 33 biopsies per examination were necessary to exclude a diagnosis of dysplasia with 90% confidence. A major limitation of optical colonoscopy is the difficulty in detecting dysplasia by visualization of the mucosa by the endoscopist. To potentially enhance the detection of dysplasia, targeted biopsies with use of magnification chromoendoscopy can be used. With this technique, indigo carmine or methylene blue is used and sprayed over the mucosa of the colon and rectum to improve the visualization of the mucosa. The uptake of the methylene blue dye is different for dysplastic compared to colitic mucosa; the use of indigo carmine details the space between the colonic crypts (facilitating detection of dysplastic tissue from colitis tissue). This technique may be combined with either narrow-band imaging or confocal laser endomicroscopy to further enhance the detection of dysplasia. An advantage of these techniques includes increased detection of dysplastic lesions. Despite this, at present, there are no longitudinal studies showing that the increased detection of lesions resulting from chromoendoscopy decreases cancer-related morbidity or mortality. Switching to chromoendoscopy may increase yield on dysplasia and increase number of colectomies without impacting on mortality and morbidity. The role of chromoendoscopy has promise and continues to evolve. Patients with pancolitis who have had symptoms for 8 or more years should undergo surveillance colonoscopy every 1 to 2 years. Total proctocolectomy with or without ileal pouch–anal anastomosis is the

recommendation for patients with cancer, non–adenoma-like dysplasiaassociated lesion or mass, or high-grade dysplasia.21 The management of low-grade dysplasia in the setting of ulcerative colitis remains somewhat controversial. Progression to high-grade dysplasia rates vary widely from 0% to over 50%. There may be a role for chemoprevention with 5-aminosalicylic acid (5-ASA), but there are little prospective data. One meta-analysis of 9 observational studies showed a reduced risk of developing colorectal cancer or dysplasia with 5-ASA use.22 Following restorative proctocolectomy, routine surveillance of the ileal pouch mucosa for detection of dysplasia is generally not recommended.21 A small number of pouch-related cancers have been reported, mainly in patients who had colorectal cancer and/or dysplasia at the time of initial pouch construction. Similarly, there is also little evidence to support routine surveillance of the 1- to 2-cm rectal cuff; however, there may be residual inflammation in this area, and a small number of cancers have been reported. Selected surveillance may be performed and patients counseled as to the potential risk of cancer. Patients with small bowel Crohn’s disease are also at increased risk for small bowel cancer. When performing a strictureplasty, biopsy of the mucosa has been suggested.

REFERENCES 1. Ahuja V, Tandon RK. Inflammatory bowel disease in the Asia-Pacific area: a comparison with developed countries and regional differences. J Dig Dis. 2010;11:134-137. 2. Geltzeiler CB, Lu KC, Diggs BS, et al. Initial surgical management of ulcerative colitis in the biologic era. Dis Colon Rectum. 2014;57:1358-1363. 3. Sagar PM, Pemberton JH. Intraoperative, postoperative and reoperative problems with ileoanal pouches. Br J Surg. 2012;99:454-468. 4. Lovegrove RE, Heriot AG, Constantentinides V, et al. Meta-analysis of short and long term outcomes of J, W and S ileal reservoirs for restorative proctocolectomy. Colorectal Dis. 2007;9(14):310-320. 5. Seow-Choen A, Tsunoda A, Nicholls RJ. Prospective randomized trial comparing anal function after handsewn ileoanal anastomosis versus stapled ileoanal anastomosis without mucosectomy in restorative proctocolectomy. Br J Surg. 1991;78;430-434. 6. Luukkonen P, Jarvinen H. Stapled versus hand sutured ileoanal anastomosis in restorative proctectomy: a prospective randomized trial. Arch Surg. 1993;128:437-440. 7. Reilly WT, Pemberton JH, Wolff BG, et al. Randomized prospective trial comparing ileal pouchanal anastomosis performed by excising the anal mucosa to ileal pouch anal anastomosis. Ann Surg. 1997;225:666-676. 8. Bednarz W, Olewinski R, Wojczys R, Sutkowski K, Domoslawski P, Balcerzak W. Ileoal-pouchanal anastomosis after restorative proctocolectomy in patients with ulcerative colitis or familial

adenomatous polyposis. Hepatogastroenterology. 2005;52:1101-1105. 9. Hsieh M, Kuo L, Chi, C, Huang W, Chin C. Pursestring closure versus conventional primary closure following stoma reversal to reduce surgical site infection rate: a meta-analysis of randomized controlled trials. Dis Colon Rectum. 2015:58:808-815. 10. Ahmed Ali U, Keus F, Heikens JT, et al. Open versus laparoscopic (assisted) ileo pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis. Cochrane Database Syst Rev. 2009;1:CD006267. 11. Indar AA, Efron JE, Young-Fadok TM. Laparosocopic ileal pouch-anal anastomosis reduces abdominal and pelvic adhesions. Surg Endosc. 2009;23(1):174-177. 12. Holubar SD, Cima RR, Sandborn WJ, Pardi DS. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev. 2010;6:CD001176. 13. Gustavsson A, Jarnerot G, Hertervig E, et al. Clinical trial: colectomy after rescue therapy in ulcerative colitis-a three year follow-up the Swedish-Danish controlled infliximab study. Aliment Pharmacol Ther. 2010:32:384-399. 14. Beddy D, Dozois EJ, Pemberton JH. Perioperative complications in inflammatory bowel disease. Inflamm Bowel Dis. 2011;17(7):1610-1619. 15. Selvaggi F, Pellino G, Canonico S, Sciadone G. Effect of preoperative biologic drugs on complications and function after restorative proctocolectomy with primary ileal pouch formation: systematic review and meta-analysis. Inflamm Bowel Dis. 2015;21:79-92. 16. El-Hussuna A, Theede K, Olaison G. Increased risk of post-operative complications in patients with Crohn’s disease treated with anti-tumour necrosis factor alpha agents: a systematic review. Dan Med J. 2014;61(12):A4975. 17. Eaden JA, Abrams KR Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a metaanalysis. Gut. 2001;48:526-535. 18. Bernstein CN, Blanchard JR, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population based study. Cancer. 2001;91:854-862. 19. Lakatos L, Mester G, Erdelyi Z, et al. Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: a population-based study. Inflamm Bowel Dis. 2006:12:205-211. 20. Collins PD, Mpofu C, Watson AJ, Rhodes JM. Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease. Cochrane Database Syst Rev. 2006;2:CD000279. 21. Ross H, Steele SR, Varma M, et al. Practice parameters for the surgical treatment of ulcerative colitis. Dis Colon Rectum. 2014;57:5-22. 22. Velayos FS, Terdiman JP, Walsh JM. Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2005;100:1345-1353.

HEREDITARY COLORECTAL CANCER AND POLYPOSIS SYNDROMES Jennifer L. Irani • Elizabeth Breen • Joel Goldberg

OVERVIEW Hereditary colon cancer is a heterogeneous conglomeration of genetic defects that are mostly autosomal dominant in nature and lead to variable risk of colon cancer and other associated cancers. Some of these syndromes are characterized by the formation of traditional adenomas and are caused by defects in tumor suppressor genes and others are in mismatch repair genes. The most common of these include mutations in the tumor suppressor adenomatous polyposis coli (APC) gene that is associated with familial polyposis. Genetic defects in tumor mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) are also associated with the development of adenomas, and these occur in multiple genes that are associated with tumors that have high levels of microsatellite instability (MSI). Finally, there is a

group of less common genetic defects that result in hamartomatous polyposis syndromes such as juvenile polyposis and Peutz-Jeghers syndrome, to name the two most common. We will outline the genetic defects, epidemiology, diagnosis, clinical manifestations, and clinical management for these syndromes.

FAMILIAL ADENOMATOUS POLYPOSIS Introduction Familial adenomatous polyposis (FAP) is an inherited condition characterized by thousands of polyps in the colon. FAP occurs with a frequency of about 1:10,000 to 1:18,000 live births in Northern Europe and other similar Caucasian populations.1-3 It accounts for less than 1% of all colorectal cancers. Males and females are affected equally.

Genetics FAP is an autosomal dominant colorectal cancer syndrome caused by a germline mutation in the APC gene, located on chromosome 5q21-22. The APC gene is a tumor suppressor gene that functions by suppressing the formation of adenomas in the colon and tumors elsewhere in the body. Approximately 10% to 25% of germline APC mutations are new in individuals without a family history of FAP.3-5 There is nearly 100% penetrance of the colonic manifestations of FAP but variable penetrance of the extracolonic manifestations of the disease.6 Patients with FAP who inherit a single APC mutation acquire a somatic mutation (or “second hit”) in the second allele of the APC gene. A cell with this functional loss of the APC gene has no functional APC protein. This leads to defects in the Wnt signaling pathway, abnormal intracellular accumulation of beta-catenin, unregulated cell growth and division, and formation of adenomas.7,8 Over 1000 different mutations in the APC gene associated with FAP have been described, and the location of the mutation may influence the phenotypic expression. In other words, there is variable phenotypic expression depending on the location of the mutation in the gene.9

For example, patients with mutations near codon 1300 generally develop particularly severe disease with over 1000 polyps and earlier cancer onset.9,10 Attenuated FAP (100 colorectal adenomatous polyps prior to age 40. Nearly 100% of people with FAP will develop colorectal cancer because of the sheer number of adenomas that develop at an early age. One or more of these polyps usually progresses to form a cancer. Polyps usually start appearing in the late teens to early twenties, and progress to cancer by age 40. Attenuated FAP is characterized by at least 10 to 20 adenomas, but fewer than 100. Patients usually present later in life than those with classic FAP, and have later onset of colorectal cancer (mean age 55).12 In attenuated FAP the polyps are found more frequently proximal to the splenic flexure.

EXTRACOLONIC Extracolonic manifestations of FAP include upper gastrointestinal polyps that occur in nearly all patients with FAP. Fundic gland polyps occur in most patients with FAP; they are small and rarely progress to cancer.13,14 In contrast, gastric adenomas are much less common in patients with FAP, are typically located in the antrum, and have a relatively low risk of cancer

progression.15 Around 90% of patients with FAP will develop duodenal adenomas; however, only about 5% progress to duodenal cancer.16 Approximately half of duodenal cancers are ampullary or periampullary.17

DESMOID TUMORS After colorectal cancer and duodenal cancer, desmoid disease is the third leading cause of death in FAP patients.18 Desmoid tumors are usually found in an intra-abdominal location, especially in the small bowel mesentery and in the abdominal wall. Risk factors for development include trauma, prior surgery, and female sex.19 In fact, delay of prophylactic colectomy is advocated in patients at high risk for intra-abdominal desmoid disease, if safe. Surgery is to be avoided if possible for intra-abdominal desmoids as the majority are in the small bowel mesentery and can lead to extensive loss of bowel and bleeding. The primary treatment is medical, and includes NSAIDs and antiestrogen therapy.19 More aggressive regimens include vinblastine/methotrexate and doxorubicin/dacarbazine, and imatinib.19-21

OTHER EXTRA-INTESTINAL MALIGNANCIES These include thyroid cancer, which is usually papillary, and presents in the second or third decade of life. Lifetime risk is about 2%. Annual physical exam with or without neck ultrasound is generally recommended.19 Other associated tumors such as pancreatic adenocarcinoma, hepatoblastoma, medulloblastoma, and adrenal and biliary cancers have risks 50% improvement. All fecal incontinence–related quality of life scores improved.59 Injectable Bulking Agents. For patients with minor fecal incontinence due to internal anal dysfunction, injection of various biocompatible bulking agents has been shown to be modestly effective, although so far, only NASHA Dx (non–animal-stabilized hyaluronic acid/dextranomer) is FDA approved for use in the United States. Injection of NASHA Dx is a simple, noninvasive

procedure that can be performed in an outpatient setting. The bulking gel is injected into the anal submucosa, above the dentate line. It is thought that the injection increases the resting anal sphincter pressures by mass effect, as well as by restoring anal symmetry.60FDA approval of the agent was granted after Graf et al61randomized 206 patients to either NASHA Dx or sham injection. Seventy-one patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%). They recorded 128 treatment-related adverse events, of which 2 were serious (1 rectal abscess and 1 prostate abscess).61 In general, patients considered for both Secca and NASHA Dx injections should first undergo Secca. The goal is to avoid subsequent superinfection of NASHA Dx if the Secca radiofrequency needles are deployed through the implant. Though there have been no reports of adverse events with Secca following NASHA Dx injection, this remains a preferred sequence of interventions. Reconstruction of the Sphincter Complex Sphincteroplasty. In the appropriately selected patient, sphincter repair can reduce and even cure fecal incontinence (Fig. 53-7). The overall success rate is around 60%, and patients should be selected based on normal PNTMLs, reduced anal sphincter pressure on manometry, and a sphincter defect on ultrasound. The operation is best performed in the jackknife prone position. An elliptic incision on the perineal body is made, and the rectum is separated from the vagina all the way to the levators. The external anal sphincter is identified and freed to allow for overlap of the edges (Fig. 53-8). Slowly absorbable sutures are then used to approximate the scar and muscles in the overlapped position. The repair is covered with interrupted sutures, and the skin is closed loosely. Barisic et al62examined 65 patients undergoing overlapping anal sphincter repair; 72.3% were a result of obstetric trauma. At a mean follow-up of 80 months, 55.5% of patients reported excellent results. Bravo et al63followed 191 patients for 10 years and noted that results worsened significantly between the assessments at 3 and 10 years, with only 6% of patients reporting no incontinence at 10 years. Gearhart et al64studied 20 women with large sphincter defects (>50%) and noted that overlapping anal sphincter repair improved absolute resting and squeeze pressures and

Fecal Incontinence Severity Index scores. In addition, patients with lower scores had higher increases in their pressures postoperatively.64

FIGURE 53-7 Anal sphincter overlapping muscle repair. A. Anterior incision and perineal view of muscles. B. Rectal flap is created, and sphincter muscles are isolated. C. Muscle flaps are fully mobilized. D. Muscle flaps are overlapped around a 15-mm rubber dilator or fingertip. E. Muscle flaps are sutured in place, and the perineal body is repaired. F. A drain is placed behind the vaginal wall and the wall closed. (Reproduced with permission from Zuidema GD: Shackleford’s Surgery of the Alimentary Tract, 4th ed. Philadelphia, PA: WB Saunders; 1996.)

FIGURE 53-8 Overlapping sphincteroplasty. Artificial Bowel Sphincter. For patients who fail all other treatments, an artificial sphincter of silicone with a water-filled circumanal cuff may be implanted. The fluid is shifted from the sphincter-encircling cuff to a balloon implanted in the space of Retzius. The 2 reservoirs are connected via silicone tubing. The artificial bowel sphincter (ABS) has produced good results and has been FDA approved for nearly 2 decades. In patients who can tolerate device implantation without complications, overall results of ABS are excellent, with 85% of patients reporting complete or near-complete continence to solid stool. However, if results are measured on an intent-totreat basis, the success rate was 53%, mostly due to the need to explant devices that become infected or break.65Even with improved experience, the incidence of surgical revision and explantation remains high, highlighting the importance of careful patient selection (Figs. 53-9 and 53-10).66

FIGURE 53-9 Patient needs artificial bowel sphincter revision because anal cuff snapped open and it is not encircling the anus circumferentially.

FIGURE 53-10 Artificial bowel sphincter can also leak at site of numerous tubing connections between balloon, cuff, and control button. Magnetic sphincter augmentation, which is currently not FDA approved, may ameliorate some of the concerns regarding the frequent need for device explanation seen with traditional ABS breakage while providing equivalent benefits (Fig. 53-11).67 In the largest study to date, 18 patients were implanted with the magnetic sphincter augmentation device. Bowel diary results showed that 76% of the patients with implants experienced a ≥50% reduction in the number of fecal incontinence episodes per week.68 Further study on this device is required.

FIGURE 53-11 Magnetic sphincter does not have many connections, so likelihood of explant once healed is lower. Rewiring the Defecatory Neuromuscular Pathway Sacral Nerve Stimulation (SNS). SNS was initially developed for urinary incontinence before Matzel et al69described its use for fecal incontinence. The goal is stimulation of the sacral nerves to recruit additional inactive motor units to improve muscle strength, resulting in an increase in resting anal pressure.70SNS is offered to all patients who do not have a large sphincter injury that may be amenable to a simpler sphincter repair and who report loss of a full bowel movement more than twice a week. It is a 2-stage procedure, with the first stage involving percutaneous nerve evaluation, which typically lasts 2 weeks. Patient who experience a 50% or greater decrease in the number of incontinence episodes are then offered placement of a permanent stimulator. The procedure is performed using fluoroscopy

under sterile conditions. (Fig. 53-12). Stimulation of the S4 nerve roots via the sacral foramina is tested, and a permanent stimulator is placed. Results reported in the literature are encouraging. Wexner et al71studied 129 patients who underwent a 2-week trial of subchronic test stimulation. One hundred and twenty patients qualified for permanent implant, and 112 patients were implanted. The mean follow-up time was 28 months, and more than 75% of patients noted persistent benefits including a 50% decrease in weekly incontinence episodes, incontinent days, and urgent incontinent episodes.71Altomare et al72reported even more robust follow-up of 272 patients who underwent SNS placement with a long-term follow-up at a median of 84 months. Significant reductions in the number of fecal incontinence episodes per week and summative symptom scores were recorded after implantation and maintained in long-term follow-up. Risk of long-term failure correlated with minor symptom score improvement during the temporary test phase.72

FIGURE 53-12 A and B. Sacral nerve stimulation implantation can be performed under local anesthesia. Posterior Tibial Nerve Stimulation. Posterior tibial nerve stimulation (PTNS) is believed to work by stimulation of the ascending afferent spinal pathways. The tibial nerve contains afferent and efferent fibers originating from the fourth and fifth lumbar nerves and the first, second, and third sacral nerves. Stimulation of the tibial nerve may lead to changes in anorectal neuromuscular function similar to those observed with SNS, but without the need for a surgically implanted device. A recent systematic review found the success rate of PTNS, based on the proportion of patients who achieved a reduction in weekly fecal incontinence episodes of at least 50%, to be 63% to 82%.73However, a recent randomized controlled trial of 227 patients assigned to PTNS or placebo questioned these data by showing no statistical significance when accounting for a placebo effect, which was as high as 31%.74 Stoma and Stoma Alternatives. For patients who fail both medical and surgical therapy, a permanent end colostomy may be appropriate. Assessment of postoperative quality of life shows that patients are generally satisfied. In a series of 69 patients who underwent colostomy for fecal incontinence, 84% indicated they would “probably” or “definitely” choose to have the stoma again.75

CONCLUSION Fecal incontinence is a common problem and can occur in both men and women. Many forms are treatable surgically. Surgical treatment is ultimately determined by etiology. A careful, tailored workup is essential to providing the best treatment. This field is a dynamic one, and research continues on innovative techniques.

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Rectum. 1999; 42(12):1525-1532. 42. Rockwood TH, Church JM, Fleshman JW, et al. Fecal incontinence quality of life scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum. 2000;43(1):9-16; discussion 16-17. 43. Nygaard I, Barber MD, Burgio KL, et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-1316. 44. Keating JP, Stewart PJ, Eyers AA, Warner D, Bokey EL. Are special investigations of value in the management of patients with fecal incontinence? Dis Colon Rectum. 1997;40(8):896-901. 45. Rogers J, Henry MM, Misiewicz JJ. Disposable pudendal nerve stimulator: evaluation of the standard instrument and new device. Gut. 1988;29(8):1131-1133. 46. Ricciardi R, Mellgren AF, Madoff RD, Baxter NN, Karulf RE, Parker SC. The utility of pudendal nerve terminal motor latencies in idiopathic incontinence. Dis Colon Rectum. 2006;49(6):852-857. 47. Loganathan A, Schloithe AC, Hakendorf P, Liyanage CM, Costa M, Wattchow D. Prolonged pudendal nerve terminal motor latency is associated with decreased resting and squeeze pressures in the intact anal sphincter. Colorectal Dis. 2013;15(11):1410-1415. 48. Gold DM, Halligan S, Kmiot WA, Bartram CI. Intraobserver and interobserver agreement in anal endosonography. Br J Surg. 1999; 86(3):371-375. 49. Norderval S, Dehli T, Vonen B. Three-dimensional endoanal ultrasonography: intraobserver and interobserver agreement using scoring systems for classification of anal sphincter defects. Ultrasound Obstet Gynecol. 2009; 33(3):337-343. 50. Falk PM, Blatchford GJ, Cali RL, Christensen MA, Thorson AG. Transanal ultrasound and manometry in the evaluation of fecal incontinence. Dis Colon Rectum. 1994;37(5):468-472. 51. Engel BT, Nikoomanesh P, Schuster MM. Operant conditioning of rectosphincteric responses in the treatment of fecal incontinence. N Engl J Med. 1974;290(12):646-649. 52. Heymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE. Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence. Dis Colon Rectum. 2009; 52(10):1730-1737. 53. Jodorkovsky D, Dunbar KB, Gearhart SL, Stein EM, Clarke JO. Biofeedback therapy for defecatory dysfunction: “real life” experience. J Clin Gastroenterol. 2013;47(3):252-255. 54. Byrne CM, Solomon MJ, Young JM, Rex J, Merlino CL. Biofeedback for fecal incontinence: short-term outcomes of 513 consecutive patients and predictors of successful treatment. Dis Colon Rectum. 2007;50(4):417-427. 55. Tjandra JJ, Dykes SL, Kumar RR, et al. Practice parameters for the treatment of fecal incontinence. Dis Colon Rectum. 2007;50(10):1497-1507. 56. Brown SR, Wadhawan H, Nelson RL. Surgery for faecal incontinence in adults. Cochrane Database Syst Rev. 2013;7:CD001757. 57. Frascio M, Mandolfino F, Imperatore M, et al. The SECCA procedure for faecal incontinence: a review. Colorectal Dis. 2014;16(3):167-172. 58. Ruiz D, Pinto RA, Hull TL, Efron JE, Wexner SD. Does the radiofrequency procedure for fecal incontinence improve quality of life and incontinence at 1-year follow-up? Dis Colon Rectum. 2010;53(7):1041-1046. 59. Takahashi-Monroy T, Morales M, Garcia-Osogobio S, et al. SECCA procedure for the treatment of fecal incontinence: results of five-year follow-up. Dis Colon Rectum. 2008;51(3):355-359. 60. Davis K, Kumar D, Poloniecki J. Preliminary evaluation of an injectable anal sphincter bulking agent (durasphere) in the management of faecal incontinence. Aliment Pharmacol Ther. 2003;18(2):237-243. 61. Graf W, Mellgren A, Matzel KE, et al. Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial. Lancet. 2011;377(9770):997-1003.

62. Barisic GI, Krivokapic ZV, Markovic VA, Popovic MA. Outcome of overlapping anal sphincter repair after 3 months and after a mean of 80 months. Int J Colorectal Dis. 2006;21(1):52-56. 63. Bravo Gutierrez A, Madoff RD, Lowry AC, Parker SC, Buie WD, Baxter NN. Long-term results of anterior sphincteroplasty. Dis Colon Rectum. 2004;47(5):727-731; discussion 731-732. 64. Gearhart S, Hull T, Floruta C, Schroeder T, Hammel J. Anal manometric parameters: predictors of outcome following anal sphincter repair? J Gastrointest Surg. 2005;9(1):115-120. 65. Wong WD, Congliosi SM, Spencer MP, et al. The safety and efficacy of the artificial bowel sphincter for fecal incontinence: results from a multicenter cohort study. Dis Colon Rectum. 2002;45(9):1139-1153. 66. Wexner SD, Jin HY, Weiss EG, Nogueras JJ, Li VK. Factors associated with failure of the artificial bowel sphincter: a study of over 50 cases from Cleveland Clinic Florida. Dis Colon Rectum. 2009;52(9):1550-1557. 67. Wong MT, Meurette G, Stangherlin P, Lehur PA. The magnetic anal sphincter versus the artificial bowel sphincter: a comparison of 2 treatments for fecal incontinence. Dis Colon Rectum. 2011;54(7):773-779. 68. Pakravan F, Helmes C. Magnetic anal sphincter augmentation in patients with severe fecal incontinence. Dis Colon Rectum. 2015;58(1):109-114. 69. Matzel KE, Stadelmaier U, Hohenfellner M, Gall FP. Electrical stimulation of sacral spinal nerves for treatment of faecal incontinence. Lancet. 1995;346(8983):1124-1127. 70. Kenefick NJ, Emmanuel A, Nicholls RJ, Kamm MA. Effect of sacral nerve stimulation on autonomic nerve function. Br J Surg. 2003;90(10): 1256-1260. 71. Wexner SD, Coller JA, Devroede G, et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. Ann Surg. 2010;251(3):441-449. 72. Altomare DF, Giuratrabocchetta S, Knowles CH, et al. Long-term outcomes of sacral nerve stimulation for faecal incontinence. Br J Surg. 2015; 102(4):407-415. 73. Horrocks EJ, Thin N, Thaha MA, Taylor SJ, Norton C, Knowles CH. Systematic review of tibial nerve stimulation to treat faecal incontinence. Br J Surg. 2014;101(5):457-468. 74. Horrocks EJ, Bremner SA, Stevens N, et al. Double blind randomised controlled trial of percutaneous tibial nerve stimulation for the treatment of faecal incontinence in adults. Gut. 2015;64:Suppl 1. 75. Norton C, Burch J, Kamm MA. Patients’ views of a colostomy for fecal incontinence. Dis Colon Rectum. 2005;48(5):1062-1069.

CANCER OF THE RECTUM Joel Goldberg • Ronald Bleday

INCIDENCE AND EPIDEMIOLOGY At the beginning of the 21st century, rectal cancer continues to be a significant medical and social problem. Currently, there are approximately 135,000 cases of colorectal cancer diagnosed in the United States each year and 50,000 deaths. Approximately 60% of all cases occur in patients older than 65 years of age. Cases that occur prior to age 65 this include 45% of men and 39% of all women diagnosed with colorectal cancer. Significant racial disparities also exist in the incidence and mortality for colorectal cancer, with non-Hispanic blacks (NHB) having the highest incidence and mortality. When compared to non-Hispanic whites (NHW), the NHB population has a 20% higher incidence of colorectal cancer and a 40% higher mortality rate. Overall survival is higher for patients with rectal cancer (67%) than colon cancer (64%), with the most likely explanation being that rectal cancer is more often diagnosed at an earlier localized stage. Overall, 40% of colorectal tumors are in the proximal colon and 60% are in the distal colon and rectum. However, women are more likely to have proximal lesions (46%) when compared to men (37%), and this disparity increases with advancing age. At younger ages (less than 50), both men

(41%) and women (36%) are more likely to be diagnosed with rectal than colon cancer. In fact, there has been a substantial absolute increase in the risk of rectal cancer in patients born after 1970. The reason for the increased risk for rectal cancer in this young population has not been identified but is most likely related to a change in environment, either an exogenous exposure or ingested material in foods such as pesticides or food additives. Increases in the sedentary lifestyle, high-fat diet, and obesity have been suggested etiologic factors as well. As pointed out above, adenocarcinoma of the rectum accounts for nearly 30% of all colorectal cancers. This translates into about 41,000 new diagnoses of rectal cancer each year and greater than 10,000 deaths attributable to this disease within the same time.1,2

HISTORY The history of modern rectal cancer resection dates to 1884, when Czérny described the first abdominoperineal resection (APR). In 1885, Kraske pioneered the transsacral approach of rectal resection and anastomosis. In 1908, Miles improved on the APR by understanding that there was a “zone of upward spread.”3 He emphasized the importance of performing a wide perineal excision. Consistent with this, current surgical technique includes a cylindrical resection at the level of the levators to include the entire anal canal such that there is not a “coning in” or “waist” on the specimen at the distalmost aspect of the specimen. Furthermore, Miles advocated removal of the rectum with a high ligation of the superior hemorrhoidal artery as well as excision of the abdominal attachments of the rectum and the iliac lymph nodes. Despite the improvements in oncologic resection, operative mortality in Miles’ first series exceeded 42%. Over the next 80 years through the late 1980s, mortality and morbidity for rectal cancer surgery improved markedly in pace with improvements in intra-, peri-, and postoperative care. Unfortunately, there were few, if any, advancements in oncologic techniques during this period. Then, in the late 1980s, William Heald described and began popularizing total mesorectal excision (TME) for carcinoma of the rectum.4 In this technique, he advocates using sharp dissection to perform the complete excision of the mesorectum and its associated lymphatics along the subtle fascial planes that encompass the rectum. Moreover, Heald described a “zone of downward spread” within the mesorectum that requires complete

excision to reduce local recurrence. Finally, local excision of small rectal cancers has been used for over 100 years in selected patients. More recently, local excision is being combined with neoadjuvant and adjuvant chemoradiotherapy to maximize local control with a minimally invasive approach.

ETIOLOGY AND RISK FACTORS In Western industrialized nations, the average lifetime risk for an individual to develop colorectal cancer is approximately 6%. This risk increases two- to fourfold if the patient has a personal history of a first-degree relative with colorectal cancer. Inflammatory bowel disease (IBD) is another risk factor. In the first 10 years after the initial diagnosis of ulcerative colitis (UC), the incidence of colorectal cancer increases, and in the past was suggested to be as high as 1% per each year of disease. Recent studies, however, have demonstrated that the cumulative risk is about 2% to 7.5% at 25 to 30 years of disease duration and as high as 13.5% at 45 years of disease.5 Pancolitis is associated with both an earlier and an increased risk for colorectal cancer when compared to left-sided colitis alone. Screening the colon yearly starting at 10 years after the diagnosis with colonoscopy and multiple biopsies in four quadrants every 10 cm from the cecum to the distal rectum is used to predict when a patient is at risk for developing colorectal cancer. If high-grade dysplasia is detected in any of the biopsies, the patient should be advised to have a total proctocolectomy. Some practitioners advocate a surgical resection for low-grade dysplasia as well, whereas some are willing to repeat a colonoscopy with multiple biopsies. If low-grade dysplasia is found on subsequent short-interval colonoscopy, then total proctocolectomy is advised. Ultimately, the most effective method for preventing colon cancer in patients with UC is to remove the colon once any type of dysplasia has been identified. Crohn’s colitis is also associated with an increased risk for colorectal cancer. This is often not appreciated by clinicians because patients with severe Crohn’s colitis often undergo proctocolectomy before their longterm risk becomes an issue. The cumulative risk for colon and rectal cancer in patients with Crohn’s colitis is 2.9% at 10 years, 5.6% at 20 years, and 8.3% at 30 years.5 Genetic risk factors also have been implicated in the development of

colorectal cancer. One is familial adenomatous polyposis (FAP), an autosomal dominant syndrome with 100% lifetime risk of developing colorectal cancer. The abnormality is caused by a defect in the APC gene located on chromosome 5q21. Patients with FAP develop hundreds or thousands of adenomas by their twenties, and colorectal cancer develops in all patients by age 50 years if untreated. Extraintestinal manifestations of this genetic defect include desmoid tumors, periampullary masses, osteomas, and medulloblastomas. A second genetic abnormality associated with the development of colorectal cancer is related to defects in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Genetic defects in these mismatch repair genes affect the repair of DNA replication errors and spontaneous base repair loss and contribute to hereditary nonpolyposis colorectal cancer (HNPCC) that is also known as Lynch syndrome. Despite the name, these cancers arise from adenomas and may account for 5% of all colorectal malignancies. In this autosomal dominant syndrome, cancers occur more often on the right side of the colon. Despite developing at a younger age, there is a better prognosis with these cancers when compared with agematched controls with a non-HNPCC colorectal cancer. In theory, a patient with HNPCC living to age 80 years would have an 80% risk for developing colorectal cancer; additionally, there is a substantial risk of endometrial cancer (50%), ovarian cancer (15%). urinary tract cancer (10%), and gastric cancer (5%). There is a smaller but substantial risk of small intestinal (1%) and hepatopancreaticobiliary (1%) tumors as well. Family members should be screened initially at age 25 years or 10 years prior to the age at which the first family member was diagnosed with a neoplasm. Screening should include yearly colonoscopy and esophagogastroduodenoscopy (EGD) every 3 years (unless there is a family history of gastric cancer when yearly EGD is advised). If an endoscopically unresectable polyp or cancer is detected, a total abdominal colectomy with an ileorectal anastomosis is recommended. Urine cytology to rule out dysplastic cells in the genitourinary tract (which is at risk for transitional cell carcinoma) is recommended. Women who desire to retain fertility should get at least once-yearly transvaginal pelvic ultrasounds and CA-125 levels. Any affected woman who has finished childbearing should consider having a total abdominal hysterectomy and bilateral salpingooophorectomy (TAH-BSO). Any affected woman who requires a colectomy should be advised to undergo simultaneous prophylactic TAH-BSO. Finally, there is MUTYH polyposis, which is an autosomal recessive genetic defect

that predisposes to colon and rectal cancer as well. This is often referred to as the autosomal recessive FAP, as this disease has very similar features to FAP. Patients who are carriers of MYH genetic defects are also at increased risk of colorectal cancer even though they do not carry genetic defects in both alleles. These patients should have colonoscopy every 5 years. Dietary fats, especially red-meat fats, have been implicated as a risk factor for colon and rectal cancer.6 People who consume less than 15% of their diet as fat have a lower incidence of colorectal cancer, whereas those who take in 20% of their diet as fat, either as unsaturated animal fat or as highly saturated vegetable oils, have an increased risk of colorectal malignancy. In the past few decades, several studies have linked alcohol consumption and tobacco use with an increased risk of colorectal neoplasia. Moreover, there appears to be a synergistic effect with an even greater increased risk of adenomatous polyps in people who are both smokers and drinkers.7

POLYPS The concept that colorectal cancers develop from polyps, or the “adenoma-tocarcinoma sequence,” was first described by Dukes in 1926. Most patients with rectal cancer have no inherited component; instead, there is an initiating genetic mutation, such as of an oncogene like Kras, that leads to abnormal cell growth. Subsequently, mutations resulting in inactivation of tumor suppressor genes, such as p53, loss of heterozygosity (LOH) on the long arm of chromosome 18 and the APC gene (even in non-FAP patients), allows for progression to cancer. In fact, in sporadic cancers, mutations in the APC gene are the most common initial genetic alteration.8 The time course for polyp development and transformation to cancer is thought to be 5 to 10 years. Most adenomas remain benign; however, histologic type, polyp size, and evidence of dysplasia are associated with transformation. Data from the National Polyp Study and St. Mark’s Hospital in London show that approximately 75% to 85% of adenomas are tubular, 8% to 15% are tubulovillous, and 5% to 10% are villous. Tubular adenomas usually form a stalk, whereas villous adenomas have a broad base (Fig. 54-1). Villous histology is associated with an increased risk of cancer development. Only 1% of polyps less than 1 cm in diameter show evidence of malignant transformation, whereas 50% of polyps greater than 2 cm in diameter harbor

areas of carcinoma.

FIGURE 54-1 Haggitt classification of a pedunculated and sessile polyp, each of which contains an invasive cancer. Clinically, it is important to diagnose the type, size, and number of polyps to risk-stratify patients for treatment and future surveillance. Endoscopic treatment likely reduces or eliminates the risk of colorectal cancer in patients. Rigid sigmoidoscopy and flexible sigmoidoscopy are all that are necessary to screen the rectum. Sigmoidoscopic screening should be followed by a complete colonoscopy if biopsy of a small rectal or sigmoid polyp shows adenomatous changes. Colonoscopy screening as the first study is indicated in high-risk populations such as those with a family history of colorectal cancer, a personal history of IBD, or a known familial genetic mutation (FAP/HNPCC/MUTYH). Autopsy studies have reported that adenomas are present in 20% to 60% of patients with a colorectal cancer, and synchronous cancers are found in 3% to 9% of patients. In patients who cannot undergo a preoperative colonoscopy, either a virtual colonoscopy or barium enema should be performed. If both procedures are contraindicated in these patients, colonoscopy evaluation should be performed 3 months after resection.

Treatment of the malignant rectal polyp is becoming more common with the increase in colonoscopy screening and the early diagnosis of small distal rectal cancers. Surgical treatment in part depends on the morphology of the polyp and the histologic evaluation of the resected lesion. Pedunculated malignant polyps are classified by Haggitt per the depth of invasion of the cancer within the head of the polyp and stalk9 (see Fig. 54-1). Malignant polyps completely resected with greater than 2-mm margins and without stalk invasion are considered adequately treated with colonoscopic removal, provided there are no poor prognostic histologic features such as lymphovascular invasion or poor differentiation (high grade). Tumors with poor differentiation and/or lymphatic/venous invasion are associated with an increased incidence of involved lymph nodes.10

ANATOMY Anatomic Landmarks The type of therapy offered to a patient with rectal cancer depends not only on the stage of the tumor but also on its location within the pelvis and its relation to the anal sphincters. Compared with colon cancer, knowledge and appreciation of anatomic landmarks are critical in determining resectability and sphincter preservation. The rectum, usually 15 to 20 cm in length, extends from the rectosigmoid junction, marked by fusion of the taenia coli into a completely circumferential muscular layer, to the anal canal. In males, the rectum tends to be longer (18 cm) when compared to females (15 cm). The rectum transitions from being intraperitoneal to being completely extraperitoneal 10 to 12 cm from the anus and the root of the sigmoid mesentery is approximately 19 cm from the anal verge on rigid sigmoidoscopy.11 The rectum is “fixed” posteriorly and laterally by Waldeyer’s fascia and the lateral stalks, respectively. In the male patient, the anterior rectum is fixed to Denonvilliers’ fascia, a fold of two layers of peritoneum that separates the rectum from the posterior prostate and seminal vesicles. In the female patient, the peritoneal cavity descends to the pouch of Douglas, with its most dependent point being adjacent to the cervix anteriorly and mid-rectum posteriorly.12 When seen endoscopically, the rectum has three valves of

Houston, the middle of which corresponds to the anterior peritoneal reflection (Fig. 54-2A).

FIGURE 54-2 Anatomic landmarks of the rectum and anus. While many surgical descriptions for rectal cancer refer to the distance of the lesion from the anal verge or the dentate line, a more accurate description for distal (palpable lesions) is the distance above the anorectal ring as palpated by the examining surgeon. For nonpalpable lesions, we use a rigid sigmoidoscope to localize the lesion and then ascertain the distance from the anal verge to the mass. At the muscular level, the anal canal starts at the top of the “high-pressure zone” that is at the proximal aspect of the anorectal ring, a muscular structure consisting of the internal sphincter, external sphincter, and puborectalis (Figs 54-2A and B). The high-pressure zone descends beyond the dentate line to the junction of the anal mucosa and the perianal skin; this junction is often referred to as the anal verge. To achieve an adequate distal margin (≥1 cm) with sphincter preservation, the lower border of a tumor must be located high enough above the top of the anorectal ring. The closer the tumor is to the anorectal ring the less likely the surgeon will be able to get extra length with rectal mobilization. This will often make sphincter preservation more difficult. This caveat even holds true with neoadjuvant chemoradiation, as scarring in the distal rectum after radiation and a lack of mesorectum fixes the tissues posteriorly, making it technically more difficult for the surgeon to gain extra length even with mobilization down to the levator ani complex. Hence, some tumors that are 1 to 2 cm above the anorectal ring and seem at initial exam to be amenable to sphincter preservation are not. Once in the operating room, the surgeon is not able to gain distal mobilization and an adequate margin is difficult to achieve and thereby sphincter preservation can prove challenging or not possible. If curative resection compromises perfect function of the sphincter apparatus, or if an adequate distal margin cannot be obtained while preserving the anorectal ring, an APR with a permanent colostomy should be constructed. Although a patient may assume that a colostomy indicates a hopelessly incurable cancer, we must emphasize that the colostomy is necessary because of the anatomic location, not necessarily the severity of the rectal cancer.

Vascular Supply Arteriography demonstrates extensive intramural anastomoses between the superior, middle, and inferior rectal arteries. The superior rectal artery

originates from the inferior mesenteric artery and descends in the mesorectum to supply the upper and middle rectum (Fig. 54-3). The inferior rectal arteries, branches of the internal pudendal arteries, enter posterolateral and provide blood supply to the anal sphincters and epithelium. The middle rectal artery, often depicted in anatomic drawings as a large and significant artery branching off the internal iliac artery on each side, is seldom greater than 1 mm in diameter.13 In one study, the middle rectal artery was observed in only 22% of cadaver specimens.12 When present, the middle rectal artery is located near the lateral rectal stalks. These stalks are primarily nerves but have been confused previously with arterial supply.

FIGURE 54-3 Vasculature of the rectum and anus. A. Arterial supply. B. Venous drainage. The superior rectal vein drains the upper and middle thirds of the rectum and empties into the portal system via the inferior mesenteric vein. The middle rectal veins drain the lower rectum and upper anal canal into the internal iliac veins. The inferior rectal veins drain the lower anal canal, emptying into the internal iliac veins via the pudendal veins. Because the

venous systems communicate, low rectal cancers may spread via the portal and systemic circulations.

Lymphatic Drainage Local recurrence after resection is common and can occur with and without distant metastatic disease. Rectal cancer can spread locally via lymphatics that follow cranially along the superior hemorrhoidal vessels. This “zone of upward spread” was described initially by Miles in his landmark paper describing the APR. Heald has described a “zone of downward spread” within the mesorectum4; this zone can encompass as much as 4 cm beyond the distal mucosal edge of the tumor.14,15 Although some surgeons and pathologists describe tumor within this zone of downward spread as tumor implants, others believe that these implants are replaced nodes. Appreciation of the zones of upward and downward spread has influenced the extent of dissection surgeons now perform for curative resection of rectal cancers. Lymph from the upper and middle rectum drains into the inferior mesenteric nodes (Fig. 54-4). Lymph from the lower rectum may drain into the inferior mesenteric system or into the network along the middle and inferior rectal arteries, posteriorly along the middle sacral artery, and anteriorly through the channels to the retrovesical or rectovaginal septum, to the iliac nodes, and ultimately, to the periaortic nodes. In a Japanese study, the obturator nodes, external to the hypogastric nerve plexus, were found to be involved with cancer in 8% of tumors located in the distal rectum, whereas these nodes were rarely, if ever, involved with proximal tumors.16 Lymphatics from the anal canal above the dentate line usually drain via the superior rectal lymphatics to the inferior mesenteric lymph nodes and laterally to the obturator and internal iliac nodes. Below the dentate line, lymph drains primarily to the inguinal nodes but may empty into the inferior or superior rectal lymph nodes. In most cases of rectal cancer, spread to the inguinal lymph nodes should be considered stage IV disease. In our experience, however, some patients whose distal rectal adenocarcinoma invades the anal canal can have regional nodal spread to the inguinal lymph nodes. These select few patients may remain curable and their radiation fields should include the involved inguinal lymph node basins.

FIGURE 54-4 Lymphatic drainage of the rectum and anus. A. Nodes at the origin of the inferior mesenteric artery. B. Nodes at the origin of sigmoid branches. C. Sacral nodes. D. Internal iliac nodes. E. Inguinal nodes.

Innervation The pelvic autonomic nerves consist of the paired hypogastric (sympathetic), sacral (parasympathetic), and inferior hypogastric nerves (Fig. 54-5).

Sympathetic nerves originate from L1 to L3, form the inferior mesenteric plexus, travel through the superior hypogastric plexus, and descend as the hypogastric nerves to the pelvic plexus. The parasympathetic nerves, or nervi erigentes, arise from S2 to S4 and join the hypogastric nerves anterior and lateral to the rectum to form the pelvic plexus and ultimately the periprostatic plexus. The inferior hypogastric nerve plexus arises from interlacing sympathetic and parasympathetic nerve fibers and forms a fenestrated rhomboid plate on the lateral pelvic sidewall. Fibers from this plexus innervate the rectum as well as the bladder, ureter, prostate, seminal vesicles, membranous urethra, and corpora cavernosa. Therefore, injury to these autonomic nerves can lead to impotence, bladder dysfunction, and loss of normal defecatory mechanisms.

FIGURE 54-5 Nerve supply of pelvic organs.

Fascial Planes The walls and floor of the pelvis are covered by the endopelvic, or parietal, fascia (Fig. 54-6). The fascia propria, an extension of the endopelvic fascia, encloses the rectum and its mesorectal fat, lymphatics, and vascular supply as a single unit; forms the lateral stalks of the rectum; and connects to the parietal fascia on the pelvic sidewall. The presacral fascia is the parietal fascia that covers the sacrum and coccyx, presacral plexus, pelvic autonomic nerves, and the middle sacral artery. Posteriorly, a thickening of this fascia, called Waldeyer’s fascia, is the anteroinferior fascial reflection from the presacral fascia at the level of S4. Anteriorly, Denonvilliers’ fascia separates the anterior rectal wall from the prostate and seminal vesicles in the male and is thought to be an entrapped extension of the peritoneum.17

FIGURE 54-6 Fascial planes. (Reproduced with permission from Michelassi F, Milsom JW: Operative Strategies in Inflammatory Bowel Disease. New York, NY: Springer-Verlag; 1999.)

DIAGNOSIS AND EVALUATION The preoperative evaluation is critically important to treat the cancer optimally and achieve sphincter preservation. With this information, surgeons

must individualize the treatment and care of each patient.

History The patient with rectal cancer usually presents to the surgeon after a definitive endoscopic diagnosis. The patient’s initial complaint may include rectal bleeding, a change in bowel habits or stool caliber, rectal pain, a sense of rectal “fullness,” weight loss, nausea, vomiting, fatigue, or anorexia; however, many patients are completely asymptomatic. Specific symptoms may assist the surgeon in deciding on the optimal approach to therapy. Tenesmus, the constant sensation of needing to move one’s bowels, usually is indicative of a large and possibly fixed stage II or III cancer. Pain with defecation suggests involvement of the anal sphincters; cancers growing directly into the anal sphincter usually are not amenable to sphincter-sparing procedures. Information pertaining to anal sphincter function is invaluable when one is contemplating a low anastomosis. If patients are incontinent, they are better served with an ostomy. Preoperative sexual function is important to know because one must discuss the risks of the procedure and the likelihood of sexual dysfunction postoperatively. Patients who have preexisting sexual dysfunction are at increased risk for worse postoperative function. Diabetics, smokers, and patients who require neoadjuvant radiation are also at increased risk of postoperative sexual dysfunction. A comprehensive medical history should be aimed at identifying other medical conditions, such as cardiopulmonary, renal, and nutritional issues that may require additional evaluation before surgical intervention. A comprehensive evaluation allows for more accurate risk stratification. Family history or factors predisposing the patient to rectal cancer, such as FAP, HNPCC, MUTYH, and IBD, are important to consider as one plans the operative procedure. For patients with UC/FAP/MUTYH and rectal cancer, the preferred operation is a total proctocolectomy with ileoanal J-pouch reconstruction or end ileostomy, depending on age and sphincter function. One must carefully consider the role of neoadjuvant chemoradiotherapy in patients with rectal cancer and these diseases because once an ileoanal Jpouch is constructed, if radiation has not been given preoperatively, postoperative radiation will severely damage the reconstruction, resulting in poor function and often in the need to remove the J-pouch. In HNPCC, the subsequent lifetime risk of a metachronous cancer is approximately 10% so

either a low anterior resection or APR or total proctocolectomy with an ileoanal J-pouch reconstruction can be considered. Whenever an ileoanal Jpouch is created, careful consideration of preoperative radiation is necessary due to the difficulty using radiation on a small bowel reconstruction in the pelvis.

Physical Examination A careful and accurate digital rectal examination (DRE) is critical in determining the clinical stage and any plans for neoadjuvant therapy. Digital exam of a palpable lesion allows for the assessment of tumor size, mobility and fixation, anterior or posterior location, relationship to the sphincter mechanism and top of the anorectal ring, and distance from the anal verge. Rigid proctoscopy is also essential to the evaluation of patients with rectal cancer because it demonstrates the proximal and distal levels of the mass from anal verge, extent of circumferential involvement, orientation within the lumen, and relationship to the vagina, prostate, or peritoneal reflection. All this information aids in determining the feasibility of local excision if indicated. Rigid proctoscopy also allows one to obtain an adequate tissue biopsy. Flexible sigmoidoscopy is not used routinely because the flexibility of the instrument can give a false distance between the tumor and the dentate line. Furthermore, a mass will often be described as a sigmoid or rectosigmoid tumor on flexible colonoscopy and then when the patient is evaluated in the office with rigid sigmoidoscopy, the lesion is often found to be much lower and in fact is often a true rectal cancer that qualifies for neoadjuvant chemoradiotherapy. Hence, rigid sigmoidoscopy is mandatory for all distal left-sided lesions. A complete colonoscopy to the cecum is essential to rule out synchronous cancers, which occur 2% to 8% of the time. We prefer colonoscopy over virtual colonoscopy so that we may not only diagnose but also excise any amenable polyps. For anterior lesions, women should undergo a complete pelvic examination to determine vaginal invasion.

Preoperative Staging Following the initial history, DRE, and rigid proctoscopy, additional preoperative staging studies can help to determine the appropriate treatment

for each patient, whether radical resection or local excision is warranted, and whether preoperative chemoradiation is recommended. Accurate preoperative staging is gaining increasing importance as combined-modality therapy and sphincter-preserving surgical approaches are considered. Abdominal and pelvic computed tomography (CT) scans can demonstrate regional tumor extension, lymphatic and distant metastases, and tumorrelated complications such as perforation or fistula formation. Its accuracy in determining the depth of invasion, however, is less than that of endorectal ultrasound (ERUS) or specialized magnetic resonance imaging (MRI). Pelvic CT scan therefore is not recommended as the only modality for evaluation of a patient’s primary tumor. For example, the sensitivity of CT scan for detecting distant metastasis is higher (75%-87%) than that for detecting perirectal nodal involvement (45%) or the depth of transmural invasion (70%). If a node is seen on CT scan, it should be presumed to be malignant because benign adenopathy is not normally seen around the rectum. Intravenous contrast given at the time of a CT scan is important to assess the liver for metastatic disease, as well as to evaluate the size and function of the kidneys. Ureteral involvement by the tumor can be assessed and allows for planning of ureteral stent placement preoperatively. Also, invasion of contiguous structures such as the vagina, prostate, and bladder can be initially evaluated on CT scan. Most importantly, lateral pelvic sidewall invasion must be ascertained as this can be very challenging to resect if the disease burden does not regress substantially with neoadjuvant chemoradiation. All patients should undergo a chest CT scan to exclude pulmonary metastases. Because of newer chemotherapies (Oxaliplatinum, Irinotecan, Avastin, and Cetuximab) and multiple treatment regimens, patients with multiple sites of metastatic disease are more likely to receive chemotherapy alone if the pelvic disease is asymptomatic and/or chemoradiation (symptomatic pelvic disease) followed by chemotherapy and may avoid a surgical resection if they have a large burden of distant disease or multiple sites of metastatic disease.

LABORATORY STUDIES Complete blood count and electrolytes often are obtained. Liver enzymes may be normal in the setting of small hepatic metastases and are not a reliable marker for liver involvement. Guidelines published by the American Society for Clinical Oncology

(ASCO) recommend that serum carcinoembryonic antigen (CEA) levels be obtained preoperatively in patients with rectal cancer to aid in staging, surgical treatment planning, and assessment of prognosis. Although neither sensitive nor specific enough to serve as a screening method for the detection of colorectal cancer, preoperative CEA levels greater than 5 ng/mL signify a worse prognosis, stage for stage, than those with lower levels. In addition, elevated preoperative CEA levels that do not normalize following surgical resection imply the presence of persistent disease and the need for further evaluation. CEA is most helpful in identifying recurrent disease with an overall sensitivity rate of 70% to 80%.

ENDOLUMINAL ULTRASOUND Compared with CT scanning, transrectal endoluminal or endoscopic ultrasound (TRUS) permits a more accurate characterization of the primary tumor and the status of the perirectal lymph nodes. Localized cancers involving only the mucosa and submucosa usually can be distinguished from tumors that penetrate the muscularis propria or extend through the rectal wall into the perirectal fat. ERUS is an office-based procedure that is well tolerated and can be performed by the surgeon for preoperative planning. Figure 54-7 shows the schematic layers seen in TRUS.

FIGURE 54-7 Schematic of transrectal endoluminal ultrasonography

illustrates the five layers seen on ultrasound. T Stage. Several studies comparing the accuracy of TRUS with CT scan and MRI suggest that TRUS is superior for T staging of rectal cancer. The range of the accuracy of TRUS is 80% to 95% compared with 65% to 75% for CT scan, 75% to 85% for MRI, and 62% for DRE. In one review, the accuracy of TRUS was greatest (95%) in distinguishing whether a tumor was confined to the rectal wall (T1, T2) versus invading into the perirectal fat (T3 or greater) and less able to distinguish accurately T1 from T2 cancers.18 It is important to understand that all of the above methods are operator dependent; if an institution regularly utilizes ERUS instead of endorectal coil MRI (ecMRI), then that modality will lead to more accurate staging for that institution, and vice-versa if it more regularly utilizes ecMRI. Sometimes, if the lymph nodes are negative and there is a question of whether the tumor is a T2 or T3 lesion, it can be beneficial to get both an ERUS and an ecMRI. Figure 54-8 demonstrates a uT2 lesion. In addition, in patients who have received prior radiation, the accuracy decreases owing to edema and fibrosis.

FIGURE 54-8 Transrectal endoluminal ultrasonography of a uT2 lesion. The arrow indicates the intact serosa. Despite these data, there is considerable inter-observer variability and a significant learning curve associated with performing TRUS. For these reasons, TRUS under-stages more frequently than over-stages the primary rectal tumor. However, TRUS under-stages the cancer less often than CT scan (15% vs 39%). A modified tumor-node-metastasis (TNM) classification for rectal cancer has been proposed based on TRUS-derived T stage (Table 54-1). TABLE 54-1: ENDOSCOPIC ULTRASOUND STAGING OF RECTAL TUMORS

N Stage. TRUS is less useful in predicting the status of perirectal lymph nodes. In several comparative studies, the accuracy of TRUS (70%-75%) was like that of CT scan (55%-65%) and MRI (60%-65%). The accuracy of nodal staging with TRUS requires the nodes to be larger than 5 mm. The contribution of TRUS-guided fine-needle aspiration (FNA) biopsy to Nstaging accuracy for rectal cancer is controversial.

MAGNETIC RESONANCE IMAGING MRI offers some advantages compared with TRUS when it comes to staging rectal cancer. It permits a larger field of view, it may be less operator- and technique-dependent (although it is reader-dependent), and it allows study of stenotic tumors that may not be even amenable to DRE or passage of the ERUS probe.19 Figure 54-9 illustrates a T3 lesion. Like TRUS, ecMRI or phased-array MRI can discriminate small-volume nodal disease and subtle transmural invasion. These specialized MRI techniques can identify involved perirectal nodes based on characteristics other than size, with reported accuracy rates of up to 95%. Another advantage over TRUS is identification of foci not only within the mesorectum but also outside the mesorectal fascia, such as the pelvic sidewall. We currently prefer phased-array MRI for staging of rectal cancers because it provides equal accuracy in staging compared to ecMRI but without the intrarectal coil.

FIGURE 54-9 Endorectal MRI of a T3 lesion. Arrowhead indicates the site of the endorectal coil. Large arrow demonstrates fingerlike projections of carcinoma invading into the mesorectal fat. Small arrow points to the anterior rectal wall. (Used with permission from Koenraad J. Mortele, MD, Beth Israel Deaconess Medical Center, Boston, MA.)

Double-contrast MRI may permit more accurate T staging of rectal cancer by allowing better distinction between normal rectal wall, mucosa, muscularis, and perirectal tissues. In one report, the specificity and sensitivity of ecMRI with combined intravenous and endorectal contrast material to predict infiltration of the anal sphincter were 100% and 90%, respectively. However, N staging was not improved with this approach. Phased-array surface coil MRI also may be beneficial in predicting the likelihood of a tumor-free resection margin by visualizing tumor involvement of the mesorectal fascia. If confirmed in other series, preoperative MRI may

prove useful in selecting patients at high risk of local recurrence for therapy prior to resection.

POSITRON EMISSION TOMOGRAPHY Fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET) is effective in assessing the extent of pathologic response of primary rectal cancer to preoperative chemoradiation and may predict long-term outcome.20 In addition, it has an accuracy of 87% for detecting recurrence of rectal cancer after surgical resection and full-dose external-beam radiation therapy.21 While PET scans are positive in 90% of primary and recurrent tumors and in distant metastatic disease, they are relatively inaccurate for nodal metastases. Rectal cancer rarely metastasizes to the bones or to the brain, and without symptoms these two areas are not included routinely in surveillance imaging. They will, however, light up on PET scan. Current guidelines recommend that PET scans not be used routinely in the standard workup of a rectal cancer.

TNM STAGING The purpose of staging any cancer is to describe the anatomic extent of the lesion. Staging by clinical examination, radiology, and pathology aids in planning treatment, evaluating response to treatment, comparing the results of various treatment regimens, and determining prognosis. Currently, the most widely accepted staging system for rectal cancer in the United States is the TNM classification system. In 1987, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (IUC) introduced the TNM staging system for colorectal cancer. The seventh edition was published in 2009 (Tables 54-2 and 54-3). The TNM staging system is based on depth of tumor invasion as well as presence of lymph node or distant metastases. In stage I disease, the tumor may invade into the muscularis propria. In stage II disease, the tumor invades completely through this layer into the perirectal fat (T3) or adjacent organs (T4). Any lymph node metastasis represents stage III disease, and metastatic spread denotes stage IV disease. Depth of invasion (T stage) of the primary tumor is an important prognostic variable as increasing depth of invasion is correlated with an increasing chance of lymph node metastases.

For instance, early-stage cancers extending into the muscularis mucosa (T1) will have up to a 10% to 13% incidence of metastasizing to perirectal lymph nodes.22,23 In 805 pathology specimens, Sitzler noted that 5.7% of T1 lesions, 19.6% of T2 lesions, 65.7% of T3 lesions, and 78.8% of T4 lesions had lymph node metastases.24 TABLE 54-2: TNM CLASSIFICATION OF RECTAL CANCER

TABLE 54-3: AJCC PROGNOSTIC STAGE GROUPS

Generally, the biologic behavior of rectal cancer cannot be predicted by its location or size although there is a consensus among experts that the more distal cancers have a poorer outcome when compared stage for stage with more proximal lesions. Poorly differentiated cancers have a worse long-term prognosis than well or moderately differentiated tumors. Other factors that portend a poor prognosis include direct tumor extension into adjacent structures (T4 lesions), lymph node metastases, lymphatic, vascular, or perineural invasion, and bowel obstruction.

PRINCIPLES OF TREATMENT

Surgical resection is the cornerstone of curative therapy. Following a potentially curative resection, the 5-year survival rate varies per disease extent25,26 (Table 54-4). However, these survival figures may improve with the increased use of adjuvant therapy. TABLE 54-4: SURVIVAL RATES

Surgical and oncologic management varies greatly depending on the stage and location of the tumor within the rectum. Superficially invasive, small cancers may be managed effectively with local excision. However, most patients have more deeply invasive tumors that require major surgery, such as low anterior resection (LAR) or APR. Yet others present with locally advanced tumors adherent to adjoining structures such as the sacrum, pelvic sidewall, vagina, uterus, cervix, prostate, or bladder, requiring an even more extensive operation. After establishing the diagnosis and completing the staging workup, a decision is made whether to pursue immediate resection or administer preoperative chemoradiotherapy. For patients with stage II and III rectal cancer, the authors advocate for combined preoperative chemoradiotherapy. The authors recommend this for all stage II and III patients with tumors located in the distal two-third of the rectum. For patients with rectal cancer in the proximal one-third of the rectum, the authors use preoperative chemoradiotherapy on a case-by-case basis depending on the size and bulkiness of the tumor and the number of involved lymph nodes as well as the patient’s medical and surgical history.

Bowel Preparation The high bacterial load in the intestinal tract requires preoperative bowel decontamination to reduce the incidence of infectious complications. Prior to

the routine use of mechanical bowel preparation and preoperative antibiotics, the reported rate of infection following colorectal surgery was 60%.27 A standard bowel preparation includes a clear-liquid diet 24 hours prior to surgery, laxatives and/or enemas, oral antibiotics (erythromycin base and neomycin base) and gastrointestinal tract irrigation with a solution of polyethylene glycol electrolyte lavage (GoLYTELY or Miralax). In two separate surveys of North American colorectal surgeons, almost two-thirds preferred the polyethylene glycol electrolyte solutions because of the reliability of the cleansing results.28,29 Certain preparations are contraindicated in patients with certain medical conditions. For example, patients with elevated creatinine or congestive heart failure should avoid the magnesium citrate preparation, whereas patients with gastroparesis should not take a large-volume polyethylene glycol preparation. Recent studies have shown that mechanical bowel preparation in conjunction with oral antibiotics, a chlorhexidine shower, and a clean closure protocol grouped together as an infection protection bundle have reduced the overall surgical site infection (SSI) rate from 19.7% to 8.2%. The chlorhexidine shower, the oral antibiotics, and the mechanical bowel preparation were all associated with decreased SSI. Moreover, patients who received both oral antibiotics and a mechanical bowel prep had an SSI of 2.7% versus 15.8% for all other patients.30 Furthermore, a mechanical bowel preparation should be performed in large part because it allows for easier manipulation of the colon and rectum with both open and laparoscopic surgery.31 Oral antibiotics are also used to further decrease the incidence of postoperative infectious complications. Although mechanical cleansing decreases the total volume of stool in the colon, it does not affect the concentration of bacteria per milliliter of effluent. The most commonly used regimen is the Nichols/Condon preparation: neomycin 1 g and erythromycin base 1 g, both non-absorbable antibiotics, by mouth at 5:00 pm and 10:00 pm on the day prior to surgery. In addition to oral antibiotics, perioperative systemic antibiotics should be given prior to incision time. A typical choice to cover both aerobic and anaerobic intestinal bacteria is a second- or thirdgeneration cephalosporin in combination with metronidazole. Postoperative antibiotic prophylaxis is not indicated. Perioperative systemic antibiotic coverage is broadened in patients with

high-risk cardiac lesions such as prosthetic heart valves, previous history of endocarditis, or a surgically constructed systemic-pulmonary shunt, and with intermediate-risk cardiac lesions such as mitral valve prolapse, valvular heart disease, or idiopathic hypertrophic subaortic stenosis. Intravenous ampicillin 2 g and gentamycin 1.5 mg/kg are administered 30 to 60 minutes before the procedure, and ampicillin is repeated once 6 hours postoperatively in place of cefazolin; metronidazole is administered as usual. Vancomycin is substituted for ampicillin if the patient is allergic to penicillin or cephalosporin.

Enhanced Recovery after Surgery Protocols Enhanced recovery after surgery (ERAS) protocols have become popularized in the last several years in colorectal surgery programs across the United States. ERAS protocols have been very successful in decreasing length of stay as well as postoperative surgical complications. These protocols include a preoperative bowel preparation as outlined above while allowing the patient to continue to consume clear liquids up to 2 hours prior to surgery. This aims to limit preoperative dehydration and thereby limit the need for intraoperative fluid administration, which itself leads to third spacing and tissue edema, and as a result, a slower recovery. Patients are also instructed to refrain from taking ACE inhibitors and diuretics the morning of surgery to prevent hypotension and thereby obviate the need for excess intraoperative fluids. In addition to the bowel preparation, a complex carbohydrate load is often given 2 hours prior to the surgery and it is hypothesized that this decreases insulin resistance because it prevents starvation physiology and thereby limits the catabolic effects of starvation generally seen around surgery. Preoperative pain control is initiated with 1000 mg of Tylenol and a COX2 inhibitor such as Celebrex and gabapentin (age- and sex-related dosing) in the holding area. Intraoperatively, fluid administration is limited and goaldirected fluid therapy is utilized. Goal-directed fluid therapy is achieved by monitoring urine output (0.25 cc/kg/h) and cardiac stroke volume as monitored with a transesophageal probe. Intraoperative narcotics are minimized. Epidurals and transversus abdominus plane (TAP) blocks and catheters are utilized to further decrease postoperative reliance on narcotics. Exogenous fluid administration is stopped within 6 hours of surgery and patients are immediately started on clear liquids and advanced to regular diet on postoperative day one. This allows for earlier usage and absorption of oral

pain medicines. Liberal use of Tylenol and NSAIDs is recommended as well. ERAS protocols have resulted in a dramatic decrease in length of stay and wound infections, among other complications. An ERAS protocol is an integral part of any program in colon and rectal surgery.

Goals of Surgery for Rectal Cancer The primary goal of surgical treatment for rectal cancer is complete eradication of the primary tumor along with the adjacent mesorectal tissue and the superior hemorrhoidal artery pedicle. Although reestablishment of bowel continuity at the time of surgery has become routine, cancer removal should not be compromised in an attempt to avoid a permanent colostomy. For tumors located in the extraperitoneal rectum, resection margins are limited by the bony confines of the pelvis and the proximity of the bladder, prostate, and seminal vesicles in men and vagina in women. Although locoregional recurrence may be inevitable, local recurrence, cure, mortality, anastomotic leaks, and colostomy rates after rectal cancer surgery are related to surgical technique as well as to the experience and volume of the individual surgeon and institution.

Resection Margins DISTAL MARGINS The optimal distal resection margin for surgically treated rectal cancer remains controversial. Although the first line of rectal cancer spread is upward along the lymphatics, tumors below the peritoneal reflection can spread distally via intra- or extramural lymphatic and vascular routes. The use of APR for low rectal cancers traditionally has been based on the need for a 5-cm distal margin of normal tissue. However, in retrospective studies, margins as short as 1 cm have not been associated with an increased risk of local recurrence.32–34 Distal intramural spread usually is limited to within 2.0 cm of the tumor unless the lesion is poorly differentiated or widely metastatic. Data from a randomized, prospective trial conducted by the National Surgical Adjuvant Breast and Bowel Project demonstrated no significant differences in survival or local recurrence when comparing distal

rectal margins of less than 2, 2 to 2.9, and greater than 3 cm.32 Therefore, a 1to 2-cm distal margin is acceptable for resection of rectal carcinoma, although a 5-cm proximal margin is still recommended.34,35

RADIAL MARGINS The importance of obtaining an adequate circumferential or radial margin has been appreciated more in the last 15 years. In fact, the circumferential radial margin (CRM) is more critical than the proximal or distal margin for local control. Tumor involvement of the circumferential margin has been shown to be an independent predictor of both local recurrence and survival. The Norwegian Rectal Cancer group reported on circumferential resection margins with 29-month median follow-up in 686 patients who had curative intent LAR with TME alone (no adjuvant radiotherapy) for rectal adenocarcinoma. The Norwegian group found that the overall local recurrence rate was 7% (22% with positive CRM and 5% with a negative CRM). Moreover, 40% of patients with a positive CRM developed distant metastases whereas only 12% of those with negative CRM developed distant disease.36 In this study, a positive CRM clearly affected survival. In another report of 90 patients undergoing resection for rectal cancer, when the radial margins were histologically positive, the hazard ratio (HR) for local recurrence was 12.2, and the HR for death was 3.2 when compared with those with clear circumferential margins. Furthermore, the length of mesorectum beyond the primary tumor that needs to be removed is thought to be 5 cm because tumor implants usually are seen no further than 4 cm from the distal edge of the tumor within the mesorectum.9,15 Therefore, in proximal rectal cancers, distal mesorectal excision 5 cm below the lower border of the tumor should be the goal. There is ample evidence, however, that in more distal tumors where there is less mesorectum, a 1- to 2-cm margin is acceptable to achieve sphincter preservation.34,35

LOCAL EXCISION Oncologic Results Several retrospective studies of local excision since the 1970s have

demonstrated a local recurrence rate of 7% to 33% and survival rates of 57% to 87%. Many of these reviews are limited, small, single-institution studies, often combining patients with tumors of different depths, including T3 lesions, positive margins, or those who underwent different forms of local therapy, such as fulguration and snare cautery. Despite these limitations, many of these studies have demonstrated that local excision for superficial tumors with negative margins may provide similar survival and local control but without the morbidity of the APR. Major risk factors for local recurrence include positive surgical margins, transmural extension, lymphovascular invasion, and poorly differentiated/high grade histology. These retrospective studies suggest that local excision of selected distal rectal adenocarcinomas may provide adequate oncologic control at considerably less morbidity than APR. Several prospective studies have been published (Table 54-5). In a study from the MD Anderson Cancer Center, 46 patients underwent transanal excision of small distal rectal cancer followed by postoperative radiation treatment.37 Patients with T3 lesions also were given chemotherapy. For patients with negative margins, there was only a 6.5% local recurrence rate (all were T3 tumors) with a 93% overall 3-year survival. Local treatments combined with radiation provided similar oncologic control for T1 or T2 small distal rectal adenocarcinomas as compared with APR. TABLE 54-5: RECURRENCE RATES AFTER LOCAL EXCISION AND ADJUVANT THERAPY

From the New England Deaconess Hospital in Boston, patients with small distal cancers (100 U/L), bleeding varices, ascites, thrombocytopenia, extensive tumor burden (>50% of liver), cardiac insufficiency, or renal insufficiency.10

COMPLICATIONS While TACE is generally well tolerated, complications include liver abscess (1%), tumor rupture (1%), acute liver failure, gastrointestinal bleeding (1%-4%), pulmonary embolism, renal dysfunction, cardiac toxicity, bile duct injury, bleeding from femoral puncture site (1%-2%), and post-embolization syndrome. This syndrome, which occurs in 4% to 10% of patients, is characterized by right upper quadrant pain, nausea, emesis, fever, and liver enzyme elevation.10,11 Although common, the syndrome typically resolves spontaneously within 7 to 10 days.

Drug-Eluting Bead Transarterial Chemoembolization TECHNIQUE Transcatheter delivery of agents such as doxorubicin and cisplatin has less systemic toxicity compared to standard systemic chemotherapy.32 Despite this, adverse effects such as acute liver failure, encephalopathy, ascites, upper GI bleeding, marrow suppression, alopecia, and renal failure still occur.10,11 Although TACE has demonstrated benefit for unresectable HCC, there remains a necessity for improved response rates and decreased complications which may allow expansion of indications. Localization of drugs specifically to the tumor with subsequent sustained release of the specific drug may result in decreased systemic effects and longer tumor exposure to the chemotherapeutic agent. By loading various chemotherapy agents onto polyvinyl alcohol-based hydrogel (DC-Beads, Biocompatibles, Surrey, UK) or a sodium acrylate and vinyl alcohol copolymer (HepaSphere, BioSphere Medical, Rockland, MA) and catheter delivery similar to standard TACE, drug-eluting bead transarterial chemoembolization (DEB-TACE) achieves directed delivery to the tumor microvasculature where the small compounds (100-300 mm and 300-500 mm, respectively) obstruct the vasculature.33 The lodged DEBs allow slow elution of chemotherapeutic agent in a sustained manner with prolonged exposure compared to TACE and lower systemic plasma levels of chemotherapeutic agent, resulting in reduced adverse effects.34,35 The technique is quite similar to TACE with the exception of the deployment of DEB microspheres impregnated with chemotherapeutic agent as opposed to chemotherapeutic agent with emulsificant and embolic agent.36 Additional considerations include presence of replaced or aberrant vessels, avoidance of embolization of cystic artery, and evaluation of phrenic artery if suspected to supply the target tumor.37

OUTCOMES In the setting of CRLM, a phase III multi-institutional prospective randomized trial evaluated DEB loaded with irinotecan (DEBIRI) compared to systemic chemotherapy including folinic acid, 5-FU and irinotecan (FOLFIRI) in patients presenting with unresectable liver metastases from

CRC (1000 Gy).42 However, indications are not limited to segmental infusions, as lobar and whole-liver treatments are also routine and can be performed safely.33

FIGURE 59-2 90Y radioembolization in a patient with multifocal hypervascular carcinoid metastases. (A) Early arterial and (B) delayed arterial phase digital subtraction angiography (DSA) images following selective right hepatic arterial injection. Note: The gastroduodenal artery has been prophylactically embolized to avoid non-target embolization of glass microspheres to the pancreaticoduodenal arcade. (C) Early arterial and (D) delayed-phase DSA images following selective left hepatic arterial injection in the same patient. Note arterial supply to segments II-IV as well as a small caudate artery coursing inferiorly off of the left hepatic artery (arrow). (E) 3D volumetric data is obtained from CT imaging performed during mapping angiography and used to facilitate dosimetric calculations for each lobar treatment. (F,G) Here, segmentation of the right hepatic lobe is used to calculate the volume of liver parenchyma perfused by the right hepatic artery. Radioembolization is accomplished 1 to 2 weeks following the simulation. Femoral catheter cannulation and subsequent angiography is utilized to delineate the vascular anatomy in the region of the tumor. The selective

internal radiation therapy then consists of infusion of 90Y loaded onto resin or glass microspheres. 90Y is pure β-emission radiation and has a mean tissue penetration of 2.5 mm (maximum 10 mm) with a relatively short half-life of 64.1 hours.42 For this reason, isolation for radiation precaution is not required and the majority of radiation energy (97%) is emitted within the first 2 weeks. Although the absorbed dose is heterogeneous based on hemodynamics and tumor vasculature, the majority of the 90Y is absorbed into the tumor compared to the normal liver parenchyma (3:1 to 20:1 ratio). The consequence of radiation exposure to tumor cells is irreversible cell damage. Patients are either observed in the hospital setting for a period of less than 24 hours or the procedure is performed on an outpatient basis. Follow-up imaging is then obtained at specified intervals in order to determine the response to therapy by RECIST criteria, World Health Organization (WHO) criteria, or European Association for the Study of Liver (EASL) criteria (Fig. 59-3). In the setting of downstaging or identifying tumor response based on size criteria alone, imaging can inadequately predict response as a result of discordance between residual size and cell viability. For example, in a study by Kulik et al. in patients with liver tumors treated with 90Y who had tumor response allowing subsequent liver transplant, there was radiologic-pathologic discordance in five of seven patients receiving liver transplant. Imaging suggested viable tumor in each of the seven patients, while pathologic analysis demonstrated complete pathologic necrosis in five patients.42 Therefore, additional characteristics such as enhancement on CT or MRI, or PET imaging can be utilized to estimate tumor volume as defined by the modified RECIST assessment or the EASL guidelines assessing percent change in enhancing tissue.43

FIGURE 59-3 90Y radioembolization treatment and follow-up imaging. (A) Contrast-enhanced CT demonstrates a 2.5 × 2.7 cm homogeneously enhancing NET metastasis in segment VIII. (B) Three-month and (C) 6month post-contrast T1WI following 90Y radioembolization confirm significant post-90Y necrosis and volume reduction.

OUTCOMES 90Y

radioembolization has been evaluated in numerous studies and is currently recognized as a treatment option for unresectable Barcelona Clinic Liver Cancer (BCLC) intermediate stage HCC in the National Comprehensive Cancer Network guidelines.40,42-44 Metastatic disease to the liver has also been demonstrated to respond to 90Y therapy and is currently a category 3 recommendation for CRLM due to limited data in a highly select patient population.29 In a single-institution analysis, Cianni et al. evaluated 110 patients with liver metastases (colorectal, breast, gastric, pancreatic, esophageal, melanoma, cholangiocarcinoma, and pharyngeal) unresponsive to systemic chemotherapy and not amenable to local therapy. Approximately 60% received whole-liver SIRT (90Y), 20% sequential, and the remainder lobar. Among CRC patients, CR or PR was seen in 46%, while in breast cancer patients CR/PR was 44%. 90Y achieved clinically relevant response rates and was well tolerated, indicating a potential therapy for patients with metastatic disease to the liver.45 The same Italian group performed a study to evaluate 90Y SIRT in 52 patients with metastatic breast cancer. The motivation arose from the fact that only 10% to 20% of patients with hepatic metastases from breast cancer can undergo attempted resection and therefore additional therapies require evaluation. The selected patients were inoperable with chemotherapyunresponsive hepatic metastases. Patients with less than 25% liver involvement had 54% PR and median survival of 14.3 months, while patients with 26% to 50% liver involvement had 60% PR and median survival of 8.2 months. Considering these patients were receiving salvage therapy, the authors suggested studies investigating earlier use of SIRT (potentially in combination with standard therapies) in metastatic disease to the liver.46 In 2012, a group of experts in the management of patients with liver

metastases from NET convened to determine appropriate treatment in patients who are not candidates for surgery or RFA. They examined 18 reports on utilization of transarterial embolization (TAE) and TACE (11 publications), or radioembolization (7 publications). In the studies evaluating 90Y treatment, there were response rates ranging from 22.5% to 71.4% and median survival ranging from 22 to 70 months, highlighting the heterogeneity of the studies and populations. In a representative study, Memon et al. investigated 90Y in 40 patients with unresectable liver metastases from NET. Median liver dose was 113 Gy and lung dose 3.81 Gy. Complete or partial response was noted in 64% with stable disease in 32.5% and median OS was 34 months. Symptom control was achieved in 84%.10 These response rates and median OS were similar to the wide array observed in TAE/TACE. The panel concluded that future studies are required for direct comparison of the intra-arterial therapies, use of intra-arterial therapy versus systemic therapy, and concomitant use of intra-arterial therapy with systemic therapy in order to optimally define the role of 90Y in NET metastases the liver.47 Unfortunately, the broad heterogeneity and rarity of this tumor will make future studies difficult to interpret, since it is unlikely an RCT will be performed. From these studies, it is apparent that 90Y treatment for liver tumors is a useful adjunct, but its specific capacity remains to be established. Therefore, due to the necessity of additional studies evaluating SIRT in metastatic disease to the liver, investigations have been established that will help clarify its role. For instance, patients with unresectable CRLM will be randomized to FOLFOX ± bevacizumab versus single-session SIRT + FOLFOX ± bevacizumab (SIRFLOX study) to determine effect on progression-free survival (PFS) and OS.48 The premise of this study (and another similar study, FOXFIRE) is the increased PFS observed in patients with CRLM that received 5-FU/LV and SIRT (18.6 months) versus 5-FU/LV (3.6 months).49 These, along with additional ongoing studies, will better delineate the optimal patient selection for 90Y-SIRT, either as monotherapy or in combination with other modalities.

INDICATIONS In general, patients with Eastern Cooperative Oncology Group (ECOG)

performance status of 0 to 2 without extrahepatic life-limiting disease, and adequate hematologic parameters with appropriate pulmonary, renal (creatinine 50 Gy multiple doses), uncorrectable flow to the gastrointestinal tract on angiography (ie, inability to occlude aberrant vessels), poor hepatic synthetic function (albumin 3 mg/dL in absence of reversible cause, ascites, encephalopathy, recent variceal hemorrhage), or significant extrahepatic disease that is life-limiting.33

COMPLICATIONS Radioembolization-induced liver disease (REILD) is a syndrome manifest from sinusoidal obstruction that occurs 4 to 8 weeks after treatment. Patients developed jaundice, ascites, and moderate increase in canalicular enzymes;

this occurs in 8% to 15% of patients undergoing partial liver radioembolization and is mostly transient but can be severe in approximately 3.1%.53 Other adverse effects from SIRT include fatigue (50%), nausea or emesis (30%), abdominal pain (20%-30%), fever (10%-15%), pneumonitis (rare), and gastrointestinal ulcers (1%-3%)—the overwhelming majority of which are grade I or II adverse events.52

ABLATION Ablative techniques achieve local control of tumor cells with minimal impact to adjacent, healthy liver tissue. In comparison to surgical resection, imageguided local control modalities offer reduced morbidity and mortality. Ablative therapy, either as monotherapy or adjunct to surgical resection, has allowed treatment of bilobar disease as well as treatment of patients who are unsuitable for liver resection due to underlying medical comorbidity. There is a vast array of ablative techniques including percutaneous ethanol injection (PEI), cryoablation, irreversible electroporation (IRE), percutaneous laser ablation (PLA; or LITT), high-intensity focused ultrasound (HIFU), stereotactic body radiation therapy (SBRT), MWA, and RFA. While many of these therapies have been used for local ablation, the most commonly used modality is RFA, with growing enthusiasm for and increasing use of MWA. In addition, SBRT is a noninvasive ablative modality that has generated much interest due to potential applications. Finally, IRE is the newest ablative technique, which offers a unique alternative, and its use has been emphasized in certain patient populations. Therefore, the focus of the ensuing section includes RFA, MWA, SBRT, and IRE.

Radiofrequency Ablation TECHNIQUE Although other ablative methods have become increasingly common, RFA is currently the most frequently used thermoablative technique. First utilized in 1990 for treatment of hepatic tumors, RFA consists of high-frequency oscillating electrical currents (460-500 kHz) delivered from one or more electrodes that produces resistive heating surrounding the electrode(s) (generally 2- or 3-cm exposed tip), ultimately causing tissue hyperthermia

(>100oC) and coagulative necrosis (Fig. 59-4).11 The frictional heat arises from ion movement due to the alternating current, and the localized tissue hyperthermia occurs immediately adjacent to the electrode centered within the tumor. Upon reaching temperatures >60oC, microvascular thrombosis, ischemia, tissue hypoxia, and protein denaturation occur.

FIGURE 59-4 Radiofrequency ablation (RFA) for hepatic metastasis. (A) RFA electrode tips with approximately 2 to 3 cm of exposed electrode. RFA consists of high-frequency oscillating electrical currents (460-500 kHz)

delivered from one or more electrodes from the exposed portion of the tip, ultimately causing tissue hyperthermia (>100oC) and coagulative necrosis. (B) A target hepatic metastasis is demonstrated in segment VI/VII of the liver prior to ablation. (C) Cross-sectional imaging obtained during the ablation procedure demonstrating RFA electrode tips within the lesion. For percutaneous RFA, patients undergo general anesthesia with placement of grounding pads and ultrasound guidance of electrode insertion into the tumor. In general, the ablation is performed with a total ablative area encompassing the tumor and 0.5 to 1.0 cm margin (Fig. 59-5).

FIGURE 59-5 Radiofrequency ablation (RFA) and follow-up imaging. (A) A metastatic lesion is present in segment VI/VII of the liver, prior to ablation.

(B) Cross-sectional imaging demonstrates an area of coagulative necrosis encompassing the entirety of the hepatic lesion, 3 days post-ablation. (C) Cross-sectional imaging demonstrates the completely ablated lesion 2 months following RFA.

OUTCOMES There have not been any randomized studies comparing surgical resection with RFA in hepatic CRLM. However, a compilation of studies investigating RFA versus surgical resection for liver metastases demonstrated that surgical resection provided superior OS compared to RFA.54 A retrospective review by Schiffman et al. sought to evaluate the impact on OS of local treatment choice (thermal ablation [n = 46] vs hepatectomy [n = 94]) in solitary CRLM. While disease-free survival (DFS) was not significantly different between the two treatment modalities (42.6 months vs 55.2 months, p = .073), median OS was substantially different (50.2 months vs 112.7 months, p = .005), indicating that even for solitary lesions, hepatic resection should be considered first-line treatment.55 McKay and colleagues performed a retrospective study of RFA versus hepatic resection for CRLM. Patients undergoing hepatic resection had increased operative time (269 vs 204 minutes, p 5000 U/mL) and an absence of tumor markers, but this should not be relied upon for a definitive diagnosis.19

INDICATIONS FOR INTERVENTION The natural history of a pseudocyst is not easy to predict. Spontaneous resolution occurs frequently and usually within 6 weeks. Size alone is a poor predictor because resolution can occur even with very large pseudocysts. When larger than 6 cm in diameter and in the case of continued enlargement, a pseudocyst is more likely to persist and develop complications. Persistence is also more likely if there is a distal stricture of the main pancreatic duct and a proximal communication between the main pancreatic duct and the pseudocyst. The two principal indications for treating pancreatic pseudocysts are to relieve symptoms and to treat complications. In the absence of symptoms or evidence of enlargement, conservative management is usually reasonable. A traditional approach that dictated treatment of all pseudocysts that have been present for more than 4 to 6 weeks is no longer justified.20 The clinical decision about whether a pseudocyst in a particular patient requires active intervention can be difficult. The desire to allow time for spontaneous resolution to occur must be balanced against the risk of complications while waiting for cyst wall maturity. The traditional indication for treatment was the development of pseudocyst complications. Now the motivation is to prevent complications. An enlarging asymptomatic pseudocyst that has been present for 6 weeks is usually treated. A natural-history study from India indicates that asymptomatic pseudocysts less than 7.5 cm in diameter and without internal debris will resolve spontaneously on an average of 5 months.21 The mean diameter of pseudocysts requiring treatment is about 9 cm.22,23 While there has been a trend toward conservative management, there has been an increase in the number of ways to treat a pseudocyst, including open surgical, laparoscopic, endoscopic, and radiological techniques. Two important rules in the treatment of pseudocysts are that a cystic neoplasm must not be treated as a pseudocyst and elective external drainage should not be done if there is downstream and unrelieved pancreatic ductal obstruction because of the high risk of an external pancreatic fistula. The approach to treatment (Table 69-4) depends on the features of the pseudocyst, the state of the main pancreatic duct (eg, stricture or communication), and the fitness and level of symptoms of the patient. Also important is the level of available expertise and experience with the various treatment modalities.

TABLE 69-4: TREATMENT APPROACHES FOR PANCREATIC PSEUDOCYST

The following general features of a pseudocyst are important in considering the most appropriate treatment: • The thickness of the pseudocyst wall, which is usually a function of the duration of the pseudocyst. This is important because adherence of the wall is more likely with maturity and is relevant for wall-opposing metal stents and for safely securing sutures for surgical drainage procedures. • The location of the pseudocyst. If adherent to the stomach or duodenum, the options are different than if the pseudocyst is deep within the retroperitoneum and covered by bowel loops. • The contents of the pseudocyst. The presence of blood may indicate the need for prior embolization of a pseudoaneurysm. Pus will require drainage, either internally or externally. The presence of solid necrosum suggests the lesion is in fact WON and may require some form of necrosectomy. • The number of pseudocysts. If multiple pseudocysts are present, then minimally invasive approaches are less feasible. Conservative management is less appropriate for multiple pseudocysts.

• The etiology of the pseudocyst. If there is evidence of acute-on-chronic pancreatitis, different treatment may be required than if it has arisen after the first episode of acute pancreatitis. • The main pancreatic duct anatomy and degree of disruption. The pancreas and the pancreatic duct require separate consideration in planning the treatment of a pseudocyst. The pancreas may warrant treatment in its own right, especially if there is a ductal stricture, a dilated duct, regional disease, or a mass warranting resection.

TREATMENT OPTIONS Although there has been a trend toward more conservative management of pseudocysts, especially in the absence of symptoms or complications, there has been an increase in the number of treatment options available (Table 695).24 The most effective and reliable means of treating a pseudocyst is probably still by internal drainage by an open surgical approach, but there is a lack of comparative studies between surgical, endoscopic, and radiological treatments. Despite this, less invasive options are now being used more frequently. TABLE 69-5: OPEN AND MINIMALLY INVASIVE APPROACHES TO THE TREATMENT OF PANCREATIC NECROSIS

Open surgery approaches Pancreatic resection Necrosectomy + wide tube drainage Necrosectomy + relaparotomy (staged reexploration) Necrosectomy + drainage + relaparotomy Necrosectomy + laparostomy ± open packing Necrosectomy + drainage + closed continuous lavage Minimally invasive approaches Laparoscopic necrosectomy Laparoscopic intracavity necrosectomy Laparoscopic-assisted percutaneous drainage Laparoscopic transgastric necrosectomy

Percutaneous necrosectomy and sinus tract endoscopy MRI–radiologically assisted necrosectomy Translumbar extraperitoneal retroperitoneoscopy Video-assisted retroperitoneal débridement Radiological Treatment. The first description of direct percutaneous aspiration and external drainage using radiologic guidance was in the early 1980s. This technique has become widely practiced, with a reported morbidity of between 10% and 30%. It can be used with an immature pseudocyst wall, although the risk of complications is higher in this setting. Percutaneous drainage is best suited to D’Egidio type I pseudocysts in which there is no significant underlying duct abnormality or communication between the duct and pseudocyst. In simple, uncomplicated pseudocysts, percutaneous drainage is usually successful but is rarely necessary since this group is rarely symptomatic, has the lowest complication rate, and has the best chance of spontaneous resolution. The introduction of a transgastric approach to percutaneous drainage has almost abolished the problem of external pancreatic fistulas (Fig. 69-5).24,25 This produces a percutaneous cystogastrostomy but requires an initial period of external transgastric drainage and then subsequent internalization at about 2 weeks. Internalization can be facilitated with a concurrent endoscopic view, especially when using double pigtail catheters. Endoscopy is used to remove the catheters when the pseudocyst has resolved on imaging. A well-matched population-based study comparing percutaneous (n = 8121) with open surgical drainage (n = 6409) in 14,914 patients with pancreatic pseudocysts revealed a longer length of hospital stay and twice the mortality (5.9 vs 2.8%) for percutaneous drainage.26 Currently there is a limited role for percutaneous catheter drainage of pseudocysts, but this is most likely to be used in unfit patients and those who are unstable with an infected pseudocyst.

FIGURE 69-5 A. CT scan showing percutaneous transgastric drainage of pseudocyst. B. Plain radiograph showing double Malecot-type stent cystogastrostomy. (Used with permission from John Chen, MD.) Endoscopic Treatment. There has been significant upsurge in the use of endoscopic treatment for pseudocysts over the last decade. Endoscopic transmural drainage is now widely used. It is wise to perform cross-sectional imaging first to ensure sound apposition of cyst and stomach. While a visible bulge from the pseudocyst may be apparent on endoscopy, EUS guidance during these procedures is now the standard of care. EUS allows greater accuracy and safety by confirming the anatomic route, assists in ruling out a cystic neoplasm, and can identify blood vessels, reducing the risk of bleeding. There are several options available once the cyst is punctured and a guidewire inserted into the cavity. If there is no solid material found in the pseudocyst, then a single pigtail catheter might be all that is required. Recurrence is a risk, especially if there is underlying communication with the main pancreatic duct. While multiple pigtail stents can be inserted following balloon dilation of the track, it is now preferable to insert a self-expanding metal stent designed for transgastric drainage.27 A recent advance is the lumen-apposing design to reduce the risk of cyst content leaking into the lesser sac (Fig. 69-6).28 These metal stents are removed endoscopically after pseudocyst resolution. Endoscopic transpapillary techniques include stenting the sphincter of Oddi to lower ductal pressures and to treat pancreatic ducts strictures. The stent can also be advanced via the pancreatic duct into the pseudocyst when there is a demonstrable communication.29

FIGURE 69-6 Lumen apposing metal stent inserted for transgastric drainage of pseudocyst. (Reproduced with permission from Itoi T, Binmoeller KF, Shah J, et al: Clinical evaluation of a novel lumen-apposing metal stent for endosonography-guided pancreatic pseudocyst and gallbladder drainage (with videos), Gastrointest Endosc. 2012 Apr;75(4):870-876.)

These endoscopic methods are still evolving but have a reported success rates over 90% with experienced practitioners, in well selected patients. Caution needs to be exercised because of the risks of perforation, peritonitis, bleeding, and infection. The risk of bleeding is significantly reduced when the initial puncture is guided by EUS. Open Surgical Treatment. There is no single surgical procedure that is appropriate for all pseudocysts, and the rise of less invasive approaches has resulted in fewer operations being performed for more limited indications. Open surgery is now rarely required for a pseudocyst but may be used to

manage complications from other interventions. As with other treatments, an important factor dictating the choice is available expertise and equipment.24 In principle, drainage operations are preferred to resection because they preserve pancreatic function, are technically easier, and have a lower mortality rate. A D’Egidio type II pseudocyst with a mature wall is best treated by internal drainage, particularly when ductal disruption or stricture is present. Recurrence rates should be less than 5%, and mortality should be less than 2%. The pseudocyst can be drained into the stomach, the duodenum, or the jejunum. The choice of surgical procedure depends on the location of the pseudocyst and its relationship to these organs. A cystogastrostomy is ideal when the pseudocyst is adherent to the posterior stomach and indenting it (Fig. 69-7). A longitudinal anterior gastrostomy is followed by the stepwise excision of a disk (~2 cm diameter) of stomach with subjacent pseudocyst wall. The tissue is sent for frozen section in all cases to exclude cystic neoplasia. Sutures are placed in stages to reduce the risk of edge bleeding as the disk is excised. Prior confirmation of the location of the pseudocyst may be required by needle aspiration, although it is usually obvious. The stoma should be large enough to allow transgastric débridement of any necrotic tissue if the collection proves to be WON rather than a pseudocyst. The disadvantage of the cystogastrostomy is that it is not a dependent stoma, and may act as a sump that allows accumulation of gastric debris. An alternative is a Roux-en-Y cystojejunostomy (Fig. 69-8) which is particularly suited to drainage of pseudocysts arising from the body and tail of the pancreas, when it is not adherent to the stomach and when it is bulging through the left transverse mesocolon.

FIGURE 69-7 Internal drainage of a pseudocyst through the posterior wall of the stomach (cystogastrostomy).

FIGURE 69-8 Internal drainage of a pseudocyst to the jejunum (Roux-en-Y cystojejunostomy). Combining internal drainage of a pseudocyst with a lateral pancreatojejunostomy should be considered in patients with chronic pancreatitis and a dilated pancreatic duct because it will improve outcome without increasing the risk of the procedure. The blind end of the Roux limb should be placed toward the tail of the pancreas because this allows the head of the pancreas to be drained and the bile duct to be bypassed using the same limb, if required. Distal pancreatic resection has a role, particularly when the head of the pancreas is relatively preserved. An endoscopic retrograde pancreatogram will help to define the extent of optimal resection. If there is no pancreatic duct obstruction there are very low recurrence and fistula rates. External surgical drainage of a pseudocyst has a very limited role in critically ill patients where radiological or endoscopic drainage is not technically feasible and the risk of a controlled external fistula is an acceptable outcome. Other rare indications for external drainage at the time of laparotomy include the control of an immature ruptured pseudocyst, and for some bleeding pseudocysts where there has been oversewing of the bleeding point. An external fistula may resolve more rapidly with placement of a transpapillary stent and with the adjunctive use of a long-acting somatostatin analogue. Minimally Invasive Surgery. All open surgical techniques can now be performed using a laparoscopic approach. Intraluminal laparoscopic surgery, where the trocars are placed through the abdominal and stomach walls, has been successful. The cystogastrostomy can be performed with a stapler or by suture. A more recent modification of this approach is the mini-laparoscopic cystogastrostomy using a 2-mm intraluminal laparoscope. The view is augmented by the insertion of an oral flexible endoscope, which also can be used to explore the cyst cavity. The balloon dilatation of a percutaneous catheter track using a similar approach to that used for percutaneous nephrolithotomy is feasible in many cases. It is worth considering this when the initial radiologic attempts have failed to bring resolution. The placement of a sheath then allows the insertion of an operating nephroscope to enable débridement of the pseudocyst and

removal of organized pancreatic necrosis and infected necrosum. This procedure can be repeated and allows the placement of a soft large-bore external drain. Summary of Treatment for Pseudocysts. The treatment of choice for pancreatic pseudocysts depends on a number of factors, including size, number, and location of pseudocysts; whether the main pancreatic duct is obstructed or communicates with the pseudocyst; and whether there are complications of the pseudocyst. The clinical context is important (see Table 69-2). With the range of approaches to treatment and the variation in the availability of equipment and expertise, it is necessary to develop a rational treatment algorithm that is appropriate for the clinical setting and the patient (see Fig. 69-9). In practice, type I pseudocysts can usually be managed conservatively. Percutaneous drainage should be considered if the pseudocyst becomes symptomatic or infected. Type II pseudocysts are best managed by internal drainage, especially when there is communication between duct and pseudocyst. Endoscopic, laparoscopic, and radiologic approaches have an emerging role in expert hands. With type III pseudocysts, consideration needs to be given to decompression of the pancreatic duct and relieving the stricture at the same time as drainage of the pseudocyst.

FIGURE 69-9 Algorithm for investigation and treatment of pancreatic pseudocysts. ERP, endoscopic retrograde pancreatogram; MRP, magnetic resonance pancreatogram.

Pancreatic Necrosis Necrosis may involve the pancreatic parenchyma and/or the peripancreatic tissue, and this differentiates necrotizing pancreatitis from edematous pancreatitis.6 Initially poorly demarcated, the solid necrosis gradually liquefies and becomes surrounded by a capsule, such that after 4 weeks it is termed WON. This partially solid and partially fluid, encapsulated lesion has been described in the literature by a range of terms, including organized necrosis, necroma, and pancreatic sequestrum. The extent of tissue necrosis is not fixed and may progress, especially as the disease evolves over the first 1 to 2 weeks. The necrotizing process can extend widely to involve retroperitoneal fat, small and large bowel mesentery, and the retrocolic and

perinephric compartments. The presence of necrosis usually determines a more severe and protracted clinical course lasting weeks to months. From a clinical viewpoint, the development of necrosis is an important event in the course of acute pancreatitis because subsequent complications, both local and systemic,2 are associated with this.

EPIDEMIOLOGY The incidence of acute pancreatitis exhibits marked regional differences, and has been reported to from 5 to 80/100,000.30,31 The proportion of patients with acute pancreatitis who develop pancreatic necrosis is approximately 20%, and of these 25% to 70% will develop infected necrosis.32,33 The risk of infection is higher when necrosis is more extensive (ie, ~30% of the gland).34 In addition, the risk of infection increases with time, from 24% by the end of the first week of illness to 36% at the end of the second week, and to 71% by the end of the third week.35 The overall mortality of edematous pancreatitis is 1% or less, that of sterile necrosis is 5%, and that of infected necrosis is 10% to 25% in the best published series.36

PATHOGENESIS Of the patients who develop pancreatic necrosis, 70% have evidence of it by 48 hours of the onset of abdominal pain, and all of them by 96 hours.35 The premature activation of proteolytic enzymes within the acinar cells and interstitium of the lobule results in extensive necrosis of pancreatic tissue and the substantial accumulation and activation of leukocytes. There are a number of factors that contribute to the failure of the pancreatic microcirculation, which is evident histologically as stasis and/or thrombosis of intrapancreatic vessels. The failure of the pancreatic microcirculation leads to ischemia, which compounds the enzymatic and inflammatory injury and leads to the full syndrome of necrotizing pancreatitis. During this first week or so, in the so-called early or vasoactive phase, there is the release of proinflammatory mediators that contribute to the pathogenesis of pulmonary, cardiovascular, and renal insufficiency. This early systemic inflammatory response and multiorgan dysfunction are frequently present with evidence of pancreatic infection. In the septic or late phase, which occurs in most patients after 3 to 4 weeks, these systemic events usually occur as a consequence of infected

pancreatic necrosis.6 Mild edematous pancreatitis does not usually progress to necrotizing pancreatitis, implying that pathophysiological events soon after the onset of the disease are decisive in determining the course of the disease.37 Necrotic lesions are most likely to permit entry of bacteria when they are demarcated by only a thin rim of granulation tissue (4-20 days). Over time, necrotic areas slowly resolve and are replaced by fibrotic scar tissue (necrosis-fibrosis sequence).37

MICROBIOLOGY OF INFECTED NECROSIS Pancreatic necrosis is most likely to become infected during the late phase of acute pancreatitis, with a median time from hospital admission to infection of 26 days.34 There are five routes by which bacteria might infect pancreatic necrosis: (1) hematogenous, (2) transpapillary reflux of duodenal content into the pancreatic duct, (3) translocation of intestinal bacteria and toxins via the mesenteric lymphatics to the systemic circulation via the thoracic duct, and possibly directly to the pancreas via lymphatic connections between the intestine and pancreas, (4) reflux of bacteriobilia via a disrupted pancreatic duct into the necrotic parenchyma, and (5) transperitoneal spread. Cultures of infected pancreatic necrosis are polymicrobial in approximately one-third of patients and monomicrobial in two-thirds of patients.38 Gram-negative aerobic bacteria are the most common organisms identified (eg, Escherichia coli, Pseudomonas, Proteus, and Klebsiella), followed by gram-positive bacteria (eg, Enterococcus, Staphylococcus aureus). Anaerobic bacteria are identified in only around 5% of positive cultures, although this probably reflects inadequate culture techniques. Fungi may also be cultured, and are more common after use of prophylactic antibiotics.39 The spectrum of bacteria cultured from infected necrosis demonstrates that enteric bacteria dominate, suggesting bacterial translocation is an important event in the pathogenesis of infected pancreatic.33

PREDICTION AND DIAGNOSIS The presentation of pancreatic necrosis is usually nonspecific, with abdominal pain, distension, guarding and associated low-grade fever, and

tachycardia. The severity of pain and the extent of hyperamylasemia do not correspond with the severity of acute pancreatitis or the extent of pancreatic necrosis. The classic skin signs of retroperitoneal necrosis, including discoloration of the navel (Cullen sign), the flanks (Grey-Turner sign), and the inguinal region (Fox sign), are rare and often not seen until the second or third week after disease onset. Patients presenting late with severe or critical disease will often have established multiorgan dysfunction. The diagnosis of pancreatic necrosis requires more than just clinical acumen. Predicting the severity of acute pancreatitis and the presence of pancreatic necrosis remains an imprecise science.40 Scoring systems, such as Ranson, Glasgow, APACHE II, or “bedside index for severity in acute pancreatitis” (BISAP), are often used for severity stratification, but are rarely better than 70% accurate.41,42 Patients with predicted severe disease and high likelihood of pancreatic necrosis require radiological confirmation of the presence and extent of necrosis, which is conventionally categorized as less than 30%, 30% to 50%, and greater than 50% of the pancreas.43 Dynamic contrast-enhanced CT (CECT) is the gold standard for diagnosing pancreatic necrosis and other local complications, but is not usually indicated within the first 48 to 72 hours after the onset of acute pancreatitis.1,6 Pancreatic hypoperfusion is usually established by about 72 hours and imaging before then probably underestimates the extent of necrosis and the ultimate disease severity.44,45 Current guidelines recommend that CECT is indicated for patients with persisting organ failure, signs of sepsis, or clinical deterioration 6 to 10 days after admission.6 Other imaging modalities have been developed to diagnose the extent of pancreatic necrosis, including MRI and echo-enhanced ultrasound (EEU), which are at least as accurate as CECT in diagnosing and determining the extent of pancreatic necrosis.46,47 In practice, the indications to diagnose and determine the extent of pancreatic necrosis with CECT are when a patient fails to improve with initial resuscitation and/or when the CRP has crossed the predictive threshold (see later). CECT can be used to score the severity of acute pancreatitis by the CT severity index as proposed by Balthazar,48 but is no better than other methods.41 It is important to recognize the limitations of CECT, where a pseudocyst and WON can be difficult to distinguish. Imaging by MR or EUS can better delineate the solid components within a collection. In the absence of a specific diagnostic marker of pancreatic necrosis, many

serum predictors have been proposed. An ideal predictor or prognostic indicator should be simple, cheap, reproducible, valid, available on admission, and specific for necrosis. While a full discussion of markers is beyond the scope of this chapter,42 there are several that fulfill most of these criteria, compare favorably with CT scanning, and have an established role in routine clinical practice. C-reactive protein (CRP) is the most widely used predictor of pancreatic necrosis and is also useful as a daily monitor of disease progress. The accuracy in predicting the presence of necrosis is about 85%, but it requires 3 to 4 days after the onset of the disease to reach this level. The threshold values depend on the assay and the study used. A commonly used threshold is greater than 120 mg/L.49 Other prognostic markers, none of which has been shown to outperform CRP, include interleukin-6 (IL-6) (threshold >14 pg/mL) which peaks a day earlier than CRP; polymorphonuclear elastase (threshold >120 µg/L), which peaks early and reflects neutrophil activation and degranulation; and phospholipase A2 type II (threshold >15 U/L). Urinary trypsinogen-activating peptide has also been proposed as a predictor of necrosis, but is not the major advance that was first anticipated.50 Procalcitonin has been proposed as a sensitive and specific marker for infected necrosis but it has not become part of routine management.6,33,34 The diagnosis of infected necrosis is very important because it is generally considered an indication for intervention. Rarely, the early invasion of gasforming organisms, such as Clostridium perfringens, makes the diagnosis of infection on CT scanning straightforward.51 It is more usual to suspect pancreatic infection with rapidly progressive disease or a secondary deterioration after 2 or 3 weeks of admission.34 This is often heralded by a significant rise in CRP. A CECT scan will usually confirm the presence of a tense collection with rim enhancement arising from the region(s) of pancreatic necrosis. The presence of gas within the tissues confirms infection, with an “air bubble” appearance (Fig. 69-1), but this is present in the minority of cases. Clinical practice guidelines are consistent in their recommendation to use FNA as the gold standard test to diagnose infected necrosis.1,52 It is true that infected ANC and WON are most accurately diagnosed by image-guided (CT or ultrasound) FNA for Gram staining and/or bacterial culture. Suspicion of infection is raised with a significant and secondary clinical deterioration and

the associated rise in serum markers (eg, CRP, procalcitonin) which makes the diagnosis of infection highly probable.39 Certainly there is usually enough suspicion to proceed with antibiotics, CECT, and percutaneous or endoscopic drainage, which allows bacterial cultures. There has been some concern that FNA is associated with a potential risk of secondary infection.53 In summary, it is better to consider FNA of ANC or WON as an adjunctive measure and one that is only undertaken in a patient in whom there is already a strong clinical suspicion of infection and in whom confirmation of infection will directly result in intervention.54

INDICATIONS FOR INTERVENTION The decision to directly intervene to treat complicated acute pancreatitis is one of the most difficult decisions in clinical practice. Intervention is defined as invasive treatments (radiologic, endoscopic, surgical) beyond medical, nutritional, and intensive care management. The primary indication for intervention is the development of infected necrosis (in ANC or WON) in conjunction with clinical deterioration, but it is no longer considered an absolute indication for intervention in many centers. Other indications for further intervention are the failure of radiologic or endoscopic drainage, where there is evidence of persistent sepsis, and organ dysfunction. The indications for intervention in the absence of infection are very limited. A rare indication for intervention, irrespective of the infection status of the necrosis, is the development of massive hemorrhage or bowel perforation (eg, colon or duodenum). Intervention on patients with sterile necrosis is no longer advocated unless there is acute clinical deterioration despite maximal supportive care and there is a well-defined target lesion to drain or debride.55,56 Intervention is also occasionally required in those patients with sterile necrosis who “fail to thrive” and are unable to be discharged. These patients often have abdominal symptoms and intolerance to oral feeding after a month or more. The vast majority of patients with sterile necrosis can and should be managed without surgery.56

TIMING OF INTERVENTION Historically, surgical intervention for pancreatic necrosis was performed during the first week after disease onset. Early surgery was advocated in

order to remove the dead tissue, the focus of infection, and terminate the inflammatory process. We now know that the inflammatory cascades are not easily switched off, and are exacerbated by the surgical procedure. Early surgery is more difficult and dangerous because the necrotic tissue is immature, poorly demarcated, and not easily separated from viable tissue, resulting in a significant risk of bleeding. In addition, early surgery may cause infection of sterile necrosis. With mortality rates of up to 65%, the trend toward early intervention has been curtailed,1,57 and intervention has become progressively later. The current concept for timing of intervention is that it should be undertaken as late as possible after disease onset (preferably 3-4 weeks), when the necrotic process has stopped extending, when there is clear demarcation between viable and nonviable tissues, and when infected necrotic tissue has become organized and “walled off.”1,57 Importantly, this delay allows time for stabilization of the patient through intensive care support, reduces the risk of new-onset organ dysfunction attributable to the intervention, and decreases the risk of bleeding and pancreatic insufficiency through the unnecessary removal of viable tissue. This delay to debridement, by whatever means, is enabled by the adoption of the step-up approach (see later) that recommends radiological or endoscopic drainage first and then supportive measures. The concept of “drain first” should include efforts to optimize drainage by up-sizing, flushing, irrigation, replacement, and additional drains, as required.58 Prior drainage often results in an improvement in the patient’s overall clinical status. The type and timing of further intervention is dictated by a number of factors, including the patient’s condition and comorbidities, local expertise, and the anatomical location and complexity of the lesion. This decision is best made in a high-volume center with experience and expertise to ensure the timing and type of intervention is optimal.1,59

TYPES OF INTERVENTION There are many different interventions, and the challenge is to select the intervention appropriate for the particular local complication, taking into account the anatomical location, infection status and complexity of the target lesion(s), the physiological status, comorbidity of an individual patient, and the availability of expertise with the type of intervention. A review of current guidelines highlights the absence of level 1 evidence to guide decision

making regarding the types of intervention.60 There have been two broad philosophies regarding the type of intervention used. Some experts state that open surgical drainage and necrosectomy remains the gold standard in the management of infected pancreatic necrosis, and reserve less invasive interventions for subsequent complications. These include percutaneous and endoscopic drainage of residual fluid complications. Such a step-down approach contrasts with the step-up approach, which advocates the use of less invasive interventions initially (eg, percutaneous or endoscopic drainage), and then stepping up to minimally invasive surgical interventions and only employing open surgical techniques later in the disease course in those who fail to respond. These two approaches have been subjected to a randomized controlled trial in the PANTER trial.61 This demonstrated that the step-up approach reduced the rate of the composite endpoint of major complications and/or death. Mortality itself was not decreased, but new-onset multiple organ failure occurred less often in patients assigned to the step-up approach. Another important finding was that a third of patients who would have previously undergone an open necrosectomy were managed by drainage alone. There is a need to standardize the description of invasive interventions to facilitate communication between clinicians, comparison of techniques, and controlled clinical trials. The VRP classification is based on the method used to Visualize the lesion, the anatomical Route taken to reach the lesion, and the Purpose of the intervention.62 • The various ways to visualize the target lesion include open procedures (where the operative site is exposed through the skin incision), endoscopic procedures (where the operative site is visualized with an endoscope (eg, gastroscope, laparoscope, or nephroscope), radiological procedures (where CT, ultrasound, or fluoroscopy are used to visualize the lesion during the procedure), and hybrid procedures that combine endoscopic and radiological techniques. • The different routes taken by reach the target lesion include the external route into the body (skin or external orifice) and the internal route to reach the target lesion (through the gastrointestinal wall, peritoneum, or retroperitoneum) (Fig. 69-10).

FIGURE 69-10 Possible routes to be taken during treatment of local complications of acute pancreatitis. R1, per-os transpapillary; R2, per-os transmural; R3, percutaneous retroperitoneal; R4, percutaneous transperitoneal; R5, percutnaneous transmural. • The overall purpose of treatment is to drain fluid and remove areas of necrotic and infected tissue. However, the way in which this is achieved varies considerably, with some procedures being considerably more aggressive than others. Therefore, the purpose of individual interventions may be to effect simple drainage alone, lavage of the necrotic cavity to assist drainage of necrotic debris, fragmentation of necrotic tissue to facilitate its drainage, débridement of necrotic tissue, and excision or resection of the pancreas. Drainage procedures involve allowing fluid and solid necrotic to drain externally out of the body or internally into the gastrointestinal tract. Lavage describes flushing away solid necrotic matter with fluid to facilitate external or internal drainage. Fragmentation is a method used to break down solid necrotic matter by instrumental or mechanical disruption to facilitate drainage. Débridement, which is often termed “necrosectomy,” involves removing solid necrotic matter (typically with blunt dissection), and may or may not include postoperative lavage. Débridement may involve removal of all or only some of the necrotic tissue, although normal tissue is not intentionally removed. Only during excision or resection of the pancreas is normal tissue intentionally

removed along with devitalized tissue. Such an approach is no longer recommended.

THE “STEP-UP APPROACH” TO INTERVENTION There have been significant changes in the approach to intervention in recent years.57 The focus shifted from resection to debridement decades ago, and we are now in the process of shifting the emphasis from debridement to drainage. Complete debridement is no longer considered essential; rather, sufficient debridement of necrotic tissue should be achieved to optimize drainage. Figure 69-11 is an algorithm for clinicians who are faced with the management of patients with infected necrosis (ANC or WON). In general, when patients deteriorate despite maximum intensive care, the intention is now to institute or optimize drainage (endoscopic or radiologic). If the patient does not show any improvement over 48 to 72 hours, then the intervention is intensified. This might entail insertion of further drains. Endoscopically, this would often mean the insertion of a self-expanding metal stent (see above) through which endoscopic debridement can be undertaken. Alternatively, a percutaneous track can be dilated or a small flank incision made to allow for minimally invasive surgical debridement using a nephroscope or laparoscope. When these approaches fail, and only then, open surgical debridement is considered.57

FIGURE 69-11 Algorithm for the management of infected necrosis (ANC or WON). The target lesion is best delineated by CECT or MRI scanning, noting the size, wall maturity, extent, complexity, and anatomical relationships. In addition, it is used to determine whether there is safe access to the lesion, and which route (Fig. 69-11) and which method (radiologic or endoscopic) is preferred for drainage.

RADIOLOGIC INTERVENTION The purpose of radiological techniques is to drain (with or without lavage) and to provide an aid to access for minimally invasive debridement (see below). Percutaneous catheter drainage can be used as a primary treatment for infected ANC/WON and more definitive treatment be delayed until the patient has clinically stabilized and wall-matured,63 or as a secondary

treatment for residual collections. Further, percutaneous drainage is the sole treatment in about half the patients.57,63 Most collections are located in the lesser sac, anterior pararenal space, into the root of the small bowel mesentery and the paracolic gutters.64 The usual internal routes to the target lesion are retroperitoneal or transperitoneal. Less commonly, transgastric, transduodenal, and transhepatic routes used.65 While transgressing the stomach poses little infection risk, gastric peristalsis may dislodge the catheter over time. Transgressing the liver carries the risk of bleeding, but in practice is generally safe. Routes should avoid colon, small bowel, spleen, and kidney to minimize the risk of hemorrhage and bacterial contamination. A retroperitoneal approach that avoids the peritoneal cavity is the preferred route, as this prevents contamination of the peritoneal cavity and possible peritonitis.64 Typically percutaneous catheters have multiple side holes and a minimum diameter of 12 to 14 Fr (4.0-4.7 mm).65 Sometimes multiple catheters are required, for large or complex lesions. Lavage can be employed to reduce the concentration of digestive enzymes and proinflammatory mediators in the lesion, help maintain patency, and to assist the removal of solid necrotic debris from the cavity.66 There have been unsubstantiated concerns that lavage might spread infection, either from infected fluid spilling over into previously sterile cavities or from the increased intracavity pressure resulting in translocation of bacteria into portal circulation. The efficacy of drainage procedures is limited by the contents of the target lesion. Success with predominantly solid lesions is rare. In patients with pancreatic necrosis treated with percutaneous catheter drainage, approximately half will be successful and not require surgical intervention.63,57 Failure of catheter drainage includes persistent systemic or local manifestation of infected necrosis, physiological deterioration despite drain patency, persistent abdominal pain, and intolerance of oral intake after the systemic inflammatory response syndrome has resolved.67 In some specialized centers, interventional radiologists have attempted debridement, through the use of snares, baskets, or by applying suction to a catheter during its removal.68−70

ENDOSCOPIC INTERVENTION

Peroral flexible endoscopic techniques follow an internal route through either the gastric or duodenal wall or duodenal papilla, and some authors consider this to be a form of natural orifice transluminal endoscopic surgery (NOTES).71,57 Initial descriptions of flexible endoscopic treatment of pancreatic necrosis used lavage and drainage without instrument-guided débridement.72 A more aggressive approach was subsequently introduced, which demonstrated necrotic tissue could be debrided with baskets, snares, forceps, and suction.73,74 ERCP may be used to diagnose any communication between the duct and cavity or duct stenosis or disruption, and transpapillary stenting can be employed to decompress the duct. Puncture of the posterior gastric wall into the target lesion is performed at the point of maximal bulging, although confirmation of the location with EUS helps achieve safe deployment to avoid injury to vessels.27 The injection of contrast with fluoroscopy can be used to determine the extent of the cavity. The gastric insertion site is balloon-dilated. For lavage and drainage, a 7 Fr nasocystic (lavage) and a 10 Fr pigtail drain (drainage) are placed in the cavity. Necrosectomy may be performed with endoscopic instruments (eg, Dormia basket or polypectomy snare), and introduction of a forward-viewing endoscope into the necrotic cavity can be used for better visualization during the necrosectomy (Fig. 69-12). Multiple necrosectomy procedures are usually required to clear the cavity of necrotic tissue.

FIGURE 69-12 Cross-sectional views depicting video-assisted debridement of infected of “walled off necrosis”(A) and endoscopic transgastric drainage and necrosectomy (B). The introduction of transgastric self-expanding metal stents (SEMS) has been a significant advance in the endoscopic treatment of infected ANC and WON. These stents are designed with a wide lumen (eg, 2.5 cm), wide flanges (to prevent migration) and even wall-apposing features (to reduce the risk of leakage) (Fig. 69-9).28 This facilitates direct endoscopic debridement, but it has been noticed that this is less often required with the wide lumen stents, possibly because of the liquefying action of gastric juice on the necrotic tissue. Flexible endoscopic debridement has also been used percutaneously (“sinus tract endoscopy”).75 A similar technique has been described following open necrosectomy through a translumbar incision, where a flexible endoscope is inserted into the cavity for débridement.76 Another endoscopic approach is to debride through a percutaneous endoscopic gastrostomy (PEG).77 Usually multiple débridement procedures are required

because of the inefficiency of extraction. The wide range of endoscopic approaches to necrosectomy and the absence of formal comparison make a recommendation for the optimal approach difficult. The selection of an endoscopic technique will be influenced by training, experience, and availability of equipment.

MINIMALLY INVASIVE SURGICAL INTERVENTION Over the last decade, a wide range of endoscopic surgical approaches for pancreatic necrosectomy have been described, including infracolic laparoscopy, transgastric laparoscopy, hand-assisted laparoscopy, retroperitoneal laparoscopy, and retroperitoneal nephroscopy.78−82 While some endoscopic procedures do not use radiologic imaging, many are hybrid procedures using fluoroscopy or EUS. This array of minimally invasive techniques can be classified by the type of scope used.83 Laparoscopic Techniques. In 1996, Gagner described the first true endoscopic treatment of necrotizing pancreatitis, where the pancreas was debrided using a laparoscopic approach.84 Most laparoscopic techniques are minimally invasive versions of open surgical techniques, and use either an anterior or lateral approach (see below). In Gagner’s original description of laparoscopic necrosectomy, two anterior routes (retrogastric retrocolic and transgastric) and one lateral route were described.84 This technique has been modified. Of the lateral approaches, one of the most widely used laparoscopic techniques is videoscopic-assisted retroperitoneal débridement (VARD) (Fig. 69-12).82,61 In this technique, prior percutaneous drainage is followed by a 4to 6-cm incision in the left flank using the drain as a guide. A finger is used to probe and confirm entry into the necrotic cavity. Fluid and loose necrotic debris are removed by suction. Using right-angled retractors, the laparoscope is inserted along with the irrigating catheter (to aid visualization) and further debridement is achieved under direct vision with the gentle use of sponge forceps. The incision can be sealed with wet sponges and towel clips to allow better visualization by insufflation with CO2. The objective is not to achieve complete debridement but optimal drainage. Large bore drains (eg, 28-32 Fr Protex chest drains) are brought out through the flank incision. These drains are used for drainage and lavage. An ostomy bag can be positioned over the flank incision between lavage sessions.

The first randomized controlled trial comparing two different minimally invasive approaches to the treatment of infected pancreatic necrosis has now been published.85 In this pilot study (“PENGUIN”), endoscopic transgastric necrosectomy was found to be superior to the VARD procedure. There was a reduction in the incidence of the predefined composite endpoint (new-onset multiple organ failure, intra-abdominal bleeding, enterocutaneous fistula, and/or pancreatic fistula) or death. There was a decrease in the incidence of new onset of multiple organ failure, supported by the finding that there was a significantly lower proinflammatory response after the procedure, and a reduction in the incidence of pancreatic fistulation. Nephroscopic Techniques. The use of a nephroscope for necrosectomy was termed “percutaneous necrosectomy” by the unit that pioneered this approach.75 The purpose is to debride necrotic tissue and establish continuous lavage. The rigid nephroscope has an irrigating channel that provides superior visualization to laparoscopic techniques. The limitation is the working channel, which limits the amount of debridement. The first step is to insert a drainage catheter under CT guidance into the pancreatic lesion. The preferred path for drainage is between the lower pole of the spleen and the splenic flexure, although in right-sided necrosis a path through the gastrocolic omentum (anterior to the duodenum) may be necessary. The patient is then transferred to the operating room and positioned in the appropriate lateral position. The drain tract is then dilated to allow insertion of a 34 Fr Amplatz sheath. The nephroscope is inserted through the sheath into the cavity, and lavage is used to clear away pus and debris. Following necrosectomy, a 32 Fr soft drainage tube is left in the cavity. An additional catheter may be used to allow continuous postoperative lavage. Repeat procedures are often required after 2 to 10 days.86

OPEN SURGICAL INTERVENTION The role of open surgical treatment of infected pancreatic necrosis is diminishing with the accumulating evidence for the less invasive approaches. It is now reserved for those who fail minimally invasive intervention and for when a laparotomy is required for additional reasons, such as abdominal compartment syndrome and intestinal infarction/perforation. Prior CECT scanning will allow determination of the extent of the target lesion and allow

formulation of the operative plan. The abdomen is best entered though a bilateral subcostal incision since this allows better access to the extremities of the gland and less contamination of the greater peritoneal sac if there are subsequent procedures. The pancreas is exposed by dividing the gastrocolic omentum (Fig. 69-11) or gastrohepatic omentum to access the pancreas through the lesser sac. The body and tail of the pancreas can be exposed by elevating the transverse colon and gaining access to the lesser sac via the transverse mesocolon (Fig. 69-12). Inflammatory adhesions may exist between the pancreas and stomach or transverse mesocolon, and great care is required during exposure. It is generally useful to take down both the hepatic and splenic flexures if possible, as this will facilitate exposure and reduce the risk of colonic fistula secondary to drain erosion. When the process involves the head of the pancreas, access might require medial mobilization of the duodenum. The plan is to drain all fluid collections, debride all devitalized tissue, and avoid hemorrhage and enteric fistulation. Infected necrotic tissue and fluid are sent for bacterial culture to confirm the causative organisms and rationalize antibiotic therapy. Débridement of necrotic tissue is performed bluntly, usually with digital dissection, careful use of instruments, and lavage. Only loosely adherent necrotic tissue should be removed, and this is easier if there has been a significant delay between onset of disease and surgery. Use of a systematic approach, such as examining in turn the retroperitoneum behind the transverse, ascending, and descending colon, helps to ensure all areas of necrotic tissue are identified and removed. If multiple procedures are planned, the first necrosectomy provides the best exposure, and therefore the most complete débridement that is safe should be accomplished at this time. The thoroughness of the initial débridement is the most important factor in determining the need for subsequent reoperation.87 The need for complete débridement has been questioned, and the risks of aggressive debridement have be balanced against the risks of persisting sepsis. A key point is to avoid sharp dissection in order to prevent major hemorrhage. Adherent necrotic tissue should be left in situ, as this will subsequently demarcate and become loose. Strands of tissue forming bridges across the cavity may be vessels and should not be avulsed. This is important, because bleeding from inflamed vessels within the retroperitoneum is difficult to control and may require formal packing.

Following débridement, extensive irrigation is used to flush away necrotic debris, inflammatory exudates, and residual bacteria. Postoperative lavage may be employed, and this can be either intermittent or continuous (Fig. 6911).88 The fluids most commonly used for this purpose are normal saline or peritoneal dialysis fluid, although there is no evidence to support the best fluid or flow rate. The choice of open surgical procedure is determined by the location, extent, and maturity of the necrotic material; status of the infection; the patient’s condition; the degree of organ dysfunction; and the preference and experience of the surgeon.33 A number of different approaches have been described (Table 69-4), some of which are only of historical interest. Interventions are complex, fraught with potentially life-threatening complications, and should only be performed by experienced surgeons in regional centers. There are several approaches to open necrosectomy, and there is no highlevel evidence to support one over the other. While the débridement technique for all the approaches is similar, they differ in terms of how they provide egress for infected fluid, debris, and tissue. Open necrosectomy with Closed Packing. The goal of necrosectomy with closed packing is to perform a single operation, with thorough débridement and removal of necrotic and infected tissue, and to avoid or minimize the need for reoperation or subsequent drainage.56 Some units use gauze-stuffed Penrose drains placed via separate stab incisions, but there are many variations in practice with regard to the type and number of drains. With the Penrose drain technique, the intention is to fill the cavity and provide compression rather than facilitate external drainage per se, and between two and twelve drains are usually placed. Additional silicon drains (eg, JacksonPratt) are placed in the pancreatic bed and lesser sac to drain fluid from the area. Primary closure of the abdomen is routine with this approach. The stuffed Penrose drains are removed once every other day, starting 5 to 7 days postoperatively. The silicone drains are removed last. Open Necrosectomy with Open Packing. The difference between this approach and closed packing is that the abdomen is left open after débridement and packing of the abdomen.91 An alternative form of open packing uses a 20-cm flank incision instead of an anterior laparotomy.89

Open packing techniques have been reported to have higher incidences of fistulae, bleeding, and incisional hernias, as well as a slightly higher mortality rate.90 However, it should be noted there are no prospective trials comparing open packing with any other techniques. Open Necrosectomy with Continuous Closed Postoperative Lavage. In this technique, débridement is followed by continuous peripancreatic lavage to remove infected necrotic debris, peripancreatic exudates, and extravasated pancreatic exocrine fluid.56,62 Drainage catheters, usually two on each side, are placed with their tips at the head and tail of the pancreas behind the ascending and descending colon. Placement of sump drains (20-24 Fr) with two lumens allows inflow of lavage fluid and outflow of drainage fluid. Larger silicon drains (28-32 Fr) allow evacuation of larger necrotic debris. During closure, a closed peripancreatic compartment is attempted by resuturing the gastrocolic and duodenocolic ligaments. Postoperative continuous lavage is instituted at 1 to 10 L per day, and is usually continued until the effluent is clear and the patient shows improvement in clinical and laboratory parameters.56,91 There is no evidence to support the best irrigation fluid, the optimal number or caliber of drains, or the duration of irrigation. Programmed Open Necrosectomy. The principle of this approach is to be more conservative with débridement, particularly if the necrosis has not fully demarcated, with the intention of performing repeat procedures until débridement is no longer required.56 Following necrosectomy, the pancreatic bed is packed and drains are placed on top of the packing. The abdominal wall is closed with a zipper or mesh sewn to the fascia. This allows easy repeated access to the abdomen and helps to prevent wound retraction. Reoperation is repeated every 48 hours until there is no further necrotic tissue to remove. In a proportion of patients, primary closure is not possible and healing by secondary intention is allowed to occur. This procedure may be modified with the addition of intra-abdominal vacuum sealing (negative pressure 50-75 mm Hg) in order to encourage granulation of the pancreatic bed.92

REGIONAL COMPLICATIONS

Vascular Complications VENOUS THROMBOSIS Thrombosis of the splenic vein is a rare complication of acute pancreatitis and one that usually develops a few weeks after the onset. The etiology is multifactorial, but extrinsic compression of the vein by the swollen pancreas and/or fluid collection is important. Other factors include hypercoagulability and hemoconcentration. The consequences of splenic vein thrombosis are splenomegaly with discomfort and possible hypersplenism. Segmental venous hypertension may result in upper gastrointestinal bleeding from gastric varices. Because the risk of gastric variceal bleeding from pancreatitis-induced splenic vein thrombosis is low (5% for CT-identified varices and 18% for endoscopically identified varices) routine splenectomy is no longer recommended.93 Portal vein thrombosis occurs insidiously, may be identified on CECT, and may be discovered after gastrointestinal hemorrhage has occurred. The consequences of acute superior mesenteric vein thrombosis are venous ischemia and infarction of the intestine. CECT scanning is helpful in the diagnosis of venous thrombosis and may show features of impaired mucosal enhancement, edematous swelling of the vessel wall, and most commonly, filling defects within the vein. The role of acute anticoagulation is controversial because of the risk of bleeding. If thrombosis occurs later in the disease course, anticoagulation can be prescribed with less trepidation. Thrombolytic therapy and surgical thrombectomy have no established role in the context of acute pancreatitis. Acute venous thrombosis is associated with a 25% recurrence rate without anticoagulant therapy and a 30% mortality. Anticoagulant therapy combined with surgery is associated with the lowest recurrence rate (3%-5%).

BLEEDING Bleeding associated with severe acute pancreatitis is usually, but not always, due to a pseudoaneurysm related to a pancreatic pseudocyst. The splenic artery is the most commonly affected artery (30%-50%) because of its proximity to the pancreas, followed by the gastroduodenal artery (10%-15%), the inferior and superior pancreaticoduodenal arteries (10%), and all others to a lesser extent.

Pathogenesis. The disruption of the pancreas by necrosis and the damage to pancreatic ducts leads to the accumulation of activated proteolytic enzymes (eg, elastase), weakens the vessel wall, and promotes aneurysmal dilatation. This process is accelerated in the presence of infection. Diagnosis. Patients usually present with hypovolemic shock or with an unexplained drop in hemoglobin concentration. Bleeding may occur into a pseudocyst and tamponade, preventing any overt evidence of bleeding. Very rarely the diagnosis will be made in a patient with a known pseudocyst who develops an abdominal bruit. Selective mesenteric angiography is the best way to make the diagnosis of pseudoaneurysm (Fig. 69-4), although it can often be detected on the arterial phase of CT scan, which is frequently used as a screening test in a stable patient. Angiography usually accurately identifies the location of the pseudoaneurysm and its relationship to named vessels. Treatment. Pancreatic or peripancreatic bleeding is one of the most formidable and life-threatening complications of acute pancreatitis. The standard of care is angioembolization, with surgery only required in patients who have failed this approach or who are not stable enough to be managed in the interventional radiology suite. Success with embolization is operatordependent, but approaches 90% in leading centers. Failure results from an inability to selectively cannulate the bleeding vessel, or poor placement of embolization material. Recurrent bleeding occurs in fewer than 40% of patients, and the overall mortality is under 20%. If emergency laparotomy is required for bleeding, it may not be possible to arrange prior angioembolization. The lifesaving surgery may involve under-running the bleeding vessel (inside or outside the pseudocyst) and/or pancreatic resection. The mortality rate following surgical treatment of arterial hemorrhage during the acute phase of pancreatitis ranges from 28% to 56%, and is higher when bleeding is from the head of the pancreas. The mortality rate following surgical treatment of massive hemorrhage is usually over 50%.

Intestinal Complications PARALYTIC ILEUS

The proximity of the inflamed pancreas to the root of the small bowel mesentery commonly results in regional self-limiting paralytic ileus affecting the duodenum, proximal jejunum, or transverse colon. Another factor that may contribute to the ileus is the relative splanchnic ischemia secondary to the reflex vasoconstriction in response to systemic hypotension, early in the disease course. An ileus gives rise to the classic “sentinel loop” and “colon cutoff” signs on plain abdominal radiographs.

INTESTINAL ISCHEMIA AND NECROSIS Subclinical mucosal ischemia is common in acute pancreatitis, particularly during the early phase, and occurs in response to hypovolemia and reflex splanchnic vasoconstriction. Intestinal ischemia might be compounded by abdominal compartment syndrome, nonselective inotropes, and the demands of early and continuous enteral feeding. These are risk factors for nonocclusive mesenteric ischemia. Full-thickness necrosis is rare and probably involves venous and/or arterial thrombosis at sites proximal to the inflammatory process. The middle mesocolic vessels and the transverse colon are most at risk.

INTESTINAL OBSTRUCTION Mechanical obstruction rarely complicates acute pancreatitis. The mechanism is usually inflammatory stenosis, which presents very late. It is unusual to require surgery.

CHOLESTASIS Biochemical and clinical jaundice occur in less than 20% of patients with acute pancreatitis. The early identification of concomitant cholangitis is important and will require early ERCP and duct decompression. Cholestasis may be due to common bile duct stones or extrahepatic bile duct compression by a peripancreatic fluid collection. Long-term total parenteral nutrition will contribute to cholestatic liver dysfunction.

SYSTEMIC COMPLICATIONS

Systemic Inflammatory Response Syndrome The systemic inflammatory response syndrome (SIRS) is common with acute pancreatitis and encompasses the hallmarks of a proinflammatory state (ie, tachycardia, tachypnea or hyperpnea, hypotension, hypoperfusion, oliguria, leukocytosis or leukopenia, pyrexia or hypothermia, and the need for volume infusion) but without end-organ damage, identifiable bacteremia, or the need for pharmacologic support. SIRS is distinct from sepsis (where there is an identified pathogen) and septic shock (where there is associated hypotension). SIRS is best regarded as an exuberant host inflammatory response and the consequence of hypoperfusion. There is no single trigger for SIRS. Instead, it represents a wholeorganism response to a variety of quite different challenges. Theories on the drivers for SIRS include the immunologic dissonance theory (where there is imbalance between the pro- and anti-inflammatory responses)94 and the gut motor theory (where decreased intestinal perfusion and subsequent damage to the mucosal and immunologic barriers may allow the translocation of endogenous bacteria or their products into the systemic circulation).95 More recently, the intestinal mucosa has been considered another source of inflammatory mediators activated by hypoperfused mucosa.96 Measurement of intramucosal pH (tonometry) can stratify mortality risk in acute pancreatitis.97 The mediation of SIRS is due to a number of well-described cytokines responsible for the proinflammatory state, a full description of which is beyond the scope of this chapter. In many patients with acute pancreatitis, SIRS progresses to multiple organ dysfunction syndrome (MODS) and possible end-organ damage. Occasionally, patients will be admitted with fulminant or early severe acute pancreatitis, often with respiratory and renal impairment from the outset, and these patients are responsible for early deaths. Organ failure on admission, which occurs in 30% to 40% of patients with necrotizing pancreatitis, is a very poor prognostic sign, doubling intensive care stay and increasing the mortality rate fourfold.35 Early aggressive volume resuscitation has an important role in attenuating the systemic inflammatory response.96

Multiple Organ Dysfunction Syndrome

The development of MODS is common in severe acute pancreatitis. The most commonly affected organ systems are cardiovascular, respiratory, and renal. It has been defined as the presence of altered organ function in a severely ill patient such that homeostasis cannot be maintained without intervention.98 Many patients with early organ failure respond rapidly to supportive treatment and appear to have an otherwise uncomplicated outcome. These patients are said to have transient organ dysfunction, if it resolves within 48 hours.1 Patients with persistence and progression of early organ failure have a mortality rate in excess of 50%. It has been shown that organ dysfunction in the first week of admission is a dynamic process and the response to the initial intensive care is an important determinant of outcome.99 Many potential early predictors of organ failure have been investigated. MODS can be predicted with reasonably high accuracy at the time of hospital admission using a combination of the anti-inflammatory cytokine IL-10 (an early marker of systemic inflammation) and serum calcium (an early marker of organ dysfunction).100 There are many different MODS scoring systems, but the one recommended for acute pancreatitis is the modified Marshall score.1 The scoring systems do not tell the clinician when specific organ dysfunction is reversible or irreversible. Practically, a simple count of organs affected and the duration of the dysfunction will stratify mortality.

Respiratory Complications Respiratory impairment can result from several causes, including atelectasis, pleural effusion, pneumonia, mediastinal pseudocyst or abscess, and/or adult respiratory distress syndrome (ARDS). Tachypnea, mild respiratory alkalosis, and mild hypoxemia are common within 2 days of the onset of acute pancreatitis. These clinical features usually can be corrected with analgesia, supplemental oxygen, and chest physiotherapy. A pleural effusion may require a chest drain. Impending respiratory failure is suggested when the arterial PO2 remains less than 60 mm Hg despite high-flow oxygen by mask. These patients should be considered for mechanical ventilation. Lungprotection ventilation strategies, with low tidal volumes for patients with ARDS, are recommended.101 ARDS may occur within a few days of admission or after the development of infected necrosis and septicemia.

ARDS results from the release of activated pancreatic enzymes, vasoactive lysosomal enzymes, and especially phospholipase A2 (which destroys surfactant). Parenchymal injury appears to be due primarily to oxidative damage from the activated neutrophils in the lung. Renal Complications. Renal impairment is usually due to both hypovolemia (prerenal failure) and direct nephrotoxicity from the inflammatory mediators of acute pancreatitis. Activation of the renin-angiotensin system may contribute to reduced renal perfusion. This manifests as oliguria (7 mm) and no dominant inflammatory mass have achieved durable pain relief over 5 to 10 years of follow-up.53,55–58 Compared to other major pancreatic operations, perioperative morbidity is low, and because no pancreatic parenchyma is removed, endocrine and exocrine functions are generally preserved relative to

preoperative levels. Failure of lateral pancreaticojejunostomy is usually due to inappropriate patient selection (underappreciated extent of disease with the presence of significant fibrosis in the pancreatic head), or ongoing fibrosis with the progressive development of neuropathic pain.

Chronic Pancreatitis with a Dominant Pancreatic Head Mass Lateral pancreaticojejunostomy has limited applicability in patients without diffuse main duct dilation. Multiple groups have reported that an isolated drainage procedure in patients with complex inflammatory changes in the pancreatic head, body, or tail results in poor clinical outcome with quick recurrence of symptoms of pain and progression to exocrine insufficiency. For patients with an inflammatory mass, extensive calcifications, or duct stones in the pancreatic head, results appear to be better either with pure resectional or with hybrid resection and drainage procedures. The four procedures used with great frequency today are pancreaticoduodenectomy (Whipple procedure, with or without pyloric preservation) and three forms of duodenum-preserving pancreatic head resection (DPPHR): the Beger procedure, the Berne procedure, and the Frey procedure. The outcomes associated with these procedures have been compared in several randomized trials enrolling small numbers of patients with headpredominant morphology. None of these studies has demonstrated any one of the techniques to be clearly superior to others (Table 71-5). There are no measurable differences in outcomes compared, the numbers in the trials are small, and the metrics used to evaluate the outcomes are variable and imperfect.59–62 As a result, no consensus opinion among pancreatic experts about which procedure is the best in any given clinical situation has emerged. In recent years, European surgeons have tended to favor a duodenumpreserving approach and American surgeons have tended to favor pancreaticoduodenectomy. One recent survey of American surgeons who were members of the Pancreas Club found that of 59 surgeons surveyed, only 34 had ever performed DPPHR and that only 23 US surgeons continue to perform these procedures on a regular basis.63

TABLE 71-5: LONG-TERM FOLLOW-UP FROM RANDOMIZED COMPARISONS OF SURGICAL METHODS ADDRESSING HEAD DOMINANT MORPHOLOGY

In spite of the lack of data supporting the relative superiority of any given procedure, we do believe that each has specific applicability to certain subtypes of head-predominant morphology. A reasonable approach is to tailor the procedure to the anatomic morphology seen on the preoperative axial imaging and ductography. Patients with a dominant head mass and a dilated main pancreatic duct but no biliary dilation may be best served by a Frey procedure (limited duodenum-preserving resection of the pancreatic head with extended lateral pancreaticojejunostomy). Patients with a dominant head mass without main duct dilation and no biliary obstruction may be better suited for the Berne modification of the Beger procedure (limited duodenum-preserving resection of the pancreatic head without extension of the lateral pancreaticojejunostomy toward the tail). Patients with biliary obstruction or imaging characteristics more suspicious for the presence of malignancy should probably undergo pancreaticoduodenectomy rather than any form of DPPHR.

PANCREATICODUODENECTOMY—TECHNIQUE The early primary objective in the pancreaticoduodenectomy is making an efficient determination of whether or not the pathology allows safe resection. This typically involves a thorough manual examination of the abdomen to rule out metastatic cancer and then a rapid exposure of the pancreatic neck superiorly and inferiorly in an effort to assess the operator’s ability to free the

hepatic artery, superior mesenteric vein, and superior mesenteric artery from the pathology in the pancreatic head safely. Pancreaticoduodenectomy may be performed through a midline laparotomy or bilateral subcostal incision. Careful inspection and palpation of the peritoneal surfaces and liver is performed first, with frozen-section biopsy obtained of any suspicious lesions. Small areas of fat necrosis or fibrosis from prior attacks of pancreatitis are easily mistaken for metastatic deposits. The base of the transverse mesocolon should be inspected for evidence of foreshortening or inflammatory involvement that may herald a difficult or dangerous dissection in the vicinity of the superior mesenteric vessels, and to confirm the absence of otherwise unsuspected tumor extension. The hepatic flexure of the colon is mobilized by freeing the lateral retroperitoneal attachments using the electrocautery, an extended Kocher maneuver is performed, and the lesser sac is then entered by separation or division of the gastrocolic omentum, as described in the previous section. The mass in the head of the gland is palpated and determined to be safely free from the superior mesenteric vein (SMV) at the inferior border of the neck of the pancreas by preliminary dissection of the plane anterior to the SMV posterior to the neck of the pancreas. Attention is then turned to the supraduodenal region. A cholecystectomy is performed, and the portal dissection is initiated by isolating the common bile duct (CBD) at the level of the cystic duct stump. The bile duct is carefully freed from the anterolateral surface of the portal vein and secured temporarily with a vessel loop. The common hepatic artery is usually found anteromedially to the portal vein, and it should be carefully isolated with a vessel loop and preserved. The lateral, free edge of the gastrohepatic ligament at the foramen of Winslow should be carefully inspected and palpated for an accessory or replaced right hepatic artery, which, if present, should also be isolated and protected during the subsequent resection. The GDA is isolated at its origin from the common hepatic artery and secured temporarily with a vessel loop. The continued presence of pulsatile flow in the proper hepatic artery after temporary occlusion of the GDA should be assured, both to confirm the vascular anatomy and to ensure that there is no stenosis in the proximal common hepatic artery or celiac trunk due to atherosclerotic plaque. Preliminary dissection of the plane anterior to the portal vein is begun. These measures demonstrate that there is no evidence of unresectable cancer and that the pancreatic head can be removed without concern for undue injury to the blood supply of the small intestine

and liver. At this point, technical resectability of the pancreatic head has been assured (Fig. 71-9). The GDA is divided between clamps and is doubly tied or suture ligated. The common hepatic duct is divided just proximal to the cystic duct entry, and bile flow is controlled with a small bulldog clamp. The right gastric artery is divided between suture ligatures. For a standard pancreaticoduodenectomy, the greater omentum is divided to a point on the greater curvature of the stomach in the vicinity of the junction of the right and left gastroepiploic arteries. The lesser omentum is divided at the level of the incisura of the lesser curvature of the stomach, and the descending branch of the left gastric artery is carefully secured. If a standard pancreaticoduodenectomy is to be peformed, the stomach is then divided with two firings of a linear gastrointestinal stapler. The lesser curve staple line is inverted with silk Lembert sutures. For pyloric-preserving pancreaticoduodenectomy, the duodenum is divided using a stapler approximately 2 cm distal to the pyloric ring. The ligament of Treitz is taken down with electrocautery, being certain to avoid injury to the inferior mesenteric vein. The proximal jejunum is divided approximately 15 cm distal to the ligament of Treitz with a linear gastrointestinal stapler. The distal staple line is oversewn with interrupted Lembert sutures, initially left long to use for traction and positioning of the limb during the reconstruction. The short mesojejunal vessels of the proximal segment are carefully isolated and secured close to the mesenteric border of the jejunum using fine nonabsorbable ligatures, surgical clips, or an electrosurgical vessel-sealing device. This dissection is continued proximally to the duodenojejunal junction, and then the proximal jejunum is advanced into the supracolic compartment by passing it under the superior mesenteric vessels. At this point blunt dissection is used to complete development of a tunnel between the neck of the pancreas and the SMV or portal vein. The superior and inferior pancreatic vascular arcades are then ligated on either side of the planned transection site at the neck of the pancreas using nonabsorbable suture. The neck is then divided with electrocautery. Gentle retraction of the pancreatic head, distracting it from the right lateral wall of the SMV or portal vein, helps to expose small venous tributaries from the uncinate process, which should then be carefully controlled with fine ties or suture ligatures. The first jejunal venous tributary may be quite large and is easily injured during this dissection. The uncinate branches from the superior mesenteric

artery (SMA) are then divided sequentially between clamps with great care to preserve the integrity of the SMA. The specimen is then oriented and submitted for pathological examination.

FIGURE 71-9 Retroperitoneal dissection for pancreaticoduodenectomy. Note the ligated gastroduodenal artery (GDA), portal vein, inferior vena cava (IVC), superior mesenteric artery and vein (SMA, SMV), and the main pancreatic duct at the edge the transected pancreas. (Reproduced with permission from Ahmad SA, Wray C, Rilo HL, et al: Chronic pancreatitis: recent advances and ongoing challenges, Curr Probl Surg 2006 Mar;43(3):127-238.)

The reconstruction begins with the pancreaticojejunostomy (Fig. 71-10). The jejunum is advanced through the transverse mesocolon either to the right or left of the middle colic vessels according to surgeon’s preference. Several techniques of pancreaticojejunostomy have been described. One commonly used approach is a two-layer method that is begun by placing a posterior row of interrupted nonabsorbable sutures between the pancreatic capsule and the seromuscular layer at the antimesenteric aspect of the jejunum. A small enterotomy is then made with bovie cautery across from the site of the main pancreatic duct at the pancreatic neck. An inner layer of four to eight interrupted fine absorbable monofilament sutures is used to secure the pancreatic duct to the intestinal wall at the enterotomy in a duct-to-mucosa

fashion. An anterior row of interrupted nonabsorbable suture is then used to secure the anterior pancreatic capsule to the anterior serosa at the antimesenteric border of the jejunal limb. The duct-to-mucosa anastomosis may also be performed over a 5 Fr pediatric feeding tube, which can then be exteriorized through the jejunal limb using a Witzel-type closure. The choledochojejunostomy is then constructed at a site approximately 15 cm distal to the pancreaticojejunostomy. A small enterotomy is made at the antimesenteric border of the jejunal limb at this location. The choledochojejunostomy is also performed in a duct-to-mucosa fashion, either with a single layer of interrupted absorbable monofilament suture or, if the bile duct is dilated, using absorbable continuous suture. The pancreaticobiliary limb is then secured to the transverse mesocolon using interrupted sutures, and any potential gap through which herniation may occur is closed. The retroperitoneal space at the level of the ligament of Treitz is also closed. Gastric continuity is reestablished by means of an antecolic loop gastrojejunotomy performed at a site sufficiently distal to the transverse mesocolon closure to prevent angulation of the afferent limb. A Hofmeister-type configuration is typically used, wherein the lesser curvature half of the gastric transection line is oversewn and the anastomosis is performed to the greater curvature half. The jejunal limb is oriented with the afferent limb toward the lesser curvature, efferent limb to the greater curvature. A two-layered anastomosis is preferred, with an outer layer of nonabsorbable interrupted seromuscular Lembert sutures and an inner continuous absorbable Connell-style layer. The abdomen is then irrigated with saline or dilute antibiotic solution and the abdominal wall closed. No closed suction peritoneal drains are necessary.

FIGURE 71-10 Pancreaticojejunostomy. At left, a duct-to-mucosa anastomosis is constructed using fine absorbable mattress sutures over a small (5 Fr) pediatric feeding tube. At right, the completed anastomosis, with transanastomotic stent exteriorized through the jejunum and abdominal wall to divert pancreatic secretions. (Reproduced with permission from Ahmad SA, Wray C, Rilo HL, et al: Chronic pancreatitis: recent advances and ongoing challenges, Curr Probl Surg 2006 Mar;43(3):127-238.)

BEGER PROCEDURE—TECHNIQUE Duodenum-preserving pancreatic head resection was first described by Beger in 1972. The operation evolved from the premise that a pancreaticoduodenectomy was unnecessarily radical for benign pathology and that a more limited resection preserving the duodenum would avoid some of the adverse sequelae associated with pancreaticoduodenectomy such as delayed gastric emptying and insulin-dependent diabetes.64 The procedure is performed through a midline laparotomy or bilateral subcostal incision. As at the start of the pancreaticoduodenectomy, the gastrocolic ligament is separated or divided, the transverse mesocolon is mobilized off the head of the pancreas and duodenum, and a wide Kocher maneuver is performed. A cholecystectomy is performed. The GDA is isolated and divided. A tunnel is then created between the pancreatic neck and superior mesenteric vein or portal vein. The pancreatic neck is divided at this location and the pancreatic head manually rotated out of the retroperitoneum so that the cut edge faces up into the midline wound. The cystic duct is cannulated with a Bakes dilator and the CBD manually palpated in the head of the pancreas. Electrocautery is

then used to core out the head of the gland with care taken to leave a rim of pancreas attached to the duodenum and to leave the bile duct intact within that rim (Fig. 71-11). The specimen is submitted to pathology for frozensection examination to confirm the absence of malignancy. Pancreaticoenteric drainage is then reestablished by means of a two-sided Roux-en-Y pancreaticojejunostomy (Fig. 71-12). A Roux limb of jejunum is fashioned and advanced into the supracolic compartment through the transverse mesocolon as described for the lateral pancreaticojejunostomy. A two-layered handsewn duct to mucosa pancreaticojejunostomy is constructed at the neck margin as done for a typical pancreaticoduodenectomy, with the exception that the anastomosis is sited closer to the mesenteric margin of the jejunum. The jejunal limb is then laid such that the antimesenteric border of the limb faces the midline wound. A second long pancreaticojejunostomy is constructed here by opening the border of the jejunal limb contralateral to the first pancreaticojejunostomy at the neck for a distance appropriate to include the entire length of the proximal pancreatic rim. This pancreatic margin is then secured to the long longitudinal enterotomy by means of a single layer of interrupted nonabsorbable suture. Intestinal continuity is then reestablished by means of a jejunojejunostomy performed as described earlier for the lateral pancreaticojejunostomy. The abdomen is irrigated and closed. No closed suction drains are necessary.

FIGURE 71-11 The anatomy following transection of the neck of the pancreas and removal of the head during the Beger procedure.

FIGURE 71-12 Final anatomy of the reconstruction following a Beger procedure.

BEGER PROCEDURE VERSUS PANCREATICODUODENECTOMY—OUTCOMES Beger has recently reviewed his three-decade experience with DPPHR for chronic pancreatitis presenting with an inflammatory mass in the pancreatic head. His perioperative results demonstrate very reasonable rates of morbidity and mortality and an impressive improvement in pancreatic pain. His pancreatic fistula rate is reported as 3.3%, the rate of delayed emptying reported is 1.5%, and perioperative mortality rate is 0.7% in 603 consecutive patients. Late outcomes reported in this series demonstrated 91.3% of patients are free of pain at a median follow-up of 5.7 years.65 There have been three randomized trials that have attempted to compare outcomes from DPPHR to those achieved with pylorus-preserving pancreatoduodenectomy (PPPD). The most widely cited is by Buchler and colleagues and has been

recently represented with long-term results. In this study 40 patients with chronic pancreatitis and a dominant focus in the pancreatic head were randomized to PPPD or DPPHR. The initial paper reported 6-month outcomes. This demonstrated a statistical advantage to DPPHR with regard to pain (75% of patients undergoing DPPHR were pain free at 6 months vs 40% of patients undergoing PPPD) and weight gain (average weight gain for those undergoing DPPHR was 4.1 kg whereas that for those undergoing PPPD was 1.9 kg).66 Length of hospital stay, perioperative morbidity, and perioperative mortality rates were statistically identical. The authors of this study have recently presented their long-term results. At median follow-up of 7 years, the early advantages of the DPPHR were no longer evident with patients in each group having identical health-related quality of life scores, identical pain scores, and identical rates of exocrine and endocrine insufficiency. The other randomized comparison again studied only 40 patients for 12 months. This study demonstrated statistically identical rates of pain relief but a slight statistical advantage in terms of scores seen on a general assessment of health-related quality of life for patients undergoing DPPHR relative to those undergoing PPPD.59 More recently, the group from Freiburg reported shortand long-term results from the third randomized trial comparing DPPHR including both Beger and Frey operations to PPPD. This study randomized 85 patients (43 to PPPD and 42 to DPPHR) and reported follow-up over 5 years. Postoperative quality of life was assessed by the EORTC QLQ-30 instrument. The authors noted a significant saving in operative time for DPPHR versus PPPD (360 minutes vs 435 minutes) but no differences in rates of postoperative morbidity, mortality, or long-term quality of life, pain control, and endocrine or exocrine function.67

FREY PROCEDURE—TECHNIQUE The disadvantage of the DPPHR as described by Beger is that it does not address disease (either diffuse parenchymal fibrosis with side branch disruption or stricturing with upstream dilation of the main pancreatic duct) that may coexist in the pancreatic body and tail. Late failures of the Beger procedure have been attributed to poor drainage of the pancreatic body and tail. In an effort to overcome this, and in large part to avoid the certain exocrine and endocrine insufficiency that comes with the near-total pancreatectomy pioneered by one of his early mentors, Frey and colleagues

developed a procedure that combines a duodenum-preserving pancreatic head resection with a hybrid resection or drainage procedure at the pancreatic body and tail (referred to as a local resection of the pancreatic head with longitudinal pancreaticojejunostomy [LR-LPJ]) (Fig. 71-13). In this procedure, no tunnel is created behind the pancreatic neck. Instead, the entire length of the pancreas is exposed anteriorly. The GDA is ligated. The gallbladder is removed. The cystic duct is cannulated using a Bakes dilator and the bile duct is identified in its course through the head of the pancreas by palpating the dilator. The pancreatic head is then excavated down to the level of the portal vein, with care taken to leave a rim of tissue surrounding the bile duct at the duodenal margin. From this cavity an extensive longitudinal unroofing of the pancreatic duct through the body and tail is made using electrocautery. If the duct is not dilated in the tail, then the body and tail may simply be excavated as done at the pancreatic head (Fig. 71-14). Pancreaticoenteric drainage is then accomplished by means of a lateral pancreaticojejunostomy covering the entire excavation cavity, typically constructed using a Roux-en-Y jejunal limb sewn to the pancreatic capsule in one or two layers.

FIGURE 71-13 Cross-sectional drawing of the pancreas following coring of the pancreatic head during a Frey procedure.

FIGURE 71-14 Pancreaticojejunostomy (Frey procedure).

FREY PROCEDURE VERSUS BEGER PROCEDURE— OUTCOMES In various reports including small randomized trials, the results of LR-LPJ appear similar to those reported for the Beger DPPHR, with postoperative mortality less than 1% and morbidity reported as 19% to 32%.61,68 Excellent pain relief is obtained in about 75% of patients and the change in postoperative pain scores and rates of postoperative exocrine and endocrine insufficiency are identical over follow-up as long as 9 years. A small prospective randomized trial compared LR-LPJ to PPPD with an average length of follow-up of 2 years. None of the published evaluations of pancreatic surgery for pancreatitis grade perioperative morbidity, and it is difficult to truly gauge the relatively complicated profiles for the various proceures available to manage chronic pancreatitis; howevever, the hybrid procedures generally seem to be less morbid than panreaticoduodenecotmy. In the small prospective trial comparing Frey to PPPD, postoperative morbidity was significantly higher in the PPPD group compared to LR-LPJ (30% vs 17%). Although there was similar improvement in pain symptoms, the LR-LPJ group demonstrated a statistically better overall quality of life as measured by a general assessment of health-related quality of life.69 Longterm results of the study were published in 2008 with a median follow-up of 7 years. At that length of follow-up, there were no statistical differences with regard to the improvement in pain, health-related quality of life, or the incidence of exocrine or endocrine insufficiency.70 More recently the group has presented 15-year outcomes for 32 patients undergoing PD and 32 patients undergoing Frey procedure. At this time point, pain control was comparable between the cohorts but the group of patients managed with the Frey procedure demonstrated statistically better quality of life scores as measured by the EORTC QLQ C30 instrument. Patients undergoing Frey procedure demonstrated scores of 100 in physical status and working ability domains, whereas those undergoing PPPD demonstrated scores of 60 in the physical status domain and 50 in working ability domain.71

BERNE PROCEDURE—TECHNIQUE AND OUTCOMES

There has been one further modification of the Beger DPPHR made in recent years. The Berne procedure adopts the technical safety advantage of the Frey LR-LPJ that comes by avoiding transaction of the neck of the pancreas off the portal vein. In this modification, as in the Beger DPPHR, no lateral pancreaticojejunostomy is performed. The anterior surface of the mass in the head is palpated and then cored out by electrocautery. A Roux limb is then sewn to the residual pancreatic rim at this location. One randomized trial comparing the Berne modification to the standard Beger DPPHR showed rough equivalence of outcomes with these procedures.60 One more recent publication has reported the results of retrospective evaluation of 160 patients managed by the Berne procedure with mean follow-up of 5.3 years (range 0.5 to 10 years). This represents one of the largest series reported on surgical management of chronic pancreatitis. The results demonstrate preserved endocrine function relative to preoperative functional tests, and significant and durable improvement in the amount of pain experienced and in quality of life relative to preoperative scores using the EORTC QLQ C30 instrument.72

Small Duct Disease or Diffuse Sclerosis In many instances, as the disease progresses there will be no dominant focus of ductal obstruction and no dominant mass. Instead, the morphology of the disease is characterized by diffuse calcification and/or diffuse fibrosis with atrophy of the pancreatic parenchyma. In these cases the pancreatic remnant may be quite small and will have a uniform firm consistency. Patients with this morphology of disease present a particular challenge, as there is no discrete target for either endoscopic or surgical intervention. Those manifesting intractable pain syndromes have had, until very recently, few and imperfect options for surgical management. These have included total or near-total pancreatectomy procedures that have traditionally been avoided due to the significant morbidity associated with profound postoperative exocrine and endocrine insufficiency. Autologous islet transplantation may mitigate the diabetic consequences of total pancreatectomy. The first human autologous islet transplant was performed at the University of Minnesota in 1977. Since that time, several hundred procedures have been reported from Minnesota, Miami, Cincinnati, Leicester, and other emerging centers.73 Taken together, the results from

these institutions suggest that in highly selected patients, complete pain relief (without the use of narcotics) and insulin independence can be achieved but that there is a significant rate of recidivism of pain after 1 year of follow-up. Although reports of assessment of quality of life after total pancreatectomy with autologous islet transplantation suggest that the procedure compares favorably to either total pancreatectomy without islet transplantation or to continue nonoperative management of pain, compelling evidence comparing this approach to alternative therapies in appropriately matched controls is lacking. Total pancreatectomy with autologous islet transplantation is costly and requires a high degree of technical expertise that is difficult to replicate. The indications for islet autotransplantation remain controversial and the overall safety and efficacy of the procedure have not been fully validated outside a handful of centers. Questions regarding the long-term viability of the islets and adverse impact on the surrounding liver parenchyma have been raised. Pathologic analysis of liver tissue that has been explanted following islet transplant has demonstrated that the transplanted islets typically migrate across the liver sinusoids and reside in the liver parenchyma. It has also been noted that the transplanted islets exhibit some degree of peri-islet fibrosis in the liver. There have been no reports of chronic hepatic fibrosis or cirrhosis in patients receiving autologous islets, but the concern exists. Complete longterm insulin independence is achieved only in a relatively small minority of patients after islet autotransplantation and that pain is persistent or recurrent in about half of patients even after total pancreatectomy.74 Currently, the strongest arguments in favor of total pancreatectomy and islet autotransplantation can perhaps be made in the setting of a limited subset of patients with hereditary pancreatitis, who otherwise carry a significant longterm risk of developing pancreatic cancer. When a more traditional surgical operation (resection or drainage) is also possible in this setting, decisionmaking must be highly individualized (Fig. 71-15).

FIGURE 71-15 Hereditary chronic pancreatitis associated with PRSS1 gene mutation. A single calcification is evident in the pancreatic head, and the main pancreatic duct shows diffuse dilation. Lateral pancreaticoduodenectomy is an appropriate surgical option; total pancreatectomy with islet autotransplantation to eliminate cancer risk associated with hereditary pancreatitis is controversial.

TOTAL PANCREATECTOMY WITH AUTOLOGUS ISLET TRANSPLANTATION—TECHNIQUE (TPAIT) Total pancreatectomy is performed as either an en bloc resection of the pancreatic head, body, and tail or, more commonly, in a staged fashion with a left pancreatectomy followed by a head resection (pancreaticoduodenectomy) allowing initial islet processing on the body and tail specimen. The isolation process relies on enzymatic and mechanical mechanisms to dissociate the islets from surrounding acinar tissue and fibrosis. Depending on the proximity of the islet isolation facilities and the efficiency of the process,

infusion of the islet preparation into the portal circulation may be performed during the same anesthetic or postoperatively (usually the same day) under radiological guidance.75 Briefly, the resected pancreas is cooled to 4°C in an organ-preserving solution (eg, University of Wisconsin Solution). The pancreas is then transected at the neck of the gland and the pancreatic duct cannulated. The ductal system is then perfused with a cold solution of the purified digestive enzyme collagenase. The gland is sectioned and then physically shaken in a small digestion chamber at 37°C. The digestion of the gland is monitored continuously by means of a microscopic examination of samples of the digestate taken throughout the process. The digestion is continued until the acinar tissue is separated from the islets but stopped before the islets begin to fragment. The islets are then partially purified from the acinar debris by gradient density centrifugation on a cold dextrose gradient. The islets are washed and resuspended in an albumin-rich transplant medium or cultured. The islets are transplanted by direct injection into portal circulation, with access to the portal circulation being achieved under ultrasound-guided percutaneous placement of a transhepatic portovenous catheter in interventional radiology or by direct operative cannulation of the portal vein.

AUTOLOGUS ISLET TRANSPLANTATION—OUTCOMES Several recent publications have demonstrated the efficacy of autoglogous islet transplantation in both adult and pediatric populations. In general, shortand long-term outcomes in selected populations of adults have been favorable. One recent publication from the University of Cincinnati reported outcomes from 166 patients undergoing TPAIT and having 5 years of followup. At the 5-year mark, 74% of patients were narcotic-independent. All patients demonstrated stable glycemic control and 27% demonstrated long term insulin idependence.76,77 These results are consistent with previous publications on long-term results from TPAIT from the University of Minnesota.78 Such successes of TPAIT in adult populations have been encouraging, and prompted groups doing the procedure to apply the technology to adolescents with severe early manifestation of hereditary froms of chronic pancreatitis. In general, TPAIT in these young people has been reported to be safe, with morbidity profiles and functional results similar to those found in adult populations undergoing TPAIT in the same centers.79,80

The technology has also been effectively employed as salvage therapy for patients with symptoms refractory to more well-established resection and drainage procedures. The group from Cincinnati has recently presented a series of 64 patients undergoing completion total pancreatecotmy with islet auto transplantation (CPIAT) following an initial operative intervention (either pancreaticoduodenectomy, Frey, Puestow, or Berne procedure). Follow-up was only short-term, but islet yields were reasonable given the fact that there had been a prior partial pancreatectomy in most cases. Nearly half (44%) of patients achieved narcotic independence. Twenty percent of patients achieved insulin independence, and quality of life as assessed by the SF-36 metric was improved in all domains.81

CONCLUSIONS Chronic pancreatitis is a relapsing inflammatory process that results in a variable degree of parenchymal destruction and fibrotic change in the pancreas, with consequent clinical manifestations typically including characteristic abdominal pain, and exocrine and endocrine insufficiency. A single unifying model for the pathogenesis of chronic pancreatitis remains elusive, although recent basic and clinical research has identified a number of gene mutations, immunologic conditions, environmental toxins, and anatomic anomalies that alone and together confer risk of developing chronic pancreatitis. The morphology of pathological change seen in the gland at the time that patients present for treatment varies significantly from one patient to the next. A myriad of endointerventional and surgical procedures have been developed over time and are now applied in the treatment of the disease. Both the endoscopic and surgical procedures used are technically demanding and carry substantial risk of morbidity. While there is substantial retrospective case-series evidence demonstrating the utility of these approaches in well-selected patients, high-level evidence comparing the efficacy of the interventions in large series is lacking. For all of these reasons, chronic pancreatitis is often best managed in experienced centers in which multidisciplinary teams collaborate to individualize treatment in the context of established local expertise with various medical, endoscopic, and surgical therapies.

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CYSTIC NEOPLASMS OF THE PANCREAS Michael J. Pucci • Charles J. Yeo

INTRODUCTION The collective phrase “cystic lesions of the pancreas,” typically described on cross-sectional imaging of the abdomen, refers to any cystic neoplasms of the pancreas and/or other cystic lesions, many of which cause “cyst-like” dilatations of the main or side branch pancreatic ducts. Specifically, the descriptor “cystic neoplasms of the pancreas” encompasses a wide variety of pathologic entities of the pancreas with variable malignant potential. The incidence of these cystic neoplasms seems to increase with age, with one autopsy study demonstrating that up to a quarter of elderly individuals harbor cystic lesions of the pancreas at their demise.1 As the use of abdominal computed tomography (CT) and magnetic resonance imaging (MRI) is increasing, cystic lesions of the pancreas are being defined more frequently, with the majority asymptomatic at discovery.2,3 Laffan and colleagues in 2008 estimated the incidence of asymptomatic discovered cysts on abdominal imaging for unrelated diagnoses at 2.6%.4 Some of these lesions will be malignant or have malignant potential at diagnosis, while others are clearly

benign and may not warrant further surveillance. Resection of benign cystic pancreas lesions or those containing only high-grade dysplasia (premalignant) leads to nearly universal survival, while surgery for invasive carcinoma associated with cystic neoplasms generally has a more favorable prognosis than the results for resection of typical pancreatic ductal adenocarcinoma.5-7 Thus, careful consideration must be given to the diagnosis and prognostic implications of these lesions. As more becomes known about these neoplasms, the treatment and observation algorithm will continue to evolve to minimize unnecessary interventions, while maximizing the impact of surgical treatment. An ideal diagnostic approach would allow for the resection of only those lesions with concurrent or near-future risk of malignancy, while excluding from surgery those individuals with either nonenlarging benign lesions or a prohibitive operative risk, thus minimizing the potential occurrence of mortality and morbidity associated with the surgical treatment of these cystic lesions. Recent advancements in imaging by CT, MRI, and endoscopic ultrasonography (EUS), linked with refinements in the pathological, molecular, and genetic understanding of cystic neoplasms of the pancreas, have furthered this effort. History and clinical criteria, such as age, gender, presence of symptoms, location of the neoplasm within the pancreas, as well as morphology by cross-sectional imaging and cyst fluid analysis by EUS with fine-needle aspiration (EUS-FNA), all may play a role in the diagnosis of pancreatic cystic neoplasms and assessment of the need for resection. While the phrase “cystic neoplasm of the pancreas” encompasses a large variety of pathologic entities, this review will focus on the most commonly encountered that may require surgical intervention. The most common non-neoplastic cysts of pancreas are typically considered to be pancreatic pseudocysts (or early post-pancreatitis acute fluid collections). Their diagnosis is aided (and typically confirmed) by a history of acute or chronic pancreatitis.8 Congenital cysts are rare and include those associated with genetic diseases such as autosomal dominant polycystic disease,9 cystic fibrosis,10 and von Hippel−Lindau (VHL) disease.11,12 Lymphoepithelial cysts are rare benign lesions of the pancreas lined with squamous epithelium.13 Peripancreatic cystic lesions (such as esophageal or intestinal duplication cysts) may be mistaken for true pancreatic cystic lesions and need to be within the differential diagnosis in select situations.14 Finally,

solid pseudopapillary neoplasms (which may have cystic components) are rare lesions occurring predominantly in young women, for which resection of the primary tumor results in an excellent opportunity for cure. Three lesions make up approximately 90% of the cystic neoplasms seen in the pancreas: serous cystic neoplasms (SCNs), mucinous cystic neoplasms (MCNs), and intraductal papillary mucinous neoplasms (IPMNs). Overall, these three common pancreatic cystic neoplasms can be classified as either “mucinous” or “non-mucinous,” a distinction that has important clinical significance. SCNs (nonmucinous lesions) rarely demonstrate a progression to malignancy. Unequivocal proof of a SCN may permit nonoperative management of these lesions, provided symptoms do not mandate resection. Although the majority of non−mucin-producing lesions are benign in nature, cystic “degeneration” of other pancreatic tumors (ie, endocrine, solid pseudopapillary, or ductal adenocarcinoma) does occur and must be considered in the workup, as these may necessitate surgical resection. Mucinproducing lesions of the pancreas can be segregated into two types, which may differ significantly in natural history. Restriction of the definition of MCNs to include only those lesions with subendothelial ovarian-type stroma has permitted an improved distinction between MCNs and IPMNs.15 Consensus guidelines developed (and recently revised) by the International Association of Pancreatology16,17 (“Sendai” and “Fukuoka” guidelines) may assist in the management of cystic neoplasms of the pancreas. The premalignant nature of MCNs (and most IPMNs) prompts resection in patients who are acceptable operative risks, while observation of some branch duct IPMNs may be tenable, with an eventual risk of malignancy less than the operative mortality of pancreatic resection.18

PATHOLOGICAL CLASSIFICATION The accurate pathological description of pancreatic cystic neoplasms has evolved significantly in the past several decades, influenced largely by an improved understanding of the malignant potential of MCNs in comparison to the largely benign nature of SCNs, and the emergence of an understanding of the pathogenesis and behavior of IPMNs. Current classification of these tumors follows the World Health Organization (WHO) International Classification of Tumors as published in 2010 (Table 72-1).15,19 While the

diagnostic criteria and organizational schema for these tumors are likely to be adapted further in future editions, the current classification system provides a means to stratify these tumors in terms of prognosis and management. In this review, particular attention will be paid to the three most common lesions: SCNs, MCNs, and IPMNs (Table 72-2). Although this chapter is organized by pathologic diagnosis, the actual workup and treatment of these cystic lesions of the pancreas may have significant overlap, as at times the diagnosis may be challenging to delineate until definitive surgical resection. TABLE 72-1: WORLD HEALTH ORGANIZATION INTERNATIONAL CLASSIFICATION OF TUMORS, 2010—CYSTIC NEOPLASMS OF THE PANCREAS

TABLE 72-2: COMMON CYSTIC NEOPLASMS OF THE PANCREAS

SEROUS CYSTIC NEOPLASMS SCNs, previously referred to either as serous cystadenomas, glycogen-rich adenomas, or microcystic adenomas, are almost always benign. Careful delineation of the radiological and clinical features that distinguish these lesions may support and facilitate nonoperative management of these lesions when appropriate (Table 72-2).

Pathological Features The majority of SCNs are polycystic or so-called “microcystic adenomas,” typically characterized by a well-circumscribed, soft mass which includes numerous small cysts filled with clear serous fluid arranged in a characteristic honeycomb-like pattern. Larger cysts may line the periphery of the lesion. The multiple small cystic loculations are well defined and are often accompanied by a central stellate scar with or without calcifications. These

features may be highly suggestive of an SCN when seen on CT or MRI (Figs 72-1 and 72-2). A small number of SCNs (≤10%) are oligocystic adenomas and present with one or more dominant cysts rather than multiple conjoined microcysts. Rarely, a single dominant cystic lesion may be identified. These unusual SCNs may be more difficult to distinguish radiographically from MCNs, IPMNs, pseudocysts, and other cystic lesions.

FIGURE 72-1 This CT image depicts a cystic neoplasm in the head and neck of the pancreas (small arrow) detected incidentally in a 75-year-old man undergoing evaluation for nephrolithiasis. The patient underwent a pyloruspreserving pancreaticoduodenectomy without complications. Final pathology revealed a 6-cm serous cystic neoplasm without evidence of malignancy.

FIGURE 72-2 A. Abdominal CT (axial image) of a 61-year-old woman who presented with pruritus and jaundice and was found to have a large cystic lesion in the head of the pancreas (arrow). B. On coronal CT image, this polycystic mass with central calcifications (arrow) abuts the proximal superior mesenteric vein (SM) and portal vein (PV), and was resected via a pylorus-preserving pancreaticoduodenectomy for complete resection. Final pathology revealed a benign serous cystic neoplasm. Beyond these gross distinctions, both microcystic and oligocystic adenomas are composed of a single layer of simple cuboidal epithelium with rounded nuclei and clear cytoplasm which is glycogen rich and stains periodic acid-Schiff-positive (Fig. 72-3). The cystic fluid is serous (clear) and typically has no mucin content, with a low carcinoembryonic antigen (CEA) level (< 5 ng/mL), factors that may provide diagnostic information upon cyst aspiration. Cytology diagnostic for SCN is present in less than 50% of cases; however, when positive the sensitivity is high.

FIGURE 72-3 Photomicrograph of a typical SCN of the pancreas. Characteristic features include the single layer of cuboidal epithelial cells lining the microcysts within the lesion, uniform round nuclear architecture,

and clear cytoplasm. The cyst cavities contain serous fluid and little cellular debris. The malignant potential of SCN is so low that most experienced centers recommend management of these lesions as benign entities. Certainly the argument can be made that a clearly documented classic-appearing SCN need not be resected unless symptomatic or enlarging. The incidence of serous cystadenocarcinoma is extremely low, and although the WHO has given serous cystadenocarcinoma a distinct definition, data on this extremely rare lesion are scarce. The WHO requires evidence of distant metastasis to verify the diagnosis. To date, there have been 42 cases of “invasive” or metastatic serous cystic neoplasms reported in the literature, with Reid et al. recently performing a critical analysis of these cases, finding that most would no longer be considered as serous “cystadenocarcinoma” based on the WHO 2010 classification.20 Khashab and colleagues reviewed the Johns Hopkins Hospital experience with 257 resected serous cystic neoplasms. Of these 257 cases, fourteen patients had “aggressive” tumors (defined as local extension or invasion), with two of these cases having liver metastases (considered malignant).21 The authors found that tumor size and location in the head of the pancreas are independent risk factors for aggressive behavior. Evidence of distant metastatic disease is considered necessary to confirm the rare diagnosis of serous cystadenocarcinoma according to the WHO, as both the primary and extrapancreatic disease may appear histologically indistinguishable from benign SCN.22,23 Importantly, vascular and perineural invasion, or local invasion of the stomach and duodenum, are not sufficient criteria for the diagnosis of malignancy of SCN.24,25 Hence, true histologic malignancy in the setting of serous cystic neoplasms is exceedingly rare.20

Clinical Presentation SCNs occur predominately in women in the sixth decade of life, while men tend to present at a later age. Bassi and colleagues described 100 patients with SCN, 87 of whom were female, with a mean age at presentation of 52 years.26 The average age of the 13 male patients was 54 years. In another study from the Massachusetts General Hospital, 75% patients were women, and the female patients were significantly younger at presentation than were

the men (60 vs 67 years, p = .018).27 In the recent review of 257 cases from the Johns Hopkins Hospital, 179 patients were female, with a mean age of 61 years.21 The majority of patients with SCN are asymptomatic. When symptoms exist, abdominal pain is the most common presenting symptom,24,26,27 weight loss is seen in 14 to 22% of patients,24,26 and fewer patients (10%)26 present with a mass or fullness. Symptoms typically associated with invasive disease, such as jaundice (6%) or pancreatitis, are uncommon (Fig. 72-2).24 Nausea and vomiting related to compression of the upper gastrointestinal tract may occur in 7% to 10% of patients.26 Traditionally, SCNs have been described as having a predilection for the pancreatic body and tail, although Le Borgne and coworkers described a relatively even distribution throughout the gland in 170 lesions (38% head, 41% body, 20% tail).28 Khashab et al. reported 39% of SCN in the pancreatic head, 21% in the body, 31% in the tail, and 9% were considered “extensive.”21 Large SCNs located in the head are surprisingly unlikely to cause biliary or duodenal obstruction, reflecting their slow pattern of growth, soft texture, and lack of invasive behavior. Rarely, extremely large tumors have been seen in elderly patients, with considerable symptoms of abdominal fullness and occasionally gastroduodenal obstruction or jaundice. One clinical condition that has been clearly associated with SCNs of the pancreas is the VHL syndrome. Simple pancreatic cysts or SCNs occur in 17% to 56% of patients with this heritable multisystem neoplastic syndrome.29 The VHL tumor suppressor gene is located on chromosome 3p25. Vortmeyer et al. demonstrated deletion of 3p25 in 7 of 10 sporadic SCN cases studied, suggesting a role for the VHL gene in SCN tumorigenesis, even in the absence of the VHL syndrome.30 A recent review of 23 patients with VHL syndrome operated on for nonfunctioning pancreatic neuroendocrine tumors described that 13 (57%) of those patients had associated SCNs of the pancreas.31

Diagnosis SCNs often have a characteristic imaging phenotype (see Figs 72-1 and 722). Most are well-demarcated solitary multicystic masses composed of innumerable small cysts. Up to one-third have a central, calcified starburst

scar.28,32 SCNs may also present as oligocystic or unilocular cystic lesions, making differentiation from other cystic lesions of the pancreas difficult. Lee and colleagues reported on the preoperative diagnostic accuracy of CT in pathologically confirmed SCN.33 Radiological features led to a correct diagnosis in only 36% of unilocular SCNs, while honeycombed microcystic and multilocular macrocystic SCNs were appropriately defined in 81% and 88%, respectively (p = .005). Overall in their series, CT diagnosis was accurate in 71% of SCNs. In 164 patients with surgically verified pancreatic cystic lesions, 28 of whom had a SCN, Shah et al. suggested that the CT features predictive of the diagnosis of SCN are microcystic appearance (22/28, 78%), surface lobulations (25/28, 89%), and central scar (9/28, 32%).34 Stepwise logistic regression analysis showed that only a microcystic appearance was predictive for the CT diagnosis of SCN (p = .0001). MRI correctly predicted the pathological diagnosis of SCN with greater frequency than did CT in the study by Bassi and coworkers.26 CT allowed for the correct diagnosis in 54%, incorrect diagnosis in 34%, and was nondiagnostic in 12% of SCNs. The results with MRI were 74%, 26%, and 0%, respectively. A recent study by Chu and colleagues using pancreas protocol CT imaging in resected SCNs revealed that only 20% of cases had the “classic appearance” of multilocular masses with central stellate scars and calcifications. CT attenuation was helpful in distinguishing SCNs from MCNs, IPMNs, pseudocysts, and insulinomas, but not pancreatic ductal adenocarcinoma. The presence of external lobulations and the absence of “aggressive” features (such as pancreatic duct dilation, vascular invasion, lymphadenopathy, and liver metastasis) were helpful in distinguishing between SCN and classic pancreatic ductal adenocarcinoma.35 The limitations of the radiological diagnosis of SCN may call for additional analysis, which is frequently sought by EUS-FNA with cyst fluid cytology and biochemical analysis. The risk of complications with EUS-FNA is relatively low.36-38 Cyst fluid aspirates from SCN are frequently sparsely cellular and may be contaminated with columnar enterocytes and mucin from the scope and needle traversing the gastric or intestinal mucosa, potentially clouding the diagnostic accuracy of cytology. Cytology alone was found to be diagnostic of SCN in only 7 of 21 cases studied by Huang and others from MD Anderson Cancer Center.39,40 Detection of intracytoplasmic glycogen was noted to enhance the diagnostic confidence for the diagnosis of SCN.

Cyst fluid analysis is an additional adjunct (beyond cytology) to improve the diagnostic accuracy of EUS-FNA. Fluid from within an SCN is typically low in viscosity and amylase due to a consistent lack of connection to the pancreatic ductal system.41 CEA levels less than 5 ng/mL have a sensitivity of 54% to 100%, and specificity of 77% to 86% in the differentiation of SCN from other pancreatic cystic lesions.42,43 The finding of a cyst fluid carbohydrate antigen (CA) 19-9 level less than 37 U/L and a CEA less than 5 ng/mL virtually excludes an MCN or IPMN. Allen et al. reported on the analysis of cyst fluid using a biomarker panel developed for pancreatic cancer.43 Assessment of protein expression within the cyst fluid led to an error rate in classification of lesions of 27% when all three types of cystic neoplasms were evaluated (SCN, MCN, and IPMN). When limiting the analysis to separating SCN from IPMN, this method had an error rate of only 8%, compared with a 14% error rate with the use of CEA levels alone. The greatest utility of protein expression analysis might be in the differentiation of cystic lesions of the head of the pancreas, as the vast majority of MCNs occur in the body and tail of the pancreas. However, the cost of this method may not be justified by the relatively small improvement in diagnostic accuracy. In addition, Cao and colleagues recently studied a three-marker panel of glycoforms of MUC5AC and endorepellian and showed 89% sensitivity and 100% specificity in distinguishing between mucinous (MCN, IPMN) and nonmucinous (SCN, pseudocysts) cystic neoplasms of the pancreas.44 Recently, Springer and colleagues examined a combination of molecular and clinical markers from a multi-institutional collaboration of resected cystic neoplasms of the pancreas and identified a combination of markers that approach 100% sensitivity and 98% specificity in diagnosing SCNs. The combination of the clinical characteristics of patients >25 years of age without abdominal pain or evidence of communication of the cyst with the pancreatic ductal system and the molecular presence of a VHL mutation and/or loss of heterozygosity of chromosome 3, as well as the absence of KRAS, GNAS, and RNF43 mutations, allowed for excellent diagnostic power.45

Treatment Observation of patients with SCN may be appropriate in asymptomatic

patients. When a secure diagnosis of SCN is made, modern series demonstrate that a growing number of SCNs are being kept under surveillance by serial imaging (Table 72-2). Typically a pathological diagnosis is not required when classic imaging characteristics are observed. Bassi and colleagues followed 32 patients with the diagnosis of SCN for a median time of 69 months, without any observed development of malignancy or significant increase in diameter of the lesion.26 Rapid rate of growth of a lesion may heighten suspicion for the development of malignancy or increase the likelihood of developing symptoms. In a report from the Massachusetts General Hospital, Tseng and coworkers found a more rapid rate of growth in SCNs greater than or equal to 4 cm in size at presentation, compared with smaller tumors (1.98 cm/yr vs 0.12 cm/yr, p = .0002).27 Tumors less than 4 cm were less likely to be symptomatic than were those greater than or equal to 4 cm (22 vs 72%, p < .001). Resection was thus suggested by these authors, even for asymptomatic SCNs that were greater than or equal to 4 cm. A recent multinational review of over 2600 SCNs revealed that the average tumor size of patients who underwent surgical resection was 40 mm, with the most common indication being an “unclear diagnosis.” Only three serous cystadenocarcinomas were encountered in this entire cohort.46 When the diagnosis of SCN is uncertain, pancreatic resection is most often performed according to oncological principles, as if the lesion was malignant or had malignant potential (Fig. 72-2). Standard procedures include distal pancreatectomy for lesions of the body or tail, or pancreaticoduodenectomy for right-sided lesions. This practice avoids performance of an inadequate cancer operation in cases in which a malignancy is found on final pathological analysis. However, if the diagnosis of SCN is confirmed preoperatively, a less radical approach may be considered. Enucleation of SCNs has been shown to be technically feasible, although it can be challenging and is associated with a significant risk of pancreatic fistula.47-49 A central pancreatectomy, with remnant pancreatic reconstruction being performed via pancreaticogastrostomy or Roux-en-Y pancreaticojejunostomy (PJ), may be considered in select patients with lesions of the pancreatic neck.50 Distal pancreatectomy with splenic preservation may also be considered, particularly for small lesions in the tail, where the splenic hilum is more easily dissected. Lesions in the head of the pancreas that are not amenable to enucleation are best treated with pylorus-preserving pancreaticoduodenectomy. Many patients undergoing

pancreaticoduodenectomy will have an otherwise normal pancreas, hence meticulous attention must be paid to the technique of PJ, since such patients have a significantly higher risk for developing a pancreatic fistula related to a failure of healing at the PJ. There has been some enthusiasm for duodenumpreserving pancreatic head resection as well, although this procedure has not had widespread application.51 The use of minimally invasive techniques is encouraged in institutions with experience and training in these complex procedures. Patients with pathologically proven, completely resected SCNs do not require serial imaging in follow-up. Recommendations for appropriate monitoring of unresected SCNs vary, but serial imaging with either CT or MRI every 6 months for 2 years and then annually or every other year thereafter seems reasonable.52

MUCINOUS CYSTIC NEOPLASMS Progress in the diagnosis and management of pancreatic cystic neoplasms has been aided in large part by the recognition of distinct pathological features that distinguish MCNs from other cystic lesions.53,54 The distinction between MCN and SCN is critical, as the premalignant and malignant behavior of MCNs stand in stark contrast to the nearly universally benign nature of SCNs. Many of the same diagnostic challenges that exist for SCNs are true for MCNs, but the management decisions may be quite different, due to the differing clinical phenotype of these lesions. While the true prevalence of MCNs is difficult to identify, more recent series suggest that approximately 15% to 30% of cystic neoplasms of the pancreas are MCNs.2,52,55,56 However, our experience at the Thomas Jefferson University Hospital reflects a lower percentage. Clinical series published prior to the establishment of the diagnostic criteria for IPMN in 1996 likely overestimated the relative prevalence of MCNs in comparison to other cystic lesions, since they included what are now categorized as IPMNs as various “mucinous tumors.”

Pathological Features MCNs (Table 72-2) are typically spherical, thick-walled, septated or unilocular cysts with a tall columnar mucin-producing epithelium

accompanied by a subendothelial ovarian-type stroma that appears as a dense layer of spindle cells with sparse cytoplasm and uniform, elongated nuclei (Fig. 72-4). This stroma regularly expresses progesterone receptors, and less frequently estrogen receptors, and over 60% of these stroma stain for human chorionic gonadotropin.57 Both the WHO and the Armed Forces Institute of Pathology (AFIP) have defined the presence of this ovarian-like stroma as a requirement for the diagnosis of an MCN.4,53,54 The original and updated International Consensus Guidelines (“Sendai” and “Fukuoka”) for the management IPMN and MCN have also required the presence of ovariantype stroma as a necessary criterion for the diagnosis of MCN, so as to prevent the misclassification of IPMN as MCN.16,17 In addition, MCNs typically do not communicate with the pancreatic ductal system, and this serves as another distinction between IPMNs.58 Given the similarity of the histology and immunohistochemistry between MCNs and ovarian mucinous cystadenomas, MCNs have been postulated to arise from ovarian rests (or ovarian-like stem cells) within the pancreas.59

FIGURE 72-4 MCNs of the pancreas are distinguished by a uniform columnar epithelium (top) associated with a dense underlying ovarian-like stroma (bottom). MCNs exhibit characteristics of an adenoma-carcinoma sequence.

Dependent on the degree of atypia, they are classified as mucinous cystadenomas, mucinous cystic tumors (borderline lesions), in situ lesions (high-grade dysplasia), or invasive cystadenocarcinomas (mucinous cystadenocarcinomas). Atypical changes within the lining epithelium may be patchy and sparse, with abrupt transitions to normal mucosa. Classification of MCN should be based upon the highest degree of atypia present, and the entire lesion should be examined pathologically.60,61 Invasive carcinomas arising within MCNs are usually tubular or ductal type, although some may be undifferentiated carcinoma with osteoclast-like giant cells,62 adenosquamous carcinoma,63 choriocarcinoma, or even high-grade sarcomas.64 Colloid carcinomas are extremely rare in MCN, but they occur commonly in IPMN.61 The molecular pathway of the pathogenesis of MCNs is not clearly understood. K-ras and p53 mutations have been implicated, as well as loss of DPC4.65,66 Interestingly, a recent study using a mouse model showed that APC haploinsufficiency coupled with p53 loss resulted in the development of MCN with invasive carcinoma with 100% penetrance.67

Clinical Presentation In light of the mandatory presence of the underlying ovarian-type stroma, not surprisingly MCNs are now diagnosed almost entirely in women.57,59,68-73 This requirement, combined with the usual lack of communication with the pancreatic duct, defines a unique phenotype separate from IPMN. In a combined report from the University of Verona and the Massachusetts General Hospital, Crippa and colleagues reviewed their experience with 163 MCNs that met the WHO criteria for diagnosis.72 Of the 163 patients, 95% (155 patients) were perimenopausal females. Only eight males were identified, and they were significantly older than the female patients (63 vs 44 years, p = .011). The location of MCN within the gland was almost entirely confined to the body and tail of the pancreas (97%), and only five lesions were found in the pancreatic head. In reviewing the literature regarding MCN, these researchers noted the importance of segregating studies according to whether or not the presence of ovarian-type stroma was required for inclusion of pathological specimens within collected reports. Goh et al. reviewed those studies where the presence of ovarian-type stroma was a mandatory criterion for the diagnosis of MCN and found that 99.7% of

the patients were women, the mean age at presentation was 47 (range, 18-95) years, and 95% of MCNs occurred to the left of the pancreatic neck.74 By comparison, when this criterion was previously not a prerequisite to diagnose MCN, patients were older, more often male, and the lesions were located in the head with a frequency exceeding 30%. Abdominal pain or discomfort is the most common presenting symptom, occurring in over 70% of patients.69–71 A history of acute pancreatitis may also be elicited in 9% to 13% of patients, although less commonly than in patients with IPMN.4,69,72 Patients with an MCN with an associated invasive carcinoma present 11 years later than those with noninvasive neoplasms, likely representing the longer time required to progress to overt malignancy within these neoplasms.72

Diagnosis In a female patient with a macrocystic lesion in the body or tail of the pancreas, MCN should be strongly considered. In addition, MCNs have some characteristic features that may be evident during imaging or preoperative evaluation. Classically, MCNs contain large septated cysts with thick irregular walls that may be well visualized on CT, MRI, or ultrasound evaluation. Papillary projections from the epithelium often extend into the cystic cavities and may be visible, particularly on high-quality axial or endoscopic ultrasound imaging. In a minority of cases, the wall of the MCN may contain calcifications, a characteristic associated with a higher likelihood of malignancy.75 MCNs may also present as large unilocular cysts that may appear similar on cross-sectional imaging to long-standing pseudocysts (Fig. 72-5). Two distinguishing characteristics in this scenario that suggest the diagnosis of MCN are the lack of surrounding inflammatory changes beyond the wall of the neoplasm in MCNs and the absence of pancreatitis.8 Demonstration of ductal communication with the cyst by MRI or magnetic resonance cholangiopancreatography (MRCP) may distinguish pseudocysts or IPMNs from MCNs, although MCNs can in rare instances exhibit a connection with the pancreatic duct.74

FIGURE 72-5 Abdominal CT performed on a 69-year-old healthy man who had a palpable abdominal mass detected on routine physical examination. The mass (arrow) was homogeneous in character and was initially presumed to be a pseudocyst. Pylorus-preserving pancreaticoduodenectomy was performed, revealing an 8.5-cm mucinous cystic neoplasm without malignancy. Similar to SCN, determination of a treatment plan for MCN is predicated upon whether or not a given lesion is mucinous. Analysis of cyst fluid aspirated from MCNs typically show elevated levels of CEA and low amylase concentrations (as MCNs do not typically communicate with the pancreatic ductal system). The Cooperative Pancreatic Cyst Study demonstrated that a cyst fluid CEA value greater than 192 ng/mL achieved the greatest efficiency for differentiating mucinous from nonmucinous lesions.32 The accuracy of cyst fluid CEA (88/111, 79%) was greater than the accuracy of EUS morphology or cytology (p < .05). No combination of tests further improved diagnostic accuracy. A cyst fluid CEA level greater than 800 ng/mL has a specificity of 98% for predicting MCN, but a sensitivity of only 48%.76 Khalid and his coinvestigators tested the utility of DNA analysis

of cyst fluid to diagnose mucinous and malignant cysts.77 The presence of a K-ras mutation was highly specific for a mucinous cyst (96%) but had a low sensitivity of only 45%. A considerable selection bias was introduced by the study design, which may have overestimated the ability of DNA analysis to define a mucinous cyst.78 Presence of a K-ras mutation in cyst fluid may provide additional information when CEA levels are not discriminative, particularly in lesions that appear to not have clear imaging patterns that allow separation of SCN versus MCN. A recent multi-institutional review of resected pancreatic cystic neoplasms showed promising results using a combination of a panel of molecular markers known to be implicated in pancreatic cysts and clinical features to predict lesions requiring resection versus observation. In reviewing MCNs, the authors approached 90% sensitivity and 97% specificity with the combination of certain molecular markers (including the absence of CTNNB1I and GNAS mutations, loss of heterozygosity on chromosome 3, and aneuploidy in chromosome 1q and 22q) and the following clinical markers: age 10 mm. In

addition, “worrisome” characteristics (requiring additional workup with EUS) are defined as the following: a cyst ≥3 cm, thickened or enhancing cystic wall, main pancreatic duct size 5 to 9 mm, nonenhancing mural nodule, or abrupt change in caliber of pancreatic duct with distal pancreatic gland atrophy.17 In combination with clinical history, this guideline frames an algorithm for clinicians to stratify patients. The initial Sendai consensus guidelines published in 2006 included a cyst >3 cm in size in the “high-risk” group. This was based on available data at the time that revealed imaging features suggestive of the presence of malignancy, including tumor size (cyst diameter ≥30, 40, or 50 mm), MDIPMN, main duct dilatation greater than or equal to 10 or 15 mm, patulous papilla, mural nodules (≥ 3, 5, or 10 mm in size), presence of biliary ductal dilatation greater than or equal to 15 mm, a solid mass, or occurrence of an area of abnormal attenuation in the surrounding pancreas.107-115 Importantly, Salvia and colleagues, in Verona, Italy, followed 121 patients with multifocal branch duct IPMN (median diameter of the largest lesion being 1.7 cm) over a 40-month observation period.116 All of the 121 patients remained alive, without surgery, and all remained asymptomatic. Thus, there is clearly a role for conservatism in the management of patients with BD-IPMNs and no additional worrisome features. Critical review of these initial Sendai guidelines confirmed the rising practice leading to resection of low-grade BD-IPMNs utilizing the >3 cm size criteria. This ultimately prompted the “revised” Fukuoka consensus guidelines published in 2012 to change the >3 cm size criteria to a “worrisome” feature instead of a “high-risk” feature (See Table 72-3), perhaps favoring a more conservative posture. Recently, Ammori and colleagues reviewed their experience with resected IPMNs, specifically examining cases with either isolated uncinate process ductal dilation or a combination of main pancreatic duct and uncinate process ductal dilation. In 184 cases, 47 patients had dilation of the uncinate process duct and 50 patients had an uncinate process cystic lesion. While uncinate process cystic lesions were not associated with high-grade dysplasia or invasive carcinoma (pathologic IPMN), dilation of the uncinate process duct was associated with pathologic IPMN in 64% of cases. In cases of only uncinate process duct dilation (without associated main pancreatic duct dilation), 65% of patients harbored high-grade dysplasia or invasive carcinoma. This is in stark contrast to the 18% of patients who harbored pathologic IPMN in the setting of only branch-duct dilation (without main

pancreatic or uncinate duct dilation). These data suggest that uncinate process duct dilation may be considered an additional risk factor for pathologic IPMN.117 EUS is an important adjunct in select patients requiring further investigation (worrisome features). Ohno et al. demonstrated that the finding of a papillary mural nodule or a nodule exhibiting an invasive component on EUS was predictive of malignancy with a sensitivity of 60%, specificity of 93%, and an accuracy of 76%.118 EUS-FNA may also be useful in reinforcing a decision not to resect a BD-IPMN if it is otherwise without features predictive of malignancy. Marie and colleagues found that the combination of a CEA level less than 200 ng/mL and a CA 19.9 level greater than 40 U/mL retrieved from the cystic material of an IPMN together had a 96% negative predictive value for the diagnosis of malignancy.119 In addition, endoscopic sampling of cyst fluid is an area of active investigation at many high volume centers. Unfortunately, results have been less than definitive. Cyst fluid CEA and amylase may add important objective data, however, is not universally consistent. Interestingly, cytologic or molecular analysis (such as cyst inflammatory markers) may allow for advancements in diagnosis, and continues to be an area of active investigation.120 The addition of positron emission tomography (PET) with CT (PET/CT) using 18F-fluoro-deoxyglucose has been investigated in an effort to improve identification of IPMN with high-grade dysplasia or invasive carcinoma. Recently, Roch et al. studied the use of PET/CT in combination with the 2012 International Consensus Guidelines and found an increase of the sensitivity and specificity of detecting IPMN with malignancy to 78% and 100%, respectively. In addition, the combination of PET/CT and guideline criteria increased the sensitivity and specificity in detecting IPMN with highgrade dysplasia to 100% and 71%, respectively.121 With the creation of the Sendai and Fukuoka guidelines, as well guidelines from the American Gastroenterological Assoication,16,17,86 debate on the appropriate management of pancreatic cystic neoplasia continues. Fundamental differences in the viewpoint regarding the risks of pancreatic surgery and the risk of progression to malignancy allows for discord between clinicians managing patients affected with pancreatic cysts. In addition, the relatively new nature of this field of study lends for confusing, at times conflicting, and typically low-quality data, making definitive management

guidelines challenging. Thus, clinicians managing these patients must take into account the individual patient situation as well as all available information on the cyst (ie, imaging characteristics, etc), as well as access to high-volume quality pancreatic surgeons.122 Critical appraisal of the updated Fukuoka guidelines both confirms and questions the accuracy of strict adherence in detecting malignant cysts. Kaimakliotis and colleagues compared the original Sendai criteria to the updated Fukuoka guidelines and showed no difference in either guideline in predicting patients with advanced neoplasia; however, two patients considered “low risk” using the Fukuoka guidelines had high-grade dysplasia.123 Recent reviews, including a systemic review of 1382 patients, confirm that some malignant IPMNs would be missed with strict adherence to the Fukuoka guidelines.124,125 These reviews underscore the imprecise nature of the best expert consensus guidelines and the need for patient-specific consideration on a case-by-case basis (with the inclusion of pancreatic surgeons).

Treatment The goals of treatment for IPMN include minimizing the exposure to unnecessary surgical risk while optimizing the removal of all premalignant neoplasia and frank carcinoma. In addition, the natural history of IPMN must be compared to the individual patient’s clinical status and situation. The Japan Pancreas Society performed a multi-institutional, retrospective study of 1379 cases of IPMN drawn from 98 of their member programs in 2004. The clinicopathologic features of benign IPMN (adenoma [low-grade dysplasia] and borderline lesions [moderate dysplasia]; n = 564) were strikingly different when compared with tumors containing frank adenocarcinoma (n = 445).110 Patients with adenocarcinoma were significantly older (67 vs 65 years, p = .0002) and more frequently symptomatic (49 vs 35%, p < .0001), as compared to the noncarcinoma group. Cancer occurred more commonly in either main duct-type or combined-type tumors, as compared to branch ducttype neoplasms (60%, 65%, and 30% respectively, p < .001). The preoperative imaging of patients who were subsequently found to have adenocarcinoma on pathology demonstrated a higher incidence (63% vs 28%) and size of mural nodules (12 vs 5 mm) when compared with those who had benign lesions (both p < .0001). Branch duct-type tumors with

cancer were larger (35 vs 28 mm, p < .0001) than those without cancer. Based on the data generated in the earlier report, the International Association of Pancreatology convened a consensus conference in Sendai, Japan, in 2004. The subsequent guidelines published in 2006 (and then revised in 2012) have become a new benchmark for the management of IPMN (Table 72-3).16,17 The current “Fukuoka” guidelines recommend the resection of all IPMN of a main duct type and mixed variants, those showing main pancreatic duct dilatation greater than or equal to 10 mm, as well as those with the presence of enhancing mural nodules (solid components), or a positive cytology, provided the patients are reasonable candidates for surgery with an acceptable life expectancy. All symptomatic IPMNs (abdominal pain or obstructive jaundice) were deemed to warrant resection. These recommendations were predicated upon the risk of carcinoma in symptomatic or main duct type lesions. Additional “worrisome” stigmata were included in the guidelines, and patients with these stigmata should undergo additional work-up with endoscopic ultrasound evaluation. These stigmata include cyst size greater than 3 cm, prior pancreatitis, thickened or enhancing cyst wall, main pancreatic duct size of 5 to 9 mm, nonenhancing mural nodule, or an abrupt change in the caliber of the main pancreatic duct with distal gland atrophy. And while the original “Sendai” guidelines recommended that BDIPMNs greater than 30 mm in diameter undergo resection, more recent data suggest that this may overtreat many patients with low-grade pathology. This has led to the revision of the guidelines to move BD-IPMN greater than 3 cm to the “worrisome” group requiring further investigation, instead of recommending surgical resection for these cysts without further worrisome features. Data suggest that BD-IPMNs less than 30 mm in diameter, without evidence of mural nodules or main duct dilatation, have low malignant potential and that such patients are candidates for careful observation. At follow-up examinations, appearance of symptoms, cyst enlargement to greater than 30 mm, detection of positive cytology on FNA, development or identification of mural nodules or main pancreatic duct dilatation (≥6 mm) were deemed indications for resection. Since the development and revision of the Sendai guidelines, much of the subsequent literature has sought to examine the accuracy of the recommendations, particularly with regard to the observation of asymptomatic BD-IPMN. Pelaez-Luna and colleagues identified 147 patients with BD-IPMN, of whom 66 underwent resection at diagnosis and 81 were

followed over time (of which 11 were resected during the follow-up period).126 Of the patients undergoing resection who demonstrated Sendai consensus guideline indications for surgical therapy, 9/61 (15%) had carcinoma on pathology, whereas none of the 16 patients without consensus indications for resection had malignancy (p = .1). A single guideline indication for resection taken as an indicator of carcinoma had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 23%, 14%, and 100%, respectively. Several studies have suggested that the development of mural nodules is predictive of the risk of developing malignancy, while a progressive dilatation of duct size remains controversial. Schmidt and colleagues identified 103 patients with BD-IPMN.127 The mean size of the 20 malignant lesions was 2.0 ± 0.1 cm, while the mean size of the nonmalignant neoplasms was 2.2 ± 0.1 cm, suggesting that size alone is an insufficient indicator of malignancy. In multivariate analysis, only the presence of mural nodules and atypical cytopathology were predictive of the presence of carcinoma. Tanno et al. prospectively followed 82 patients with flat lesions within BD-IPMN diagnosed by CT or MR and EUS.128 During a median follow-up of 59 months, 9/82 patients (11%) exhibited progressive dilatation of the cystic lesion. Six elected to continue regular screening, while three underwent resection; the IPMNs resected were staged as IPMN-adenoma in two and IPMN-borderline in one. Four patients (5%) developed mural nodules during a median follow-up of 105 months. All four of these individuals were resected, demonstrating IPMN-adenoma in three and carcinoma in situ in the fourth. Sixty-nine of the 82 patients (84%) showed no changes in their dilated branch duct lesions over a median follow-up of 57 months. A study from Kyushu University in 2009 attempted to determine whether cyst size is predictive of the malignant potential in flat BD-IPMN.129 One hundred seventy patients with BD-IPMNs without mural nodules were retrospectively identified from their previous 10-year experience. Seventythree patients underwent resection of their IPMN: 26 patients had lesions less than 30 mm in size, while 47 patients had neoplasms greater than 30 mm in diameter. Importantly, all of the noninvasive (n = 5) and invasive (n = 1) malignancies were seen in the IPMN of greater than or equal to 30 mm. In a similar report, Salvia and coworkers followed 89 patients with flat BDIPMNs less than or equal to 3.5 cm in size for a median time period of 32

months.130 Five patients (5.6%) exhibited an increase in diameter of the cystic lesion, none of which demonstrated carcinoma in the resection specimen pathologically. Alternatively, a study by Fritz and colleagues identified malignancy (invasive carcinoma or high-grade dysplasia) in 25% of “Sendai Negative” branch-duct IPMNs that were resected at their institution.131 Clearly, longer follow-up and further investigation will be needed to determine whether or not these guidelines accurately predict highrisk or malignant disease in small, flat, asymptomatic BD-IPMNs. As might be anticipated, increasing knowledge and follow-up have raised questions about the universal accuracy of the consensus guidelines. The majority of studies, particularly those following IPMNs conservatively in a prospective fashion, would suggest that the development of invasive carcinoma in flat BD-IPMN less than 30 mm in size is unusual. The occurrence of high-risk stigmata (mural nodules, dilated main duct, or positive cytology) clearly has great predictive value for the ultimate finding of malignancy. EUS appears to be an important adjuvant to fully evaluate IPMN patients for the presence of mural nodules, as well as for aspiration of cytologic specimens. Some authorities insist that any lesion that is to be followed conservatively should be examined by EUS at regular intervals. We have tended to use MRI or MRCP for serial surveillance of small (8 days 4. Output >50 mL/d of amylase-rich fluid after postop day 11 or for >11 days Four final definitions summarizing the current pancreatic fistula concept according to the literature. Reproduced with permission from Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition, Surgery 2005 Jul;138(1):8-13.

In 2005, the ISGPS released a report to categorize pancreatic fistula into three grades: grade A (mild), grade B (moderate), and grade C (severe). This system was modified recently and the details are outline in Table 76-2. TABLE 76-2: GRADES OF PANCREATIC FISTULA FROM ISGPF

Imaging is not required to diagnose pancreatic fistula; however, it may be helpful to assess the size and location of the potential intraabdominal abscess, placement of the surgical drain, and the existence of complications that lead to gastric outlet obstruction from anatomical abnormalities.

TREATMENT The treatment of pancreatic fistula is mostly conservative, and fortunately, most pancreatic fistulae (70%-82%) will resolve within weeks with conservative management. This is true for both pancreaticoduodenectomy and distal pancreatectomy.

With biochemical leak pancreatic fistula, which is the most common form of pancreatic fistula, the patients can still feed orally. Total parenteral nutrition (TPN) or somatostatin analog such as octreotide is not required and this class of fistula rarely delays hospital discharge. In contrast, grade B pancreatic fistula requires significant adjustment from the standard clinical pathway. The patient may require strict NPO and TPN. Octreotide may be indicated if the volume is significant. If the patient has fever or leukocytosis, antibiotics are also needed. Hospital discharged is likely to be delayed as these patients may need interventional drainage of fluid collections or angiographic embolization for hemorrhage, and readmission is more likely to occur. However, the patient can often be discharged home with surgical drain in place and followed up in an outpatient setting. Grade C pancreatic fistula requires major changes of the standard clinical pathway. The patient often requires NPO, TPN, intravenous antibiotics, and somatostatin analog and care in an intensive care unit. CT scan may show peripancreatic fluid collection. Hospital stays are often lengthened. If the patient continues to deteriorate clinically, reoperation may be required to repair or revise the pancreaticoenteric anastomosis. In extreme conditions, completion pancreatectomy may be necessary.

PREVENTION Over the years, there have been many studies on potential methods to prevent pancreatic fistula. Fibrin glue and other hemostatic agents have been tested. One of the early trials by Kram et al. (1991) has shown promising results. In their report, no pancreatic fistula occurred in 15 patients. However, late reports consistently failed to show the advantage of fibrin glue (Lillemoe et al., 2004; Orci et al., 2014). For example, Lillemoe et al. (2004) reported that out of 125 patients, pancreatic fistula occurred in 26% of the fibrin-glue group, compared to 30% of the control group. A variation of this method, by internal occlusion of the pancreaticojejunostomy anastomosis, also failed to find a significant difference in the incidence of pancreatic fistula (Lorenz et al., 1988). A double-blinded randomized clinical trial by Allen et al. (2014) from Memorial Sloan-Kettering Cancer Center has shown promising results with pasireotide for prevention of pancreatic fistula. Pasireotide is another somatostatin analog with higher half-life and better binding capacity than

octreotide. Pasireotide or placebo is administered subcutaneously twice daily for 7 days after pancreatectomy. The authors found significant decrease in pancreatic fistula in the pasireotide group compared to the placebo group (9% vs 21%).

Delayed Gastric Emptying DGE is characterized by oral intolerance, inability to remove the nasogastric tube, and/or the necessity of reinserting the nasogastric tube several days after the operation. It can significantly delay the patient recovery, nutritional improvement, and the initiation of adjuvant therapy. In most reports, the rate of DGE ranges from 19% to 57%. (Martignoni et al., 2000; Miedema et al., 1992; Richter et al., 2003; Wente et al., 2007a; Yamaguchi et al., 1999; Yeo et al., 1997).

ETIOLOGY/RISK FACTORS The mechanism of DGE is largely unknown. It has been postulated that the resection of duodenum can trigger DGE, and this is supported by the fact that there is less DGE with duodenum-preserving pancreatic head resection. In addition, distal pancreatectomy that does not involve duodenal resection rarely causes DGE. Decreased motilin level has also been suggested to trigger DGE, given that the prokinetic drug erythromycin, which is a motilin agonist, can reduce the incidence of DGE. Pylorus-preserving pancreaticoduodenectomy is one of the most common variations of the classic pancreaticoduodenectomy, and some reports have claimed that it is associated with higher incidence of DGE, while others have shown the opposite. The etiology of this may be that pylorus-preserving pancreaticoduodenectomy can cause devascularization or denervation of the pylorus with subsequent pylorospasm.

CLINICAL PRESENTATION DGE is frequently manifested as failure to tolerate PO intake, failure to remove nasogastric tube, or emesis after removal of nasogastric tube.

DIAGNOSIS

There have been many definitions of DGE historically. In order to reconcile the difference, the ISGPS has released a consensus definition of DGE in 2007 and also classified DGE into three grades, as shown in Table 76-3. TABLE 76-3: THE ISGPS DEFINITION OF DELAYED GASTRIC EMPTYING

In contrast to pancreatic fistula, for which imaging is often not required, diagnosis of DGE frequently requires imaging. The most commonly used study is fluoroscopic upper gastrointestinal series. CT scan can also be used to visualize distended stomach and also rule out stenosis in the gastric outlet, which may require reoperation or endoscopic management.

TREATMENT Grade A DGE is not commonly associated with vomiting. Prokinetic medications and TPN may not be required in the first 14 days after the operation. It only causes minor adjustment of the standard clinical pathway, and hospital discharge is often not delayed. In contrast, grade B DGE involves significant adjustment of the standard clinical pathway. The patients often have vomiting if a nasogastric tube is not in place, necessitating replacement of this. TPN and prokinetic medications are frequently required. Hospital discharge is often delayed, as well patient recovery and likely the initiation of adjuvant therapy. Grade C DGE necessitates major changes in clinical management and is often associated with other complications such as pancreatic fistula and intraabdominal abscess, which frequently requires radiological or even operative intervention. Prokinetic medications, nasogastric tube, and TPN are required. Hospital discharge and adjuvant therapy are frequently delayed. Table 76-4 shows parameters of DGE.

TABLE 76-4: PARAMETERS OF DGE

Post-Pancreatectomy Hemorrhage Perhaps the most severe complication of pancreatectomy, PPH only accounts for 1% to 8% of all complications after pancreatectomy. However, PPH results in an 11% to 38% overall mortality rate. In the early era of pancreatectomy, PPH was one of the major causes of postoperative death, partially due to the severity of bleeding, lack of intensive care units and interventional radiology, and the generally poor health status of the patients. Today PPH is rare in high-volume surgical centers. However, the importance of recognizing and treating PPH cannot be overemphasized.

ETIOLOGY/RISK FACTORS Based on timing, PPH can be categorized as either early or late, according to the ISGPS definition (Table 76-5). Early PPH occurs within 24 hours postoperatively and is often a result of surgical error or patient coagulopathy. Late PPH occurs after 24 hours postoperatively and is often a sign of erosion of major blood vessels by the pancreatic juice. It is therefore common to find other complications such as pancreatic fistula or intraabdominal abscess along with late PPH. Another scenario of late PPH is pseudoaneurysm resulting from vascular injury during the index operation. PPH can occur in major visceral arteries or veins, pancreaticoenteric anastomosis, raw surface

of the pancreas after resection, and biliary stent placed intraoperatively. The common vascular source of PPH includes the stump of the gastroduodenal artery, splenic artery, branches of the superior mesenteric artery (eg, inferior pancreaticoduodenal artery), the splenic vein stump, or, rarely, an intrapancreatic artery (Wente et al., 2007b). TABLE 76-5: DIAGNOSTIC DEFINITION OF POST-PANCREATECTOMY HEMORRHAGE

CLINICAL PRESENTATION PPH can manifest itself in a variety of ways, such as bleeding from the nasogastric tube or surgical drains, hematemesis, melena, unexplained hypotension, tachycardia, etc. A small initial bleed from the nasogastric tube or surgical drain can be a sentinel bleeding, heralding a massive hemorrhage within a few hours. High clinical suspicion is therefore paramount in identifying and diagnosing PPH.

DIAGNOSIS There has been a significant variety in the definition of PPH in the literature. In 2007, ISGPS released a consensus definition of PPH based on three criteria: (1) timing of onset: early (within 24 hours of the index operation), or late (after 24 hours since the index operation); (2) location: intraluminal (eg, pancreatic surface, anastomoses, gastric/duodenal ulcer/erosion, or hemobilia), or extraluminal (eg, arterial or venous vessel, operating field, external suture or staple line, or pseudoaneurysm); (3) severity of bleeding: mild or severe. Mild bleeding is characterized as a small or medium volume blood loss (drop of hemoglobin concentration of less than 3 g/dL) with no or minimal clinical impairment, no need for invasive intervention (reoperation or interventional angiography), and successful conservative treatment (fluid resuscitation and blood transfusion of 2 to 3 units packed red blood cells if it is an early bleed, or three units while hospitalized and late bleed). Severe bleeding is a larger-volume blood loss (decrease in hemoglobin concentration of ≥3 g/dL) and potentially life-threatening complications with tachycardia, hypotension, and/or oliguria; treatment involves the need for blood transfusion (≥3 units packed red blood cells) and/or invasive treatment (reoperation or interventional angiography). Grade A PPH requires only a minor and temporary adjustment from the standard clinical pathway and has no major clinical impact. Hospital discharge is often not delayed. Grade B PPH, on the other hand, requires adjustment of a standard clinical pathway and often involves workup and intervention such as transfusion, radiological intervention such as embolization, reoperation, readmission, and/or intensive care unit transfer. Hospital discharge is often delayed. Grade C PPH is the most severe form and often requires immediate workup and interventions such as embolization

or reoperation. Intensive care unit admission is frequent, and hospital stay is almost always prolonged.

TREATMENT PPH is often a significant complication that requires prompt recognition and management. Once PPH is suspected, resuscitation is mandatory, while diagnostic testing may be carried out at the same time to identify the location and cause of the bleed. The diagnostic tests include, but are not limited to, complete blood count, coagulation panel, CT angiography, etc. Transfusion may be required for grade B PPH and is often necessary for grade C PPH. For pseudoaneurysm, radiological embolization is frequently used. If the PPH is caused by disruption of the anastomosis or erosion of the visceral vessels by the pancreatic juice, reoperation is frequently necessary.

Biliary Leak Biliary leak is a fairly uncommon complication following pancreaticoduodenectomy. This is perhaps due to the resection of the distal, also the narrowest, portion of the common bile duct, and the common use of larger-caliber anastomosis from hepatojejunostomy. Miedema et al. (1992) reported 24 patients with postoperative biliary-enteric anastomotic leak rate out of 279 patients (9%) who underwent pancreaticoduodenectomy at the Mayo Clinic from 1980 to 1989. Sohn et al. (2003) further reported that of 1061 patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital from 1995 to 2000, only 39 (3.7%) required postoperative drainage for biliary leaks from etiologies such as from biliary anastomotic disruption, undrained biliary segments, or T-tube/bile stent dislodgment. Of note, out of 1061 patients, 342 had preoperative biliary drainage, which may have decreased the incidence of postoperative biliary leak. In a report by Behrman et al. (2004) from the University of Tennessee, no biliary complication was reported out of 125 patients who underwent pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy. Nevertheless, biliary leak increases postoperative morbidity and mortality. In Miedema’s report, mortality increased from 2% to 17% with biliary leak (p 40, Injury Severity Score >24, and grade III to V injury, with moderate evidence for presence of contrast extravasation or “blush” on CT scan.20 Splenic artery embolization (SAE) is an important adjunct for NOM, but its precise role remains controversial.18 A meta-analysis to evaluate NOM of blunt splenic injury found that the overall failure rate was 8.4% (95% confidence interval [CI], 6.7%-10.2%) with failure rates increasing with more severe injuries, from about 5% in grade I to 83% in grade V.21 The addition of SAE was associated with higher splenic salvage rates for more severe injuries compared to observational management alone (56% vs 83% for grade IV and 17% vs 75% for grade V).21 Most studies have suggested that splenic function is preserved after SAE, but multiple different parameters were used. There are no reported cases of overwhelming postsplenectomy infections after SAE, and routine vaccination is not used.22 Splenic embolization, however, has its own risks and may be complicated by splenic abscess, infarction, pain, fever, coil migration, pleural effusion, contrast nephropathy, and bleeding.23 Currently, angiography is recommended for hemodynamically stable patients with grade III to V injuries, contrast blush, moderate hemoperitoneum, or clinical evidence of ongoing bleeding.18 NOM of splenic injuries should not exceed 24 hours. Failure of NOM is defined as persistent bleeding evident by laboratory testing, hemodynamic changes, or persistent requirement of blood transfusion after 24 hours. Failure of NOM is treated by laparotomy and splenectomy or splenorrhaphy. After discharge, there is a lack of consensus on restriction of activities,

with most restricting activity for >2 months for high-grade injuries managed nonoperatively.24 Patients should be aware of the risk of delayed splenic rupture, with the 180-day risk of readmission for splenectomy of 1.4% in one population-based study.25

LOCAL SPLENIC DISORDERS Splenic Artery Aneurysm Splenic artery aneurysm was first described by Baussier in 1770, and St. Leger Brockman described one of the first surgical cases in 1930. Although mycotic aneurysm can be seen in the splenic artery, the majority are idiopathic. The splenic artery is the most common visceral artery aneurysm and the third most common site of intra-abdominal aneurysms, after aneurysms of the abdominal aorta and iliac arteries. The incidence in autopsy series ranges between 0.02% and 0.16%, with a female predominance (4:1). They are commonly associated with pregnancy and portal hypertension. The incidence of splenic aneurysm is much higher in patients with cirrhosis and portal hypertension. Splenic artery aneurysms have been reported in 14% of patients awaiting liver transplant, which can lead to major hemorrhage after transplant.26 Splenic artery aneurysms are also seen at a higher incidence in patients with arteritis, arterial fibrodysplasia, collagen vascular disease, and α1-antitrypsin deficiency.27 Most are true aneurysms, but pseudoaneurysms may also develop as complications of pancreatitis and trauma. In a contemporary review of 217 splenic aneurysms seen at the Mayo Clinic, the mean age at presentation was 62 years, with 79% of patients being female. Over 90% of the patients were asymptomatic, with a mean aneurysm size of 3.1 cm. Although more than 10% of men presented with a rupture, this rate was less than 3% in women, in large part due to larger aneurysm sizes in men. The mean size for nonruptured cases was 2.2 cm, and the smallestdiameter aneurysm to rupture was 2.2 cm.28 Splenic artery aneurysms are often incidental findings in asymptomatic patients. Most are under 2 cm in size, but on occasion, they can be much larger. They are generally saccular and solitary, and occur at a bifurcation in the splenic hilum.29 Peripheral calcification and mural thrombus are

frequently noted (Fig. 77-10). Patients may present with symptoms of left upper quadrant or epigastric pain radiating to the shoulder. The overall risk of rupture is less than 2% but is higher for aneurysms larger than 2 cm, in liver transplant patients, and in pregnancy.29 Such ruptures have been associated with maternal and fetal death rates of 22% and 15%, respectively.30 Ruptures occur in the third trimester of pregnancy in 69% of cases.31

FIGURE 77-10 A CT scan of a large splenic artery aneurysm with calcified wall. This calcified wall can also be seen on plain abdominal roentgenogram. Rupture of the aneurysm is manifested by sudden abdominal pain. If the rupture is initially contained in the lesser sac, the patient may have upper abdominal pain but be hemodynamically stable. Once the rupture overflows into the peritoneal cavity, diffuse pain and hemorrhagic shock ensue. This sequence of events is termed the “double rupture phenomenon.” Mortality after emergency surgery is as high as 40%.32 Surgical resection in all symptomatic aneurysms is recommended; however, criteria for elective repair of asymptomatic aneurysms are not firm. In general, the presence of an aneurysm larger than 2 cm is an indication for surgery if the patient is a reasonable operative risk.29 Asymptomatic patients with aneurysms between 1 and 2 cm should be closely monitored with serial

imaging done initially every 6 months.33 Aneurysms of any size detected in pregnancy should be treated because many of the ruptured aneurysms during pregnancy are less than 2 cm in size.30 This should be done before the third trimester, when the risk of rupture is at its peak. Liver transplant patients have a higher incidence of aneurysms and a higher risk of rupture, including in the posttransplant period, with a mortality over 50%. This has led to recommendations to treat splenic artery aneurysms over 1.5 cm in size with embolization prior to liver transplantation.34 The traditional approach to repair for lesions in the proximal or middle of the artery includes resection and primary end-to-end anastomosis, or proximal and distal ligation with resection of the involved segment.35 Proximal ligation is reasonable because the spleen will not become ischemic following central ligation of the main splenic artery. Distal lesions located close to the hilum generally require splenectomy with resection of the involved splenic artery, now generally done laparoscopically (Fig. 77-11). The overall mortality rate ranges from 1% to 3%, with a perioperative complication rate of 9% to 25% due to splenic or pancreatic injury.33

FIGURE 77-11 A 3-dimensional CT reconstruction of a partially thrombosed large splenic artery aneurysm with a smaller aneurysm more distal. Both aneurysms were treated by a laparoscopic splenectomy. Percutaneous transcatheter embolization techniques have been increasingly used and are preferred over surgery for most splenic artery

aneurysms if the anatomy is suitable.36 The endovascular therapeutic options include stenting, coil embolization, and the use of glue, N-butyl-2cyanoacrylate; their uses vary based on aneurysm size and location, and there is not enough evidence to support the use of one over another. These techniques have been increasingly used since 2000, and a systematic review reports a technical success rate of over 95%.37 Complications of endovascular repair include treatment failures, postprocedural pain, and abscess formation, as well as pancreatitis due to occlusion of the pancreatica magna vessel.38 Major postoperative complications are higher in the open repair (1.1%) versus endovascular patients (0.8%). In the long term, however, there are more late complications in the endovascular group with a greater need for subsequent interventions compared to open repair (3.2% vs 0.5% per year).37 Follow-up after endovascular repair is mandatory. Decision analysis modeling suggests that the endovascular approach is less costly and more effective than open surgery.39 The endovascular approach has also been used in the emergency setting to treat ruptured aneurysms.

Cysts Splenic cysts are classified as primary or secondary (pseudocysts). Some splenic tumors may also have a cystic component (Fig. 77-12). Primary cysts have an epithelial lining and can be nonparasitic or parasitic (echinococcal).

FIGURE 77-12 A. A large splenic cyst seen on CT. B. A large splenic cyst that, on careful review, had septations and calcifications. Patient underwent a splenectomy, and pathology confirmed an 8-cm lymphangioma.

PARASITIC PRIMARY CYSTS Worldwide, Echinococcus infection (hydatid disease) is the most common cause of a splenic cyst. The spleen is the third most common site of disease, after the liver and lung. Echinococcus granulosus, the most commonly implicated species, usually results in a unilocular cyst composed of an inner germinal layer (endocyst) and an outer laminated layer (ectocyst) surrounded by a fibrous capsule. Unlike the nonparasitic cysts, these are filled with fluid under positive pressure and also contain daughter cysts and infective scolices. Echinococcal cysts are usually asymptomatic unless they reach a size causing pressure symptoms or become secondarily infected or rupture. Overall, splenic involvement is rare, even in endemic areas, and comprises only 0.5% to 4% of all hydatid disease.40 Once splenic disease is found, concomitant disease is usually found in other organs, with the liver and peritoneum the most common locations. Splenic hydatid cysts grow slowly, approximately 0.3 to 2.0 cm per year,41 and most patients remain asymptomatic for a long time. Symptoms occur due to the mass effect on nearby organs, usually with nonspecific and/or left upper quadrant abdominal pain. Diagnosis is made using imaging tests including ultrasound, CT, and magnetic resonance imaging (MRI) studies that demonstrate a septated cystic mass that contains daughter cysts. For diagnostic purposes, the older Casoni skin test has been replaced with serologic testing. Multiple serologic tests are available and include immunophoresis, enzyme-linked immunosorbent assay (ELISA), and latex and indirect hemagglutination. Sensitivity rates of 85% to 90% are seen with both ELISA and indirect hemagglutination testing; overall, ELISA testing is thought to be optimal. These are used for screening and diagnosis and can also be used on follow-up to detect any recurrences.40,41 Recommended management of splenic hydatid cysts is based on size and concomitant disease; options include medical management, percutaneous techniques (puncture, aspiration, injection, reaspiration [PAIR]), and surgical intervention. Medical management with anthelmintics (eg, albendazole, mebendazole, praziquantel) as a sole treatment modality is controversial

given low absorption of orally administered medication and subtherapeutic concentration in the cyst. Some still advocate for small cysts being treated with anthelmintic drugs alone.41 The PAIR technique is used in conjunction with anthelmintic therapy in patients with prohibitive surgical risks or who refuse surgery and is safe for cysts under 5 cm in diameter. Larger and/or symptomatic cysts are treated surgically due to the risk of rupture. Traditionally, a complete splenectomy is advocated to reduce the risk of recurrence and is the treatment of choice. This is especially true for multiple or centrally located cysts or in patients with concomitant abdominal disease elsewhere. Care should be taken to avoid spilling the contents of the cyst. Intraoperatively, the lesions can be sterilized by instilling a 3% sodium chloride solution into the cysts. If intraperitoneal spillage occurs during the dissection, anaphylactic hypotension may occur and require epinephrine. With newer techniques emerging and concern for postsplenectomy septic complications, splenic-preserving procedures are being considered for small or peripherally located cysts. These include partial splenectomy, cyst enucleation, deroofing with omentoplasty, and internal drainage with cystojejunal anastomosis. Small case series show no recurrence after spleenpreserving procedures for small peripheral cysts in young patients.40 Other studies comparing outcomes after total splenectomy and spleen-preserving surgery have found no difference in recurrence; however, these are all retrospective and heterogeneous studies, and definitive recommendations cannot be made. Larger studies are yet to be done, and the role of splenicpreserving procedures for hydatid cysts is not well established. The use of laparoscopy has also not been widely accepted in treating hydatid cysts because of a fear of spillage and anaphylaxis.42

NONPARASITIC PRIMARY CYSTS Nonparasitic primary cysts are increasingly discovered incidentally on imaging done for a variety of reasons. According to Morgenstern’s classification, nonparasitic splenic cysts are classified based on pathogenesis as congenital, neoplastic, traumatic, or degenerative (Table 77-2).43 TABLE 77-2: CLASSIFICATION OF NONPARASITIC SPLENIC CYSTS

Cysts with mesothelial, epidermoid, or transitional epithelial linings are probably congenital in origin, originating from an infolding of peritoneal mesothelioma during splenic development. The cellular lining can desquamate and be absent in places, but these cysts have a characteristic gross appearance, with a white, glistening interior containing coarse fibrous trabeculations.43 The cyst fluid can be clear or cloudy and ranges in color from almost clear to yellow, green, or brown. The fluid may show elevated levels of carcinoembryonic antigen (CEA) and CA 19-9. A calcified portion of the cyst wall may also observed in a small proportion of these cysts. Congenital cysts of the spleen occur in children and in young adults in 75% of cases. About two-thirds of the patients are female. The clinical manifestations are dependent on the size and can include left upper abdominal discomfort, pain, or fullness. True dermoid cysts of the spleen are exceedingly rare; less than 10 cases have met the pathologic criteria of a squamous epithelium with dermal appendages such as hair follicles and sweat glands. It can be difficult to differentiate these cysts from one another based on

imaging only, and usually the diagnosis is made when symptomatic cysts, usually greater than 5 cm, are excised and analyzed histologically.44 Asymptomatic cysts, which are often smaller, are observed with no need for surgical resection. The recommendation for resection of splenic cysts over 5 cm originated in 1992 based on a report by Musy et al45 and was reinforced in subsequent literature.43 Some sources cite the 25% spontaneous rupture risk for cysts larger than 5 cm with an associated high mortality rate, but this was in the context of hemangiomas. More recent work by Kenney et al46 reviewed 115 patients with splenic cysts, including 16 with cysts larger than 5 cm. There was only 1 patient with a large cyst who presented with rupture after a fall. The authors concluded that size should not be used to determine the need for intervention.46 This applied to asymptomatic cysts with typical imaging findings, including smooth, regular wall contours and no solid component. Aspiration of the cyst is not a definitive treatment because it is usually not successful. Only compete removal of the cyst avoids recurrence. Spleenconserving approaches are feasible for most cysts, unless they are centrally located. One attractive approach with very low morbidity is near total resection of the cyst wall, leaving just the part of the wall of the cyst attached to the spleen in situ (“unroofing” or “decapsulation”). This is associated with low morbidity, but radiologic recurrence in children may be >65%47,48; however, these recurrences are usually smaller than the original cyst, and many are asymptomatic and can be managed conservatively.47 In adults, reported long-term recurrence rates range from 20% to 60%.49-51 Although partial splenectomy has higher potential morbidity related to bleeding or ischemia of the remnant, it is becoming a more common option given that it allows resection of the cyst itself but leaves splenic tissue behind, maintaining immunologic function. Leaving at minimum 25% of splenic tissue is thought to confer adequate immunologic function.52 This can also be done safely via the laparoscopic approach, as discussed below.

Splenic Abscess Splenic abscesses tend to be rare, due to the spleen’s ability at fighting infections and bacteria. They are more frequently seen in areas with a high incidence of sickle cell anemia, with associated thrombosis of parenchymal

vessels and subsequent splenic infarction. The major risk factors for such abscesses in the West are intravenous drug use, human immunodeficiency virus (HIV) infection, other hematogenous spread (endocarditis), splenic trauma, and contiguous spread. Endocarditis can be complicated with splenic abscesses in 5% of cases. These are often multiple abscesses similar to what is seen in other organs; the spleen is just a part of overwhelming sepsis.53 Most infections are polymicrobial and include such organisms as Staphylococcus, Salmonella, Escherichia coli, Proteus mirabilis, Streptococcus group D, Klebsiella pneumoniae, Peptostreptococcus, Bacteroides, Fusobacterium, Clostridium, Candida albicans, and Mycobacterium. The symptoms are usually nonspecific, such as malaise, weight loss, left upper quadrant pain, and fever. Most patients have a leukocytosis, and an ultrasound, CT, or MRI study establishes the diagnosis of a splenic abscess. Treatment consists of broad-spectrum antibiotics and percutaneous drainage, which, if it fails, will require laparoscopic or open splenectomy. Many patients have multiple other abscesses in other organs. Antibiotic treatment should continue until the drains or percutaneous catheters have been removed. If the spleen has multiple abscesses, splenectomy may be required.54

Splenic Tumors Splenic masses may be identified during workup of symptoms or incidentally during other imaging. Some of these masses have a large cystic component (see Fig. 77-12). Management of such lesions may result in difficult clinical decision making as imaging alone does not always result in a definitive diagnosis. Often, these lesions may need to be followed serially, or if concerning, splenectomy should be considered. The underlying pathology may depend on referral patterns. In a series of 44 such cases, half of whom were symptomatic and treated surgically, 75% of lesions were benign while the remainder were malignant.55 In a similar study of 28 patients, the risk of a malignant diagnosis was significantly higher at 72%, although 25% of these patients had a previous history of lymphoproliferative disorder.56 There are increasing data on the use of image-guided splenic fine-needle aspiration to differentiate such masses, with low complication rates.57 Sensitivity and

specificity of such aspiration have been reported as 94% and 79%, respectively,58 with low risk of complications, even for core-needle biopsy.59

BENIGN NEOPLASMS Splenic neoplasms generally arise from the lymphoid or vascular elements of the spleen. They include a broad range of lesions, from benign (hemangioma, hamartoma, lymphangioma, and sclerosing angiomatoid nodular transformation) to intermediate (littoral cell angioma, hemangioendothelioma, and hemangiocytoma) to malignant (angiosarcoma). The more commonly found benign lesions are discussed here. Hemangiomas are the most common benign neoplasms of the spleen with an incidence ranging from 0.02% to 16% and can be single or multiple.60 Most are now diagnosed incidentally during imaging for other pathology. Hemangiomas vary from well-circumscribed to irregular vascular proliferations. They consist of a benign overgrowth of nonencapsulated proliferation of new blood vessels of variable size, from capillary to cavernous formations. They are thought to be congenital in origin, and most are cavernous in nature. On CT scan, hemangiomas appear as homogeneous, hypodense, or multicystic lesions with variable calcification and peripheral enhancement. On MRI, they have high signal intensity on T2-weighted images with peripheral enhancement on delayed images.61 The potential for malignant transformation to angiosarcoma is not known but appears to be low. The majority of splenic hemangiomas do not require surgical intervention. Most are asymptomatic. Splenectomy is reserved for tumors that become symptomatic due to size or consumptive coagulopathy. Although there has traditionally been concern about risk of spontaneous rupture or rupture with blunt trauma, a contemporary series from the Mayo Clinic reported no spontaneous rupture among 32 patients with splenic hemangioma, 80% of whom were entirely asymptomatic.60 Attempts at treatment using embolization of arterial branches or radiofrequency ablation have been reported, but more data are needed to understand their efficacy. Sclerosing angiomatoid nodular transformation (SANT) is a benign vascular lesion first defined by Martel et al62 in 2004. SANT consists of altered red pulp trapped by nonneoplastic stromal proliferation.63 There is

often a central stellate scar. Patients are usually asymptomatic with a solitary splenic mass found incidentally on imaging. There is a 2:1 female predominance. Ultrasound shows a hypoechoic lesion. CT and MRI studies may show a central scar, enhancing capsule, and radiating bands corresponding to fibrosis.61,64 The lesion may have 18F-fluorodeoxyglucose (FDG) avidity on positron emission tomography (PET) scan.64 The average size in a case series of resected patients was 5.8 cm (range, 3.2-10.2 cm).65 Although SANT often displays characteristic radiologic findings, differentiation from other benign and malignant lesions may be challenging, and splenectomy may be required (Fig. 77-13).

FIGURE 77-13 A 5.8 × 3.8 × 4.8 cm lesion located centrally in the spleen on magnetic resonance imaging. This was initially found incidentally on an ultrasound done for symptomatic gallstones. On positron emission tomography scan, the lesion was hypermetabolic with heterogeneous increased radiotracer accumulation, with a maximum standardized uptake value of 4.4. She underwent laparoscopic splenectomy and cholecystectomy. The pathology revealed sclerosing angiomatoid nodular transformation (SANT) in the spleen. Littoral cell angioma (LCA) is a rare vascular tumor of the spleen. It is an

endothelial cell neoplasm arising from the cells lining the sinus channels of the splenic red pulp. These rare lesions express vascular and histiocyteassociated antigens. The autopsy incidence ranges from 0.03% to 14%. They are seen at any age range, with no sex-based predilection. Two forms of LCA are seen: diffuse multiple nodular LCA and the more rare solitary form. Imaging features on ultrasound vary widely from heterogeneous echotexture with no specific nodules to hyperechogenic-, hypoechogenic-, or isoechogenic-appearing lesions. A comparison between sonographic and pathologic features has shown that lesions with minimal blood-filled spaces appear as hypoechoic spaces, whereas lesions with lots of blood-filled spaces appear as hyperechoic spaces. On an unenhanced CT imaging study, nodular LCA lesions are not visible unless they have a hemorrhagic component. On a contrast CT in the portal venous phase, LCAs appear as low-attenuation lesions; LCAs are iso-attenuating on delayed images. Although classified as benign, recent literature classifies LCAs as having uncertain biologic behavior.66 Malignant transformation to littoral cell angiosarcoma is very rare, but cases with dissemination to the liver and brain have been reported. An association with malignant lymphomas and other visceral organ cancers, including thyroid, colon, lung, pancreas, liver, brain, hematologic, ovarian, and testicular, has been reported.67 This leads to reluctance in classifying it as a completely benign lesion. In addition, LCA is also associated with various congenital and immunologic conditions, including inflammatory bowel disease, Wiskott-Aldrich syndrome, Epstein syndrome, lymphocytic colitis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis, Gaucher disease, myelodysplastic syndrome, chronic glomerulonephritis, and aplastic anemia.68 The majority of patients are asymptomatic. Symptomatic patients present with abdominal pain, left upper quadrant fullness with satiety, splenomegaly, anemia, thrombocytopenia, or constitutional symptoms such as weight loss, anorexia, or fever of unknown origin.69 A preoperative diagnosis of LCA can be made with an image-guided fine-need aspiration or needle biopsy. Some authors recommend close follow-up, but given its small malignant potential and possible concomitant malignancies, splenectomy may be recommended. The potential for familial predisposition has been raised, and screening for splenic lesions in family members is suggested.66 Lymphangiomas are congenital malformations thought to be due to

obstruction of the venolymphatic system (see Fig. 77-12B). Microscopically, these endothelium-lined spaces are filled with lymph and blood elements. The lesion may be focal or multiple, a small or large cystic mass, or may diffusely involve the spleen and account for splenomegaly. The diagnosis is made by ultrasound, CT scan, or MRI that reveals water-density cystic lesion(s) of the spleen. The lymphangioma may be isolated to the spleen or occur as a generalized lymphangiomatosis with multivisceral involvement and a poor prognosis. Symptoms, when present, are related to the size and mass effect of the lesion. Splenectomy is indicated for symptomatic lesions. Inflammatory pseudotumor of the spleen is a reactive lesion characterized by a mixture of inflammatory cells and disorganized spindle cells.70 It is infiltrative in nature and may mimic malignant lymphoproliferative disease. These are seen in middle-aged and older patients, with a higher incidence in women. This tumor is typically found incidentally and is generally asymptomatic but may present with systemic symptoms such as abdominal pain, splenomegaly, or symptoms suggestive of malignancy such as fever, malaise, and weight loss. Imaging studies are nonspecific. The differential diagnosis includes lymphatic neoplasms, inflammatory granulomatous processes, hamartomas, hemangiomas, hemangioendotheliomas, and angiosarcomas. Although inflammatory pseudotumors are benign, no method with adequate sensitivity or specificity is available to make a definitive diagnosis. The diagnosis can be made via percutaneous fine-needle aspiration cytology, but splenectomy may be required to rule out malignancy if a diagnosis cannot otherwise be made. Other benign lesions of the spleen are uncommon. Splenic hamartomas are uncommon, with autopsy series noting an incidence of 0.024% to 0.13%. They are solid but may have a cystic or necrotic component.61 Peliosis is not a true neoplastic lesion but a blood-filled cystic lesion without an endothelial lining that may be associated with focal, patchy, or diffuse involvement of the spleen. This lesion is likely reactive as it has been associated with steroids, oral contraceptives, immunosuppression medications, tuberculosis, renal disease, and malignancy. Other benign splenic tumors, such as angiomyolipoma, lipoma, hemangiopericytoma, and fibroma, are rare.

PRIMARY MALIGNANT TUMORS Primary, nonlymphoid, malignant tumors of the spleen are exceedingly rare.

These include angiosarcomas, malignant fibrous histiocytomas, and plasmacytomas. Angiosarcoma is the most common nonlymphoid primary malignant neoplasm of the spleen. The clinical presentation may include abdominal pain, left upper quadrant abdominal mass, and constitutional symptoms. Metastasis is frequent and often involves the liver. Spontaneous rupture has been reported and is associated with a dismal outcome. Normocytic anemia is present in the majority of cases. Splenomegaly with hypersplenism is also seen. CT imaging often identifies a splenic lesion with central necrosis. The primary treatment is splenectomy. Cisplatin-based chemotherapy has also been used. However, even without rupture, splenic angiosarcoma holds a poor prognosis. Recent studies have reported 1-, 3-, and 5-year survival rates of 60%, 40%, and 40%, respectively.71

METASTATIC TUMORS Splenic metastasis of nonhematologic malignancies is rarely seen clinically and usually represents widespread dissemination of disease. In a review of a German oncologic database, only 0.002% of patients with a malignancy developed reported splenic metastasis, with isolated splenic metastasis being extremely rare.72 Despite the rarity of clinically evident splenic metastasis, postmortem evidence is reported to be higher, although the exact prevalence of this is debated, with older literature reporting rates as high as 34%, while contemporary reports put this rate at approximately 3%.73 The most frequent sites of primary tumors with splenic metastasis are lung, colorectal, ovary, melanoma, and breast.74 The diagnosis of malignancy can be confirmed by PET scanning, although percutaneous biopsies for isolated lesions can also be performed (Fig. 7714).75 Splenectomy may be indicated to treat isolated metastatic disease, especially for patients with chemosensitive tumors or in whom cytoreductive surgery can improve outcomes.74

FIGURE 77-14 The patient was found to have a splenic lesion on CT of the chest in the context of a right lung cancer. Percutaneous biopsy revealed adenocarcinoma consistent with lung primary. She underwent splenectomy for this isolated metastasis.

HEMATOLOGIC DISORDERS In 1887, Sir Thomas Spencer Wells, the renowned gynecologist, performed a therapeutic splenectomy for what proved to be hereditary spherocytosis. The first splenectomy for autoimmune hemolytic anemia (AIHA) was performed in 1911 by Micheli. Six years later, Schloffer, at the suggestion of a medical student, Kaznelson, performed a splenectomy for idiopathic thrombocytopenic purpura.1 The indications for splenectomy in hematologic disease are continuously evolving, but there are many conditions for which splenectomy plays an important role. The most common hematologic indications for splenectomy are immune thrombocytopenia purpura, hereditary spherocytosis, and AIHA.

ANEMIAS Splenectomy is indicated for specific cases of anemia. The major categories

of anemia that benefit from splenectomy are those caused by the following: • • • •

Membrane abnormalities: Hereditary spherocytosis and elliptocytosis Enzyme defects: Pyruvate kinase deficiency Hemoglobinopathy: Thalassemias and sickle cell AIHA

Hereditary Spherocytosis Hereditary spherocytosis (HS) is a hemolytic anemia that results from a genetic defect or deficiency in one of the components of the red cell cytoskeleton. It results in spherically shaped erythrocytes on blood smear, reticulocytosis, and splenomegaly. HS is transmitted as an autosomal dominant trait but occurs sporadically in rare instances. HS is the most common cause of familial chronic hemolytic anemia in North America and Northern Europe, with an incidence of 1 to 5 in 10,000 births, or even higher if mild cases of osmotic fragility are included.76 Abnormalities of the proteins in the red cell membrane (spectrin, ankyrin, band 3, and/or protein 4.2) cause increased osmotic fragility and changes in morphology, resulting in the spherical shape and decreased deformability. The red cell membrane change results in splenic trapping of the abnormal cells in the microcirculation, followed by their destruction by phagocytosis.77 Thus, the spleen plays a critical role in the pathophysiology of HS, as it is the main site of hemolysis. Cells that escape the spleen on first passage are more susceptible to trapping and destruction during each successive passage. The salient clinical features include anemia, jaundice, and splenomegaly, with spherocytes on blood smear, increased osmotic fragility, and positive family history.77 The severity of disease varies widely and is classified as mild, moderate, and severe based on hemoglobin, bilirubin, and reticulocyte count (Table 77-3).78,79 Approximately 30% of cases are mild, maintaining near-normal hemoglobin and bilirubin levels and compensatory reticulocytosis. Patients with severe spherocytosis are transfusion dependent with baseline hemoglobulin level less than 6 g/dL. TABLE 77-3: CLASSIFICATION OF SPHEROCYTOSIS AND INDICATIONS FOR

SPLENECTOMY

The disease severity is related to the degree of red cell cytoskeleton protein deficiency, particularly spectrin shortage. The jaundice usually parallels the severity of anemia and generally is not intense. It is related to increased red cell destruction, resulting in abundant bile pigment that cannot be cleared by the liver. Most patients have mild to moderate spleen enlargement, but splenomegaly alone is not an indication for surgery. Increases in splenic size in patients with HS may be seen in the presence of acute infection. Periodic worsening of the associated anemia and jaundice may be seen, often following infection, emotional stress, fatigue, or prolonged exposure to cold. Gallstones are the most common complication of HS but are unusual in children younger than age 10 years. The gallstones are generally pigmented. Splenectomy is effective in reducing the hemolysis associated with HS but at the price of a lifelong risk of severe sepsis from encapsulated organisms, and emerging evidence links splenectomy to late vascular complications such as pulmonary hypertension and atherosclerosis.79 Splenectomy should not be recommended simply due to the diagnosis of HS but is based on the severity of anemia (see Table 77-3). Failures are uncommon and often reflect missed accessory spleens, which can be identified using radiocolloid liver-spleen scans.77 The preferred approach is laparoscopic as it is associated with less postoperative morbidity and pain. Because of the increased risk of serious postsplenectomy sepsis among young children, with a subsequent mortality rate of 50% to 80%, splenectomy is reserved preferably for patients older than 6 years79 and should not be done in children younger than age 3, even if chronic transfusions are needed.78 Concern over postsplenectomy sepsis risks, especially in young children, has led to investigation of the effectiveness of partial splenectomy to control hemolysis while leaving some functional spleen behind for immunologic

purposes.80,81 Either the lower pole, based on the gastroepiploic, or the upper pole, based on the uppermost short gastrics, is preserved. This approach has somewhat less effective hemolytic control. A recent review of moderatequality evidence reported that partial splenectomy resulted in increases of hemoglobin of 2.3 to 3.9 g/d, compared to 4 to 5 g/dL with total splenectomy, but both resulted in decreased reticulocyte counts, anemic crises, and transfusions. Most studies suggested that partial splenectomy maintained splenic immune function and phagocyte activity, but there was a lack of longer term studies comparing adverse events such as sepsis or vascular complications.82 A multi-institutional review of 62 children of all ages undergoing a partial splenectomy showed a good response with no postsplenectomy sepsis with up to 18 years of follow-up and only 4.8% of patients requiring completion splenectomy. They noted that splenic remnant regeneration correlated with the degree of recurrence of anemia and clinical symptoms,83 but this is not a consistent finding.84 The Splenectomy in Hemolytic Anemia (SICHA) Consortium Registry compared outcomes after total and partial splenectomy. Excellent hematologic response through 1 year was seen after both procedures, with a more robust response (ie, greater increase in hemoglobin) after total splenectomy.85 Guidelines conclude that partial splenectomy may be beneficial, but further follow-up studies are required.79 Concomitant cholecystectomy is performed if gallstones are present. Prophylactic cholecystectomy in the absence of stones is not required because patients no longer develop pigmented stones after splenectomy.79 In a cohort of patients younger than 18 years, none developed cholelithiasis after splenectomy over a mean follow-up of 15 years.86 The presence of Gilbert disease increases the risk of subsequent gallstones.87 On the other hand, symptomatic gallstones have traditionally been an indication for concomitant splenectomy in children, due to the concern for the development of future biliary duct stones. This is now controversial in children with mild disease. In a series of 16 patients with mild HS having cholecystectomy without splenectomy, only 3 required subsequent splenectomy.88

Hereditary Elliptocytosis Hereditary elliptocytosis is a red cell hemolytic anemia affecting 3 to 5 of

every 10,000 people with a heterogeneous array of genotypes and phenotypes. It is more common in people of African and Mediterranean origin, presumably because it results in some resistance to malaria.77 It is a group of erythrocyte disorders that have in common the presence of elongated, oval, or elliptically shaped RBCs on the peripheral blood film. Most are transmitted as an autosomal dominant trait. Most patients are asymptomatic or have a mild form of the disease with compensated hemolytic anemia, as the defects often do not significantly shorten the red cell life span despite striking abnormalities seen on blood film. The presence of hemolysis often is a familial characteristic, and it has been suggested that excessive hemolysis occurs only when the gene for elliptocytosis is present in the homozygous form or is modified in some other way. The signs and symptoms are related directly to the severity of hemolysis resulting from the extent of decreased membrane stability and subsequent loss of membrane surface area. Occasionally an acute hemolytic episode may be precipitated by infection. The clinical syndrome is indistinguishable from that described for HS. Gallstones and chronic leg ulcers have been reported in symptomatic patients. The spleen is usually palpably enlarged in symptomatic cases. Diagnosis is established by the smear. Therapy is rarely required. Indication for splenectomy is the same as for HS and is almost always followed by lasting effects. Decreased hemolysis and corrected anemia result from longer circulatory life span of the red cells, although the morphologic abnormality of the RBC remains unchanged. Associated cholelithiasis should be managed as in HS.

Pyruvate Kinase Deficiency Pyruvate kinase deficiency is the most common RBC enzyme deficiency causing congenital nonspherocytotic hemolytic anemia. It is an autosomal recessive condition that has a much lower frequency than glucose-6phosphatase deficiency (G6PD); however, it a more common cause of anemia because G6PD patients rarely suffer hemolysis. Clinical manifestation varies from transfusion-dependent anemia to compensated chronic hemolysis. Splenomegaly is common. There is no curative therapy. Splenectomy has a role in transfusion-dependent individuals and can reduce or even abolish the need for transfusion.89 As with other

children being evaluated for splenectomy, the procedure should be delayed until after age 3 due to the immunosuppressive effect of the surgery.

Thalassemia Thalassemia (Mediterranean anemia) is a congenital disorder transmitted as a dominant trait in which the anemia is primarily the result of a defect in hemoglobin synthesis. Thalassemias are the most common monogenetic disease in man and have been referred to as Cooley anemia, erythroblastic anemia, and target-cell anemia. The disease is classified as alpha, beta, and gamma types, determined by the specific defect in the synthesis of the relevant globulin chain of the adult hemoglobulin. As a consequence of the defect, there is imbalance in production of globulin chains with resultant formation of atypical hemoglobulin proteins that can lead to intracellular precipitates (Heinz bodies) that contribute to premature red cell destruction. The hemoglobin-deficient red cells are small, thin, and misshapen, and have a characteristic resistance to osmotic lysis. Over 200 genetic mutations have been identified that lead to β-thalassemia.90 The high prevalence and diversity of the thalassemias are related to heterozygote protection against malaria.91 In the United States, most patients suffer from β-thalassemia, and there is a quantitative reduction in the rate of β-chain synthesis, resulting in a decrease in hemoglobin A. The characteristic feature is the persistence of hemoglobin F and a reduction in hemoglobin A. Precipitation of the excess α chains in erythroid precursors causes dyserythropoiesis and results in membrane defects and hemolysis in mature RBCs.92 Gradations of the disease range from heterozygous thalassemia minor to severe homozygous thalassemia major. The latter is manifested by chronic anemia, jaundice, and splenomegaly. Patients with homozygous thalassemia major usually present with clinical manifestations in the first year of life. In addition to the anemia and consequent pallor, failure to thrive, gastrointestinal symptoms, and feeding problems are also seen. With adequate transfusions, the children grow and develop normally, avoiding the typical features of Cooley anemia, including retarded body growth and enlargement of the head, leg ulcers, and infections.91 Some patients present with repeated episodes of left upper

quadrant pain related to splenic infarction. Cardiac dilatation occurs, and in advanced stages, there is subcutaneous edema and effusion into serous cavities. Intercurrent infections occur frequently, often leading to death in more severe cases. These infections may be associated with aplastic crises. Gallstones have been reported in up to 24% of cases. Therapy is directed only at symptomatic patients, those having thalassemia major or intermedia. In these patients, transfusions are usually required at regular intervals. Because most children with thalassemia major accommodate to low hemoglobin levels, transfusions are given when the hemoglobin level is less than 10 g/dL. By age 10, complications develop related to iron overload, including cardiomyopathy, liver fibrosis, and endocrine disturbances.92 Iron overload is reduced using iron chelators. Stem cell transplantation from an human leukocyte antigen–identical donor is an exciting advance with a high rate of remission, especially in young, fit patients prior to the development of complications from iron overload or viral hepatitis.92 Although splenectomy does not influence the basic hematologic disorder, it may eliminate or reduce the hemolytic process responsible for accelerated destruction of normal donor red cells within the patient’s circulation, and this reduces transfusion requirements. In general, the best results associated with splenectomy have been obtained in older children and in young adults with large spleens in whom excessive splenic sequestration of red cells has been demonstrated. Splenectomy should be avoided in children younger than age 5 years.91 Occasionally, splenectomy may be indicated because of mass effect symptoms associated with marked splenomegaly or repeated episodes of abdominal pain due to splenic infarction.

Sickle Cell Disease Sickle cell anemia, first reported in 1910, is a hereditary disorder of hemoglobin characterized by the presence of crescent-shaped erythrocytes that, because of a lack of deformability, are trapped in the splenic cords. In this disorder, the normal hemoglobin A is replaced by hemoglobin S. Under conditions of reduced oxygen tension, hemoglobin S molecules undergo crystallization within the cell, which elongates and distorts the cell. The sickle cells increase the blood viscosity and circulatory stasis, thus

establishing a vicious cycle. Although the sickle cell trait occurs in approximately 9% of the black population, the majority of patients are asymptomatic. Sickle cell anemia is observed in 0.3% to 1.3% of blacks. Many body systems can be affected by sickle cell disease. Depending on the vessels affected by vascular occlusion, the patients may have bone or joint pain, osteomyelitis, priapism, neurologic manifestations, or skin ulcers. Abdominal pain and cramps due to visceral stasis are frequent. The spleen is commonly affected in these patients. Sickling occurs so rapidly that blood flow through both the fast and slow compartments of the spleen is obstructed; as a consequence, a series of microinfarcts develop and eventually lead to “autosplenectomy.” In most adult patients, only a fibrous area of the spleen remains, but autosplenectomy is preceded by splenomegaly in about 75% of patients. Calcification may occur with autoinfarction (Fig. 77-15). Such functional asplenia is defined and detected by the presence of Howell-Jolly bodies in the blood film and can be confirmed by absence of technetium-99m (99mTc) splenic uptake. Patients are subsequently at risk of developing infection by encapsulated organisms such as Streptococcus pneumoniae, due to impaired filtration and antibody production of the spleen. Rarely thrombosis of the splenic vessels may result in the complication of splenic abscess manifested by splenomegaly, splenic pain, and spiking fever. Percutaneous drainage of such abscesses may be attempted, but it may require a splenectomy.

FIGURE 77-15 Calcified spleen in a patient with sickle cell disease causing persistent pain. Splenectomy relieved the patient’s pain. For most patients with sickle cell anemia, only palliative therapy is available. Adequate hydration and partial exchange transfusion may help the crisis. Randomized multicenter studies have shown a role for hydroxyurea in treatment of adults with sickle cell disease. Such treatment leads to reduction in frequency of painful crisis, hospitalization, and transfusion.93 The beneficial effects are in part due to an increase in hemoglobulin F levels, although the mechanism underlying this process is not known. Hydroxyurea is therefore recommended in patients with 3 or more crises per year.94 Other hemoglobulin F–inducing agents and stem cell transplant are also currently under investigation. There are 2 situations in sickle cell anemia where the spleen is a pathologic red cell reservoir, and splenectomy may have a role. The first is a form of chronic hypersplenism that usually occurs in childhood or adolescence and is manifested by reduced red cell survival, leukopenia, and thrombocytopenia. In these patients, for some unknown reason, there is a failure to undergo autosplenectomy. In this rare circumstance, splenectomy will correct the leukopenia and thrombocytopenia and will also increase the

rate of red cell survival and can lead to reduced transfusion requirement.94 The second abnormality has been termed acute splenic sequestration and is marked by sudden splenic enlargement associated with worsening anemia and profound hypotension. It usually occurs in the first 5 years of life in a homozygous child; streptococcal pneumonia infection may act as a precipitating event in these patients. The acute splenic sequestration is usually effectively treated with packed red cell transfusion. If there is a propensity for recurrence, splenectomy may be indicated.

Immune Hemolytic Anemia The first description of this disease is credited to Chauffard and Troisier who, in 1908, demonstrated autohemolysins in the serum of several patients with acute hemolytic anemia. Three years later, Micheli performed the first planned, successful splenectomy, thus stimulating the application of splenectomy for hematologic disease. Immune hemolytic anemia (IHA) is a disorder in which immunoglobulin G (IgG) and/or IgM antibodies bind to erythrocyte surface antigens and stimulate erythrocyte destruction. This occurs through the complement and reticuloendothelial systems. IHA is classified as autoimmune, alloimmune, or drug-induced. Alloimmune hemolytic anemia occurs only after exposure to allogeneic erythrocytes, such as through blood transfusion, pregnancy, or transplant. There is no antibody reactivity against autologous red cells. Acute hemolysis after transfusion is estimated to occur in 0.0003% to 0.0008% of patients, and a delayed response is seen in 0.05% to 0.07%.95 Drug-induced IHA occurs as drug-induced antibodies recognize red cell antigens or erythrocyte-bound drug. More than 150 drugs have been associated, including methyldopa, ibuprofen, penicillin, and second- and third-generation cephalosporin.96 Drug-induced IHA should resolve with cessation of the medication in question but may require corticosteroids and have a protracted recovery. Autoimmune hemolytic anemia (AIHA) is estimated to occur in 1 per 100,000 per year, with a prevalence of 17 per 100,000.97 It is an antibodymediated process that involves IgG or IgM antibodies. In cases of IgGmediated disease, antibodies bind to the erythrocyte and are recognized by the Fc receptors of macrophages and other phagocytic cells of the

reticuloendothelial system. In contrast to IgG antibodies, IgM antibodies readily activate the classical complement pathway and may lead to intravascular hemolysis. Additionally, IgM-bound erythrocytes may undergo extravascular hemolysis, particularly in the liver. Both warm and cold antibodies have been reported. Warm antibodies react best at 98.6°F (37°C), account for the approximately 70% of cases, and are mainly due to IgG.96 Secondary causes of warm AIHA have been reported, most notably in the context of lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL), lupus, infectious mononucleosis, HIV, and autoimmune hepatitis.96 The presentation of warm AIHA is variable and includes vague constitutional symptoms consistent with anemia, such as weakness and dizziness. Additionally, fever, abdominal pain, cough, and bleeding may be seen. Symptoms vary with the severity of the hemolysis. Mild jaundice is often present. Splenomegaly is seen in approximately half of cases, and 25% may have associated cholelithiasis. While reticulocytopenia may occur early in the disease prior to adequate marrow response, reticulocytosis and elevated mean cell volume (MCV) are generally seen. Mild to moderate indirect hyperbilirubinemia and elevated lactate dehydrogenase (LDH) are often seen. Platelets are usually normal, but occasionally, AIHA and immune thrombocytopenic purpura occur together (Evan syndrome). More than 95% of patients with warm AIHA have a positive Coombs test (direct antiglobulin test), which indicates that antibodies or complement system are bound to the red cell surface antigens in vivo. Therapy is guided by the severity of the hemolysis, with first-line treatment being corticosteroids. Prednisone therapy (1-1.5 mg/kg/d) is maintained for 3 weeks, with rapid response being the norm. If a satisfactory response is achieved, the steroid is gradually tapered over 6 months to avoid relapse. Approximately 80% of patients have a partial or complete response to steroids, but only 20% to 30% are cured.96 In nonresponders or those requiring maintenance steroid dose greater than 10 to 15 mg of prednisone daily, second-line therapy should be considered. These options include splenectomy or rituximab, a monoclonal antibody against CD20 found on the surface of B cells. Splenectomy can lead to good short-term results, with early response in approximately 70% of patients and cure in 20% to 60%. Drawbacks are lack of a reliable way to predict outcome to splenectomy,98 risk of long-term sepsis, and possible increased risk of thrombosis. Rituximab is increasingly used as second-line treatment, with response rates that appear

similar to splenectomy. There are no randomized trials comparing secondline therapies, so the choice of splenectomy or rituximab is based largely on patient and physician preferences and availability of newer medications.96 In contrast, cold agglutinin disease is due to IgM, resulting in intravascular hemolysis. Acute cold agglutinin disease is due to infections, whereas the chronic form occurs in lymphoproliferative or neoplastic diseases.96 Primary cold agglutinin disease may only present with mild anemia and may respond favorably to cold exposure avoidance. Corticosteroids are less effective than in warm AIHA and require high doses. Rituximab is recommended as firstline therapy, with a 60% response rate. Plasmapheresis offers a temporary response in acute hemolytic crises. Splenectomy is ineffective in cold agglutinin syndrome. Paroxysmal cold hemoglobinuria is an uncommon form of AIHA and is generally self-limited and treated with supportive care. Most cases occur in children, usually after a viral illness. Corticosteroids are often given to children with severe anemia but with unclear effectiveness.

PURPURAS Immune Thrombocytopenia Immune thrombocytopenia (ITP) is the most common hematologic indication for splenectomy. The terminology of primary ITP replaces the previous term idiopathic thrombocytopenia purpura.99 ITP is an acquired disorder in which platelets are destroyed by circulating antiplatelet antibodies, often IgG antibodies targeted against glycoprotein IIb/IIIa proteins. Antibody-coated platelets bind to antigen-presenting cells via Fc receptors primarily in the spleen, leading to platelet destruction. An alternate mechanism for platelet destruction is via T-cell–mediated lysis. The spleen is the source of antiplatelet antibody production as well as the major site of plateletantiplatelet antibody complex destruction by macrophage-induced phagocytosis. Antiplatelet glycoprotein antibodies also impair platelet production in the bone marrow by megakaryocytes, impairing the ability to compensate for the increased rate of platelet removal from the blood.100,101 The diagnostic criteria for primary ITP are a platelet count less than 100 ×

109/L without an obvious initiating or underlying cause, whereas secondary ITP encompasses ITP associated with underlying diseases, infections, or medications.99 The incidence is estimated to be between 1.6 and 4 per 100,000 per year.99 Female patients outnumber males 3 to 1. Many patients are diagnosed incidentally on routine evaluations.102 Bleeding in ITP is usually not severe, even with very low platelet counts. Mucocutaneous bleeding involving the skin, oral cavity, and gastrointestinal tract is the most common clinical presentation.101 Central nervous system (CNS) bleeding is estimated to occur in 1.4% (95% CI, 0.9%-2.1%) of adult patients with chronic ITP generally with platelet counts 30 × 109/L and no bleeding complications.99 The goal of all medical therapies is to increase platelet count to a safe level and not to cure. Treatment in newly diagnosed ITP is aimed at rapid increase of platelets to treat or prevent bleeding. First-line treatment is usually a short course of corticosteroids (1 mg/kg/d for 2-3 weeks and rapidly tapered) and/or intravenous immunoglobulin infusion if a more rapid increase in platelets is needed.99,106 Most patients respond within 1 week, but platelet counts

decrease again when the dose is tapered, with long-term remission in only 5% to 30% of patients.102 A shorter course of high-dose dexamethasone may also be effective.106 Intravenous immunoglobulin (IVIg) or anti-Rh(D) (in Rhpositive patients) can be used if corticosteroids are contraindicated. In adults who do not respond to corticosteroids or with chronic ITP who require more than a minimal dose of corticosteroids to maintain safe platelet counts, second-line therapy is indicated. The objective of second-line therapy is to provide long-term and durable results. Splenectomy remains the most effective single therapy for ITP, with a complete or partial response rate of >80% and a cure rate of about 60% at 10 years.108,109 In most patients, the platelet count rises to >100 × 109/L within 7 days. Rarely, platelet normalization is more gradual over a period of months. Indications for splenectomy include patients who fail to respond to first-line therapies, who recur after steroid taper, who respond to medical therapy but cannot tolerate the side effects, or who develop intracranial bleeding or profound gastrointestinal bleeding and do not respond to intensive medical treatment. The use of splenectomy as second-line treatment is declining, as new second-line therapies, such as rituximab and thrombopoietin receptor (TPOR) agonists, emerge.110 While initial response rates with rituximab are >50%, long-term response after 5 years is 4-6 cm and heterogeneity).22,57 Recently, this paradigm has been challenged— especially at high-volume centers—with the success laparoscopic resection of malignant adrenal disease.18,58,59 Donatini et al. showed that there was a decrease in postoperative morbidity but no difference in overall survival in patients who underwent laparoscopic section for stage I or II ACC with tumor size less than 10 cm as compared to open adrenalectomy.60 At our institution, we do not attempt minimally invasive adrenalectomy when local invasion is determined on preoperative imaging. Intraoperative difficulty with establishing tissue planes between the adrenal gland and neighboring structures, due to tumor extension, portends malignancy and should prompt immediate conversion to open adrenalectomy. In contrast to patients who require attempted curative resection of primary ACC, it is reasonable to consider endoscopic palliative adrenalectomy of primary tumors and metastases. Strong et al. report equivalence between laparoscopy and open surgery in terms of local recurrence, disease-free interval, and overall survival.61 Furthermore, there is a role for palliative laparoscopic resection for patients with symptomatic secondary tumors. Attempts at laparoscopic metastasectomy should be avoided in any patient with radiographic evidence of local invasion, as complete resection without

capsular disruption is unlikely.

Retroperitoneoscopic The posterior retroperitoneoscopic (RP) approach has quickly gained traction as an alternative, minimally invasive method to adrenal surgery that offers a more direct route to the retroperitoneal glands. This approach is usually performed in nonobese patients who have smaller lesions. Further, it is favored for bilateral lesions, as repositioning is not necessary.62 The posterior approach is particularly useful for patients with adrenal disease who have undergone prior abdominal surgery, since these patients might have dense adhesions that make an intra-abdominal exposure formidable. A few anthropometric parameters have been correlated with successful RP surgery: (1) less than 5 cm distance from Gerota’s fascia to the skin, (2) the 12th rib at or rostral to the renal hilum.63 Further, many surgeons will not perform RP surgery in obese patients given the difficulty with positioning and ventilation. However, this has been recently challenged.64,65 Epelboym and colleagues showed a decreased length of stay in patients with BMI >30 who were offered a posterior laparoscopic as compared to a transperitoneal approach.64 Walz et al. retrospectively analyzed 560 consecutive RP adrenalectomies performed from 1994 to 2006 for tumors ranging from 0.5 to 10 cm. They showed that this approach was safe (1.3% major complication, 14.4% minor complication, and 0% mortality rate) when performed by an experienced surgeon.66 Furthermore, when compared with transperitoneal laparoscopic adrenalectomy, the RP approach has been shown to take less time, result in less—albeit not likely clinically significant—blood loss, and is associated with fewer conversions to an open procedure.64

Partial Adrenalectomy Partial adrenal resection has the perceived benefit is sparing of the necessity of steroid replacement. Multiple small studies have found this approach a reasonable alternative procedure for benign, well circumscribed, and peripherally located tumors.47,67 In a small, randomized clinical trial of RP total versus partial adrenalectomy for aldosterone-secreting adenomas, Fu et

al. showed essentially noninferiority of partial adrenalectomy in terms of postop complications and functional outcome. There was a statistically significant but clinically irrelevant increase in operative blood loss in the partial adrenalectomy group.68 While some studies have shown benefit, Quillo et al. showed that in nearly 21% of patients undergoing total unilateral adrenalectomy for hyperaldosteronism, there was additional hyperfunctional tissue. Further, they were unable to identify any preoperative predictors of having nonsolitary versus solitary adenomas.69 Thus, given the significant risk of missing an additional functional adenoma during partial adrenalectomy, most surgeons opt for a total adrenalectomy. From a technical perspective, partial adrenalectomy is carried out in a similar way to total adrenalectomy as far as positioning and steps of dissection. While in general, preservation of the adrenal vein is recommended, division has been shown not to be detrimental to the function of the gland.47

EXPOSURES AND OPERATIVE TECHNIQUE General Considerations First, any bleeding substantially impairs visualization. Dissection should be gentle and every act of tissue division accompanied by a hemostatic maneuver. Second, obscuring blood is difficult to evacuate, and thus it tends to accumulate and obscure the bed of dissection. Third, removal of blood by suction tends to collapse the operative field and lead to tedious adjustment of retraction. For these reasons, we recommend small neurosurgical patties or rolled Kitner sponges to remove blood and to control minor bleeding. The use of instruments with hemostatic capability, such as ultrasonic shears or bipolar vessel sealing devices, can shorten operative times and make the use of clips or ligatures unnecessary. Fourth, patients with wide hips impair manipulation of instruments through the most lateral port. Port sites should be placed at least 7 cm apart to avoid limitations from instrument crowding. Finally, retraction of the adrenal can cause rupture and bleeding. When possible, retract the gland by touching the periadrenal fat rather than applying force to the capsule of the gland. The specimen side of the adrenal vein after ligation

can also be used as a handle for retraction. Otherwise, a rolled Kitner sponge held with a grasper can provide gentle and effective traction. For retraction we recommend using a fan retractor. This is an adjustable broad-based, atraumatic instrument that provides excellent retraction on larger organs like the liver and smaller areas like the periadrenal fat. When combined with hook cautery or LigaSureTM, the surgeon has the ability to be expedient around the lateral liver edge and precise around the IVC.

Positioning As in all operations, patient positioning and exposure are critical to the success of adrenalectomy. The details of the positioning depend upon the approach selected. Figure 78-1 depicts the positioning for the laparoscopic transperitoneal approach. Patients are placed in the lateral decubitus position, which favors retraction of the abdominal viscera by gravity and facilitates exposure of the adrenal gland. We use a pneumatic beanbag to help secure patients in the proper position. In obese patients, it may be useful to position the anterior border of the patient’s body near the edge of the bed and allow the abdominal pannus to hang over the edge. Of note, the hips should be relatively open as compared to the shoulders.

FIGURE 78-1 Optimal positioning of patient for a left laparoscopic adrenalectomy in the lateral decubitus position. The midabdomen is placed over the break in the table to optimize trunk extension and reduce interference with instrument movement by the iliac crest. The anterior abdominal wall should not be compressed. To facilitate exposure, the surgical table should be flexed and a kidney bar elevated with the apex located slightly higher than the midpoint between the costal margin and the iliac crest. Care should be taken during flexion in the elderly and in patients with spine disease. The patient should be secured to the table with wide tape, an axillary roll placed, and all pressure points should

be adequately protected, including the peroneal nerves. When preparing for RP adrenalectomy, the endotracheal tube and intravenous, arterial, and Foley catheters are placed with the patient in the supine position. The patient is then flipped into the prone position, with the hips and knees flexed. This positioning requires the use of bolsters across the chest and hips, as well as sufficient padding for the face, arms, and knees. The abdomen should hang down between the two transversely positioned bolsters.

Laparoscopic Adrenalectomy RIGHT LAPAROSCOPIC ADRENALECTOMY Step 1: Port Positioning. The patient is placed in the left lateral decubitus position, and the surgeon marks four port sites along the right costal margin from the xiphoid to the midaxillary line. Either a Veress needle entry or a muscle-splitting open entry can be used to gain access to the peritoneal cavity. After insufflation of the peritoneal cavity and placement of additional ports under direct vision, the fan retractor is placed in the most medial port and the camera is placed in the second most medial port (Fig. 78-2).

FIGURE 78-2 Port placement for a right laparoscopic adrenalectomy. In this example, abdominal entry is gained under direct visualization through the most medial site. Step 2: Expose the Retroperitoneum. The hepatic flexure of the colon is

freed from its attachments and allowed to retract inferomedially by gravity (Fig. 78-3). The fan retractor initially retracts the right lobe of the liver in the medial direction, and the right triangular ligament is taken down with a hook electrocautery (Fig. 78-4). This mobilization enables superior and anterior retraction of the right lobe of the liver, which uncovers the retroperitoneum near the adrenal gland (Fig. 78-5). In most cases, the kidney, periadrenal fat, and IVC are visible after this maneuver (Fig. 78-6).

FIGURE 78-3 Initial view of right upper quadrant in a right laparoscopic adrenalectomy. The arrow indicates the direction of liver retraction from the epigastric port.

FIGURE 78-4 View during right laparoscopic adrenalectomy with the liver retracted from the epigastric port. Some attachments of the right lobe of the liver to the diaphragm have been divided. The dotted line indicates the line of further peritoneal incision to mobilize the right lobe of the liver from the diaphragm.

FIGURE 78-5 View during right laparoscopic adrenalectomy after initial dissection to mobilize the right adrenal. The dotted line shows the peritoneal incision under the retracted liver that exposes the adrenal.

FIGURE 78-6 Dissection to expose the adrenal gland during right laparoscopic adrenalectomy. Step 3: Approach the Adrenal Gland. We begin the dissection in the superolateral border of the periadrenal fat with a hook electrocautery. This exposes the diaphragm posteriorly, and the dissection is carried out in the medial direction along the superior border of the periadrenal fat. A few small arteries are typically located in this area, which can be controlled with electrocautery or a hemostatic device. Careful dissection with blunt graspers should be used while approaching the IVC, near the superomedial border of the periadrenal fat. Step 4: Divide the Adrenal Vein. After establishing the superomedial corner of the periadrenal fat, the dissection is carried down in the caudal direction between the IVC and periadrenal fat. The tissue plane between the IVC and the adrenal vein is extremely thin, and thus blind use of hook cautery should be avoided. We prefer to use a combination of gentle, blunt dissection and the LigaSure device. The adrenal vein typically resides near the top third of this medial border and approaches the IVC at approximately a right angle. After

clip or stapler ligation of the adrenal vein, this medial plane of dissection opens significantly (Fig. 78-7). Notably, some surgeons routinely divide the adrenal vein with the LigaSure device without the use of a clips or staples.

FIGURE 78-7 Dissection to expose the adrenal vein during right laparoscopic adrenalectomy. The length of the right adrenal vein is exaggerated in this schematic. Step 5: Dissect the Adrenal Gland from the Retroperitoneum. At this point, the specimen side of the adrenal vein can be grasped for retraction. The inferomedial border of the dissection also requires careful blunt dissection, with special attention to avoid injuring the renal hilar vessels. The dissection is then carried laterally along the superior surface of the kidney. Special care must be taken to avoid accidental ligation of any arterial branches to the superior pole of the kidney. Once the plane of dissection is established between the inferior border of the periadrenal fat and the kidney, the only remaining attachments are posterior and lateral to the adrenal gland. A blunt grasper can be used to elevate the adrenal gland in the anterior direction, with special care taken to avoid disruption of the adrenal capsule. The remaining

posterior and lateral attachments can be divided with a LigaSure or Harmonic scalpel device. The dissection should clear all fibro-fatty and lymphatic tissue from the diaphragmatic surface. Step 6: Removal of the Adrenal Gland. Once all attachments are divided, the gland is placed into an endoscopic bag for removal. If appropriate, the mouth of the bag can be exteriorized and the specimen can be morcellated and removed through a port incision. This maneuver should always be performed under laparoscopic vision, as opposed to blind morcellation. Alternatively, the specimen can be removed intact and en bloc, which typically requires dilation of the fascia and skin.

LEFT LAPAROSCOPIC ADRENALECTOMY Step 1: Port Placement. The patient is placed in the right lateral decubitus position and the surgeon marks three or four port sites along the costal margin from the xiphoid to the posterior axillary line. Sometimes the fourth port is not needed, as the spleen retracts medially with gravity (Fig. 78-8).

FIGURE 78-8 Port placement for left laparoscopic adrenalectomy in the right lateral decubitus position. In this example, initial abdominal entry is gained through a medial incision. A fourth port is often not required on the left. Step 2: Expose the Retroperitoneum. The splenic flexure of the colon is taken down (Fig. 78-9). The left liver and spleen are mobilized from the diaphragm using hook electrocautery. With medial mobilization of the spleen, the retroperitoneum is exposed. The left kidney, periadrenal fat, and tail of the pancreas are often visualized at this point.

FIGURE 78-9 View during left laparoscopic adrenalectomy, showing division of the peritoneum over the kidney and progressive detachment of the spleen from the left diaphragm. Step 3: Approach the Adrenal Gland. The dissection begins in the superolateral corner and proceeds in the medial direction between the spleen and the superior border of the adrenal gland. The splenic vessels are often in close proximity to this plane of dissection. Once the superomedial corner is reached, the tail of the pancreas and the inferior phrenic vein can often be seen. Note that the pancreas tail can appear similar to the adrenal gland (Fig.

78-10).

FIGURE 78-10 View during left laparoscopic adrenalectomy. The spleen had been partially mobilized and is retracting to the right by gravity. The separation between the posterior pancreas and the anterior surface of the left adrenal had been developed. The left renal vein is exposed, as well as the takeoff of the left adrenal vein. Step 4: Divide the Adrenal Vein. The dissection continues in the inferior direction along the medial border. The inferior phrenic vein can be used as an anatomic landmark and can be divided if necessary. The left adrenal vein is often located in the inferomedial portion of the dissection and often joins the inferior phrenic vein prior to joining with the renal vein (Fig. 78-11).

FIGURE 78-11 View during left laparoscopic adrenalectomy. The spleen is fully mobilized. The adrenal vein has been divided between endoclips. The dotted line indicates the line of resection. Step 5: Dissect the Adrenal Gland from the Retroperitoneum. After adrenal vein ligation, the dissection continues along the inferior border between the adrenal gland and the kidney. In a similar fashion to the right adrenalectomy, the remaining posterior and lateral attachments are divided flush to the surface of the kidney and diaphragm, and the adrenal tumor is removed in bloc with the surrounding periadrenal fat. Again, the specimen side of the divided adrenal vein can be grasped as a handle for retraction.

RETROPERITONEOSCOPIC

Step 1: Port Placement. A small transverse incision is made just caudal to the tip of the 12th rib, and sharp dissection is used to dissect through the subcutaneous tissues and deep fascia. The length of this incision should be around 1.5 cm, which should be enough to accommodate the surgeon’s index finger. Digital examination with the index finger can be used to confirm that the dissection is through the deep fascia, and it allows palpation of the smooth underside of the ribs. Some authors recommend placement of the trocars 1 to 2 cm caudal to the 12th rib to prevent neuralgia.63 A second lateral 5-mm port is placed at near the midaxillary line at the same craniocaudal level under direct palpation, using the index finger as a guide through the first incision. Then a third 5-mm port is placed similarly under digital palpation, just lateral to the paraspinous muscles at the same craniocaudal level. This medial port should be approximately 3 or 4 cm caudal to the lowest rib. Then a 12-mm balloon port is placed in the middle incision to ensure an airtight seal. The space is insufflated to a pressure of 20 to 30 mm Hg. A 30-degree 10-mm scope is placed in the middle trocar with the angled view facing the ceiling. Step 2: Expose the Peritoneal Lining. A blunt grasper is used though the lateral port to dissect through the Gerota fascia. Using blunt dissection, the tissues around the medial and lateral ports are cleared and space is created posterior to the kidney and adrenal gland. Usually, the paraspinous muscles can be seen medially. With some blunt dissection, the peritoneal lining can be visualized laterally. Inferiorly, at the floor of the dissection (anterior), careful blunt dissection can be used to visualize the kidney. Step 3: Approach the Adrenal Gland. Dissection is carried along the superior border of the kidney from lateral to medial to separate the top of the kidney from periadrenal fat and to mobilize the kidney off the peritoneum such that it autoretracts inferiorly, which is necessary to expose the inferomedial portion of the adrenal gland. Usually during this portion of the dissection, the adrenal gland itself becomes evident through the periadrenal fat. On the right side, the IVC is found anterior and medial to the inferomedial border of the periadrenal fat. Step 4: Divide the Adrenal Vein. The adrenal vein is usually anterior and thus can be difficult to visualize. In contrast to the laparoscopic approach, the

adrenal vein is seen relatively late in the dissection when performing an RP adrenalectomy. Division of the adrenal vein can be done with a LigaSure device with or without clips. The specimen side of the adrenal vein can be used to retract the adrenal gland in the cephalad and posterior directions. Step 5: Dissect the Adrenal Gland from the Retroperitoneum. The remaining attachments between the periadrenal fat anteriorly and superiorly can be divided with a LigaSure device or electrocautery. Step 6: Removal of the Adrenal Gland. Removal of the specimen can usually be achieved without morcellation or extension of the incision. Closure of the deep fascia in the middle incision usually requires only a single simple nonabsorbable suture. Hernia through these posterior incisions is uncommon. As with laparoscopic adrenalectomy, the small adrenal arteries can be controlled with either hook electrocautery or a hemostatic device; clips are usually not required. Small holes in the peritoneum are of no significant consequence and do not require repair.

Open Adrenalectomy ANTERIOR The anterior approach allows access to both adrenal glands as well as extraadrenal foci as in the case of pheochromocytoma. The patient is placed in the supine position on the operating table, and either a midline laparotomy or bilateral subcostal incision can be used. We find that the subcostal incision is adequate but the exposure is not as open as in the thoracoabdominal approach (below). For right-side access, the hepatic flexure of the colon is taken down inferiorly, the liver is retracted superiorly, and a Kocher maneuver is performed to expose the retroperitoneal space. The Gerota fascia is identified and incised. Once the adrenal gland is exposed, the lateral and superior aspects of the gland are mobilized and the adrenal vein is ligated and divided. Given the proximity of the right adrenal gland to the IVC, the surgeon must use care when dissecting and ligating the right adrenal vein. The left adrenal gland can be exposed from an anterior approach by a

medial visceral rotation of the stomach, spleen, splenic flexure of the colon, and pancreas toward the midline. The left adrenal vein can drain either into the left renal vein or the left inferior phrenic vein. The remainder of the dissection is similar to the right side.

Thoracoabdominal Approach For open adrenalectomy, we prefer the thoracoabdominal approach due to the superior exposure that it allows, the close proximity of the incision to the lesion, and the improved ability to remove large tumors. Much like in the laparoscopic approach, the patient is placed in the lateral decubitus position with the hips open and the shoulders closed. The shoulders should be roughly 90 degrees to the table. The dissection is carried down between the eighth and ninth ribs, allowing the full exposure of the adrenal gland, renal fossa, and surrounding tissues. A vascular load GIA stapler is used to divide the diaphragm close to the lateral attachments, which facilitates closure at the end of the case. The remainder of the dissection is carried out as mentioned previously. A tube thoracostomy should be placed or the pneumothorax can be evacuated during closure.

RETROPERITONEAL In this operation, the patient is placed in the prone position on the operating table, and a curvilinear incision is made starting in the paramedian line and extending laterally. After the skin and subcutaneous tissues are incised, the latissimus dorsi muscle is divided with electrocautery near its origin and the serratus posterior is divided in a similar way. The 12th rib is removed to facilitate the exposure, and the 11th rib and the pleura are retracted superiorly, which exposes the underlying the Gerota fascia. The fascia is incised, and the adrenal gland and the kidney are exposed. The superior vessels are ligated and divided, and the superior aspect of the gland is dissected free. After the gland is mobilized, the adrenal vein is isolated, ligated, and divided. When the gland has been removed, closure is performed in layers.

COMPLICATIONS

The intraoperative risks of adrenal surgery are due largely the close proximity to large vascular structures and other retroperitoneal organs. Consequently, minimally invasive adrenalectomy poses the same anatomic risks as open adrenalectomy: major vascular injury (IVC, splenic vessels, renal vessels) and injury to the spleen, liver, and colon. Although rare, transection of the porta hepatis, hepatic artery, ureter, and renal artery has been reported.70 Pneumoperitoneum poses several risks for this operation aside from traumatic injury relating to port placement. The dissection of the adrenal gland is in close proximity to the posterior aspect of the diaphragm, making ipsilateral pneumothorax a potential complication necessitating a tube thoracostomy in some. Further, pneumoperitoneum can impair venous return, which can be particularly dangerous in the setting of catecholamine surges during resection of pheochromocytoma. This risk can be minimized with preand intraoperative hydration. The spleen and liver are also at risk for injury during laparoscopic adrenalectomy; these organs can sustain trocar injuries, capsular tears from grasping or retraction, or vascular injury. The most life-threatening complication of adrenalectomy is a vascular injury. On the right, the renal vein can have an oblique course and course through the inferior portion of the dissection, causing confusion with the adrenal vein. The right adrenal vein is often well visualized with laparoscopic technique but is also of variable location in a superior-inferior plane and anterior-posterior plane. A vein with a diameter significantly smaller than the length of a standard endoscopic clip should be viewed with skepticism if thought to be the adrenal vein. A vein with a diameter significantly larger than an endoclip or that does not clearly connect to the variegated dark yellow adrenal gland is a suspect for the renal vein and should not be divided without certain identification. On the left, there can be a segmental upper pole renal artery that lies just deep to the lower portion of the adrenal. The adrenal arteries are all quite narrow and can be ligated with the electrocautery or vessel-sealing device without the use of clips. Regarding RP adrenalectomy, higher insufflation pressures are tolerated well with less hemodynamic compromise, in comparison to the laparoscopic technique. Releasing insufflation and hyperventilating the patient can relieve intraoperative hypercarbia. Subcutaneous emphysema and subcostal nerve dysfunction can be observed after RP adrenalectomy, and both are transient in nature. Hypoglycemia is a well-recognized complication in adrenalectomies performed for pheochromocytoma. In our experience, roughly 4% of patients

develop blood glucose levels less than 50 mg/dL, thought to be due to rebound hyperinsulinemia. This most often occurs in the first 24 hours and is associated with higher 24-hour urinary metanephrine levels, longer operative times, and larger neoplasms.71 In an effort to identify correctable causes of post-adrenalectomy complications, Hauch et al. performed a cross-sectional analysis of 7829 adrenalectomies included in the Nationwide Inpatient Sample from 2003 to 2009. They found that surgeons performing less than five adrenalectomies per year were more likely to have pulmonary, cardiovascular, bleeding, and technical complications than their counterparts performing greater than five adrenalectomies per year. Similarly, there were more complications seen in bilateral operations and those for malignancy.72

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INDEX Please note that index links point to page beginnings from the print edition. Locations are approximate in e-readers, and you may need to page down one or more times after clicking a link to get to the indexed material. Page numbers followed by f denote figures; those followed by t denote tables. A AAA. See abdominal aortic aneurysm AASLD. See American Association for the Study of Liver Diseases AAST. See American Association for the Surgery of Trauma abdominal aortic aneurysm (AAA), 290, 358–363, 361f–363f abdominal compartment syndrome, 353, 366 abdominal wall enterocutaneous fistulas and, 274 hernias bariatric surgery and, 654 SBO and, 679 incisions, 167–179 abdominothoracic, 170–172, 175f for appendectomy, 167, 170, 172f closure, 179–186 Kocher subcostal, 169–170, 172f L- and J-shaped, 172, 178f mass closure, 180, 181f midline, 168–169, 168f, 169f

muscle-splitting, 169, 173f paramedian, 169, 169f, 170f, 171f Pfannenstiel, 170, 174f retention sutures for, 181–182 retroperitoneal and extraperitoneal, 172–176, 177f, 179f surgical site preparation for, 168 temporary closure, 182–183 transverse and oblique, 169–170 vertical, 168–169 pediatrics, 138–141 abdominoperineal resection (APR) for anal margin cancer, 1025–1026 for anal melanoma, 1027 for anal SCC, 1019, 1021, 1024–1025, 1024t HALS for, 915 instruments for, 897 laparoscopy for, 913–915, 914f for rectal cancer, 977, 980, 981, 984, 1002–1005, 1003f–1004f abdominothoracic incisions, 170–172, 175f ablation. See also radiofrequency ablation endoscopic, for BE, 417 for liver metastases, 1104–1114 MWA, 1099, 1108–1110, 1110f Ablation Intestinal Metaplasia-II (AIM-II), 456 abnormal pancreaticobiliary duct function (APBDJ), 1223 Abraxane. See albumin-bound (nab)-paclitaxel ABS. See artificial bowel sphincter abscesses, 257–277, 259f. See also specific organs bowel blunt trauma and, 322 clinical presentation, 258 Crohn’s disease and, 796, 802, 812, 812f diagnosis, 258–259 diverticular disease and, 772–773 management, 259–263, 259t–262t

pathophysiology, 257–258 perforated appendicitis and, 730 from RFA, 1108 source control for, 261–263, 262t stitch, 188 UC IPAA and, 834 visceral artery aneurysms and, 367 ABW. See adjusted body weight acarbose, 520 ACC/AHA. See American College of Cardiology/American Heart Association ACCORD-03. See Action Clinique Coordonees en Cancerologie Digestive ACCs. See adrenocortical carcinoma acetaminophen, 37 acetylcholine, 395 achalasia, 382–387, 382t, 385t–387f, 444 acidosis, 141, 182, 328 metabolic, 20, 21, 136 ACOSOG. See American College of Surgeons Oncology Group acquired immune deficiency syndrome (AIDS), 322, 685, 736, 1016, 1217 ACS. See American College of Surgeons ACTH. See adrenocorticotrophic hormone actinomycosis, 307, 309, 685, 957 Action Clinique Coordonees en Cancerologie Digestive (ACCORD-03), 1022 acute appendicitis, 728–746, 731f–733f, 732t, 733t acute complicated diverticulitis, 774–775 acute gastric stasis, 520 acute mesenteric insufficiency, 349–352, 350f–352f acute mesenteric lymphadenitis (AML), 303 acute mesenteric thrombosis, 349 acute myelogenous leukemia (AML), 564 acute necrotic collections (ANCs), 1262–1263, 1269, 1270 acute pancreatic fluid collection (APFC), 1269–1270

acute pancreatitis, 1259f, 1260f, 1303 analgesia for, 1294 ANCs for, 1262–1263, 1269, 1270 bacteremia and, 1294 bleeding with, 1287–1288 cholecystectomy for, 1261–1262 complications, 1269–1290, 1270t DBC for, 1260 debridement for, 1264–1266, 1264f, 1265f diagnosis, 1258–1259 ERCP for, 1257, 1261–1262 etiology, 1257–1258, 1258t fluid resuscitation for, 1261, 1294 infections and, 1294–1295 management, 1293–1299 MODS with, 1289 nutrition for, 1261, 1295 RAC for, 1260, 1261t, 1269, 1270t, 1293, 1293t, 1294t recurrence, 1305 recurrence of, 1306f severity, 1294 SIRS and, 1262, 1288–1289 thrombosis with, 1287 Acute Physiology and Chronic Health Evaluation (APACHE), 48, 260, 262, 293, 1035, 1041, 1167 acute pancreatitis and, 1258, 1294 pancreatic necrosis and, 1281 acute ulcerative colitis, 828–830 acute uncomplicated diverticulitis, 774 adalimumab, 758, 827 ADAMS13, 1412 Adams, W., 475 Addisonian crisis, 1434 adenocarcinoma. See also specific organs

ampulla of Vater, 1348 cholangiocarcinoma as, 1231 chronic pancreatitis and, 1305 CRC, 869–870 Cronkhite-Canada syndrome and, 852 gallbladder cancer as, 1223 mesenteric cysts and, 304 obscure lower GI bleeding and, 298, 298f staging, 449t, 450t UC IPAA and, 836 adenomas. See also specific organs CRC and, 862–863, 866–867, 866t, 867f, 867t, 868f gallbladder cancer and, 1223 MAP and, 846 rectal cancer and, 978–979, 979f adenomatous gastric polyps, 562–564, 563f, 564f adenomatous polyposis coli (APC), 91, 843, 863 adenomyomatosis, 1225–1226 ADH. See antidiuretic hormone adhesions bowel obstruction and, 19, 154, 677 Crohn’s disease and, 812 diverticular disease and, 773 with epiphrenic diverticula, 377 GISTs and, 585 from IPOM, 206 laparoscopy and, 97, 696, 895 laparotomy and, 243 from LIHR, 227 from mesh, 221 omentum, cholecystectomy and, 1166 radiation enteropathy and, 699 SBO and, 682–683, 697 Seprafilm® and, 233

stomach, 482 adjustable gastric band (AGB), 648-649, 649f laparoscopy for, 653, 662–664, 662f–664f revisions of, 666–668 adjusted body weight (ABW), 26–27 adjuvant chemoradiation, 476, 1240 for gallbladder cancer, 1229 for rectal cancer, 1010, 1011t adjuvant chemotherapy, 467, 559, 1027 for cholangiocarcinoma, 1240 for GISTs, 586t, 588–589, 601 for MCNs, 1331 for periampullary adenocarcinoma of pancreas, 1361 for rectal cancer, 977 adjuvant radiotherapy, 466, 559, 1240 ADMA. See asymmetric dimethyl arginine adrenal glands, 1433–1445, 1434t, 1445t adenomas, 1433–1436 cancer, FAP and, 844 cortex, 1433–1436 incisions to, 173–174 medulla, 1436–1437 metastases, 1438 adrenalectomy, 1438–1445 laparoscopy for, 1438, 1439f, 1440–1444, 1440f adrenocortical carcinoma (ACC), 1434, 1436 adrenocorticotrophic hormone (ACTH), 1433, 1434 adult respiratory distress syndrome (ARDS), 1289 Advanced Trauma Life Support (ATLS), 315 AFAP. See attenuated FAP afferent loop obstruction, 521 aflatoxin, 1077–1078 AFP. See α-fetoprotein AGA. See American Gastroenterological Association

AGB. See adjustable gastric band β-agonists, 17 Ahmed, Ali U., 830 Ahrendt, S. A., 1218 AIDS. See acquired immune deficiency syndrome AIHA. See autoimmune hemolytic anemia AIM-II. See Ablation Intestinal Metaplasia-II AIN. See anal intraepithelial neoplasia AIP. See autoimmune pancreatitis AirSeal, 924 AJCC. See American Joint Committee on Cancer Alabaz, O., 808 alanine aminotransferase (ALP), 1172, 1183 albendazole, 105, 1049 Albert, M., 1099 albumin, 688 albumin-bound (nab)-paclitaxel (Abraxane), 1376 Alcock’s canal, 933 alcohol acute pancreatitis and, 1257 ALDH2 and, 443 chronic pancreatitis and, 1303–1304 CRC and, 860 enterocutaneous fistulas and, 264 GERD and, 393, 404 HCC and, 1077 LES and, 395 rectal cancer and, 978 withdrawal from, 11 aldehyde dehydrogenase 2 (ALDH2), 443–444 aldosteronomas, 1435–1436 alkaline aminotransferase (ALT), 876 alkaline reflux gastritis, 521–522, 522f Allis clamps, 100, 236, 348, 355, 620f

ALP. See alanine aminotransferase ALPPS. See associating liver partition and portal vein ligation for staged hepatectomy ALT. See alkaline aminotransferase; anterolateral thigh flap ALTE. See apparent life-threatening events Altieri, M. S., 667 Altomare, D. F., 973 Altorki, N. K., 501 Alvarado, A., 731, 731t Amdrup, E., 603 amebic liver abscesses, 1041–1045, 1042t, 1043t, 1044f, 1045t American Association for the Study of Liver Diseases (AASLD), 1081, 1133, 1134 American Association for the Surgery of Trauma (AAST), 321, 321t, 323, 325, 325t, 1399 American Board of Surgery, 57 American College of Cardiology/American Heart Association (ACC/AHA), 12, 13 American College of Gastroenterology, 398, 416, 445, 845 American College of Surgeons (ACS), 5, 652 American College of Surgeons Oncology Group (ACOSOG), 565, 589, 599, 896 American Gastroenterological Association (AGA), 540 American Hospital Association, 5 American Joint Committee on Cancer (AJCC), 311, 710, 719, 870, 986, 1015, 1081, 1225. See also tumor-node-metastasis staging system on anal SCC, 1020–1021, 1020t on esophageal cancer, 447–449 on GISTs, 583 on lymph node stations, 451f American Society for Clinical Oncology (ASCO), 984 American Society for Metabolic and Bariatric Surgery (ASMBS), 652 American Society of Anesthesiologists (ASA), 10, 57, 699 American Society of Colon and Rectal Surgeons, 962, 1018 American Thoracic Society, 799

amine precursor uptake and decarboxylation (APUD), 712 aminoglycosides, 878 aminosalicylates, 800, 825 5-aminosalicylic acid (5-ASA), 296, 800, 825–826, 842 amitriptyline, 969 AML. See acute mesenteric lymphadenitis; acute myelogenous leukemia Ammori, J. B., 1335 amoxicillin, 15, 569, 774 amoxicillin-clavulanic acid, 878 amphotericin B, 1039 ampicillin, 988, 1184 ampulla of Vater, 148–150, 1348 Anal Cancer/HSIL Outcomes Research (ANCHOR), 1019 anal crypt, 796, 934, 957 anal fissures, 948, 949f anal intraepithelial neoplasia (AIN), 957, 1017–1019 anal manometry, 938, 962, 963f, 968 anal margin cancer, 1025–1026, 1025f, 1026f anal transition zone (ATZ), 832, 836, 934, 1015, 1019 anal verge, 980 analgesia. See also nonsteroidal anti-inflammatory drugs for acute pancreatitis, 1294 for CRC surgery, 878–879 for endoscopy, 57–58, 58t epidural, 9–10, 11, 18–19, 35–36 local, 9–10 opioid, 9, 19, 655 PCA, 9, 10, 11, 19 regional, 9–10, 214 TAP for, 10, 35 anaphylactic shock, 1052, 1117, 1403 anastomosis AAA and, 361 CDD and, 1180

cecal volvulus and, 788–789 cholangiocarcinoma and, 1239 Crohn’s disease and, 804, 817–818, 817f diverticular disease and, 770 duodenal atresia and, 150 EA/TEF and, 145, 146, 147 end ileostomy and, 240 enterocutaneous fistulas and, 268, 274 esophagectomy and, 493–494 imperforate anus and, 160, 160f IPAA, 250–251, 830, 832–836, 839–840, 845, 916–918, 917f, 918, 918f IRA, 831, 847 JIA and, 152 Kono-S, 817–818, 817f left hemicolectomy and, 906 meconium ileus and, 154 mucosectomy with handsewn anastomosis, for UC, 832 right colectomy and, 925, 925f right hemicolectomy and, 903 robotic surgery and, 923 single anastomosis gastric bypass, 666 tri-incisional esophagectomy and, 483–486, 486f UC and, 831 anastomotic leak, 322, 476, 479, 834 CDD and, 1180 EA/TEF and, 147 gastrectomy and, 544 GJ and, 603 IBD and, 264 MBP and, 34, 232 MIE and, 459 NEC and, 140 rectal cancer surgery and, 1008 TME and, 129

UC IPAA and, 834 ANCHOR. See Anal Cancer/HSIL Outcomes Research ANCs. See acute necrotic collections anemia, 11, 32, 283, 398 iron deficiency, 290, 653 PEH and, 412, 423 pyrogenic liver abscesses and, 1036 splenectomy for, 1406–1410 anesthesia, 3 for hemorrhoidectomy, 946–948, 947f for inguinal hernia repair, 197–198, 214 for liver resection, 1121 aneurysms AAA, 290, 358–363, 361f–363f celiac artery, 364t, 366 gastroduodenal, 366 gastroepiploic, 366 hepatic artery, 364t, 365 IMA, 366 pancreas, 366 pancreaticoduodenal, 366 renal artery, 364, 364t SMA, 364t, 365–366 splanchnic artery, 364–366, 364t splenic artery, 364–365, 364t, 1400–1401, 1401f stomach, 366 visceral artery, 363–367, 364t angiodysplasia, 295, 295f, 298, 298f, 771 angiography, 12, 285–286, 352. See also computed tomography angiography angiosarcoma, 568 angle of His, 395, 405, 431 ankylosing spondylitis, 797 anorectal abscess, 950–957, 953f anorectal ring, 831, 934, 980, 1015

anorectal varices, 296 anorectoplasty, 159 anoscopy, 284 Anson, B. J., 1433 antacids, 289, 511 antegrade colonic enema, 966 anterior proximal vagotomy, 633–634, 634f anterolateral thigh flap (ALT), 458 anthrax, 3–4 antibiotics, 4 for acute pancreatitis, 1262 for adrenocortical carcinoma, 143 for amebic liver abscesses, 1043–1044 for appendicitis, 736, 738 for cholangitis, 1184 for CRC surgery, 878 for Crohn’s disease, 296, 800 for diverticulitis, 774 for EA/TEF, 147 for enterocutaneous fistulas, 267, 268 for gastroschisis, 138 for H. pylori, 508 for imperforate anus, 159 for intestinal stoma MBP, 232–233, 233t for JIA, 152 for MVP, 14–15 for omphalocele, 140 for PEG, 59 for PF, 1383 for pouchitis, 835 for pyrogenic liver abscesses, 1037–1038 for rectal cancer surgery, 988 with splenectomy, 1414–1415 for SSIs, 185

anticoagulants, 15–16, 23, 59, 86, 352, 878 antidiuretic hormone (ADH), 106 antifungals, 1039 antihelminthics, 1049 anti-integrin antibodies, 801 antiphospholipid syndrome, 308 antithrombin III, 352 antithrombotic medications, 14–15, 15t antithymocyte globulin (ATG), 765 anti-TNF therapies, 801, 817, 827, 841 antrectomy, 6, 514, 615–621 anus adenocarcinoma, 1027–1028 anatomy, 933–934, 935f, 1015, 1016f chlamydial infections, 957–958 Crohn’s disease, 796–797 fistulas, 951–957, 954f–956f gonorrhea, 958 herpes simplex virus, 958 HIV and, 957 HPV and, 957 imperforate, 146, 158–160, 158f–160f melanoma, 1026–1027 SCC, 1015–1026 AIDS and, 1016 AIN and, 1017–1019 APR for, 1021, 1024–1025, 1024t HIV and, 1016, 1018, 1023–1024 HPV and, 1016–1017 metastases and, 1025 neoadjuvant chemoradiation for, 1021–1022, 1022t pathology, 1019–1020, 1020f smoking and, 1017 staging, 1020–1021, 1020t

syphilis, 958–959 vascular supply, 936f aorta, 101, 342–344, 343f aortic arch, 144 aortic regurgitation (AR), 14 aortic stenosis (AS), 13–14 aortocaval fistula, 359 aortoenteric fistula, 290–291, 291f APACHE. See Acute Physiology and Chronic Health Evaluation APBDJ. See abnormal pancreaticobiliary duct function APC. See adenomatous polyposis coli; argon plasma coagulation aphthous ulcers, 794 apnea, 136 APPAC. See Appendicitis Acuta apparent life-threatening events (ALTE), 137 appendectomy for carcinoids, 722 interval, 745 LA, 738–739, 740f–741f laparoscopy for, 124 McBurney incision for, 167, 170, 172f NSAIDs for, 10 OA, 738–744, 742f–744f Rocky-Davis incisions for, 167, 170, 172f appendicitis acute, 728–746, 731f–733f, 732t, 733t AIDS and, 736 chronic, 746 diverticulitis and, 769 HIV and, 736 liver abscess and, 1033 management, 736–744, 737t pediatrics, 734 perforations, 729, 730, 744–745

in pregnancy, 735–736 retroperitoneal abscess and, 309 Appendicitis Acuta (APPAC), 736, 737 appendicoliths, 746 appendicostomy, 254 appendix, 727, 728f adenocarcinoma, 747 cancer, 746–748, 746f, 747f carcinoids, 722, 722f, 747–748 fistulas, 265 mucoceles, 746–747, 746f, 747f normal, 745 apple-peel deformity, 151, 152 APR. See abdominoperineal resection APUD. See amine precursor uptake and decarboxylation AR. See aortic regurgitation Ardila-Hani, A., 536 ARDS. See adult respiratory distress syndrome Areja, D., 479 argon plasma coagulation (APC), 61, 61f, 290, 375 Aristotle, 1393 Arnbjörnsson, E., 729 arrhythmias, 13, 21, 366, 1114, 1289 arterial stimulation venous sampling (ASVS), 1370 arteriovenous fistula, 356–357 artery repair, 348 artificial bowel sphincter (ABS), 972, 972f, 973f AS. See aortic stenosis ASA. See American Society of Anesthesiologists 5-ASA. See 5-aminosalicylic acid Ascaris lumbricoides, 1171 ascites, 110f, 117, 117f, 220, 1132–1133 ASCO. See American Society for Clinical Oncology Asgeirrson, T., 38

ASMBS. See American Society for Metabolic and Bariatric Surgery aspartate aminotransferase (AST), 876, 1172 Aspergillus spp., 1077–1078 aspiration achalasia and, 382 COPD and, 17 of splenic cysts, 1403 aspiration therapy (AT), 75, 78f for amebic liver abscess, 1044 Aspire Assist, 643, 644t aspirin, 16, 523, 850–851 associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), 1119 AST. See aspartate aminotransferase asthma, 17, 397 ASVS. See arterial stimulation venous sampling asymmetric dimethyl arginine (ADMA), 33 asymptomatic appendicoliths, 746 AT. See aspiration therapy atelectasis, 11 ATG. See antithymocyte globulin athletic pubalgia, 217 ATLS. See Advanced Trauma Life Support atrial fibrillation, 15 atrophic gastritis, 509, 510t, 526, 562 attenuated FAP (AFAP), 844, 864 atypical neuroleptics, 11 ATZ. See anal transition zone Augmentin. See clavulanate autoimmune hemolytic anemia (AIHA), 1406, 1409–1410 autoimmune hepatitis, 1217, 1409 autoimmune pancreatitis (AIP), 1305 Avicenna, 551 azathioprine, 758, 801, 826–827, 1257

B Babcock clamp, 234, 333, 620f Bacillus anthracis, 3–4 bacteremia, 1041, 1294 bacterial translocations, 681–682, 728 Bacteroides spp., 258, 259, 309, 738, 774 BAE. See balloon-assisted enteroscopy Baer, J. L., 735, 1062 Bagloo, M., 544 Baik, Y. H., 128–129, 920 Baker, A. R., 1181 Bakker, N., 31 Balaphas, A., 1426 balloon dilation, 69, 76f, 1210–1211, 1210f, 1279 balloon expulsion testing, 962 balloon retrograde transvenous occlusion/obliteration (BRTO), 1135, 1145, 1146f, 1147f balloon sphincteroplasty, 1173–1174 balloon-assisted enteroscopy (BAE), 542 balsalazide (Colazal), 800 Balthazar, E. J., 732 Bancroft procedure, 618, 620f Bannayan-Riley-Ruvalcaba syndrome, 852, 865–866 Barabino, M., 113 Bardoczky, G. I., 106 bariatric surgery. See also Roux-en-Y gastric bypass cholelithiasis and, 668–669 ERAS for, 654–655 evaluating medical problems for, 653–654 nutrition and, 655 for obesity, 644, 647–650, 648f–650f, 654t pregnancy and, 669 robotic surgery for, 123 Barisic, G. I., 971

barium enema. See contrast enema barium esophagram, 382–383, 383f, 388, 388f, 389f barium swallow, 494 for epiphrenic diverticulum, 376, 376f for esophageal benign tumors, 378, 378f for esophageal cancer, 450, 452f for PEH, 424f, 425f, 435, 435f, 436 Barmparas, G., 679 Barrett esophagus (BE), 397, 414–419, 415f–419f, 447f, 455–457, 455t bariatric surgery and, 654 esophageal adenocarcinoma and, 444, 445 esophageal cancer and, 444 flexible endoscope for, 55, 56f gastrectomy for, 460–461 Roux-en-Y jejunal loop reconstruction for, 460–461 Barroso, F. L., 610 BARRxTM, 417 Bassi, C., 1326, 1327 Bassini, E., 193–194, 213, 214 Bayliss, W., 532 BE. See Barrett esophagus Beaumont, William, 6, 531–532 Beckwith-Wiedemann syndrome, 140, 1436 Beer, Edwin, 767 Beger, H. G., 1315–1316 Beger technique, 1315–1317, 1316f Behçet disease, 800 Belachew, M., 648 Bemelman, W. A., 808 Benefiber. See dextran Bengmark, S., 729 benign biliary strictures cholecystectomy for, 1212 from laparoscopic cholecystectomy, 1199–1213, 1204f–1210f, 1212t,

1213t from pancreatitis, 1213–1214, 1214f QoL with, 1213 benign diseases, 439–440, 441t benign tumors colon, 870–873 esophagus, 378 liver, 1061–1073, 1061t, 1062f, 1063t, 1064f–1066f, 1065t, 1068f–1070f, 1069t, 1072f, 1073f small bowel, 709–710 spleen, 1404–1405 benzathine penicillin G, 959 benzimidazoles, 1049 benzodiazepines, 11 Bergman, J. J., 1211 Berne technique, 1318 bevacizumab, 469 bezoars, 526 Bianchi, A., 755, 760 Bielefeldt, K., 538 bilateral oophorectomy, 1006 bilateral salpingo-oophorectomy (BSO), 850, 978 bile acids, 705, 860 bile ducts. See also benign biliary strictures; cholangiocarcinoma; common bile duct adenocarcinoma, 1347–1348 adenoma, 1071–1072 anatomy, 1159, 1160t injury MWA and, 1110 TACE and, 1100 laparoscopy for, 1245–1248, 1246f, 1248f obstruction, 1241–1242 biliary dyskinesia, 1251

biliary leak, 83f, 1052, 1121, 1166, 1200, 1386 biliopancreatic diversion (BPD), 648, 649f Billroth, T., 551, 603, 1382 Billroth I, 520, 544, 616–617, 616f–619f, 622f–625f Billroth II, 519, 520, 521, 523, 536, 544, 617–621, 622f biofeedback, 965, 969 biologics, 827, 835, 839 biomedical engineering, 6 bipolar electrosurgery, 105 bisacodyl (Dulcolax), 965 bismuth, 508 Bismuth, H., 1182, 1203 bladder cancer, 306 inguinal hernia repair and, 209 Bleday, R., 992 BLEED study, 293 bleeding. See also gastrointestinal bleeding with acute pancreatitis, 1287–1288 anal SCC and, 1020 CRC and, 874, 883 diverticular disease and, 771 esophageal varices, 1135f from esophagectomy, 495 from hemorrhoids, 945 pancreatic pseudocysts and, 1272 PPH, 1385–1386, 1386t from rectal cancer surgery, 1009 from splenic trauma, 1399 from stress ulcers, 523–524, 523t Bleibel, W., 1125 Blessman, J., 1044 α-blockers, 1346 β-blockers, 13, 282, 293, 695

for pheochromocytoma, 1346 retroperitoneal fibrosis and, 309 for varices, 1134 blood banks, 6 blood groups, 6 blood urea nitrogen (BUN), 20–21, 759, 876 blowhole colostomy, 238, 239f Bluett, M. K., 327 Blumgart, L. H., 1239 blunt trauma to bowel, 320–322, 320t, 321t hematoma from, 354 to liver, 324–330, 325f, 325t, 326t, 327f, 329f to spleen, 322–324, 323f splenic injury from, 1398 Boerma, D., 1185 Bogotá bag, 183, 335 second-look laparotomy and, 353 Bookwalter retractor for CRC surgery, 880 for vagotomy, 605f Boone, B. A., 1354 borborygmi, 520 Borchardt’s triad, 412 Boshier, P. R., 494 Bosi, H. R., 206 botulinum toxin (Botox) for achalasia, 384–385 for constipation, 966–967 for DES, 388 for gastroparesis, 526, 539–540 Bovie, William T., 6 Bovie device, 104 bowel obstruction, 19. See also ileus; large bowel obstruction; small bowel

obstruction with acute pancreatitis, 1288 from adhesions, 154 adhesions and, 677 carcinoids and, 717 CRC and, 679, 882–883 incisional hernia and, 220 malrotation and, 143 omphalocele and, 141 Bowen’s disease, 1018 Bozzini, Phillipp, 7, 7f BPD. See biliopancreatic diversion Bradley, D. D., 430 bradycardia, 136 Brandsborg, S., 835 Braun enteroenterostomy, 521 Bravo, G. A., 971 breast cancer GC and, 552 mesentery metastases and, 306 Brenner, M., 276, 337 bronchiolitis obliterans syndrome, 537 bronchoscopy for EA/TEF, 143–144, 147 for esophageal cancer, 450, 486 Brown, A., 1259 Brown, J. J. S., 735 Brown, M. R., 264 BRTO. See balloon retrograde transvenous occlusion/obliteration Brunet, C., 328 Brunner gland adenomas, 709 Brunschwig, Alexander, 1382 BSO. See bilateral salpingo-oophorectomy Bucher, P., 34

Budd-Chiari syndrome, 1054, 1093, 1125, 1126, 1136, 1137 Bueman, B., 332 bulking agents, 970 BUN. See blood urea nitrogen bupivacaine, 946–948 bupropion, 642–643, 643t burns, 523, 1108 Buscarini, E., 1176 Buschke-Löwenstein tumors, 1028 Byrne, C. M., 969 C CABG. See coronary artery bypass grafting Cadiere forceps, 125, 924, 926 caffeine, 395 Cagir, B., 1026–1027 CAIRO, 1007 calcium. See also hypercalcemia; hypocalcemia choledocholithiasis and, 1171 CRC and, 850 gastrectomy and, 523 gastrinoma and, 1369 calcium channel blockers, 384, 388–389, 1346 Calot triangle, 1159, 1166 Cameron’s erosions, 412, 423 Campos, A. C. L., 265 Campylobacter spp., 297, 824 Canavarro, K., 37 cancer, 439. See also metastases; specific organs and types cecal volvulus and, 789 Crohn’s disease and, 803 diverticular disease and, 773 gastric outlet obstruction and, 513 GERD and, 397

mesenteric venous thrombosis and, 352 minimally invasive surgery for, 114–117 obesity and, 640t SBO and, 700, 700f UC and, 828, 836 Candida spp., 309, 382, 1035, 1039, 1404 Cao, H. S., 1362 Cao, Z., 1328 capecitabine (Xeloda), 885 capecitabine/irinotecan (CAPEIRI), 885 capecitabine/oxaliplatin (CAPEOX), 885 CAPEIRI. See capecitabine/irinotecan CAPEOX. See capecitabine/oxaliplatin capnothorax, 107 capsule endoscopy, 284–285, 798–799 Carafate, 289 carbohydrate loading, 33–34 carbolic acid, 4 carbon dioxide H. pylori and, 507 incisions and, 177–178 laparoscopy and, 97, 105, 106, 107 for cholecystectomy, 1159 laser, 375 carboxymethylcellulose, 697 carcinoembryonic antigen (CEA), 876–877, 984, 1224, 1274, 1377 MCNs and, 1330 periampullary adenocarcinoma of pancreas and, 1348 SCNs and, 1324, 1328 splenic cysts and, 1403 carcinoid syndrome, 713–714, 721, 724 carcinoids, 525–526, 525t, 717–725 appendix, 722, 722f, 747–748 colon, 717, 722–723, 871

gastric, 561–562, 561f, 562f, 717, 719–720 metastases and, 724 obscure lower GI bleeding and, 298 rectum, 723–724, 723f SBS and, 757 small bowel, 705, 717, 718f, 721–722, 721f TNM for, 719, 719t cardiac output, 366 cardiac troponin, 11 cardiogenic shock, 11 cardiomyotomy, 377 cardiophrenicopexy, 431 cardiovascular disease (CVD). See also specific types obesity and, 639, 640t, 641 Cardona, K., 111 Carmona, R. H., 328 Carney’s triad, 581 Carney-Stratakis syndrome, 581 Caroli disease, 1195, 1198, 1231 Carr, B. I., 1099 Carrel, Alexis, 755 Carter-Thomason System, 182 Case, J. T., 768 case mix, 48, 50 catecholamine, 13 β-catenin, 1070–1071, 1223 Caudwell, E. W., 1433 CBD. See common bile duct CCD. See charge coupled device CCK. See cholecystokinin CDAI. See Crohn’s Disease Activity Index CDC. See Centers for Disease Control and Prevention CDD. See choledochoduodenostomy CDJ. See choledochojejunostomy

CEA. See carcinoembryonic antigen cecal bascule, 789 cecal volvulus, 686, 686f, 785, 786, 786t, 787f, 788–789 cecostomy, 788 CECT. See contrast-enhanced computed tomography celiac artery, 344, 364t, 366, 1376t celiac disease, 444, 705, 1126 celiotomy, 326, 351–352 cellulitis, 188 Centers for Disease Control and Prevention (CDC), 186t–187t Centers of Excellence, 652 central vascular ligation (CVL), 881 central venous catheter (CVC), 755 cephalosporin, 1038, 1184 cervical esophageal cancer, 457–458, 478 cetrimide, 1050 cetuximab, 469 CF. See cystic fibrosis CgA. See chromogranin A CHADS score, 15 Chagas disease, 382, 785, 786 Chandler, J. G., 101 Chang, D. T., 1111 Charcot’s triad, 1183 charge coupled device (CCD), 555 Chassard, J. L., 1025, 1026 chemoradiation adjuvant, 476, 1240 for gallbladder cancer, 1229 for rectal cancer, 1010, 1011t definitive, 467 neoadjuvant for anal SCC, 1021–1022, 1022t for esophageal cancer, 111, 467

for rectal cancer, 1010–1012, 1011t chemotherapy. See also adjuvant chemotherapy; neoadjuvant chemotherapy for anal SCC, 1021 for desmoids, 306 hemorrhoids and, 946 for liver cancer, 1098–1099 liver resection and, 1122 for PNETs, 1372 for rectal cancer, 1007 Chemotherapy for Oesphageal Cancer Followed by Surgery Study (CROSS), 469, 476 Chen, S. C., 693 CHF. See congestive heart failure Childs-Phillips transmesenteric plication, 696 Child-Turcotte-Pugh (CTP), 1083, 1083t, 1127, 1128t chlamydial infections, 957–958 chlorhexidine, 168, 957, 1050 chloroquine, 1044 Cho, M. J., 1199 chocolate, 395, 404 Choi, J. J., 736 Choi, Y. B., 115 cholangiocarcinoma, 1230–1242, 1232f, 1235f, 1347–1348 in choledochal cysts, 1196 diagnosis, 1231–1233, 1232f HCC and, 1079 hepaticojejunostomy for, 1239–1240, 1240f metastases, 1240–1241 MRCP for, 1232, 1236f pancreaticoduodenectomy for, 1237–1240, 1238f–1240f pathogenesis, 1231 with PSC, 1218 PTC for, 1232, 1236f risk factors, 1230–1231, 1230t

TNM for, 1233, 1233t, 1234t Cholangiocarcinoma Study Group, 1091 cholangiography, 1039. See also percutaneous transhepatic cholangiography for benign biliary strictures, 1205, 1209–1210, 1210f, 1211 for choledochal cysts, 1194 ERC, 1245–1246, 1247, 1349–1350, 1350f IOC, 1162–1163, 1163f, 1177–1179, 1245–1246 LAERC, 1247 MRC, 1245–1246 for PSC, 1217, 1217f for recurrent pyogenic cholangitis, 1215, 1216f for sphincter of Oddi stenosis, 1216 cholangitis, 1180–1185, 1216–1218, 1217f benign biliary strictures and, 1206–1207 cholecystectomy for, 1251–1253, 1253t choledochal cysts and, 1195 ERCP for, 82, 1184–1185 recurrent pyogenic, 1215–1216, 1216f cholecystectomy, 1162f–1165f. See also laparoscopic cholecystectomy for acute pancreatitis, 1261–1262 bariatric surgery and, 654 for benign biliary strictures, 1207, 1212 for cholangitis, 1185, 1251–1253, 1253t for cholecystitis, 1155–1157 for choledocholithiasis, 1177–1179, 1184f for cholelithiasis, 1156–1157 CRC and, 860 CVS for, 1251–1253, 1253t duodenal switch and, 666 for FGD, 1157–1158, 1158t for gallbladder cancer, 1226–1229, 1228f gastroparesis and, 537 NOTES for, 1169 NSAIDs for, 10

robotic surgery for, 124 SILS for, 1168 for small bowel carcinoids, 721 for sphincter of Oddi stenosis, 1216 cholecystitis, 733, 748, 1034, 1089 cholecystectomy for, 1156–1157 laparoscopic cholecystectomy for, 1166–1167 TG for, 1251, 1251t, 1252t cholecystokinin (CCK), 395, 561, 1158 choledochal cysts, 1191–1199, 1191t, 1192f–1196f, 1197f, 1231, 1248f, 1253 choledochoceles, 1192, 1198 choledochoduodenostomy (CDD), 1180–1182 LCD, 1247 choledochojejunostomy (CDJ), 1180, 1181–1182 choledocholithiasis, 1171–1182, 1257 cholecystectomy for, 1177–1179, 1184f ERCP for, 81–82, 82f, 1172–1182, 1173f, 1180f IOC for, 1177–1179 US for, 1172–1173 choledochoscopy, 1179 choledochotomy, 1179, 1207 cholelithiasis, 668–669, 1089, 1155–1156, 1158, 1223 cholera, 4 cholescintigraphy, 1156–1157 cholestyramine, 520 Christo, Campos, 1399 chromoendoscopy, 875 chromogranin A (CgA), 718, 722 chromosomal instability (CIN), 862 chronic appendicitis, 746 chronic calcifying pancreatitis, 1303 chronic gastric stasis, 520–521 chronic inflammatory pancreatitis, 1303 chronic lymphocytic leukemia (CLL), 1409

chronic obstructive pancreatitis, 1303 chronic obstructive pulmonary disease (COPD), 16–17, 397, 894 chronic pancreatitis, 1303–1320, 1307f, 1308f AIP, 1305 calcifying, 1303 clinical presentation, 1306–1307 ERCP for, 1307–1308, 1308f EUS for, 1308–1309, 1309t genetic, 1304–1305 idiopathic, 1304 inflammatory, 1303 lateral pancreaticojejunostomy for, 1311–1312, 1312f Marseilles-Rome classification for, 1303 medical management, 1309–1311 MRCP for, 1308, 1308f obstructive, 1303 pancreatectomy for, diabetes from, 1387 pancreaticoduodenectomy for, 1313–1315, 1314f, 1315f pathophysiology, 1306 PF and, 1383–1384 TIGAR-O system for, 1304, 1304t chronic ulcerative colitis, 830–833 CHRPE. See congenital hypertrophy of the retinal pigment epithelium Chu, H., 538 Chu, K. M., 479, 495 Chu, L. C., 1327 Chua, T. C., 747 Churchill, E., 486 chyle leak, 495 Cianni, R., 1101 cimetidine, 524 CIN. See chromosomal instability cinedefecography, 937 ciprofloxacin, 800, 835

circumferential resection margin (CRM), 924, 989 cirrhosis, 292, 513, 1081, 1172, 1231 bowel blunt trauma and, 322 PHTN and, 1125, 1127 spleen blunt trauma and, 323 cisplatin, 469 cisplatin, interferon α-2b, doxorubicin, and fluorouracil (PIAF), 1086–1087, 1086f, 1087f clarithromycin, 508, 509f, 569 Clark, H. B., 579 Clarke, J. O., 543 CLASICC. See Conventional Versus Laparoscopic-Assisted Surgery in Colorectal Cancer clavulanate (Augmentin), 774 CLE. See confocal laser endomicroscopy clindamycin, 15, 878 Clinical Outcomes of Surgical Therapy (COST), 896 clipping, 62–63, 63f, 64f CLL. See chronic lymphocytic leukemia Clonorchis sinensis, 1171, 1231 clopidogrel, 16 closed-loop obstruction, 677–678, 681 Clostridium difficile, 524, 827, 878 Clostridium spp., 187, 1404 closure. See also sutures abdominal wall incisions, 179–186 enterocutaneous fistulas, 266, 271, 273, 275–276, 275t fascia, 179–180 for laparoscopy, 182 APR, 914–915 loop ileostomy, 243 mesh for, 182 open abdomen technique for, 183, 183f PEH repair, 429, 429f

for SBO, 695–696 skin, 180–181 sutureless, 138, 139f, 202, 203f trocar-associated hernias and, 684 VAC, 183, 269, 957 CME. See complete mesocolic excision CMV. See cytomegalovirus coagulopathy, 59, 86, 524, 789 cocaine, 151 Cochrane Collaboration, 206 13C-octanoate acid breath test, 535 coffee bean sign, 786, 787f Colazal. See balsalazide COLDFIRE-1, 1113 colectomy. See also specific types for cecal volvulus, 788 for CRC, 880–881 complications, 884–885 laparoscopy for, 116–117, 116t for diverticular disease, 776 robotic surgery for, 123–124, 125 for sigmoid volvulus, 788 splenic injury from, 1398 for UC, 828–829, 831, 833 colitis. See also ulcerative colitis Crohn’s disease and, 813 infectious, 297, 800 lower GI bleeding and, 296–297, 296f, 297f collagen, 220, 769, 841 Collins, C., 1178 Collis gastroplasty, 407–408, 408f, 409f, 432 colon. See also colorectal cancer; large bowel obstruction anatomy, 873, 873f benign tumors, 870–873

cancer laparoscopy for, 896–897, 897t, 898f, 899f liver abscess and, 1033–1034 robotic surgery for, 123–124 carcinoids, 717, 722–723, 871 Crohn’s disease, 796, 813–816, 813f, 815f diverticular disease, 767–777 EMR in, 89–91, 90f ESD in, 89–91, 90f FAP, 844 GISTs, 871–872 ischemia, 681 visceral artery aneurysms and, 367 lipomas, 870–871 lymphomas, 872 metastases, 872–873 motility, 768 NETs, 871 penetrating trauma, 334 polyps in, 89–91, 90f tumors, 857–885, 858t volvulus, 686 Colon Cancer Laparoscopic or Open Resection (COLOR), 882, 896, 1007 colon cancer syndrome X, 851 colon conduit, 146 colonic fistulas, 265 colonic interposition, 489–491, 489f, 490f colonic transit testing, 962–963 colonic volvulus, 785–790, 786t, 787f, 788f colonoscopy for angiodysplasia, 295f complications, 88 contraindications, 86 for CRC, 875

decompression, 91–92 diverticular disease and, 771, 772 for FAP, 845 for GI bleeding, 284 indications for, 85, 85t lower GI bleeding and, 91 for Paget disease, 1028 for polypectomy, 88–89, 89f for rectal cancer, 979 splenic injury from, 1398 techniques, 86–88, 86f–88f for UC, 825 variable stiffness control for, 56–57, 56f COLOR. See Colon Cancer Laparoscopic or Open Resection colorectal cancer (CRC). See also familial adenomatous polyposis adenocarcinoma, 869–870 adenomas and, 862–863, 866–867, 866t, 867f, 867t, 868f bleeding and, 874, 883 bowel obstruction and, 679, 882–883 classification, 869t clinical presentation, 874–877 Crohn’s disease and, 874 differential diagnosis, 874 diverticulitis and, 769 epidemiology, 857 hamartomas and, 865–868 HNPCC, 846–850, 847t, 848t, 850t, 864, 864t IBD and, 841–842, 860–861 laparoscopy for, 113 for colectomy, 116–117, 116t MAP and, 846 pathogenesis, 861–863, 862f perforation and, 883 polyps and, 866–869, 866t, 867f, 867t, 868f

right colectomy for, 924–925, 924f, 925f risk factors, 857–861, 859t–861t robotic surgery for, 923–928, 924f–928f TME for, 925–928, 926f–928f splenectomy and, 1398 staging, 870, 870t stem cells and, 863 TNM for, 870, 870t treatment, 877–886, 879t, 886t colorectal liver metastases (CRLM), 113, 1099, 1117, 1118–1119 colostomy adjuvant chemoradiation and, 1022 blowhole, 238, 239f for Crohn’s disease, 804 divided loop, 240 end, 233–236, 234f, 235f, 973–974 for enterocutaneous fistula, 273 for HD, 157 for imperforate anus, 159 for intestinal stomas, 233–240, 234f, 235f, 237f–239f with laparoscopic APR, 915 leveling, 157 loop, 157, 236–238, 237f, 238f loop-end, 240 Comfort, M. W., 1303 common bile duct (CBD), 1156, 1158, 1159, 1162–1163. See also choledocholithiasis gallbladder cancer and, 1223, 1228 LCBDE for, 1178–1179 sphincterotomy and, 81 Common Terminology Criteria for Adverse Events (CTCAE), 1112 community-acquired peritonitis, 259–260, 259t complete mesocolic excision (CME), 575, 881 completion total pancreatectomy with islet auto transplantation (CPIAT),

1320 compression devices for laparoscopy, 98 for PEH, 426 for retroperitoneal hematomas, 335 for VTE, 22 computed tomography (CT) for AAA, 359, 359f for abscesses, 258–259, 259f for acute mesenteric insufficiency, 349 for acute mesenteric lymphadenitis, 303 for acute pancreatitis, 1259–1260, 1259f, 1260f for afferent loop obstruction, 521 for aldosteronomas, 1435 for amebic liver abscess, 1043 for appendicitis, 731–732, 732f, 732t, 734 for appendix, 733f for benign biliary strictures, 1204, 1204f for bezoars, 526 for bowel blunt trauma, 320, 321t for bowel obstruction, 19 for carcinoids, 718 for cholangitis, 1183–1184 for cholecystitis, 1157 for choledochal cysts, 1194, 1194f, 1253 for choledocholithiasis, 1175 for chronic pancreatitis, 1307–1308, 1307f, 1308f for colon carcinoids, 722 for CRC, 113, 861 for Crohn’s disease, 797, 799 for CRS/HIPEC, 113 for cystadenoma, 1055–1056, 1056f for DD, 748–749 for delirium, 11

for desmoids, 306 for diverticular disease, 770, 773 for early postoperative bowel obstruction, 697–698 for EA/TEF, 147 for enterocutaneous fistulas, 272 for esophageal benign tumors, 378 for esophageal cancer, 450–451, 454, 477 for FNH, 1067, 1068f–1069f for gallbladder cancer, 1224–1225, 1225f, 1230f for gastric carcinoids, 562 for gastric lymphoma, 568, 569f for gastrinoma, 1368 for GC, 554 for GEJ, 111 for GISTs, 566, 582, 582f for HCC, 1080, 1080f for hepatolithiasis, 1185 for hydatid liver abscesses, 1047–1048, 1048f for ICC, 1091, 1091f for imperforate anus, 158 for inguinal hernia, 213 for IRE, 1113 for laparoscopy, 895 for liver adenomas, 1071 for liver blunt trauma, 325, 326 for liver hemangiomas, 1063 for liver resection, 1118 for marginal ulcers, 523 for MCNs, 1330, 1330f for mesenteric cysts, 304 for mesenteric panniculitis, 303–304, 304f for obstructing PUD, 513 for omentum, 307 for Paget disease, 1028

for pancreatic cancer, 113, 1375 for pancreatic cystic neoplasms, 1323, 1377 for pancreatic necrosis, 1271f for pancreatic pseudocyst, 1271f, 1272–1273, 1272f for PCLD, 1054 for PEG, 67 for PEH, 423, 425f for penetrating trauma, 332 for periampullary adenocarcinoma of pancreas, 1348, 1348f, 1351f for PF, 1383 for pheochromocytoma, 1346 for PHTN, 1129 for PNETs, 1370, 1370f for pyrogenic liver abscesses, 1036–1037, 1038f, 1040f for rectal cancer, 984 for rectal carcinoid, 724 for recurrent pyogenic cholangitis, 1215 for retroperitoneal abscess, 309 for retroperitoneal fibrosis, 309–310 for retroperitoneal hemorrhage, 308 for retroperitoneal sarcoma, 311 SANT, 1404 for SBO, 687, 690–691 for SCNs, 1326f, 1327, 1328 for SI-NETs, 707 for small bowel adenocarcinoma, 710 for small bowel tumors, 707 for splenectomy, 1416–1417, 1416t, 1417f for splenic artery aneurysm, 1401f for splenic cancer, 1406, 1406f for splenic cysts, 1402, 1402f for suprarenal aorta, 354 for trauma, 318–320, 320t for traumatic liver cysts, 1057, 1057f

for UC, 824, 824f, 825f for vascular emergencies, 341–342, 342f for vascular trauma, 353 computed tomography angiography (CTA) for diverticular disease, 771, 771f for GI bleeding, 285 for PPH, 1386 for renal artery injury, 358 SMA, 349, 350f, 351f computed tomography arteriography (CTA), 1129 computed tomography colonography, 876 computed tomography enterography (CTE), 799, 803, 895 computed tomography venography (CTV), 1129 Condon, R. E., 34, 232 conduit emptying, 495–496 confocal laser endomicroscopy (CLE), 554 congenital heart disease, 140, 144, 150 congenital hypertrophy of the retinal pigment epithelium (CHRPE), 843, 844 congenital liver cysts, 1053–1055, 1054t, 1055f congestive heart failure (CHF), 13–14, 15, 20 Conn, Jerome, 1435 Connolly, P. T., 273 constipation, 961–967, 962t, 966f anal manometry for, 962, 963f appendicostomy for, 254 colonic volvulus and, 785 CRC and, 874 EMG for, 962, 964f pelvic floor outlet obstruction and, 942 rectal intussusception and, 940 constipation-predominant irritable bowel syndrome (IBS-C), 961 Contant, C. M., 34 continent ileostomy, 250–254, 250f–255f contrast enema

for CRC, 876 for HD, 156, 156f, 157 for intestinal stoma colostomy, 236 for meconium ileus, 153, 154f for SBO, 690 for sigmoid volvulus, 786, 787f for UC, 828f contrast esophagography, 398 contrast-enhanced computed tomography (CECT), 1281 for acute pancreatitis, 1294 for pancreatic necrosis, 1295 Conventional Versus Laparoscopic-Assisted Surgery in Colorectal Cancer (CLASICC), 882, 896, 1007 Convie, L., 111 Cooper’s ligament repair, 193, 201, 215 COPD. See chronic obstructive pulmonary disease Coppa, G. F., 34 Corman, M. L., 1021 coronary artery bypass grafting (CABG), 13 coronary disease, 12–15 corticosteroids acute pancreatitis from, 1257 for AIHA, 1409 for Crohn’s disease, 800–801 for immune thrombocytopenia, 1411 for retroperitoneal fibrosis, 310 for UC, 825, 827 cortisol, 1434 COST. See Clinical Outcomes of Surgical Therapy da Costa, R. S., 205 Costi, R., 1172 Cote, G. A., 1211 Couinaud, C., 1119 Cowden syndrome, 525, 564, 852, 865

Cowlam, S., 963 COX-2 inhibitors CRC and, 850–851 for PUD, 287 CPIAT. See completion total pancreatectomy with islet auto transplantation CPM. See cricopharyngeal myotomy CRC. See colorectal cancer C-reactive protein (CRP), 1044 acute pancreatitis and, 1259 chronic pancreatitis and, 1309 pancreatic necrosis and, 1281 crenolanib, 591 cricopharyngeal myotomy (CPM), 373–374 Crile, George W., 6 Crippa, S., 1329, 1331 Critical View of Safety (CVS), 1251–1252 CRITICS, 559–560 CRLM. See colorectal liver metastases CRM. See circumferential resection margin Crohn, B. B., 793 Crohn’s disease, 793–818, 841 abscesses and, 262, 796, 802, 812, 812f anal SCC and, 1017 anorectal abscesses and, 957 appendicitis and, 733 classification, 795, 795t clinical presentation, 795–797 colon, 796, 813–816, 813f, 815f CRC and, 861, 874 CTE for, 895 diagnosis, 797–799, 798f differential diagnosis, 799–800 duodenum, 810–811, 810f end ileostomy and, 240

epidemiology, 793–794 esophagitis and, 289 etiology, 794 fistulas, 796, 802, 811–812, 815–816 GI bleeding and, 803, 813 history, 793 location, 796–797 lower GI bleeding and, 296–297, 296f medical management, 800–802 pathology, 794–795 perforations, 796, 802–803, 812–813 postoperative prevention and maintenance, 816–818, 817f postoperative recurrence, 816 rectal cancer and, 978 retroperitoneal abscess and, 309 SBO and, 684–685, 688 SBS and, 757–758 small bowel, 796, 811–813, 811f, 812f, 842 adenocarcinoma and, 705 surgical treatment, 801–809, 804f–810f Crohn’s Disease Activity Index (CDAI), 816 Cronkhite-Canada syndrome, 852, 866 Croome, K. P., 1354 CROSS. See Chemotherapy for Oesphageal Cancer Followed by Surgery Study CRP. See C-reactive protein CRS/HIPEC. See cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion cryoprecipitate, 22 cryotherapy, 418, 1008 cryptorchidism, 141 Csikesz, N., 1167 CT. See computed tomography CTA. See computed tomography angiography; computed tomography

arteriography CTCAE. See Common Terminology Criteria for Adverse Events CTE. See computed tomography enterography CTLA-4. See cytotoxic T lymphocyte-associated antigen 4 CTP. See Child-Turcotte-Pugh CTV. See computed tomography venography cuffitis, 836, 836f Cullen sign, 1258 culling, spleen, 1397 Cummings, B. J., 1026 Cushing, Harvey, 6, 17, 1433 Cushing syndrome, 1433–1435 CVC. See central venous catheter CVD. See cardiovascular disease CVL. See central vascular ligation CVS. See Critical View of Safety cystadenocarcinoma, 1056–1057, 1324, 1331 cystadenoma, 1055–1056, 1056f cystic fibrosis (CF), 151, 152, 153–154, 156, 1304, 1323 cystic neoplasms. See pancreatic cystic neoplasms cystogastrostomy, 1276–1277, 1277f cysts. See also liver choledochal, 1191–1199, 1191t, 1192f–1196f, 1197f, 1231, 1248f, 1253 esophagus, 378–379, 379f mesenteric, 304 retention, 1303 spleen, 1402–1403, 1402f, 1403t, 1428 cytomegalovirus (CMV), 297, 827, 835 cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC), 113 cytotoxic chemotherapy, 1372 cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), 591 D da Vinci Surgical Systems, 7, 121, 122, 527, 920

for GC, 578 technologic features, 123t for TME, 129 dacarbazine, 306, 714 Dallemagne, B., 404, 433 damage control, 182–183 for trauma, 335–336 for vascular trauma, 353–354 D’Amico, G., 1133 D’Angelica, M., 112 D’Annibale, A., 920 DARPA. See Defense Advanced Research Project Administration dasatinib, 591 DBC. See Determinant-Based Classification DBE. See double balloon enteroscopy; double-balloon enteroscopy dCCA. See distal cholangiocarcinoma DCI. See distal contractile integral DD. See duodenal diverticula De Quervain, F., 768 Deb, S., 541 Debakey forceps, 103 debridement, 25, 184, 187–188, 354, 1005, 1264–1266, 1264f, 1265f, 1286 VARD, 1265, 1285, 1285f, 1296–1297, 1297f DEB-TACE. See drug-eluting bead transarterial chemoembolization deep enteroscopy, 284–285 deep venous thrombosis (DVT), 11, 98, 827, 996, 1160 defecography, 937, 942, 962, 969 Defense Advanced Research Project Administration (DARPA), 121 definitive chemoradiation, 467 D’Egidio, A., 1272, 1275 dehiscence, 181–182, 188–189, 274 dehydration, 11, 759 with gastroschisis, 138 mesenteric venous thrombosis and, 352

omphalocele and, 140 dehydroepiandrosterone (DHEA), 1433 Delaney, H. M., 128, 328 delayed gastric emptying (DGE), 440, 496 with GERD, 70 pancreatectomy and, 1384, 1385t PD and, 1381, 1384 vagotomy and, 603 delirium, 10–11, 10t Dellinger, E. P., 1262 Demartines, N., 1176 DeMeester, T. R., 404 DeMeester score, 401, 402t, 431 Demetriades, D., 322 Dennis, C., 728 Denonvilliers’ fascia, 833, 933, 980, 982, 995 Dermabond, 62 DES. See diffuse esophageal spasm Desarda technique, 215 desmoids, 305–306, 844 desmopressin, 22 Determinant-Based Classification (DBC), 1260 Deutsch, A. A., 1181 Devaney, K., 1056 Dexon, 180 dextran (Benefiber), 965 DGC. See diffuse gastric cancer DGE. See delayed gastric emptying DHEA. See dehydroepiandrosterone Dhiman, R. K., 1177 D’Hoore, A., 938–939, 967 diabetes, 12 bariatric surgery and, 654 chronic pancreatitis and, 1307

gastroparesis and, 526, 531, 534 hemorrhoids and, 946 hypertension and, 20 incisional hernia and, 220 MPS and, 155 obesity and, 639, 640t from pancreatectomy for chronic pancreatitis, 1387 radiation enteropathy and, 699 RYGB for, 669 diagnostic laparoscopy (DL), 555 diagnostic peritoneal lavage (DPL), 317, 325, 332 dialysis, 20 diamond of success, for laparoscopic ports, 98, 98f diaphragm hernia, MWA and, 1110 omphalocele and, 141 PEH repair and, 434 pinch-cock mechanism, 394 thoracoabdominal incisions and, 172 diarrhea CRC and, 874 Crohn’s disease and, 793, 810 fecal incontinence and, 969 HCC and, 1079 ileosigmoid fistulas and, 811 SBS and, 758 TV and, 520 diazoxide, 520 Dieulafoy lesions, 290, 526–527 diffuse esophageal spasm (DES), 387–388, 388f diffuse gastric cancer (DGC), 552 diffuse sclerosis, 1318–1320 DiFronzo, L. A., 1182 digitalis, 352

diltiazem, 388, 389f DIOS. See distal intestinal obstruction syndrome diphenoxylate-atropine, 248 dipyridamole, 12 direct coupling, 104 direct inguinal hernias, 194–195 direct percutaneous endoscopic jejunostomy (DPEJ), 542 disseminated intravascular coagulation, 1062, 1289–1290 distal bile duct cancer, 1347–1348 distal cholangiocarcinoma (dCCA), 1230–1242 distal contractile integral (DCI), 388 distal gastrectomy, 518–519, 518f distal intestinal obstruction syndrome (DIOS), 153, 154 distal margins, for rectal cancer surgery, 989 distal pancreatectomy, 1352–1353, 1367, 1367f, 1369f, 1381–1382 distal splenorenal shunt (DSRS), 293 Ditillo, M. F., 729 diuretics, 13 hypokalemia and, 21 thiazide, 1257 diverticula small bowel, 748–751 vasa recta and, 768, 768f diverticular disease abscesses and, 772–773 cancer and, 773 colon, 767–777 Crohn’s disease and, 800 esophagus, 373–378, 374f, 376f laparoscopic colectomy for, 776 LBO and, 772 lower GI bleeding and, 295 diverticular inversion, for Zenker diverticulum, 374 diverticulectomy

for epiphrenic diverticulum, 377 for Zenker diverticulum, 373–374 diverticulitis abscesses and, 262 acute complicated, 774–775 acute uncomplicated, 774 appendicitis and, 733–734 classification, 773–774, 774f enterocutaneous fistulas and, 269 liver abscess and, 1033–1034 peridiverticulitis and, 769 presentation, 769–770 retroperitoneal abscess and, 309 SBO and, 679 diverticulopexy, 374 diverticulosis, 768 diverticulotomy, for Zenker diverticulum, 375 divided loop colostomy, 240 DL. See diagnostic laparoscopy dobutamine, 12 Dohlman, G., 375 Dominguez, Escobar, 206 domperidone, 526, 539 Donatini, G., 1438 Dong, K., 535 Dong, X. D., 1099 dopamine, 1289 Dor, J., 404 Doria, A. S., 734 double balloon enteroscopy (DBE), 564 double rupture phenomenon, 1401 double-balloon enteroscopy (DBE), 85, 708 double-barrel enterostomy, 152 double-staple technique, 832, 840, 938, 939f, 1000f

dovitinib, 591 Down syndrome, 148, 150, 382 doxorubicin, 306, 714 doxorubicin, gemcitabine, cisplatin, and mytomycin C (MMC), 1021–1022, 1026, 1098–1099 doxycyline, 959 DPEJ. See direct percutaneous endoscopic jejunostomy DPL. See diagnostic peritoneal lavage DPPHR. See duodenum-preserving pancreatic head resection Dragstedt, Lester, 6, 603 drop test, 177 drug-eluting bead transarterial chemoembolization (DEB-TACE), 1100–1101 DS. See dumping syndrome; duodenal switch DSRS. See distal splenorenal shunt Duchenne muscular dystrophy, 534 Dudrick, Stanley, 6 Duhamel operation, 157 Dulcolax. See bisacodyl dumping syndrome (DS) EA/TEF and, 146 after gastrectomy, 519–520 octreotide for, 520, 520t duodenal atresia, 146, 148–150, 148f–150f duodenal diverticula (DD), 748–749 duodenal switch (DS), 648, 649f, 664–666, 665t duodenoduodenostomy, 149 duodenoplasty, 150, 150f duodenotomy, 1368 duodenum adenocarcinoma, 1348 adenomas, 844 cancer, 844 carcinoids, 720 Crohn’s disease, 810–811, 810f

fistulas, 265 penetrating trauma, 334 ulcers, 285–288, 287f, 288f, 508, 514, 733 duodenum-preserving pancreatic head resection (DPPHR), 1313–1318 Beger technique for, 1315–1317, 1316f Berne technique for, 1318 Frey technique for, 1317–1318, 1317f, 1318f duplications esophagus, 378–379 KIT, 583 DVT. See deep venous thrombosis dyspepsia, 508, 509 dysphagia achalasia and, 382 EA/TEF and, 148 esophageal cancer and, 447 GERD and, 398 nutcracker esophagus and, 388 Zenker diverticulum and, 373 dysplasia BE and, 415, 416 esophageal adenocarcinoma and, 444 FAP and, 845 gallbladder cancer and, 1223 HIV and, 957 HPV and, 957 polyposis and, 868 pouchitis and, 835 rectal cancer and, 978 UC and, 828 UC IPAA pouch and, 836 E EA. See esophageal adenocarcinoma; esophageal atresia

early postoperative bowel obstruction, 679, 697–698 Eastern Cooperative Oncology Group (ECOG), 567, 896 EBV. See Epstein-Barr virus ECG. See electrocardiogram Echinococcus spp. See hydatid liver abscess echo-enhanced ultrasound (EEU), 1281 Eck, Nicolai, 1125 ECL. See enterochromaffin-like cells ECOG. See Eastern Cooperative Oncology Group ectopic pregnancy, 734 Edmunds, L. H., 265 Edwards, Garren, 668 Eesa, M., 1133 EEU. See echo-enhanced ultrasound efferent loop obstruction, 521 efficacy index (EI), 460 EGD. See esophagogastroduodenoscopy EGFR. See epithelial growth factor receptor EHE. See epithelioid hemangioendothelioma Ehlers-Danlos syndrome diverticulitis and, 769 gastroparesis and, 535 inguinal hernias and, 196, 213 EHS. See European Hernia Society EI. See efficacy index Ekeloef, S., 33 elastic ligation, for hemorrhoids, 945–946, 945f elastin, 769 electrocardiogram (ECG), 12 for arrhythmias, 13 for CRC, 877 for MI, 11 electrocautery for cholecystectomy, 1164

EMR and, 64 for rectal cancer, 1008 for sphincterotomy, 949 for Zenker diverticulum, 375 electrogastrography for chronic gastric stasis, 521 for gastroparesis, 538 electromyography (EMG), 938 for constipation, 962, 964f for pelvic floor outlet obstruction, 942 ELISA. See enzyme-linked immunosorbent assay Ell, C., 456 Ellis, H., 683 Ellison, E. C., 1366, 1369 eltrombopag, 1411 EMG. See electromyography empyema, 1040, 1045 EMR. See endoscopic mucosal resection end colostomy, 233–236, 234f, 235f, 973–974 end ileostomy, 240–242, 241f, 242f, 829, 833, 835 Endo Stitch, 635 EndoBarrier, 76, 77f endocarditis, 14–15, 14t, 1404 Endoclose, 182 Endo-GIA stapler, 377 endoleak, 362–363, 363f Endoloop, 901 endoluminal devices for GERD, 70 for obesity, 74–78, 75f–79f for weight loss, 74–78, 75f–79f, 643–644, 644t endoluminal radiofrequency, 410, 410f EndoMAXX, 70 endometrial cancer, 848

endometriosis, 872 endoscopic band ligation, 62 endoscopic dilation, 68 endoscopic mucosal resection (EMR) for BE, 418–419, 456 electrocautery and, 64 endoscopic band ligation with, 62 for gastric carcinoids, 562, 720 for polypectomy, 63–64, 64f, 65f for rectal carcinoids, 724 RFA and, 65–66 for SCC esophagus, 454–455 “suck-and-cut,” 64 “suck-and-ligate,” 65 endoscopic retrograde cholangiography (ERC), 1245–1246, 1247, 1349– 1350, 1350f endoscopic retrograde cholangiopancreatography (ERCP), 57, 79–85 for acute pancreatitis, 1257, 1261–1262, 1295 for benign biliary strictures, 1205–1207, 1205f, 1214 for cholangiocarcinoma, 1232–1233 for cholangitis, 82, 1184–1185 for cholecysterectomy, 1158 for cholecystitis, 1157 for choledochal cysts, 1194, 1195, 1198 for choledocholithiasis, 81–82, 82f, 1172–1182, 1173f, 1180f for chronic pancreatitis, 1307–1308, 1308f for gallstone pancreatitis, 82 for hydatid liver abscesses, 1048 indications for, 80t for Mirizzi syndrome, 1215 for pancreas pseudocyst, 83–84 for pancreatic necrosis, 1284 for pancreatic pseudocyst, 1273 pancreatitis and, 84–85, 1175

perforations and, 84–85 for PSC, 1217 for recurrent pyogenic cholangitis, 1215 for SEMS, 82–83, 82f, 83f for SOD stenosis, 1216 for sphincterotomy, 81, 81f, 82f endoscopic sclerotherapy (ES), 1135, 1135f endoscopic sleeve gastroplasty, 643, 644t, 668 endoscopic submucosal dissection (ESD), 62, 65 for BE, 418–419 in colon, 89–91, 90f for esophageal cancer, 453f for SCC esophagus, 455 endoscopic ultrasound (EUS), 57 for carcinoids, 525 for cholangiocarcinoma, 1232–1233 for cholecystitis, 1157 for choledocholithiasis, 1175–1176 for chronic pancreatitis, 1308–1309, 1309t for esophageal cancer, 451–453, 453f, 477–478, 477f for gallbladder cancer, 1224 for gastric carcinoids, 561 for gastrinoma, 1368, 1370, 1370f for GC, 554–555 for GEJ, 111 for GISTs, 566, 585 for marginal ulcers, 523 for pancreatic cancer, 1375 for pancreatic cystic neoplasms, 1323, 1377 for pancreatic necrosis, 1284 for pancreatic pseudocyst, 84, 1275–1276 for periampullary adenocarcinoma of pancreas, 1349 for rectal cancer, 984–985, 985f, 985t for subepithelial gastric tumors, 525

endoscopic variceal band ligation (EVL), 1134–1135, 1136f endoscopy, 55–93. See also specific types for ablation, for BE, 417 for afferent loop obstruction, 521 analgesia for, 57–58, 58t for BE, 415–416, 415f for bezoars, 526 for clipping, 62–63, 63f, 64f for constipation, 961–962 for Crohn’s disease, 798 for DD, 748–749 for diverticulotomy, for Zenker diverticulum, 375 for esophageal benign tumors, 378 for foreign bodies, 68, 68f for gastroparesis, 539 for GERD, 397, 398 for GISTs, 582, 583f ITx and, 765 for necrosectomy, for acute pancreatitis, 1265–1266 for pyloromyotomy, 541 for rectal cancer, 979 for sleeve gastroplasty, 75, 77f for small bowel tumors, 707–709 for stress ulcers, 524 for sutures, 62, 63f for transoral surgery, for Zenker diverticulum, 375 for UC, 826f for UGI, 60–66 for upper GI bleeding, 292–293 for Zenker diverticulum, 373 EndoStich, 105 endovascular repair for ruptured AAA (rEVAR), 361–363, 363f EndoWrist, 121–122, 125 end-stage achalasia, 386–387

end-stage renal disease, 20 Eng, K. E., 34 Engel, B. T., 969 enhanced (early) recovery after surgery (ERAS), 27, 32 for bariatric surgery, 654–655 for rectal cancer surgery, 988 enhanced recovery protocols (ERPs), 31–39, 39t anemia and, 32 carbohydrate loading and, 33–34 early ambulation, 37 early feeding, 37 epidural analgesia and, 35–36 esophagectomy and, 38 guided fluid management and, 36–37 ileus prophylaxis and, 35 MBP and, 34 pancreatectomy and, 38 sarcopenia and, 32–33 TAP and, 35 Enochsson, L., 1179 ENS. See enteric nervous system entacapone, 309 Entamoeba spp. See amebic liver abscess enteral nutrition, 26 for enterocutaneous fistulas, 271 for gastroparesis, 541–542 enteric nervous system (ENS), 534 enteroatmospheric fistulas, 265 enteroceles, 942 enterochromaffin-like cells (ECL), 561, 719–720, 721 enteroclysis, 298, 707, 749, 797 Enterococcus spp., 260, 1280 enterocolitis, 157–158 enterocutaneous fistulas, 263–276, 263t, 266t, 267t, 269f, 270f

closure, 266 Crohn’s disease and, 812 enterostomal therapist (ET), 231 enterostomy, 138 enterotomy, 273 enterovaginal fistulas, 812 enzyme-linked immunosorbent assay (ELISA), 1047, 1402 Eovist, 1067 Epelboym, I., 1438 epidural analgesia, 9–10, 11, 18–19, 35–36 epigastric hernia, 225 epinephrine, 62, 946–948, 1289 epiphrenic diverticulum, 376–377, 376f epithelial growth factor receptor (EGFR), 885 epithelioid hemangioendothelioma (EHE), 1093 Epstein-Barr virus (EBV), 568, 706 ERAS. See enhanced (early) recovery after surgery ERC. See endoscopic retrograde cholangiography ERCP. See endoscopic retrograde cholangiopancreatography Eriksson, S., 737 ERPs. See enhanced recovery protocols erythema nodosum, 797 erythrocytosis, 1079 erythromycin, 15, 232, 526, 539, 959 ES. See endoscopic sclerotherapy Escherichia coli, 259 appendix, 738 infectious colitis from, 297 pancreatic necrosis and, 1280 pyrogenic liver abscesses from, 1035 retroperitoneal abscess and, 309 splenic cysts and, 1404 ESD. See endoscopic submucosal dissection ESMO. See European Society for Medical Oncology

esophageal adenocarcinoma (EA), 111, 444, 445, 455–457 BE and, 414 demographics, 447, 447t GEJ, 111, 448–450, 452f GERD and, 397 esophageal atresia (EA), 137 esophageal atresia/tracheoesophageal fistula (EA/TEF), 143–148, 143f–146f, 147t esophageal cancer, 450f barium swallow for, 450, 452f diagnosis, 444–445 epidemiology, 443 esophagectomy for, 457–463, 458f complications, 465 reconstruction after, 463–464 etiology, 443–444, 444f EUS for, 451–453, 453f, 477–478, 477f histological grade for, 448t Lugol’s iodine for, 445, 445f LUS for, 111 lymphadenectomy for, 459–463, 461f multimodality treatment strategies, 466–477 palliative treatment, 470, 470f PET for, 453–454, 453f, 469, 469f, 477 staging, 477–478 surgical procedures, 475–496 TNM for, 447–448, 448t treatment, 454–463 tri-incisional esophagectomy for, 480–486, 480f–486f tumor classification, 454t esophageal lengthening, for PEH repair, 430–431 esophageal manometry for achalasia, 383 for epiphrenic diverticulum, 376–377

EsophyX and, 72 for GERD, 399–401, 400f, 401t for Zenker diverticulum, 373 esophageal outflow obstruction, 434–435, 435f esophageal stricture, 396 esophagectomy anastomosis and, 493–494 for BE, 456–457 for benign tumors, 378 bleeding from, 495 conduit emptying and, 495–496 ERPs and, 38 for esophageal cancer, 457–463, 458f complications, 465 reconstruction after, 463–464 with fundoplication, for BE, 419, 419f laryngeal nerve injury and, 494 left thoracoabdominal approach to, 488–489, 488f Lewis, 487 MIE, 114–115, 459 for PEH repair, 429 PLE, 457 respiratory failure and, 494–495 THE, 458, 478–480, 487–488, 487f, 488f tri-incisional, 480–486, 480f–486f TTE, 458, 478–480 esophagitis, 289–290, 393, 396, 436 esophagoesophagostomy, 145 esophagogastroduodenoscopy (EGD), 57 for aortoenteric fistula, 291f for chronic gastric stasis, 521 contraindications for, 59 for dyspepsia, 509 for esophageal varices, 1134, 1134f

for FAP, 845 for gastric carcinoids, 561 for gastric epithelial polyps, 524 for gastroparesis, 538–539 for GC, 554 for GI bleeding, 284 for HNPCC, 849 indications for, 58, 58t for lower GI bleeding, 293 for PEH, 412, 426, 436f for PHTN, 1131–1132, 1131f for rectal cancer, 978 for small bowel adenocarcinoma, 710 for subepithelial gastric tumors, 525 techniques, 59–60, 60f for UC, 825 for UGI, 60–61 esophagus benign diseases, 439–440, 441t colonic interposition, 489–491, 489f, 490f cysts, 378–379, 379f diverticular disease, 373–378, 374f, 376f duplications, 378–379 fistulas, 264 jejunal interposition, 491–493, 491f–493f motility, 381–389, 382t, 383f, 385f, 385t, 386f–389f GERD and, 397 normal functioning, 381 perforations, PEH repair and, 434, 436 SCC, 386, 444 demographics, 447, 447t staging, 448t, 449t treatment for, 454–455 varices, 62, 283, 1126, 1126t, 1133–1145, 1134f, 1135f

EsophyX, 72–74, 73f Esposito, C., 738–739 estrogens, 1017, 1061, 1257 ET. See enterostomal therapist European Hernia Society (EHS), 195, 202 European Society for Medical Oncology (ESMO), 585 EUS. See endoscopic ultrasound Evenson, A. R., 267 evisceration, wound management, postoperative for, 188–189 exercise testing, 12 extrahepatic biliary ducts, 330 extraperitoneal incisions, 172–176 F Fabian, T. C., 328, 332 factor IX deficiency, 308 factor V Leiden, 352 factor X deficiency, 308 factor XI, 22 familial adenomatous polyposis (FAP), 240, 305, 524, 705, 843–845, 863– 864, 978 fundic gland polyps and, 562–563 GC and, 552 familial gastric polyposis (FGP), 563 famotidine, 524 Fan, A. C., 542 Fantus, Bernard, 6 FAP. See familial adenomatous polyposis Faried, M., 966–967 FAST. See focused abdominal sonography for trauma FDA. See Food and Drug Administration FE-1. See fecal human elastase FEC. See Flexible Endoscopy Curriculum fecal human elastase (FE-1), 1309 fecal incontinence, 967–974, 969f

ABS for, 972, 972f, 973f adjuvant chemoradiation and, 1022 appendicostomy for, 254 bulking agents for, 970 Crohn’s disease and, 815 etiology, 934, 937t, 967–968, 968t PTNS for, 973 rectal intussusception and, 940 Secca procedure for, 969–970 SNS for, 972–973, 973f sphincteroplasty for, 971–972, 971f, 972f sphincterotomy and, 951 fecal occult blood tests (FOBTs), 861 Feliciano, D. V., 328, 335 Felty syndrome, 1413 femoral hernias, 195, 197, 210–211, 210f, 211f, 683 Fernández-Cruz, L., 115 Fernandez-del Castillo, C., 1342 Fernstrom, I., 1176 α-fetoprotein (AFP), 1081 Fevang, B. T., 694 FFP. See fresh frozen plasma FGD. See functional gallbladder disorder FGP. See familial gastric polyposis fiber for constipation, 965 diverticular disease and, 768 for fecal incontinence, 969 for intestinal stomas, 248 risk factors, 857–859 FiberCon. See polycarbophil fibrinogen, 22 fibronectin, 22 fibrosarcoma, 568

fibrosis, 1303 CF, 151, 152, 153–154, 156, 1304, 1323 pulmonary, 397 retroperitoneal, 309–310, 309t, 310t fibrostenotic lesions, Crohn’s disease, 796 FICE. See flexible spectral color enhancement endoscopy; Fujinon intelligent color enhancement Finney, M. T., 1382 Finney pyloroplasty, 515, 516f, 613, 614f Finney strictureplasty, 806, 806f, 810 Fiorica, F., 476 FIRM-ACT, 1436 Fischer, J. E., 267 FISH. See fluorescence in situ hybridization fistulas. See also specific organs and types Crohn’s disease and, 796, 802, 811–812, 815–816 diverticular disease and, 770–771 RV, 956–957 fistulotomy, 815, 954 Fleming, Alexander, 4 Fleshman, J., 1007 Fleshner, P. R., 693 flexible endoscopy, 55–57, 56f for pancreatic necrosis, 1284 for robotic TME for CRC, 928 for Zenker diverticulum, 375 Flexible Endoscopy Curriculum (FEC), 57 flexible sigmoidoscopy, 284, 827, 875 flexible spectral color enhancement endoscopy (FICE), 554, 875 floppy cecum syndrome, 686, 786 FLR. See future liver remnant FLS. See Fundamentals of Laparoscopic Surgery fluconazole, 1039 fludrocortisone, 1434

fluid overload, 21 fluid resuscitation, 267, 316, 330 for acute pancreatitis, 1261, 1294 for anastomotic leak, 834 for GI bleeding, 282 for mesenteric insufficiency, 349 fluorescence in situ hybridization (FISH), for esophageal cancer, 445 fluoropyrimidines, 1020, 1021 fluoroquinolone, 292 for cholangitis, 1184 for CRC surgery, 878 5-fluorouracil (5-FU), 469, 714, 885 for anal margin cancer, 1026 for anal SCC, 1021–1022 for GC, 559 for HPV, 957 for rectal cancer, 1007 FNH. See focal nodular hyperplasia FOBTs. See fecal occult blood tests focal nodular hyperplasia (FNH), 1063t, 1066–1067, 1066f, 1068f–1069f focused abdominal sonography for trauma (FAST) for liver blunt trauma, 325 for penetrating trauma, 332 for splenic injury, 1399 for trauma, 318 for vascular trauma, 353 Foker procedure, 146, 146f FOLFIRINOX, 1361, 1362, 1376 FOLFOX, 885 Food and Drug Administration (FDA) ABS and, 972, 973f AGB and, 648 da Vinci surgical system and, 121 GES and, 540

imatinib and, 599 infliximab and, 840 KIT and, 565 NASHA Dx and, 970 Orbera intragastric balloon and, 74 SNS and, 966 weight loss drugs and, 642–643, 643t weight loss endoluminal devices and, 643–644, 644t food bolus bezoars, 526 foregut benign diseases, 439–440, 441t Crohn’s disease, 796 foreign bodies bezoars and, 526 endoscopy for, 68, 68f formalin, 1050 Fornage, B., 1049 Forstner-Barthell, A. W., 544 Frantz, V. K., 1365 free jejunal transfer, esophagus, 492–493, 493f Freeny, P. C., 1263 fresh frozen plasma (FFP), 22, 23 Frey, C. F., 1173 Frisch, M., 1017 Fritz, S., 1337 Fry, D. E., 39 Fu, B., 1439 5-FU. See 5-fluorouracil Fujinon intelligent color enhancement (FICE), 554, 875 functional bowel obstruction. See ileus functional gallbladder disorder (FGD), 1157–1158, 1158t Fundamentals of Laparoscopic Surgery (FLS), 57 fundic gland polyps, 524, 562–563, 563f fundoplication

for epiphrenic diverticulum, 377 esophagectomy with, for BE, 419, 419f gastroparesis and, 536 for GERD, 386 laparoscopic, 396 Heller myotomy with fundoplication for achalasia, 385–386, 385t, 386f for epiphrenic diverticulum, 377 POEM and, 75 robotic surgery for, 121, 123, 125–126 Nissen for duodenal atresia, 150 for EA/TEF, 147 for GERD, 137, 404, 405–407, 407f for PEH, 414, 430f, 435f, 436f robotic surgery for, 123 Thal, 147–148 TIF, 70, 411, 411f EsophyX and, 72–74, 73f Toupet, 408, 409f, 414 funnel syndrome, 1180 furosemide, 1257, 1289 future liver remnant (FLR), 1118–1119, 1122–1123, 1234, 1236, 1239

G G6PD. See glucose-6-phosphatase deficiency gabalins, 37 Gagner, M., 1285 Galen, 1393 gallbladder bariatric surgery and, 654 cancer, 1223–1230, 1228f, 1230f cholecystectomy for, 1226–1229, 1228f CT for, 1224–1225, 1225f, 1230f laparoscopy for, 111–112 metastases and, 1229 risk factors for, 1223–1224, 1224t TNM for, 1225, 1225t US for, 1224, 1224f laparoscopy for, 115 penetrating trauma, 334 perforations, 1167 polyps, 1158 Gallegos, N. C., 209 gallstone pancreatitis, 82, 1155, 1158 gallstones, 1214–1215. See also choledocholithiasis; cholelithiasis hereditary elliptocytosis and, 1408 US for, 1156, 1156f Gamblin, T. C., 1054 gamma-glutamyl transpeptidase (GGT), 1172, 1183 Garcia-Pagan, G., 1141 Gardner syndrome, 757, 844, 863 Garg, P. K., 1174 Garrison, J. R., 328 gas gangrene, 188 gastrectomy for BE, 460–461

for carcinoids, 526 distal, 518–519, 518f dumping syndrome after, 519–520 ERPs and, 38 gastroparesis and, 535, 536–537, 543–544 for GC, 552, 555–556, 557f, 558f, 577–578, 625–628, 626f–628f for GISTs, 585 jejunal pouch with, 628, 631f laparoscopy for, 634–636, 635f LDG, 114–115 MIG, 558–559 minimally invasive surgery for, 634–636, 635f for obstructing PUD, 513 ODG, 114 for perforated PUD, 513 postgastrectomy syndromes, 519–523 robotic surgery for, 123–124, 125, 634, 635f for Roux stasis syndrome, 522 SG, 526, 536, 649, 650f, 653, 656–658, 656f, 657f, 670–671 STG, 556, 557f, 558f total, 556 wedge resection in, 408, 409f, 634, 635f weight loss after, 523 gastric acid, 6, 283, 287, 511, 518, 604 gastric adenocarcinoma, 551–561 gastric aneurysms, 366 gastric antral vascular ectasia (GAVE), 290, 290f gastric atony. See gastroparesis gastric bleeding, 18 gastric cancer (GC), 551–561, 575–578, 576f, 577f adjuvant chemotherapy for, 559 adjuvant radiotherapy for, 559 DL for, 555 gastrectomy for, 552, 555–556, 557f, 558f, 577–578, 625–628, 626f–628f

H. pylori and, 508, 551 HNPCC and, 849 laparoscopy, 111 lymphadenectomy for, 556–558, 557f, 559f MIG for, 558–559 robotic surgery for, 126–128, 127t RYGB for, 628–629, 629f–631f TNM for, 552, 553t gastric carcinoids, 561–562, 561f, 562f, 717, 719–720 gastric diverticula, 527 gastric electrical stimulation (GES), 521 for gastroparesis, 540–541 with PP, for gastroparesis, 543 gastric emptying. See also delayed gastric emptying duodenal switch for, 665 esophagus and, 463 gastroparesis and, 536, 538–539 pyloromyotomy and, 146 SG and, 670 vagotomy and, 6, 518 gastric epithelial polyps, 524–525, 524t gastric fistulas, 264–265 gastric ischemia, 433 gastric lymphoma, 568–569, 569f gastric manometry, 521, 538 gastric necrosis, 433 gastric neuroendocrine tumors (NETs). See carcinoids gastric outlet obstruction, 423, 513 gastric perforation, 433, 434, 436 gastric polyps, 562–564, 563f, 564f gastric stasis, 520–521 gastric ulcers, 289, 733 gastric varices, 62, 1133–1145 gastric volvulus, 412, 423, 527

gastrinoma, 1367–1369, 1368f, 1369f EUS for, 1370, 1370f pancreas, 1378 gastritis alkaline reflux, 521–522, 522f atrophic, 509, 510t, 526, 562 H. pylori and, 507, 508 OLGA for, 509, 525 stress, 289 gastrocolic reflux, 146 gastroduodenal aneurysms, 366 gastroduodenal artery (GDA), 1312 gastroenteritis, 733, 769 gastroepiploic aneurysms, 366 gastroesophageal junction (GEJ) esophageal adenocarcinoma and, 111, 448–450, 452f gastric diverticula and, 527 GERD and, 393, 394f, 398 GISTs and, 600 intrathoracic esophageal cancer and, 458 PEH and, 412, 423, 426 POEM and, 76 gastroesophageal reflux disease (GERD), 396t, 403f, 439 bariatric surgery and, 654 BE and, 415 choledocholithiasis and, 1171 duodenal atresia and, 150 EA/TEF and, 145, 146, 147–148 EGD for, 58 endoluminal devices for, 70 esophageal adenocarcinoma and, 444 esophageal manometry for, 399–401, 400f, 401t esophageal stricture and, 396 esophagitis and, 289–290, 393, 396

EsophyX for, 72–74, 73f fundoplication and, 386, 396 gastroschisis and, 140 GEJ and, 393, 394f, 398 Hill classification for, 398, 399f HRQL for, 70 LES and, 393–395, 395f Los Angeles classification for, 398, 398t management, 403–411, 404t, 405f–411f omphalocele and, 141 pediatrics, 137–138 PEH and, 414, 423, 431 pH and, 397–398, 401–402, 401f, 401t QoL with, 396, 398, 402–403, 403t RYGB for, 653, 669 Stretta for, 70–72–71f gastroesophageal varices, upper GI bleeding from, 291–292, 292f Gastrografin, 493, 690, 778, 834 gastrointestinal (GI) bleeding, 273, 281–298, 282f Crohn’s disease and, 803, 813 duodenal carcinoids and, 720 initial assessment, 281–282 lower, 293–298, 293t, 294f–298f PEH and, 423 resuscitation for, 282 TACE and, 1100 transfusions for, 282–283 upper, 286–293, 286f–292f, 286t gastrointestinal evaluation, 17–20 gastrointestinal stromal tumors (GISTs), 525, 564–567, 566f, 567f, 579–594, 580f, 582f, 588f, 594f adhesions and, 585 adjuvant chemotherapy for, 586t, 588–589, 601 colon, 871–872

cryoreductive surgery for, 592 endoscopy for, 582, 583f esophagus, 378 imatinib for, 586–591, 587t, 600–602 inflammatory fibroid polyps and, 564 KIT for, 565, 567, 579–581, 580f, 599, 705, 715, 872 laparoscopy for, 585, 586f liver, 1097 mesentery, 306 metastases and, 567, 589–590, 593f, 601–602 minimally invasive surgery for, 527 neoadjuvant chemotherapy for, 586–588, 586t, 600–601 PDGFRA for, 565, 567, 579, 580–581, 580f, 599, 705, 715, 872 risk stratification for, 583–584, 583t, 584t small bowel, 705, 714–715, 714t TKI for, 600–602 upper GI bleeding and, 290, 290f gastrojejunostomy (GJ), 116, 603 for bleeding PUD, 514 for Crohn’s disease, 805 dumping syndrome with, 520 for gastroparesis, 526, 541–542 gastroparesis and, 536 hyperplastic polyps and, 524 for obstructing PUD, 513 for perforated PUD, 513 gastroparesis (gastric atony), 526, 531–545, 533t, 540f fundoplication and, 536 gastrectomy and, 535, 536–537 pancreatectomy and, 537 QoL with, 544–545 Roux-en-Y gastroenterostomy and, 536 symptoms, 538 vagotomy and, 521, 535–536

gastroplasty Collis, 407–408, 408f, 409f, 432 endoscopic sleeve, 643, 644t, 668 VBG, 648, 648f wedge, 408 gastroschisis JIA and, 150, 151, 152 pediatrics, 138–140, 138f, 139f SBS and, 756 gastrostomy tube for EA/TEF, 145, 147 for enterocutaneous fistulas, 274 for gastroparesis, 526, 542 for PEH, 433 for small bowel adenocarcinoma, 710 Gaucher disease, 1425 GAVE. See gastric antral vascular ectasia GC. See gastric cancer GCD. See giant colonic diverticulum GCS. See Glasgow Coma Score GDA. See gastroduodenal artery Gearhart, S. L., 971 Gebski, V., 476 GEJ. See gastroesophageal junction gemcitabine, 469 gemcitabine-cisplatin, 1229 GEMINI, 827 general anesthesia, 3 genomewide association studies (GWAS), 639–640 gentamicin, 988 GERD. See gastroesophageal reflux disease Gerndt, S. J., 542 GES. See gastric electrical stimulation GGT. See gamma-glutamyl transpeptidase

ghrelin receptor agonists, 539 GI bleeding. See gastrointestinal bleeding giant colonic diverticulum (GCD), 773 giant prosthetic reinforcement of visceral sac (GPRVS), 215 Gilbert, A. I., 202 Gilbert disease, 1407 Giorgio, A., 1039 GIP. See glucose-dependent insulinotropic peptide GISTs. See gastrointestinal stromal tumors Giulianotti, P. C., 126 GJ. See gastrojejunostomy Glasgow Coma Score (GCS), 315 for acute pancreatitis, 1258 Glenn, F., 1228 Glinkova, V., 1061 glucagon-like peptide-1 (GLP-1), 670 glucagon-like peptide-2 (GLP-2), 756, 759 glucagonoma, 1369 glucose-6-phosphatase deficiency (G6PD), 1408 glucose-dependent insulinotropic peptide (GIP), 670 glues for Crohn’s disease, 816 for fistulotomy, 954 for PEH repair closure, 430 for PF, 1383 for skin closure, 181 glutamate, 443–444 α-glutathione S transferase (α-GST), 688 glycemic control, 21 glyceryl trinitrate (GTN), 1175 glycoprotein IIb/IIIa, 22 goblet cell carcinoma, 748 Goere, D., 112 Goh, B., 1329, 1330

Goldmine, M., 478, 495 Goligher, J. C., 603 golimumab, 827 GoLYTELY, 86, 988 gonorrhea, 958 Gonzalez, J. M., 78 Gonzalez, R. J., 1438 Goodsall's rule, 953–954, 954f Gouma, D.J., 1181 GPRVS. See giant prosthetic reinforcement of visceral sac Graf, W., 970 de Graff, G. W., 111 graft-versus-host disease (GVHD), 765, 1217 Gramlich, L. M., 39, 271 Grant, D., 762, 765 Graser, E., 767 Greenall, M. J., 1026 Greenberg, R., 336 Grey-Turner sign, 1258 Griffen, W., Jr., 648 groin hernias. See inguinal hernia Gronchi, A., 311 Gross, B. H., 1172 Group A Streptococcus, 188 Gruner, O. C., 767 Grynfeltt’s triangle, 224 α-GST. See α-glutathione S transferase GTN. See glyceryl trinitrate Guillain-Barré syndrome, 534 Guillem, J. G., 994 Gunay, K., 1052 Guo, Z., 817 GVHD. See graft-versus-host disease GWAS. See genomewide association studies

H H2 blockers, 18, 285, 289, 404, 511, 524 HAART. See highly active antiretroviral therapy Haecker, F. M., 257 Haemophilus influenza, 324, 1353, 1414 Haggitt, R. C., 979, 979f, 1021 hairy cell leukemia (HCL), 1413 Halabi, W., 789 Hall, N. C., 1371 HALO90, 456 Halo-360, 417, 456 haloperidol, 11 HALS. See hand-assisted laparoscopic surgery Halsted, William, 4, 6, 182, 1381 hamartomas, 525, 709, 852, 865–868, 1072–1073, 1405 small bowel, 706 Hammar, O., 535 Han, H. S., 1186 hand-assisted laparoscopic surgery (HALS), 893 for APR, 915 for IPAA, 918 for left hemicolectomy, 906–907, 906f, 907f for low anterior resection of rectum, 913 for sigmoid colectomy, 907–909, 908f, 909f for splenomegaly, 1417, 1421–1422, 1421f, 1422f for transverse colectomy, 910, 910f Hanley procedure, 954, 955f Harbaugh, C. M., 32 HARM. See Hospital Stay, Readmission, and Mortality Rates Harmonic Ultrasonic Shears, 123 Harms, B. A., 830 Hartmann pouch, 322, 829, 1168 Hartmann procedure, 272, 334, 788 for colonic volvulus, 779

for end colostomy, 233 for enterocutaneous fistula, 273 for LBO, 772 for sigmoid volvulus, 788 for UC, 839–840 Hashizume, M., 126 Hasson technique, 101, 109 Hauch, A., 1445 Hauser, C. J., 332 Hays, D. M., 1228 HBV. See hepatitis B virus HCC. See hepatocellular carcinoma HCL. See hairy cell leukemia HCV. See hepatitis C virus HD. See Hirschsprung disease HDGC. See hereditary diffuse gastric cancer Heald, William, 977, 994 health care-associated peritonitis, 259t, 260 health-related quality of life (HRQL), 70 heart failure, 366, 1181 Hegazi, R. A., 33 Heidenhain pouches, 6 Heineke-Mikulicz pyloroplasty, 150, 515, 515f, 611–613, 612f Heineke-Mikulicz strictureplasty, 805–806, 805f Helicobacter pylori, 507–509, 508t, 509f, 532 AIP and, 1305 Crohn’s disease and, 794 dyspepsia and, 508, 509 esophageal adenocarcinoma and, 444 fundic gland polyps and, 562 gastric lymphoma and, 568–569 gastrinoma and, 1368 GC and, 508, 551 GI bleeding and, 285

HNPCC and, 849 hyperplastic polyps and, 525 immune thrombocytopenia and, 1411 marginal ulcers and, 523 NHL and, 712 PUD and, 286, 287, 510–511, 513, 514 Heller myotomy with fundoplication for achalasia, 385–386, 385t, 386f for epiphrenic diverticulum, 377 POEM and, 75 robotic surgery for, 121, 123, 125–126 hemangiomas Bannayan-Riley-Ruvalcaba syndrome and, 852 esophagus, 378 liver, 1061–1066, 1062f, 1063t, 1064f–1065f, 1065t small bowel, 709–710 hemangiopericytoma, 568 hematochezia, 141, 283, 293, 733 hematologic evaluation, 22–24 hematoma, 188 from blunt trauma, 354 after inguinal hernia repair, 208 from IRE, 1114 MWA and, 1110 from penetrating trauma, 354 retroperitoneal hemorrhage and, 308 from trauma, 354 hematopoiesis, 1398 hemicolectomy, 879t hemobilia, 291 hemochromatosis, 1126 hemolytic uremic syndrome (HUS), 1412 hemoperitoneum, 323, 332 hemorrhoidectomy, 946–948, 947f, 1025

hemorrhoids, 942–948, 944f elastic ligation for, 945–946, 945f GI bleeding and, 283, 284 lower GI bleeding and, 296 pelvic floor outlet obstruction and, 940, 942 hemostasis with hemorrhoidectomy, 947 introduction, 6 with laparoscopy, 104 hemosuccus pancreaticus, 291, 1307 hemothorax, 1110 heparin, 426. See also low-molecular-weight heparin; unfractionated heparin heparin-induced thrombocytopenia (HIT), 23 hepatectomy, 38, 115, 123–124, 1239 hepatic angiosarcoma, 1092 hepatic artery, 330, 364t, 365, 1349 hepatic encephalopathy, 1147–1148 hepatic hydrothorax, 1133 hepatic vein pressure gradient (HVPG), 1126, 1126t, 1132 hepaticoduodenostomy, 1182 hepaticojejunostomy, 1186, 1239–1240, 1240f, 1253. See also Roux-en-Y hepaticojejunostomy LHJ, 1247, 1248f hepatitis, autoimmune, 1217, 1409 hepatitis B virus (HBV), 1077, 1081, 1126, 1231 hepatitis C virus (HCV), 1077, 1081, 1126, 1231, 1411 hepatobiliary iminodiacetic acid (HIDA), 522, 1205 hepatoblastoma, 844 hepatocellular carcinoma (HCC), 1067, 1077–1088, 1078f–1082f, 1078t, 1080t, 1082t–1084t, 1084f–1088f, 1086t cholangiocarcinoma and, 1079, 1231 liver resection for, 1117 liver transplantation for, 1084–1085 PHTN and, 1129

PVE for, 1084–1085, 1086t, 1087–1088 RFA for, 1086, 1107 TACE for, 1086, 1088f, 1089f–1090f, 1112 hepatocyte nuclear factor-1-α (HNF1-α), 1069–1070 hepatojejunostomy, 1387 hepatolithiasis, 1089, 1185–1186 hepatomegaly, 1055, 1224 hepato-pancreato-biliary (HPB), 429 hepatopulmonary syndrome (HPS), 1148 hepatorenal syndrome, 1127, 1148 Hepp-Couinard technique, 1210 Herceptin. See trastuzumab hereditary diffuse gastric cancer (HDGC), 552 hereditary elliptocytosis, 1407–1408 hereditary multiple intestinal atresia (HMIA), 151 hereditary nonpolyposis colorectal cancer (HNPCC), 846–850, 847t, 848t, 850t, 864, 864t, 978 hereditary spherocytosis (HS), 1406–1407, 1407t hernias. See also specific types abdominal wall bariatric surgery and, 654 SBO and, 679 diaphragm, MWA and, 1110 from laparoscopic ports, 101 SBO and, 683–684, 683f, 684f trocars and, 684 hernioplasty, 215 herpes simplex virus (HSV), 958 Hess, D. S., 648 Hesselbach’s triangle, 194 Heymen, S., 969 5-HIAA. See 5-hydroxyindoleacetic acid hiatal hernia, 123, 404. See also paraesophageal hernias Hicks, C. W., 966

HIDA. See hepatobiliary iminodiacetic acid hidradenitis suppurativa, 957 high-grade anal squamous intraepithelial lesion (HSIL), 957 HIV and, 1018–1019 HPV and, 1016–1017 highly active antiretroviral therapy (HAART), 1017 highly selective vagotomy (HSV), 515, 517–518, 518f, 603, 607–610, 608f– 610f, 633 high-output ileostomies, 247–248, 248t high-resolution anoscopy (HRA), 1018, 1019 high-resolution manometry (HRM), 383–384, 384f, 388, 389f, 399–401, 400f, 401t Hill classification, for GERD, 398, 399f Hill-Ferguson retractor, 949–951, 952 HIPEC. See hyperthermic intraperitoneal chemotherapy Hippocrates, 9, 1033 Hirota, S., 565, 579 Hirschsprung disease (HD) colonic volvulus and, 786, 790 constipation and, 962 JIA and, 151, 152 meconium ileus and, 153 MPS and, 154, 156 pediatrics, 156–158, 156f, 157f SBS and, 756, 757 histologic gastritis, 521 HIT. See heparin-induced thrombocytopenia HIV. See human immunodeficiency virus HMG-CoA. See hydroxymethylglutaryl-coenzyme A HMIA. See hereditary multiple intestinal atresia HNF1-α. See hepatocyte nuclear factor-1-α HNPCC. See hereditary nonpolyposis colorectal cancer Hodgkin lymphoma, 1413 Honkoop, P., 494

horseshoe fistula, 954, 955f Horton, M. D., 732 Hospital Standardization Program, 5 Hospital Stay, Readmission, and Mortality Rates (HARM), 39 Howard, John M., 1381 Howell-Jolly bodies, 1397, 1409, 1411 HPB. See hepato-pancreato-biliary HPS. See hepatopulmonary syndrome; hypertrophic pyloric stenosis HPV. See human papillomavirus HRA. See high-resolution anoscopy HRM. See high-resolution manometry HRQL. See health-related quality of life HS. See hereditary spherocytosis HSIL. See high-grade anal squamous intraepithelial lesion Hsu, C., 748 HSV. See herpes simplex virus; highly selective vagotomy Huang, C. J., 1035 Hubbard, T. B., 181 Hübner, M., 33 Hughes, B. D., 38 Hui, C. K., 1174 Hulscher, J., 479 human immunodeficiency virus (HIV). See also acquired immune deficiency syndrome AIHA and, 1409 amebic liver abscess and, 1041 anal SCC and, 1016, 1018, 1023–1024 anus and, 957 appendicitis and, 736 gastric lymphoma and, 568 hemorrhoids and, 946 HSIL and, 1018–1019 immune thrombocytopenia and, 1411 Kaposi sarcoma and, 297, 735, 872

lower GI Bleeding and, 297 nodular lymphoid hyperplasia and, 872 SBO and, 685 small bowel lymphoma and, 706 splenic cysts and, 1404 human papillomavirus (HPV), 444, 957, 1016–1017, 1019, 1028 Hunter grasper, 103 Hunter syndrome, 196 Hurler syndrome, 196 HUS. See hemolytic uremic syndrome HVPG. See hepatic vein pressure gradient hyaluronic acid, 455, 697 hydatid liver abscess, 1045–1053, 1046f, 1047t, 1048f, 1049t, 1051f, 1052t, 1053f hydralazine, 309 hydrocortisone, 827 5-hydroxyindoleacetic acid (5-HIAA), 561, 718, 722, 724, 871 hydroxymethylglutaryl-coenzyme A (HMG-CoA), 1078 hydroxyurea, 306, 1409 hyperaldosteronism, 1439 hyperamylasemia, 1180, 1183, 1258, 1280 hyperbaric oxygen, 697 hypercalcemia, 1079, 1304 hypercapnia, 106–107 hypercholesterolemia, 1079 hypercortisolism, 1433–1434 hypergammaglobulinemia, 1217 hypergastrinemia, 523, 526, 561 hyperglycemia, 21, 27, 535, 654, 1289 hyperkalemia, 20, 21, 1435 hyperlipidemia, 639, 1304 hyperparathyroidism, 1369 hyperphosphatemia, 20 hyperplastic polyps, 524–525, 563, 563f, 868

hypersensitivity, 538 hypertension, 12, 20, 182, 639, 640t, 1435–1436. See also portal hypertension pulmonary, 513, 654 refractory, 328 hyperthermic intraperitoneal chemotherapy (HIPEC), 305, 747 hypertonic saline, 1050 hypertrophic cardiomyopathy, 14 hypertrophic pyloric stenosis (HPS), 135, 135–136f hypoalbuminemia, 666, 1036, 1348 hypocalcemia, 1289 hypogastric nerve, 933, 982 hypoglycemia, 21, 520, 759, 1079, 1377, 1445 insulinoma and, 1367 omphalocele and, 140 hypokalemia, 21, 1435 hypoperfusion, 105 hypotension, 13, 105, 359, 520, 523, 535 hypothermia, 138, 140, 182, 326, 366 hypovolemia, 11, 141, 520, 1289, 1294 hypovolemic shock, 1062 hysterectomy, 10, 771, 812, 900, 942 TAH, 849, 850 TAH-BSO, 978 I iatrogenic bleeding, 291 IBD. See inflammatory bowel disease IBS. See irritable bowel syndrome IBS-C. See constipation-predominant irritable bowel syndrome IBW. See ideal body weight iCCA. See intrahepatic cholangiocarcinoma ideal body weight (IBW), 26 ideal-sigmoid knot, 790 IDF. See International Diabetes Federation

idiopathic gastroparesis, 537 idiopathic thrombocytopenic purpura (ITP), 324, 507 I-FABP. See intestinal fatty acid-binding protein IFALD. See intestinal failure-associated liver disease IGFBP-3. See insulin-like growth factor-binding protein 3 IgM. See immunoglobulin M IGV. See isolated gastric varices IHA. See immune hemolytic anemia IHC. See intrahepatic cholangiocarcinoma IIT. See intensive insulin therapy I-ITx. See isolated intestine grafts IL. See interleukins ileal pouch-anal anastomosis (IPAA), 250–251, 830, 832–836, 839–840, 845, 916–918, 917f, 918, 918f ileocecectomy, 808–809, 808f–810f ileorectal anastomosis (IRA), 831, 847 ileosigmoid fistulas, 811, 811f ileostomy for constipation, 967 continent, 250–254, 250f–255f for Crohn’s disease, 804 end, 240–242, 241f, 242f, 829, 833, 835 for enterocutaneous fistula, 273 for intestinal stomas, 240–248, 241f–248f, 248t complications of, 246 loop, 242–244, 242f–244f, 835 loop-end, 244–245, 244f, 245f for malrotation, 142 separated, 245–246 for UC, 830, 839 ileovesical fistulas, 811–812 ileus (functional bowel obstruction), 18–19, 35, 535, 678–679, 678t, 681 meconium, 153–154, 153f–155f paralytic, 1288

terminal ileus disease, 813 iliac arteries, 101, 344, 347f, 355–356, 358–363 iliac vein, 101, 356 IMA. See inferior mesenteric artery imatinib mesylate, 565–566, 586–591, 587t, 599, 600–602 imatinib mesylate, sunitinib, and regorafenib, 567 imipramine, 388 immune hemolytic anemia (IHA), 1409–1410 immune thrombocytopenia (ITP), 1410–1411 immunoglobulin M (IgM), 1398, 1409–1410 immunomodulators, 296, 801, 825 imperforate anus, 146, 158–160, 158f–160f IMV. See inferior mesenteric vein inborn errors of metabolism, 196 incarceration hemorrhoids, 946 inguinal hernias, 196, 197 SBO and, 683, 683f incisional hernias, 220–223, 221t, 683 incisions abdominal wall, 167–179 abdominothoracic, 170–172, 175f for appendectomy, 167, 170, 172f closure, 179–186 Kocher subcostal, 169–170, 172f L- and J-shaped, 172, 178f mass closure, 180, 181f muscle-splitting, 169, 173f paramedian, 169, 169f, 170f, 171f retention sutures for, 181–182 retroperitoneal and extraperitoneal, 172–176, 177f, 179f surgical site preparation for, 168 temporary closure, 182–183 transverse and oblique, 169–170

vertical, 168–169 for CRC surgery, 880 for inguinal hernia, 198–199, 198f–199f for laparoscopy, 176–179 closure of, 182 for loop ileostomy, 242 McBurney, for appendectomy, 167, 170, 172f midline, 168–169, 168f, 169f for enterocutaneous fistula, 273–274 for ITx, 764 for liver blunt trauma, 326 Pfannenstiel, 170, 174f for right colectomy, 925 for robotic TME for CRC, 927 relaxing, for PEH repair, 430 for umbilical hernias, 220 for vagotomy, 604–605 for Zenker diverticulum, 375 indirect inguinal hernias, 194 induction therapy, 825 infections. See also surgical site infections acute pancreatitis and, 1294–1295 early problems with, 3–4 incisional hernia and, 220 after inguinal hernia repair, 208 ITx and, 765 pancreatic necrosis and, 1263 after splenectomy, 1398 visceral artery aneurysms and, 366 infectious colitis, 297, 800 inferior mesenteric artery (IMA), 352, 366, 872, 934 AAA and, 360, 361 robotic rectal TME for CRC and, 925–927, 927f trauma to, 357

inferior mesenteric vein (IMV), 925–927, 926f, 927f inferior rectal arteries, 934 inferior vena cava (IVC), 22–23, 355, 356, 763 adrenal glands and, 1433 aortocaval fistula and, 359 periampullary adenocarcinoma of pancreas and, 1349 renal arteries and, 346 inflammatory bowel disease (IBD), 429, 839–842. See also Crohn’s disease; ulcerative colitis anal SCC and, 1017 diverticulitis and, 769 enterocutaneous fistulas and, 264 lower GI bleeding and, 296–297 PSC and, 1216–1217 rectal cancer and, 977, 979 strictureplasty for, 893 inflammatory fibroid polyps, 564 inflammatory polyps, 868 inflammatory pseudotumors, 1405 infliximab, 758, 801, 804, 815, 828, 835, 840–841 infrarenal aorta, 344, 355–356 infrarenal IVC, 356 Ingkakul, T., 1334 inguinal canal, 195 inguinal hernia anatomic classification for, 194–195 anesthesia for, 197–198, 214 bladder injury from, 209 clinical manifestations, 196 diagnosis, 213 epidemiology, 194 etiology, 195–196, 213 groin anatomy and, 195 hematoma after, 208

incarceration, 196, 197 incisions for, 198–199, 198f–199f infections after, 208 laparoscopy for, 194, 205–207 Maloney dam for, 215 management, 213–217 Marcy technique for, 215 mesh for, 201–202, 204f, 206 NSAIDs for, 10 Onstep technique for, 205 pain after, 208–209 physical examination for, 196–197 plug and patch for, 202, 203f pregnancy and, 196, 213 preperitoneal space and, 202–205, 204f recurrence after, 207–208 repair, 197 bilayer prosthetics for, 216 complications of, 207–210 Cooper’s ligament repair for, 193, 201, 215 Desarda technique for, 215 hernioplasty for, 215 Kugel/Ugahary technique for, 216 laparoscopy for, 216 Nyhus-Condon technique for, 215 operative techniques for, 198–207 Read-Rives technique for, 215 Stoppa technique for, 215 TAPP, 216 TEP, 216 robotic surgery for, 194 SBO and, 683 seroma after, 208 Shouldice technique for, 193–194, 199–201, 200f, 215

strangulation, 196, 197, 209–210 surgical techniques for, 214–216, 215t sutureless closure for, 202, 203f TAPP, 205–206 TEP, 206 testicular injury from, 209 vas deferens injury from, 209 WW for, 213–214 inguinal lymph nodes, 1022 inguinodynia, 208–209 injection sclerotherapy, 62 Inoue, H., 76, 386 INR. See international normalized ratio insufflators, 103 insulin resistance, 33, 639 insulin-like growth factor-binding protein 3 (IGFBP-3), 860 insulinoma, 1367, 1367f, 1379 intensive insulin therapy (IIT), 21 interferon-α, 714, 1028 interleukins (IL), 33 abscesses and, 257 acute pancreatitis and, 1257 metabolic syndrome and, 642 UC and, 826 internal hernia bowel obstruction and, 19 after laparoscopy for SBO, 683–684 after RYGB for SBO, 683–684, 699 for SBS, 756, 757f International Diabetes Federation (IDF), 641 international normalized ratio (INR), 16, 22, 23, 876, 1348 International Study Group of Pancreatic Surgery (ISGPS ) on DGE, 1384, 1384t

on PF, 1382–1383, 1383t on PPH, 1385 International Study Group on Pancreatic Fistula (ISGPF), 115 International Union Against Cancer (UICC), 447, 1020–1021 interoperative ERCP (IO-ERCP), 1179 interval appendectomy, 745 intestinal failure (IF). See short bowel syndrome intestinal failure-associated liver disease (IFALD), 756, 759 intestinal fatty acid-binding protein (I-FABP), 688 intestinal lengthening, 759–761, 760f, 761f intestinal motility, 681 intestinal stomas blowhole colostomy for, 238, 239f colostomy for, 233–240, 234f, 235f, 237f–239f continent ileostomy for, 250–254, 250f–255f Crohn’s disease and, 804 divided loop colostomy for, 240 end colostomy for, 233–236, 234f, 235f end ileostomy for, 240–242, 241f, 242f ET for, 231 high-output ileostomies for, 247–248, 248t ileostomy for, 240–248, 241f–248f, 248t ischemia, 250, 250f loop colostomy for, 236–238, 237f, 238f loop ileostomy for, 242–244, 242f–244f loop-end colostomy for, 240 loop-end ileostomy for, 244–245, 244f, 245f MBP for, 232–233, 232f, 233t prolapse, 249 retraction, 249–250, 250f separated ileostomy for, 245–246 site marking for, 231–232, 232f, 233t stenosis, 250 intestinal transplantation (ITx), 761–765, 762f–764f

intra-abdominal packing, 335–336 intra-abdominal pressure gastroschisis and, 140 incisional hernia and, 221 laparoscopy and, 105, 106 omphalocele and, 141 intracranial pressure, 366, 523 intractable/nonhealing PUD, 514–515, 514t intraductal papillary mucinous neoplasms (IPMNs), 1323–1324, 1325t, 1331–1341, 1377–1378 intraepithelial papillary capillary loop (IPCL), 445, 446f intragastric balloon, 74–75, 643, 644t, 668 intrahepatic cholangiocarcinoma (IHC, iCCA), 112, 1088–1092, 1091f, 1092t, 1230–1241 intraluminal pressure, 681 intraoperative cholangiography (IOC), 1162–1163, 1163f, 1177–1179, 1245– 1246 intraoperative radiation therapy (IORT), 311f, 1009 intraoperative ultrasound (IOUS), 1178, 1242 intraperitoneal onlay mesh technique (IPOM), 206, 221, 224, 225 intrathoracic esophageal cancer, 458 intravenous pyelogram (IVP), 358 intussusception, 19 continent ileostomy and, 251–252, 251f, 252f JIA and, 150 rectum, 937–940, 937f–940f, 938t SBO and, 685 SI-NETs, 713, 713f IOC. See intraoperative cholangiography IO-ERCP. See interoperative ERCP IORT. See intraoperative radiation therapy IOUS. See intraoperative ultrasound IPAA. See ileal pouch-anal anastomosis IPCL. See intraepithelial papillary capillary loop

IPMNs. See intraductal papillary mucinous neoplasms IPOM. See intraperitoneal onlay mesh technique ipratropium, 17 IRA. See ileorectal anastomosis IRE. See irreversible electroporation irinotecan, 469 iron, gastrectomy and, 523 iron deficiency anemia, 290, 653 irreversible electroporation (IRE), 1112–1114 irritable bowel syndrome (IBS), 429 CRC and, 841–842, 860–861 diverticulitis and, 769, 775 enterocutaneous fistulas and, 271, 272 gastroparesis and, 538 IBS-C, 961 inflammatory polyps and, 868 ischemia colon, 681 visceral artery aneurysms and, 367 intestinal stomas, 250, 250f PF and, 1383 SBO and, 691–692 solitary rectal ulcer syndrome and, 942 ischemic colitis, 297, 297f, 769 ISGPF. See International Study Group on Pancreatic Fistula ISGPS. See International Study Group of Pancreatic Surgery isolated gastric varices (IGV), 291 isolated intestine grafts (I-ITx), 762 isosorbide dinitrate, 384 Ito, C., 648 ITP. See idiopathic thrombocytopenic purpura; immune thrombocytopenia ITx. See intestinal transplantation Ivatury, R. R., 328, 332 IVC. See inferior vena cava

Iversen, L. H., 114 IVP. See intravenous pyelogram J Jaboulay gastroduodenostomy, 515–517, 517f Jacobi, C. A., 479 Jancelewicz, T., 692 jaundice with acute pancreatitis, 1288 AIHA and, 1409 with appendicitis, 730 benign biliary strictures and, 1208 choledocholithiasis and, 1172 with pyloric stenosis, 135 with small bowel adenomas, 709 TDS and, 1180 Jaworski, W., 532 Jayakrishnan, T. T., 113 jejunal interposition, 491–493, 491f–493f jejunal pouch, 628, 631f jejunoileal atresia (JIA), 150–153, 151f, 152f jejunoileal bypass, 648 jejunoileal diverticula (JID), 749–750 jejunostomy tube for enterocutaneous fistulas, 274 for gastroparesis, 526, 541–542 for MVTx, 764 PEG with, 67 for Roux stasis syndrome, 522 for small bowel adenocarcinoma, 710 JIA. See jejunoileal atresia JID. See jejunoileal diverticula Jodorkovsky, D., 969 Johansson, J., 501, 502

Johansson, M., 1167 Johnson, David, 604 Johnston, D., 603 Jones, K., 691 J-pouch, 840 cuffitis, 836, 836f with RPC, 814 staplers for, 897 for UC, 831–832, 831f, 832f J-shaped incisions, 172, 178f Jung, B., 34 Jurkovich, G. J., 330 juvenile polyposis, 564, 851–852, 865 juxtahepatic venous injuries, 328–330, 329f K Kaimakliotis, P., 1336 Kaposi sarcoma, 297, 735, 746, 872 Kasabach-Merritt syndrome, 1062–1063, 1064, 1065 Kasten, K. R., 789 Kausch, Walther Carl Eduard, 1381 Ke, Z. W., 1176 Keating, J. P., 968 Keck, J. O., 272 Kegel exercises, 969 Kehlet, Henrik, 31 Kejriwal, R., 1176 Kelley, C. J., 1239 Kelsen, D. P., 477 Kendrick, 115 Kenney, C. D., 1403 ketorolac, 98 Khashab, M. A., 541, 1326, 1327 kidney. See also renal

trauma to, 320t kidney bean sign, 786, 787f Kim, H., 761 Kim, M. H., 1186 Kimura, A., 332 Kimura procedure, 145–146 Kingham, T. P., 1113 Kiran, R. P., 34 KIT, for GISTs, 565, 567, 579–581, 580f, 599, 705, 715, 872 Klatskin tumors, 1230, 1239f Klebsiella spp., 1035–1036, 1280, 1404 Knight, R., 101 Koch, Robert, 3–4 Kocher clamps/maneuver, 233–234 for colon carcinoids, 722 for gastrinoma, 1368 for Jaboulay gastroduodenostomy, 515 for pancreatic cancer, 113 for penetrating trauma, 333–334 for renal artery exposure, 346 subcostal incision, 169–170, 172f Kock pouch, 833, 833f Koh, Y. X., 585, 1342 Kolodner, Richard, 847 Kono-S anastomosis, 817–818, 817f Körte, Werner, 1382 Kram, H. B., 1383 Kraske approach, to rectal cancer surgery, 992–993, 992f Kristensen, J. K., 332 Kudo, S., 867 Kugel/Ugahary technique, 216 Kuhl, E., 332 Kulaylat, A. N., 734 Kulik, L. M., 1101

Kullman, E., 1177 Kumar, S., 697 Kupffer cells, 1033, 1042 Kwon, S. K., 1177 L LAARP. See laparoscopy-assisted anorectoplasty lactate dehydrogenase (LDH), 1409 Lactobacillus spp., 532 lactobezoars, 526 Ladd bands, 141–142, 143, 148, 149 Ladd procedure, 142, 142f, 143 LAERC. See laparoscopy-assisted endoscopic retrograde cholangiography Laffan, T. A., 1323 Lam, S. W., 535 Lamb, J. M., 328 Landercasper, J., 693 Landsteiner, Karl, 6 Langenbuch, Carl, 1155 Langnas, A. N., 758 lanreotide, 1379 laparoscopic anterior resection, of rectum, 910–911 laparoscopic appendectomy (LA), 738–739, 740f–741f laparoscopic biliary bypass, 1247–1248 laparoscopic CBD exploration (LCBDE), 1178–1179, 1246–1247 laparoscopic cholecystectomy advantages and disadvantages, 1165, 1165t benign biliary strictures from, 1199–1213, 1204f–1210f, 1212t, 1213t for cholecystitis, 1166–1167 complications, 1167–1168 dissection in, 1162, 1162f operating room setup, 1160, 1161f pneumoperitoneum and, 1160 port placement, 1160–1161, 1169f

laparoscopic choledochoduodenostomy (LCD), 1247 laparoscopic colectomy, 918–919, 919f laparoscopic distal gastrectomy (LDG), 114–115 laparoscopic hepaticojejunostomy (LHJ), 1247, 1248f laparoscopic incisional hernia repair (LIHR), 227–229 laparoscopic low anterior resection, of rectum, 911–913, 912f, 913f laparoscopic rectopexy, 915–916 laparoscopic ultrasound (LUS), 110, 110f, 111, 112, 113, 1163 laparoscopic unroofing, for splenic cysts, 1428 laparoscopy, 102f. See also hand-assisted laparoscopic surgery adhesions and, 97, 696 for adrenalectomy, 1438, 1439f, 1440–1444, 1440f for AGB, 653, 662–664, 662f–664f for appendectomy, 124 for APR, 913–915, 914f for bile ducts, 1245–1248, 1246f, 1248f bipolar electrosurgery, 105 for cancer, 109–117 for cecal volvulus, 789 challenges, 124, 125t for cholecystectomy, 1155, 1156t contraindications, 1158–1159, 1159t for colectomy, 116–117, 116t for diverticular disease, 776 for colon cancer, 896–897 instruments, 897, 897t, 898f patient position and room setup, 897–899, 899f for congenital liver cysts, 1054 contraindications, 894–895, 894t for CRC, 113, 882, 923 for CRS/HIPEC, 113 for duodenal atresia, 150 equipment for, 101–103, 102f esophageal adenocarcinoma, 111

for esophageal cancer, 454 for femoral hernia repair, 211 fundamentals, 97–107 for fundoplication, for GERD, 396, 408, 409f for gallbladder, 115 cancer, 111–112 for gastrectomy, 634–636, 635f for GC, 111, 578 for GERD, 405–407, 405f for GISTs, 585, 586f, 600 hemostasis with, 104 for hepatectomy, 115 for hydatid liver abscesses, 1050–1052 hypercapnia and, 106–107 for ileoanal pouch, 840 for ileocecectomy, for Crohn’s disease, 808–809, 808f–810f ileus and, 18 for incisional hernia, 222–223, 227–229 incisions for, 176–179 closure of, 182 indications for, 893–894, 894t for inguinal hernia repair, 194, 205–207, 216 instrumentation for, 103–105, 104f insufflators for, 103 for intestinal stoma colostomy, 235–238 intraoperative evaluations, 895–896 introduction, 7 for IPAA, for UC, 830 for JIA, 151–152 for left hemicolectomy, 903–906, 904f, 905f light sources for, 103 for liver, 115 cancer, 111–112 monopolar electrosurgery, 104–105

for myotomy, for epiphrenic diverticulum, 377 for pancreatic cancer, 112–113, 115–116, 116t for pancreatic necrosis, 1285–1286 patient positioning for, 97–98 patient selection for, 97 for PD, 115–116, 116t for PEG, 67 for PEH, 413–414, 413f, 414f, 426–433, 427f–432f, 433t for periampullary adenocarcinoma of pancreas, 1351, 1353–1355 for PNETs, 1371 pneumoperitoneum and, 894 physiologic effects of, 105–107 port placement, 98–101, 98f–100f, 109, 110f in pregnancy, 107 preoperative evaluations, 895 for pyloromyotomy for gastroparesis, 526 for HPS, 135, 136f for pyloroplasty, for gastroparesis, 543 for rectal cancer, 896–897, 1007–1008 instruments, 897, 897t, 898f patient position and room setup, 897–899, 899f for right hemicolectomy, 899–903, 900f–903f for SBO, 695, 696 internal hernia after, 683–684 for sentinel node navigation, 636 for splenectomy, 1414, 1416–1423, 1418f, 1420f–1421f for sutures, for rectal prolapse, 938–939 for TME, 128 ultrasonic shears for, 105 for vagotomy, 629–634, 632f–634f video camera for, 103 video monitors for, 103 laparoscopy-assisted anorectoplasty (LAARP), 159

laparoscopy-assisted endoscopic retrograde cholangiography (LAERC), 1247 laparotomy for acute pancreatitis, 1264 adhesions and, 243 for bowel blunt trauma, 322 for cholecystectomy, 1166 for CRC, 882 for enterocutaneous fistulas, 269 for IHC, 112 for iliac artery repair, 356 for incisional hernia, 220 for intestinal stoma ischemia, 250 for pancreatic cancer, 112 for penetrating trauma, 331t, 333–334 for SBO, 696 second-look, 183, 352–353 for spleen blunt trauma, 323 LAPC. See locally advanced pancreatic cancer LAR. See low anterior resection large bowel obstruction (LBO), 681 colonic volvulus and, 785 diverticular disease and, 772 SEMS for, 92, 92f large intestine. See colon large-balloon dilation, 1174 large-duct chronic pancreatitis, 1311–1312 laryngeal nerve injury, 494 laser-induced thermotherapy (LITT), 1099 lateral nodal dissection, 994–995 lateral pancreaticojejunostomy, 1311–1312, 1312f laudanum, 3 laxatives, 965 lazy C loop, 351, 351f LBO. See large bowel obstruction

LCA. See littoral cell angioma LCD. See laparoscopic choledochoduodenostomy LDG. See laparoscopic distal gastrectomy LDH. See lactate dehydrogenase LeBlanc, K. A., 227 Ledgerwood, A. M., 182 Lee, J., 1438 Lee, S. E., 1327 Lee, T. C., 457 left gastric vein (LGV), 1129 left hemicolectomy HALS for, 906–907, 906f, 907f laparoscopy for, 903–906, 904f, 905f left thoracoabdominal approach, to esophagectomy, 488–489, 488f leiomyomas, 298, 525, 527, 567–558, 567f, 710 leiomyosarcomas, 298, 567–568 LES. See lower esophageal sphincter leucovorin, 885 leukemia, hemorrhoids and, 946 leukocytosis, 11, 136, 307 acute pancreatitis and, 1259 pyrogenic liver abscesses and, 1036 leveling colostomy, 157 levosulpiride, 539 Levy, E., 265 Lewis, Ivan, 443, 475, 478, 479, 487 LFTs. See liver function tests LGV. See left gastric vein; lymphogranuloma venereum LHJ. See laparoscopic hepaticojejunostomy Li, N., 699 Lichtenstein, I. L., 193, 195, 202 lichtleiter, 7, 7f Li-Fraumeni syndrome, 552, 1436 LIFT. See ligation of the intersphincteric fistula tract

LigaSure, 104, 897 ligation of the intersphincteric fistula tract (LIFT), 954–955 LIHR. See laparoscopic incisional hernia repair Lillehei, Richard, 755 Lillemoe, K. D., 1212 linaclotide, 965 line of Toldt, 904, 927, 996 Lipham, J. C., 544 lipomas, 709, 870–871 liraglutide, 643, 643t Lister, Joseph, 4, 4f Listeria monocytogenes, 794 LITT. See laser-induced thermotherapy littoral cell angioma (LCA), 1404–1405 Littré, A., 767 L-ITx. See liver-intestine graft liver. See also hepatic abscesses amebic, 1041–1045, 1042t, 1043t, 1044f, 1045t hydatid, 1045–1053, 1046f, 1047t, 1048f, 1049t, 1051f, 1052t, 1053f MWA and, 1110 pyrogenic, 1033–1041, 1034f, 1035t, 1036t, 1037f, 1040f, 1041t, 1042t TACE and, 1100 adenomas, 1063t, 1067–1071, 1069t, 1070f, 1072f, 1073f bacteria in, 692 benign tumors, 1061–1073, 1061t, 1062f, 1063t, 1064f–1066f, 1065t, 1068f–1070f, 1069t, 1072f, 1073f blunt trauma to, 324–330, 325f, 325t, 326t, 327f, 329f cancer, 1077–1093, 1078f–1082f, 1078t, 1080t, 1082t–1084t, 1084f–1091f, 1086t, 1092t laparoscopy for, 111–112 cysts, 1053–1057 congenital, 1053–1055, 1054t, 1055f neoplastic, 1055–1057, 1055t, 1056f

traumatic, 1057, 1057f GISTs, 1097 hamartomas, 1072–1073 hemangiomas, 1061–1066, 1062f, 1063t, 1064f–1065f, 1065t laparoscopy for, 115 LUS, 110, 110f metastases ablation for, 1104–1114 DEB-TACE for, 1100–1101 IRE for, 1112–1114 MWA for, 1099, 1108–1110, 1110f PNETs and, 1380 RFA for, 1099, 1105–1108, 1106f, 1107f RILD for, 1110 SIRT for, 1101–1104, 1102f–1104f TACE for, 1097–1100, 1098f NETs, 1097 omphalocele and, 141 penetrating trauma, 326, 334–335, 335t resections, 1117–1123, 1118t, 1119f–1121f, 1120t, 1123f FLR and, 1118–1119, 1122–1123 Kocher subcostal incision for, 169 MIS for, 1121 robotic surgery for, 124 transplantation for Caroli disease, 1198 for cholangiocarcinoma, 1236 for HCC, 1084–1085 for HPS, 1148 for hydatid liver abscesses, 1052 for ICC, 1092 Kocher subcostal incision for, 169 for PCLD, 1055 for PHTN, 1137, 1140–1141

for PSC, 1218 liver failure, 220, 648, 1052, 1100 liver function tests (LFTs), 1155, 1158 liver-intestine graft (L-ITx), 762 LMWH. See low-molecular-weight heparin local analgesia, 9–10 locally advanced pancreatic cancer (LAPC), 1375 Lockhart-Mummery, H. E., 793 Logan, A., 460 Loganathan, A., 968 LOH. See loss of heterozygosity Long, Crawford, 3 Longo, W. E., 1024 loop colostomy, 157, 236–238, 237f, 238f loop ileostomy, 242–244, 242f–244f, 835 loop-end colostomy, 240 loop-end ileostomy, 244–245, 244f, 245f loperamide, 248 lorcaserin, 642, 643t Los Angeles classification, for GERD, 398, 398t loss of heterozygosity (LOH), 862, 978 Lourenco, A., 205 low anterior resection (LAR), 994–995 low anterior resection of rectum, HALS for, 913 Lowe, L. H., 746 lower esophageal sphincter (LES), 381 achalasia and, 382–387, 382t, 385t, 386f GERD and, 393–395, 395f hypotension, gastroparesis and, 535 lower GI bleeding, 293–298, 293t, 294f–298f colonoscopy and, 91 obscure bleeding, 297–298 low-grade anal squamous intraepithelial lesion (LSIL), 957, 1016–1017 low-molecular-weight heparin (LMWH), 16, 23, 878, 1160

L-shaped incisions, 172 LSIL. See low-grade anal squamous intraepithelial lesion lubiprostone, 965 Lucas, C. E., 182 Lugol’s iodine, 445, 445f Luketich, J., 478 lumbar hernia, 224–225, 224f LUS. See laparoscopic ultrasound lymph nodes acute mesenteric lymphadenitis, 303 bacteria in, 692 colon carcinoids and, 722 inguinal, 1022 rectal cancer and, 979, 981–982, 982f resections, 123, 125, 575–576 spleen and, 1397 stations, 451f lymphadenectomy for carcinoids, 526 for esophageal cancer, 453–454, 459–463, 461f for gallbladder cancer, 1228 for GC, 556–558, 557f, 559f for ICC, 1092 for liver adenomas, 1071 for PNETs, 1378 robotic surgery for, 126–128, 636, 636f lymphogranuloma venereum (LGV), 958 lymphomas colon, 872 gastric, 568–569, 569f mesentery, 306 NHL, 564, 706, 711–712, 712f, 1413 obscure lower GI bleeding and, 298 small bowel, 705, 706

spleen, 1413 Lynch, Henry T., 847 Lynch syndrome. See hereditary nonpolyposis colorectal cancer lysine, 443–444 M MAGIC. See Medical Research Council Adjuvant Gastric Infusional Chemotherapy magnetic resonance angiography (MRA), 1131 magnetic resonance cholangiography (MRC), 1245–1246 magnetic resonance cholangiopancreatography (MRCP), 80 for benign biliary strictures, 1205, 1205f, 1206, 1214 for cholangiocarcinoma, 1232, 1236f for cholangitis, 1184 for choledochal cysts, 1194 for choledocholithiasis, 1175–1176 for chronic pancreatitis, 1308, 1308f for gallbladder cancer, 1224–1225 for hydatid liver abscesses, 1048 for MCNs, 1330 for pancreatic pseudocyst, 1273 for periampullary adenocarcinoma of pancreas, 1349, 1350f for PSC, 1217 for recurrent pyogenic cholangitis, 1215 for small bowel adenocarcinoma, 710 for sphincter of Oddi stenosis, 1216 magnetic resonance enterography (MRE), 691, 707, 799, 849 magnetic resonance imaging (MRI) for abscesses, 259 for acute pancreatitis, 1259 for aldosteronomas, 1435 for amebic liver abscess, 1043 for anal fistula, 956 for appendicitis, 731, 734 for carcinoids, 718

for cholangiocarcinoma, 1232 for cholangitis, 1184 for colon carcinoids, 722 for congenital liver cysts, 1053, 1053f for constipation, 962 for Crohn’s disease, 797 for CRS/HIPEC, 113 for desmoids, 306 for esophageal cancer, 454 for FNH, 1067 for gallbladder cancer, 1224 for gastrinoma, 1368 for gastroparesis, 538–539 for GISTs, 582, 582f for HCC, 1080 for hepatolithiasis, 1185 for imperforate anus, 158, 159 for inguinal hernia, 213 for IRE, 1113 for liver adenomas, 1071, 1072f for liver hemangiomas, 1063, 1064f–1065f for MCNs, 1330 for mesenteric panniculitis, 304 for pancreatic cancer, 1375 for pancreatic cystic neoplasms, 1323, 1377 for pancreatic necrosis, 1281 for PCLD, 1054 for pheochromocytoma, 1346 for PHTN, 1131 for PJ, 564 for rectal cancer, 985 for rectal carcinoid, 724 for rectal prolapse, 937 SANT, 1404, 1405f

for SCNs, 1324, 1328 for splenic cysts, 1402 magnetic resonance venography (MRV), 763, 1131 maintenance therapy, for UC, 825 Maithel, S. K., 112 Makela, J. T., 182 Mallo, R. D., 691 Mallory–Weiss tear, 283, 289, 527 malnutrition, 25 acute pancreatitis and, 1290 chronic pancreatitis and, 1306 dumping syndrome and, 520 duodenal switch and, 666 enterocutaneous fistulas and, 263, 271 gastroparesis and, 526 work of breathing and, 17 Maloney dam, 215 malrotation, 141–143, 142f, 149, 150, 151 MALT. See mucosa-associated lymphoid tissue mammalian target of rapamycin (mTOR), 724, 1379 manometry anal, 938, 962, 963f, 968 esophageal, 72, 373, 376–377, 383, 399–401, 400f, 401t gastric, 521, 538 HRM, 383–384, 384f, 388, 389f, 399–401, 400f, 401t MAP. See MUTYH-associated polyposis Maple, J. T., 542 Marceau, D. S., 648 Marcy technique, 215 Marescaux, Jacques, 121 Marfan syndrome, 196, 213, 769 marginal ulcers, 523 Marie, F., 1336 Marie, I., 535

Marks, J. M., 1169 Marseilles-Rome classification, for chronic pancreatitis, 1303 Marshall, B. J., 507, 532 Martel, M., 1404 Martin, Franklin H., 5 Martin, R. C., 1108 Maryland dissector, 104, 104f Mason, E., 648 Mason, R. J., 738 Masoomi, H., 738 mass closure, abdominal wall incisions, 180, 181f mastinib, 591 Matas, Rudolph, 6 Mathieu, D., 1066 matrix metalloproteinase, 769 Matthias, Nicolaus, 1399 Mattox, K. L., 335 Mattsson, O., 375 Matzel, K. E., 972 Maxon, 180 Mayo, W. J., 220, 1382 Mayo clamp, 234 Mazur, M. T., 579 MBP. See mechanical bowel preparation MBSAQIP. See Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program McAuliffe, J. C., 586 McBurney incision, 167, 170, 172f McBurney’s point, 729 McCallum, R. W., 541, 544 McCormick, William, 331 McDowell, Ephraim, 6 McFadzean, A. J. S., 1033 McKeown, K. C., 443, 475, 480–486, 480f–486f

McKune, William, 79 Mcleod, R. S., 817 McNeer, G., 551 MCNs. See mucinous cystic neoplasms McVay, Chester, 193, 201, 215 MD Anderson Cancer Center (MDACC), 586, 989, 1021, 1027, 1121, 1375 SCNs and, 1327 MDCT. See multiple-detector computed tomography mean resting pressure, 968 mean squeeze pressure, 968 mebendazole, 1049 mechanical bowel obstruction, 677–678, 678t, 680–682, 687 mechanical bowel preparation (MBP), 33, 34, 232–233, 232f, 233t, 267, 803– 804 mechanical lithotripsy, 1174 Meckel diverticula, 283, 298, 298f, 750–751 meconium ileus, 153–154, 153f–155f meconium plug syndrome (MPS), 154–156 Medical Research Council (MRC), 476–477 Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC), 477, 559–560 medulloblastoma, 844 megacolon, 785, 786, 829, 829f megaesophagus, 386–387 megarectum, 940 melanoma, 306, 1026–1027 MELD. See Model for End-Stage Liver Disease Melton, G. B., 1213 Melvin, W. S., 126 Memon, M. A., 434, 1102 Memorial Sloan Kettering Cancer Center (MSKCC), 565, 1021, 1025, 1026 MEN-1. See multiple endocrine neoplasia type 1 Meng, H., 536–537 Menzies, D., 683

6-mercaptopurine (6-MP), 758, 801, 817, 826–827 Merendino procedure, 457 mesalamine, 800 mesenteric cysts, 304 mesenteric insufficiency, 349 mesenteric panniculitis, 303–304, 304f mesenteric tumors, 304–306, 305f mesenteric veins, 357 mesenteric venous thrombosis, 352 mesentery, 303–306, 304f, 305f mesh for closure, 182 for epigastric hernia, 225 for incisional hernia, 221, 221t for inguinal hernia repair, 201–202, 204f, 206 for intestinal stoma colostomy, 235 for PEH repair, 429–430, 431f for rectal prolapse, 938–939 for Spigelian hernia, 224 for umbilical hernia repair, 220 mesogastrium, 575 mesothelioma, 304–305, 305f metabolic acidosis, 20, 21, 136 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), 652 Metabolic Response Evaluation for Individualization for Neoadjuvant Chemotherapy in Oesophageal and Oesophagogastric Adenocarcinoma (MUNICON), 469 metabolic surgery, for obesity, 651t, 652, 654t, 669–671 metabolic syndrome cholangiocarcinoma and, 1231 obesity and, 640–642, 641t meta-iodobenzylguanidine (MIBG), 1437 Metamucil, 965

metastasectomy, 724 metastases. See also liver adrenal glands, 1438 anal SCC and, 1025 BE and, 415 carcinoid and, 724 cholangiocarcinoma, 1240–1241 colon, 872–873 CRC and, 883–884 CRML, 113, 1099, 1117, 1118–1119 gallbladder cancer and, 1229 GISTs and, 567, 589–590, 593f, 601–602 mesentery, 306 PNETs, 1372 rectal cancer, 1009 retroperitoneal sarcoma, 312 SBO and, 684, 685f small bowel, 715 splenic cancer and, 1405–1406, 1407f Metcalf, A. M., 963 Metcalfe, M. S., 1177 Metchnikoff, I., 532 methotrexate, 804 α-methyldopa, 309 methylenetetrahydrofolate, 352 methylprednisolone, 801, 827 methysergide, 309 metoclopramide, 526, 539 metronidazole, 569 for amebic liver abscess, 1043–1044 for cholangitis, 1184 for CRC surgery, 878 for Crohn’s disease, 800 for H. pylori, 508

for intestinal stoma MBP, 232 for pouchitis, 835 Meyer, A., 544 Meyer, C., 1179 Meyhoff, H. H., 1180 Mezhir, J. J., 1066, 1067 MI. See myocardial infarction MIBG. See meta-iodobenzylguanidine Michaelson, R. A., 1021 Michelassi strictureplasty, 806–807, 806f, 807f microsatellite instability (MSI), 850, 862, 865t microwave ablation (MWA), 1099, 1108–1110, 1110f mid-esophageal diverticulum, 375–376 midgut volvulus, 141, 142, 142f, 143, 756 midline incisions, 168–169, 168f, 169f for enterocutaneous fistula, 273–274 for ITx, 764 for liver blunt trauma, 326 MIE. See minimally invasive esophagectomy Miedema, B. W., 1386 Miettinen, M., 579 MIG. See minimally invasive gastrectomy migrating motor complex (MMC), 532, 533f MII-pH. See multichannel intraluminal impendence-pH Miles, W. E., 981 minimally invasive esophagectomy (MIE), 114–115, 459 minimally invasive gastrectomy (MIG), for GC, 558–559 minimally invasive surgery (MIS). See also laparoscopy; robotic surgery for benign gastric diseases, 527 for cancer, 114–117 for gastrectomy, 634–636, 635f for GISTs, 566 introduction, 7 for liver resection, 1121

for lumbar hernias, 225 for lymphadenectomy, 636, 636f for pancreatic necrosis, 1285–1286, 1296 for pancreatic pseudocysts, 1279 for periampullary adenocarcinoma of pancreas, 1353–1355 for rectal carcinoid, 724 robotic surgery as, 124 for Spigelian hernia, 224 Miralax, 988 Mirizzi syndrome, 1215 MIS. See minimally invasive surgery mismatch repair (MMR), 847, 847t, 848–849, 862 for gallbladder cancer, 1229 Misra, S., 1211 mitemcinal, for gastroparesis, 539 mitomycin-C, 1025 mitral regurgitation, 14 mitral stenosis, 14 mitral valve prolapse (MVP), antibiotics for, 14–15 MMC. See doxorubicin, gemcitabine, cisplatin, and mytomycin C; migrating motor complex MMR. See mismatch repair MMVTx. See modified multivisceral grafts Model for End-Stage Liver Disease (MELD), 1127, 1128t, 1140 modified multivisceral grafts (MMVTx), 763 MODS. See multiple organ dysfunction syndrome monopolar electrosurgery, 104–105 Montemurro, M., 591 Moore, Francis, 6 Morise, Z., 115 morphine, 3 Morson, B. C., 768, 793 Morton, William T. G., 3 motility

colon, 768 esophagus, 381–389, 382t, 383f, 385f, 385t, 386f–389f GERD and, 397 intestinal, 681 stomach, 531–533 Moya, P., 33 Moynihan, B., 767 6-MP. See 6-mercaptopurine MPD. See multifocal progressive disease MPS. See meconium plug syndrome MRA. See magnetic resonance angiography MRC. See magnetic resonance cholangiography; Medical Research Council MRCP. See magnetic resonance cholangiopancreatography MRE. See magnetic resonance enterography MRI. See magnetic resonance imaging MRV. See magnetic resonance venography MSI. See microsatellite instability MSKCC. See Memorial Sloan Kettering Cancer Center MSOF. See multisystem organ failure mTOR. See mammalian target of rapamycin mucinous ascites, 117, 117f mucinous cystic neoplasms (MCNs), 1323–1324, 1325t, 1328–1331, 1329f, 1330f, 1377 mucoceles, appendix, 746–747, 746f, 747f mucosa-associated lymphoid tissue (MALT), 507 gastric lymphoma and, 568–569 H. pylori and, 508 NHL and, 712 mucosectomy, for UC, 840 mucosectomy with handsewn anastomosis, for UC, 832 Mühe, Erich, 1155 multichannel intraluminal impendence-pH (MII-pH), 397, 402 multifocal progressive disease (MPD), 567 multiple endocrine neoplasia type 1 (MEN-1)

ACC and, 1436 carcinoids and, 525 duodenal carcinoids and, 720 gastric carcinoids and, 561, 720 PNETs and, 1365–1373, 1378–1380 multiple organ dysfunction syndrome (MODS) with acute pancreatitis, 1289 TDS and, 1180 multiple sclerosis, gastroparesis and, 534 multiple-detector computed tomography (MDCT), 1129, 1130f multisystem organ failure (MSOF) perforated PUD and, 513 visceral artery aneurysms and, 366 multivisceral grafts (MVTx), 762–763 Munasinghe, A., 111 MUNICON. See Metabolic Response Evaluation for Individualization for Neoadjuvant Chemotherapy in Oesophageal and Oesophagogastric Adenocarcinoma Murphy, J., 272 Murray, Joseph, 6 muscle-splitting incision, 169, 173f Musy, P. A., 1403 MUTYH-associated polyposis (MAP), 552, 846, 978 MVP. See mitral valve prolapse MVTx. See multivisceral grafts MWA. See microwave ablation Mycobacterium spp., 4, 794, 1035, 1404 myeloid neoplasms, 1412–1413 myelolipomas, 1436 Myers, J. G., 542 myocardial infarction (MI), 11, 12–13, 513, 1099, 1181 myocardial ischemia, 14 myotomy. See also Heller myotomy with fundoplication CPM, 373–374

laparoscopic, for epiphrenic diverticulum, 377 for nutcracker esophagus, 389f POEM, 75–78, 386, 387, 388, 389 myotonic dystrophy, 534 N naltrexone, 642–643, 643t Nance, F. C., 331 narrow-band imaging (NBI), 55, 56f NASA. See National Aeronautics and Space Administration NASHA Dx, 970 nasogastric decompression, 692–693, 692f, 700 nasogastric tube (NG) for CRC surgery, 878 for EA/TEF, 145 for GI bleeding, 284 for highly selective vagotomy, 610 for HPS, 135 PEH and, 412 for SBO, 695 for upper GI bleeding, 292 natalizumab, 801 Nath, J., 111 National Aeronautics and Space Administration (NASA), 121 National Cancer Institute (NCI), 312, 857, 896–897 National Cholesterol Education Program (NCEP), 641 National Comprehensive Cancer Network (NCCN), 312, 476, 584, 636, 844, 1021 National Health and Nutrition Examination Survey (NHAMES), 639, 641, 967 National Hospital Discharge Survey, 729 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 536, 538 National Institutes of Health (NIH), 565 National Surgical Quality Improvement Program (NSQIP), 32, 432, 465, 667,

738 natural orifice specimen extraction (NOSE), 893, 920 Natural Orifice Surgery Consortium for Assessment for Research (NOSCAR), 920 natural orifice transluminal endoscopic surgery (NOTES), 893, 920, 1169, 1284 NBI. See narrow-band imaging NCCN. See National Comprehensive Cancer Network NCEP. See National Cholesterol Education Program NCI. See National Cancer Institute NDBE. See nondysplastic Barrett esophagus near-infrared (NR) laparoscopy, 882 robotic surgery, 130 NEC. See necrotizing enterocolitis necrosectomy, 1284, 1286–1287, 1296, 1297–1299, 1298f for acute pancreatitis, 1265–1266 necrotizing enterocolitis (NEC), 135–137, 136f, 137f, 140 necrotizing fasciitis, 188 necrotizing wound infections, 185–188 Neisseria meningitides, 1414 Nelson, G., 32 neoadjuvant chemoradiation for anal SCC, 1021–1022, 1022t for esophageal cancer, 111, 467 for rectal cancer, 1010–1012, 1011t neoadjuvant chemotherapy for esophageal cancer, 111, 466–467 for GC, 559 for GISTs, 586–588, 586t, 600–601 for periampullary adenocarcinoma of pancreas, 1361–1362 neoadjuvant radiotherapy, 466 neomycin, 232, 878, 988 neoplasia. See also specific types

lower GI bleeding and, 295–296, 295f obscure, 298, 298f neoplastic liver cysts, 1055–1057, 1055t, 1056f nephrectomy, 358 nephroscopy, 1286 NERD. See nonerosive reflux disease nerve of Latarjet, 603, 605, 605f, 608 neuroendocrine tumors (NETs), 717. See also carcinoids chronic pancreatitis and, 1305 colon, 871 liver, 1097 PNETs, 1365–1373, 1366f, 1370f, 1378–1380 SI-NETs, 705, 707, 712–715, 713f neurofibromatosis (NF), 581, 720, 1365 neutropenia, 136 NF. See neurofibromatosis NG. See nasogastric tube Nguyen, N. Q., 535 Nguyen, N. T., 648 NHAMES. See National Health and Nutrition Examination Survey NHL. See non-Hodgkin lymphoma Nicholls, R. J., 839 Nichols, R. L., 34, 232 Nichols/Condon preparation, 988 NIDDK. See National Institute of Diabetes and Digestive and Kidney Diseases nifedipine, 384 Nigro, Norman, 1021–1022 NIH. See National Institutes of Health nilotinib, 591 Nissen fundoplication for duodenal atresia, 150 for EA/TEF, 147 for GERD, 137, 404, 405–407, 407f

for PEH, 414, 430f, 435f, 436f robotic surgery for, 123 Niti-S stent, 470 nitrates, 384 nitroimidazoles, 1043 nitrosamines, 444 nitrous oxide, 97 Noble plication, 696 nodular lymphoid hyperplasia, 872 nodular regenerative hyperplasia (NRH), 1071 NOMI. See nonocclusive mesenteric ischemia nondysplastic Barrett esophagus (NDBE), 416, 417 nonerosive reflux disease (NERD), 393, 404 non-Hodgkin lymphoma (NHL), 564, 706, 711–712, 712f, 1413 nonocclusive mesenteric ischemia (NOMI), 349, 352 nonselective shunts, 1137, 1137f nonsteroidal anti-inflammatory drugs (NSAIDs), 10, 22, 36–37 alkaline reflux gastritis and, 521 CRC and, 850–851 Crohn’s disease and, 800 for desmoids, 306 diverticular disease and, 771 diverticulitis and, 776 duodenal atresia and, 148 GI bleeding and, 283 for laparoscopy, 98 lower GI bleeding and, 297 marginal ulcers and, 523 PUD and, 286, 287, 510, 511, 513, 514 UC and, 824 norepinephrine, 1289 norepinephrine reuptake inhibitors, 538 NOSCAR. See Natural Orifice Surgery Consortium for Assessment for Research

NOSE. See natural orifice specimen extraction NOTES. See natural orifice transluminal endoscopic surgery NR. See near-infrared NRH. See nodular regenerative hyperplasia NSAIDs. See nonsteroidal anti-inflammatory drugs NSQIP. See National Surgical Quality Improvement Program Nurses’ Health Study, 639 Nusko, G., 866 nutcracker esophagus, 388–389, 389f nutrition. See also enteral nutrition; malnutrition; total parenteral nutrition for acute pancreatitis, 1261, 1295 bariatric surgery and, 655 for enterocutaneous fistulas, 271 evaluation, 25–27, 26t gastrectomy and, 523 GERD and, 393 incisional hernia and, 220 PEH repair and, 434, 436 Nyhus-Condon repair, 215 O OA. See open appendectomy Obalon intragastric balloon, 74, 76f, 668 Oberndorfer, Siegfried, 717 obesity, 17, 640t achalasia and, 382 appendicitis and, 732, 734 bariatric surgery for, 644, 647–650, 648f–650f, 654t BE and, 415 cholangiocarcinoma and, 1231 Cushing syndrome and, 1434 as disease, 650–651, 650t–651t duodenal switch for, 648, 649f, 664–666, 665t endoluminal devices for, 74–78, 75f–79f

esophageal adenocarcinoma and, 444 gallbladder cancer and, 1223 GERD and, 393 HCC and, 1078 incisional hernia and, 220 inguinal hernias and, 213 laparoscopy, for AGB, 653, 662–664, 662f–664f laparoscopy and, 895 metabolic surgery for, 651t, 652, 654t, 669–671 metabolic syndrome and, 640–642, 641t prevalence, 639, 640t RYGB for, 648, 648f, 658–662, 658f–661f, 1247 revisions to, 667–668 SG for, 649, 650f, 656–658, 656f, 657f weight loss for, 642–644, 643t, 644t Objective Structured Assessment of Technical Skills (OSATS), 52f oblique incisions, 169–170 obscure bleeding, 297–298 obstructed defecation syndrome (ODS), 961, 963, 964, 966 obstructing peptic ulcer, 513 Ochsner, A., 1033, 1039 OCPs. See oral contraceptive pills octreotide for dumping syndrome, 520, 520t for enterocutaneous fistulas, 270 for gastrinoma, 1368 for GI bleeding, 285 for insulinoma, 1367 for marginal ulcers, 523 for PF, 1383 for SI-NETs, 707 for VIPomas, 1369 O’Daly, B. J., 691 ODG. See open distal gastrectomy

ODS. See obstructed defecation syndrome odynophagia, GERD and, 398 Oelschlager, B. K., 433 Ogata, M., 692 Ogilvie syndrome, 91 Ohsawa, T., 443 olanzapine, 11 OLGA. See operative link on gastritis assessment OLGIM. See operative link on gastric intestinal metaplasia oliguria, 21, 21t acute pancreatitis and, 1289 Olmstead County study, 535 Omaha technique, 762 omentum, 110, 110f adhesions, cholecystectomy and, 1166 cysts, 307 IPAA and, 830 torsion and infarction, 306–307 tumors, 307 omphalocele, 140–141, 140f ondansetron (Zofran), 98 Ong, G. B., 457 Onstep technique, for inguinal hernia repair, 205 open abdomen technique, for closures, 183, 183f open adrenalectomy, 1444 open appendectomy (OA), 738–744, 742f–744f open cholecystectomy, 1166 open distal gastrectomy (ODG), 114 open repair AAA, 360–361, 361f, 362f incisional hernia, 221–222 for Spigelian hernia, 224 open splenectomy, 1423–1424, 1424f, 1425f operative link on gastric intestinal metaplasia (OLGIM), 509

operative link on gastritis assessment (OLGA), 509, 525 opioid analgesia, 9, 19, 655 opioids, delirium and, 11 Opisthorchis spp., 1089, 1231 opium, 3 OPSI. See overwhelming post-splenectomy infection optical trocars, 100, 100f oral contraceptive pills (OCPs), 1061, 1066, 1068–1071 oral fistulas, 264 Orbera intragastric balloon, 74–75, 643, 644t ORC. See oxidized regenerated cellulose organectomy, 764 orlistat, 642, 643t ornidazole, for amebic liver abscess, 1043 Orringer, M. B., 542 Orsenigo, E., 636 OSATS. See Objective Structured Assessment of Technical Skills Oshawa, T., 475 osteomyelitis, retroperitoneal abscess and, 309 OTS. See over-the-scope clips Otsuka, T., 332 outcomes feedback, for performance measurement, 51–52, 51t ovarian cancer GC and, 552 HNPCC and, 848 mesentery metastases and, 306 ovarian torsion, appendicitis and, 734 OverStitch, 62, 63f, 75, 668 over-the-scope (OTS) clips, 62, 64f overwhelming post-splenectomy infection (OPSI), 324, 1414, 1415t Owen, R. M., 273 oxaliplatin, 469 oxidized regenerated cellulose (ORC), 697

P Pachter, H. L., 330 packed red blood cells, for GI bleeding, 282 Paget disease, 1028 pain. See also analgesia with AAA, 359 with appendicitis, 729 after inguinal hernia repair, 208–209 management, 9–10 with mechanical bowel obstruction, 687 PAIR. See puncture, aspiration, injection, respiration p-ANCA. See perinuclear autoantibody cytoplasmic antibodies pancolitis, 842 rectal cancer and, 978 pancreas adenocarcinoma, 1376t FAP and, 844 aneurysms, 366 carcinoids, 717 division, 1305–1306 gastrinoma, 1378 penetrating trauma, 334 pseudocyst, 1271–1280, 1271f–1273f, 1272t, 1274t, 1275f–1279f ERCP for, 83–84 EUS for, 84, 1275–1276 pancreatectomy biliary leak from, 1386 for chronic pancreatitis, diabetes from, 1387 complications, 1381–1387 DGE and, 1384, 1385t distal, 1352–1353, 1367, 1367f, 1369f, 1381–1382 ERPs and, 38 gastroparesis and, 537 for IPMNs, 1378

laparoscopy for, 115–116, 116t for MCNs, 1331 pancreatic insufficiency from, 1387 PF from, 1382–1384, 1383t for PNETs, 1379 PPH from, 1385–1386, 1386t robotic surgery for, 124 TPAIT, 1319–1320 pancreatic cancer, 1375–1380 HNPCC and, 849 laparoscopy for, 112–113 for biliary bypass, 1247 mesentery metastases and, 306 pancreatic cystic neoplasms, 1323–1343, 1325t, 1377–1378. See also intraductal papillary mucinous neoplasms; mucinous cystic neoplasms; serous cystic neoplasms classification, 1324, 1324t pancreatic ductal adenocarcinoma, 1347 pancreatic encephalopathy, 1290 pancreatic fistulas (PF), 1275 ISGPS on, 1382–1383, 1383t from pancreatectomy, 1382–1384, 1383t pancreatic insufficiency, 1282, 1348, 1387 pancreatic intraepithelial neoplasia 1 (PanIN-1), 1378 pancreatic necrosis, 1259–1263, 1271f, 1280–1287, 1283f, 1285f debridement for, 1286 laparoscopy for, 1285–1286 management, 1295–1299, 1296f–1298f minimally invasive surgery for, 1285–1286 necrosectomy for, 1284, 1286–1287 nephroscopy for, 1286 PCD for, 1284, 1296–1297, 1297f “step-up approach” for, 1283–1284 pancreatic neuroendocrine tumors (PNETs), 1365–1373, 1366f, 1370f, 1378–

1380 pancreatic polypeptide (PP), 1365 pancreaticoduodenal aneurysm, 366 pancreaticoduodenectomy (PD), 115, 1381 for cholangiocarcinoma, 1237–1240, 1238f–1240f for chronic pancreatitis, 1313–1315, 1314f, 1315f DGE and, 1381, 1384 gastroparesis and, 535 for GISTs, 585 postoperative care, 1355–1357, 1356t, 1357f for small bowel adenocarcinoma, 710 pancreaticogastrostomy, for SCNs, 1328 pancreaticojejunostomy, 1387 lateral, 1311–1312, 1312f Roux-en-Y, 1328 pancreatitis. See also acute pancreatitis; chronic pancreatitis appendicitis and, 733 benign biliary strictures from, 1213–1214, 1214f choledochal cysts and, 1195 DD and, 748 ERCP and, 84–85, 1175 gallstone, 82, 1155, 1158 sphincteroplasty and, 1174 splenic artery aneurysm and, 1401 TDS and, 1180 visceral artery aneurysms and, 367 PanIN-1. See pancreatic intraepithelial neoplasia 1 panobinostat, 591 PANTER, 1282, 1296, 1299 papaverine, 352 papilloma, 378 Papillon, J., 122, 1025, 1026 Pappenheimer bodies, 1397 Paracelsus, A. P., 531

paracentesis, 1133, 1133f paraesophageal hernias (PEH), 411–414, 412f–414f, 423–436, 424f–432f, 433t, 434t, 435f, 436f repair closure, 429, 429f esophageal lengthening for, 430–431 esophageal outflow obstruction and, 434–435, 435f laparoscopy for, 426–433, 427f–432f mesh for, 429–430, 431f paraganglioma, 1437 paralytic ileus, 1288 paramedian incision, 169, 169f, 170f, 171f parastomal hernia, 248–249, 249f parenchymal-sparing hepatectomy (PSH), 1119–1120, 1120f parenteral nutrition (PN), 152–153, 434, 755, 758–759. See also total parenteral nutrition Parkinson disease, 382 Parkman, H. P., 538 Parmar, A. D., 537 pars flaccida, 110, 110f partial adrenalectomy, 1439 partial division of puborectalis (PDPR), 967 partial splenectomy, 1425–1426, 1426f, 1427f, 1428t partial thromboplastin time (PTT), 22, 23, 876 Partington-Rochelle procedure, 1312 pasireotide, 1384 Pasteur, Louis, 3 patient-controlled analgesia (PCA), 9, 10, 11, 19 Pavlov, Ivan, 6, 1125 Payne, J., 648 pazopanib, 591 PCA. See patient-controlled analgesia pCCA. See perihilar cholangiocarcinoma PCD. See percutaneous catheter drainage

PCI. See peritoneal carcinomatosis index PCIs. See percutaneous coronary interventions PCLD. See polycystic liver disease PD. See pancreaticoduodenectomy PDGFRA. See platelet-derived growth factor alpha PDPR. See partial division of puborectalis PDS. See polydioxanone PDT. See photodynamic therapy Pearce, M. S., 734 pectoralis major myocutaneous flap (PMF), 458 pediatrics abdominal wall defects, 138–141 appendicitis, 734 duodenal atresia, 148–150, 148f–150f EA/TEF, 143–148, 143f–146f, 147t gastroschisis, 138–140, 138f, 139f GERD, 137–138 HD in, 156–158, 156f, 157f HPS, 135–136f imperforate anus, 158–160, 158f–160f JIA, 150–153, 151f, 152f malrotation, 141–143, 142f, 149, 150, 151 meconium ileus, 153–154, 153f–155f MPS, 154–156 NEC, 135–137, 136f, 137f omphalocele, 140–141, 140f PHTN, 1149, 1149f pyrogenic liver abscesses, 1035 SBS, 137, 756 small left colon, 156 pedicled jejunal interposition, 491–492, 492f PEG. See percutaneous endoscopic gastrostomy PEH. See paraesophageal hernias PEJ. See percutaneous endoscopic jejunostomy

Pelaez-Luna, M., 1337 Pellegrini, C. A., 1182 pelvic exenteration, for rectal cancer, 1006, 1006f pelvic floor outlet obstruction, 940–942, 943f pelvis ascites, 110f innervation of, 933, 934f pembrolizumab, 1229 penetrating trauma, 330–337, 333f, 336f, 337f colon, 334 duodenum, 334 gallbladder, 334 hematoma from, 354 laparotomy for, 331t, 333–334 liver, 334–335, 335t to liver, 326 pancreas, 334 small bowel, 334 splenic injury from, 1398 stomach, 334 PENGUIN, 1285 penicillin, 15, 959, 1038, 1184 Peon clamp, 234 peptic ulcer disease (PUD), 286–288, 286f, 429, 509–519, 510t DD and, 748 diagnosis, 511 GI bleeding and, 283 H. pylori and, 286, 287, 507–508, 510–511, 513, 514 intractable/nonhealing, 514–515, 514t location, 511–512 NSAIDs and, 286, 287, 510, 511, 513, 514 obstructing, 513 perforated, 513 perforations, 513

surgery, 512–513, 512t upper GI bleeding and, 513–514 peptide receptor radionuclide therapy (PRRT), 1372, 1379 peptide YY (PYY), 670 percutaneous catheter drainage (PCD), 1049–1050, 1266, 1284, 1296–1297, 1297f percutaneous coronary interventions (PCIs), 13 percutaneous endoscopic gastrostomy (PEG), 66–67, 67f, 433, 542 for antegrade colonic enema, 966 antibiotics for, 59 for pancreatic necrosis, 1284 percutaneous endoscopic jejunostomy (PEJ), 67–68, 542 percutaneous transcatheter embolization, 1401–1402 percutaneous transhepatic cholangiography (PTC), 1176–1177, 1186 for benign biliary strictures, 1206–1207, 1206f, 1214 for cholangiocarcinoma, 1232, 1236f for choledochal cysts, 1194, 1195f for Mirizzi syndrome, 1215 for PSC, 1217 for recurrent pyogenic cholangitis, 1215 for sphincter of Oddi stenosis, 1216 perforations appendicitis, 729, 730, 744–745 from colonoscopy, 88 CRC and, 883 Crohn’s disease and, 796, 802–803, 812–813 diverticular disease and, 770 EGD and, 59 ERCP and, 84–85 esophagus, PEH repair and, 434 gallbladder, 1167 gastric, 433, 434, 436 PUD, 513 performance measurement, 47–53, 48t, 51t, 52f

case mix and, 48, 50 choosing right approach, 49, 49f sample size and, 47–48, 50 periampullary adenocarcinoma of pancreas, 1347–1362, 1348f, 1351f adjuvant chemotherapy for, 1361 diagnosis, 1348–1351 ERC for, 1349–1350, 1350f laparoscopy for, 1351, 1353–1355 minimally invasive surgery for, 1353–1355 MRCP for, 1349, 1350f neoadjuvant chemotherapy for, 1361–1362 PET for, 1349, 1350f robotic surgery for, 1354 Whipple procedure for, 1351–1352, 1352f pericystectomy, 1052 peridiverticulitis, 769 perihepatic packing, 328 perihilar cholangiocarcinoma (pCCA), 1230–1242 perineal fistula, 158, 159 perinuclear autoantibody cytoplasmic antibodies (p-ANCA), 1217 peripheral nerve blocks, 10 peripheral nerve sheath tumors, 1437 peritoneal carcinomatosis index (PCI), 113, 114f peritonitis abscesses and, 257, 259–263 amebic liver abscess and, 1045 appendicitis and, 730 benign biliary strictures and, 1208 cirrhosis and, 292 community-acquired, 259–260, 259t diverticulitis and, 769 early problems with, 3 enterocutaneous fistulas and, 268 health care-associated, 259t, 260

PEH repair and, 433 peroral endoscopic myotomy (POEM), 75–78, 386, 387, 388, 389 per-oral pyloromyotomy (POP), 75–78 PERSIST-5, 567, 601 PET. See positron emission tomography Petersen’s defect, 684 Petit’s triangle, 224 Peutz-Jeghers syndrome (PJ), 564, 852, 865 GC and, 552 GI bleeding and, 283 hamartomas and, 525 small bowel hamartomas and, 706 Peyre, C. G., 502 PF. See pancreatic fistulas Pfannenstiel incision, 170, 174f, 925, 927 pH GERD and, 397–398, 401–402, 401f, 401t PEH and, 412–413 pharmacobezoars, 526 pharyngeal fistulas, 264 pharyngoesophageal diverticulum. See Zenker diverticulum pharyngolaryngoesophagectomy (PLE), 457 pharyngostomy, 700 Phemister, D., 475 phentermine, 642, 643t phentermine-topiramate, 642, 643t phenylethanolamine-N-methyltransferase (PNMT), 1433 pheochromocytoma, 1436–1437 PHI. See postoperative hepatic insufficiency phlegmon, 744, 796 phosphodiesterase-5 inhibitors, for achalasia, 384 photodynamic therapy (PDT) for BE, 456 for bile duct obstruction, 1242

PHTN. See portal hypertension phytobezoars, 526 PIAF. See cisplatin, interferon α-2b, doxorubicin, and fluorouracil Piccolboni, P., 113 pinch-cock mechanism, diaphragm, 394 piperacillin-tazobactam, for pyrogenic liver abscesses, 1038 Pitt, H. A., 1182, 1211 pitting, spleen, 1397 PJ. See Peutz-Jeghers syndrome platelet transfusions, 22 platelet-derived growth factor alpha (PDGFRA) for GISTs, 565, 567, 579, 580–581, 580f, 599, 705, 715, 872 for HCC, 1086 platelet-rich fibrin glue (PRFG), 271 pleural effusions APFC and, 1270 MWA and, 1110 pyrogenic liver abscesses and, 1040 Pliny, 1393 plug and patch, for inguinal hernia repair, 202, 203f Plummer-Vinson syndrome, 444 PMF. See pectoralis major myocutaneous flap PMR. See polymerase chain reaction PN. See parenteral nutrition PNETs. See pancreatic neuroendocrine tumors pneumatic dilation, 385, 385t, 386 pneumonia delirium and, 11 esophagectomy and, 495 GERD and, 397 pyrogenic liver abscesses and, 1040 pneumoperitoneum laparoscopy for, 894 for cholecystectomy, 1160

PEH and, 426 physiologic effects, 105–107 pneumothorax, 11, 107, 147 PNMT. See phenylethanolamine-N-methyltransferase PNTML. See pudendal nerve terminal motor latency POEM. See peroral endoscopic myotomy polycarbophil (FiberCon), 965 polycystic kidney disease, 1198 polycystic liver disease (PCLD), 1054–1055, 1126 polycythemia, 352 polydioxanone (PDS), 67, 180, 1228, 1237 polyglactin 910, 183 polyglycolic acid, 183 polyhydramnios, 148 polymerase chain reaction (PMR), 1043 polypectomy for adenomatous gastric polyps, 525 anal SCC and, 1025 colonoscopy for, 88–89, 89f EMR for, 63–64, 64f, 65f lower GI bleeding and, 295–296, 296f polyps (polyposis) adenomatous polyposis coli, 91, 843, 863 in colon, 89–91, 90f CRC and, 857, 866–869, 866t, 867f, 867t, 868f FAP, 240, 305, 524, 705, 843–845, 863–864, 978 FGP, 563 fundic gland, 524 gallbladder, 1158 cancer, 1226 gastric, 562–564, 564f adenomatous, 563–564, 563f epithelial, 524–525, 524t HNPCC, 846–850, 847t, 848t, 850t, 864, 864t, 978

hyperplastic, 524–525, 868 inflammatory, 868 juvenile, 564, 851–852, 865 MAP, 552, 846, 978 rectal cancer and, 978–979, 979f Ponchon, T., 1177 PONV. See postoperative nausea and vomiting pooling, spleen, 1397–1398 POP. See per-oral pyloromyotomy POPH. See portopulmonary hypertension Popielski, L., 532 porcelain gallbladder, 1158, 1223 porta hepatis, 330, 1228 portal hypertension (PHTN), 1126f, 1127f causes, 1126–1127, 1128t choledocholithiasis and, 1172 CTP and, 1127, 1128t devascularization for, 1139–1140, 1140f diagnosis, 1127 EGD for, 1131–1132, 1131f HVPG and, 1126, 1126t, 1132 pediatrics, 1149, 1149f PV and, 1132f SMV and, 1132f splenectomy for, 1413 splenic artery aneurysm and, 1400 TIPS for, 1125, 1127, 1129, 1133, 1135, 1141–1145, 1141t, 1143f–1144f, 1144t upper GI bleeding and, 291–292, 292f portal hypertensive gastropathy, 1145 portal vein (PV), 330, 344, 1079, 1376t periampullary adenocarcinoma of pancreas and, 1349 PHTN and, 1127–1128, 1132f portal vein embolization (PVE)

for cholangiocarcinoma, 1236 FLR and, 1118–1119 for HCC, 1084–1085, 1086t, 1087–1088 portal vein thrombosis (PVT), 1110, 1125, 1129, 1145–1147 portal-splenic venous system (PSVT), 1416 portopulmonary hypertension (POPH), 1148–1149 positron emission tomography (PET) for cholangiocarcinoma, 1232 for CRC, 876 for esophageal cancer, 453–454, 453f, 469, 469f, 477 for gallbladder cancer, 1225 for gastric carcinoids, 562 for GC, 554 for GEJ, 111 for GISTs, 582 for mesenteric panniculitis, 304 for periampullary adenocarcinoma of pancreas, 1349, 1350f for pheochromocytoma, 1346 for rectal cancer, 986 SANT, 1404 for SI-NETs, 707 post-embolization syndrome, 1100 posterior sagittal anorectoplasty (PSARP), 159 posterior tibial flap (PTF), 458 posterior tibial nerve stimulation (PTNS), 973 posterior vaginectomy, 1005–1006, 1005f postgastrectomy syndromes, 519–523 postoperative hepatic insufficiency (PHI), 1118 postoperative nausea and vomiting (PONV), 35, 37 with laparoscopy, 98 post-pancreatectomy hemorrhage (PPH), 1385–1386, 1386t posttransplantation lymphoproliferative disorder (PTLD), 706, 765 pouch. See also specific types EA/TEF and, 143, 144, 144f

failure, 251, 814, 834, 840 fistula, 834 loop ileostomy and, 243 UC and, 830, 835 pouchitis, 253, 835, 840 Poulin, E. C., 1426 Poupart’s ligament, 193 PP. See pancreatic polypeptide; pyloroplasty PPH. See post-pancreatectomy hemorrhage PPI. See proton pump inhibitor Prajapati, H. J., 1100 Prasad, M. L., 940 prednisone, 800, 1409 preduodenal portal vein, 148, 148f pregnancy appendicitis in, 735–736 bariatric surgery and, 669 colonic volvulus and, 790 ectopic, 734 GERD and, 393 inguinal hernia and, 196, 213 laparoscopy in, 107 for cholecystectomy, 1159 LES and, 395 splenic artery aneurysm and, 1400, 1401 premature ventricular contractions, 13 preperitoneal space, 195 inguinal hernia repair and, 202–205, 204f pressure points, laparoscopy and, 97–98 PREVENT, 235 PRFG. See platelet-rich fibrin glue Priestly, James T., 1382 primary bile duct stones, 1171 primary intrahepatic stones, 1171

primary sclerosing cholangitis (PSC), 1216–1218, 1217f cholangiocarcinoma and, 1230–1231, 1233 gallbladder cancer and, 1226 Pringle maneuver, 1065 probiotics, for chronic gastric stasis, 521 process, performance measurement and, 48t, 49 proctectomy for Crohn’s disease, 814 for intestinal stomas, 234 for rectal prolapse, 940, 941f robotic surgery, 117 for UC, 831 proctitis, Crohn’s disease and, 814 proctocolectomy, 840t, 842 with IPAA, 916–918, 917f, 918f RPC, 814, 830, 840t TPC, 831–832, 833, 845, 846, 850, 897 proctocolitis, Crohn’s disease and, 813–814 proctosigmoidoscopy, 937 PROCY, 33 Prolene, 938–939 PROMID, 724 PROPATRIA, 1294 prostatectomy, for rectal cancer, 1006 protein C, 352 protein S, mesenteric venous thrombosis and, 352 prothrombin time (PT), 22, 876 proton pump inhibitor (PPI), 18, 285, 289, 382, 1368 for BE, 417, 456 carcinoids and, 526 for fundic gland polyps, 524 for GERD, 70–71, 396, 397, 398, 404 for H. pylori, 508, 508t for marginal ulcers, 523

for pancreatic insufficiency, 1387 for PUD, 508, 511 for stress ulcers, 524 TIP and, 72–74, 74f Prout, William, 531 proximal gastric vagotomy. See highly selective vagotomy PRRT. See peptide receptor radionuclide therapy prucalopride, 539 PSARP. See posterior sagittal anorectoplasty PSC. See primary sclerosing cholangitis pseudoachalasia, 382, 397 pseudocyst meconium ileus and, 153 pancreas, 1271–1280, 1271f–1273f, 1272t, 1274t, 1275f–1279f ERCP for, 83–84 EUS for, 84, 1275–1276 pseudodiverticula, 527 Pseudomonas spp., 794, 1035, 1280 pseudomyxoma peritonei, 746–747, 746f, 747f PSH. See parenchymal-sparing hepatectomy PSVT. See portal-splenic venous system psyllium, 965 PT. See prothrombin time PTC. See percutaneous transhepatic cholangiography PTEN, 525, 852, 866 PTF. See posterior tibial flap PTLD. See posttransplantation lymphoproliferative disorder PTNS. See posterior tibial nerve stimulation PTT. See partial thromboplastin time public reporting, 50, 51t PUD. See peptic ulcer disease pudendal nerve, 934, 934f, 968 pudendal nerve terminal motor latency (PNTML), 938, 968 pulmonary edema, 11

pulmonary embolism, 1100, 1180, 1181 pulmonary fibrosis, 397 pulmonary hypertension, 513, 654 puncture, aspiration, injection, respiration (PAIR), 1050 for splenic cysts, 1402–1403 PV. See portal vein PVE. See portal vein embolization PVT. See portal vein thrombosis pylephlebitis, 730 pyloric dilation, 611 pyloromyotomy, 526, 541, 611, 612f gastric emptying and, 146 for HPS, 135 POP, 75–78 pyloroplasty (PP), 6, 543, 603, 611–613, 612f pyoderma gangrenosum, 797 pyrogenic liver abscess, 1033–1041, 1034f, 1035t, 1036t, 1037f, 1040f, 1041t, 1042t pyruvate kinase deficiency, 1408 PYTHON, 1295 PYY. See peptide YY Q QoL. See quality of life quality collaboratives, 51t, 52 Quality Enhancement Research Initiative (QUERI), 39 quality of life (QoL) with benign biliary strictures, 1213 with gastroparesis, 544–545 with GERD, 396, 398, 402–403, 403t with PEH, 413 QUERI. See Quality Enhancement Research Initiative Quillo, A. R., 1439 quinolone, 878

R RAC. See Revised Atlanta Classification radiation enteropathy, 687, 687f, 699–700 radiation proctitis, 297, 297f radiation therapy. See also adjuvant radiotherapy; neoadjuvant radiotherapy for anal margin cancer, 1026 for GC, 560 IORT, 311f, 1009 Radiation Therapy Oncology Group (RTOG), 467, 586 radiation-induced liver disease (RILD), 1110, 1112 radioembolization-induced liver disease (REILD), 1104 radiofrequency ablation (RFA), 65–66, 455, 1086 for BE, 417–419, 418f, 456 for liver metastases, 1099, 1105–1108, 1106f, 1107f radiographs for Crohn’s disease, 797–798, 798f for pyrogenic liver abscesses, 1036, 1037f for SBO, 688–690, 689f, 690f Ragina, N. P., 33 RAHM. See robotic-assisted Heller myotomy RAIR. See rectoanal inhibitory reflex Rajak, C. L., 1039 Ramirez, O. M., 222 Ramirez, P., 1181 Randomized ECF for Advanced and Locally Advanced Esophagogastric Cancer 2 (REAL-2), 559 Rangel, S. J., 734 ranitidine, 524 Ranson, J. H., 1258 Rao, S. S., 541, 920 Rattner, D. W., 1167 Raut, C. P., 599 Ravitch, M. M., 6

RBCs. See red blood cells RCRI. See Revised Cardiac Risk Index RDS. See respiratory distress syndrome reactive nitrogen species, 507 reactive oxygen species, 507 Read-Rives technique, 215 REAL-2. See Randomized ECF for Advanced and Locally Advanced Esophagogastric Cancer 2 Reaumur, R. A. F., 531 rebleeding, 293 from PUD, 513–514 REBOA. See resuscitative endovascular balloon occlusion of the aorta RECIST. See Response Evaluation Criteria in Solid Tumors Reclese, Paule, 330–331 rectal irrigation, 138 rectal pouch, 158 rectal prolapse, 154, 937–940, 937f–940f, 938t rectoanal inhibitory reflex (RAIR), 962 rectoceles, 942 rectopexy, 915–916, 967 rectovaginal (RV) fistulas, 956–957 rectum. See also anorectal; colorectal cancer anatomy, 933–934, 935f, 979–980, 980f cancer, 977–1012 adenomas and, 978–979, 979f adjuvant chemoradiation for, 1010, 1011t APR for, 980, 981, 984, 1002–1005, 1003f–1004f bilateral oophorectomy for, 1006 diagnosis, 982–986, 985f, 986f GI bleeding and, 284 Kraske approach to, 992–993, 992f laparoscopy for, 896–897, 1007–1008 instruments, 897, 897t, 898f patient position and room setup, 897–899, 899f

lymph nodes and, 979, 981–982, 982f metastases, 1009 neoadjuvant chemoradiation for, 1010–1012, 1011t palliative resection for, 1006–1007 pelvic exenteration for, 1006, 1006f polyps and, 978–979, 979f posterior vaginectomy for, 1005–1006, 1005f prostatectomy for, 1006 recurrence of, 990t robotic surgery for, 1008 TEM for, 993–994, 993–999, 996f, 997f, 999f TNM for, 986, 987t transanal excision for, 991–992, 991f transcoccygeal excision for, 992–993, 992f carcinoids, 723–724, 723f fascial planes, 982, 983f innervation, 982, 982f intussusception, 937–940, 937f–940f, 938t laparoscopic anterior resection of, 910–911 laparoscopic low anterior resection of, 911–913, 912f, 913f ulcers, 296 vascular supply, 936f, 980–981, 981f recurrent pyogenic cholangitis, 1215–1216, 1216f red blood cells (RBCs), transfusions, 22 for GI bleeding, 282 refractory hypertension, 328 regional analgesia, 9–10, 214 regorafenib, 588, 591 Regueiro, M. D., 817 REILD. See radioembolization-induced liver disease relaxing incision, for PEH repair, 430 remnant liver ischemia (RLI), 1121 renal artery, 346, 358 aneurysm, 364, 364t

renal failure, 20 acute pancreatitis and, 1258 EGD and, 59 renal insufficiency, 20, 759 renal vein, 358, 1139f repeat hepatectomy, 1119 ReShape dual intragastric balloon, 643, 644t respiratory distress syndrome (RDS), 143, 147 respiratory failure, 136, 366, 494–495, 523, 524 Response Evaluation Criteria in Solid Tumors (RECIST), 1099, 1101 restorative proctocolectomy (RPC), 814, 830, 840t resuscitative endovascular balloon occlusion of the aorta (REBOA), 336– 337, 336f, 337f retention cysts, 1303 retention sutures, for abdominal wall incisions, 181–182 retraction, intestinal stomas, 249–250, 250f retroperitoneal abscess, 308–309 retroperitoneal fibrosis, 309–310, 309t, 310t retroperitoneal hematomas, 335, 335t retroperitoneal incisions, 172–176, 177f, 179f retroperitoneal sarcoma, 310–313, 311f, 312f retroperitoneoscopy (RP), 1438–1439 retroperitoneum, 307–313 hemorrhage, 307 retrorectus repair, incisional hernia, 221–222 rEVAR. See endovascular repair for ruptured AAA reverse gastric tube, for EA/TEF, 146 reverse Trendelenburg position, for laparoscopy, 98, 101 for cholecystectomy, 1160 for right hemicolectomy, 900 Revised Atlanta Classification (RAC), for acute pancreatitis, 1260, 1261t, 1269, 1270t, 1293, 1293t, 1294t Revised Cardiac Risk Index (RCRI), 12 revisions to, 667–668

Reynolds’s pentad, 1183 RFA. See radiofrequency ablation Rh system, 6 Rhoads, Jonathan, 6 Ricciardi, R., 968 Rice-Townsend, S., 734 right colectomy for CRC, 924–925, 924f, 925f robotic surgery for, 919–920, 919f right hemicolectomy, laparoscopy for, 899–903, 900f903f, 900f–903f right-sided colitis, 813 rigid proctoscopy, 875 RILD. See radiation-induced liver disease Rindani, R., 494 rituximab for AIHA, 1409 for immune thrombocytopenia, 1411 Ritz, M. A., 535 Rives, J., 202, 221, 222 Rizzetto, C., 502 RLI. See remnant liver ischemia Robbins, A. W., 195, 202 robotic surgery, 7, 123f. See also da Vinci Surgical Systems advantages, 124–125, 125t anastomosis and, 923 clinical studies, 125–129 for CRC, 923–928, 924f–928f TME for, 925–928, 926f–928f current applications, 123–124, 124t decision to use, 129, 129f development, 121–122 enhanced features, 121–122 future applications, 130 for gastrectomy, 634, 635f

for GC, 126–128, 127t, 578 for hepatectomy, 115 for inguinal hernia, 194 for lymphadenectomy, 126–128, 636, 636f as minimally invasive surgery, 124 for pancreatectomy, 115, 116t for periampullary adenocarcinoma of pancreas, 1354 for PNETs, 1371 proctectomy, 117 for rectal cancer, 1008 for right colectomy, 919–920, 919f for sigmoid colectomy, 919–920, 919t for sutures, 923 for TME, 123, 128, 128t, 129 Robotic Versus Laparoscopic Resection for Rectal Cancer (ROLARR), 129, 894, 923 robotic-assisted Heller myotomy (RAHM), 126, 129 Rocha, F. G., 693 Rocky, D. C., 1036 Rocky-Davis incisions, 167, 170, 172f Rokitansky-Aschoff sinuses, 1226 Rokke, O., 1262 ROLARR. See Robotic Versus Laparoscopic Resection for Rectal Cancer Rome III Consensus Criteria, for GERD, 397 romiplostim, for ITP, 1411 Ron, Y., 966 Rosetti, Franciscus, 1399 Rossi, S., 565 Rotondo, M. F., 182, 335 Rousseau, D. L., 1024 Roux stasis syndrome, 522 Roux-en-Y CDJ, 1181–1182 Roux-en-Y choledochojejunostomy, 1215 Roux-en-Y cystojejunostomy, for pancreatic pseudocysts, 1277–1279, 1278f

Roux-en-Y duodenojejunostomy, 810 Roux-en-Y gastric bypass (RYGB) afferent loop obstruction and, 521 for diabetes, 670 dumping syndrome with, 519 endoscopic dilation for, 69 gastroparesis and, 536 for GC, 628–629, 629f–631f for GERD, 653, 669 for obesity, 648, 648f, 658–662, 658f–661f, 1247 revisions to, 667–668 for PUD, 512 robotic surgery for, 123 for SBO, internal hernia after, 683–684, 699 SBO after, 698–699 for SBS, internal hernia after, 756, 757f Roux-en-Y gastroenterostomy, 536 Roux-en-Y gastrojejunostomy, 520, 522, 537 Roux-en-Y hepaticojejunostomy, 1196–1197, 1197f, 1198 for benign biliary strictures, 1208–1209, 1209f, 1213, 1214 for bile duct obstruction, 1242 for periampullary adenocarcinoma of pancreas, 1353 for recurrent pyogenic cholangitis, 1216 Roux-en-Y jejunal loop reconstruction, 460–461 Roux-en-Y jejunal replacement, 491, 491f Rovsing sign, 730 Rozycki, G. S., 332 RP. See retroperitoneoscopy RPC. See restorative proctocolectomy RTOG. See Radiation Therapy Oncology Group Ruiz, D., 969 Ruo, L., 1007 Russolillo, N., 112 Rutkow, I. M., 195, 202

RV. See rectovaginal fistulas RYGB. See Roux-en-Y gastric bypass S S System, 121 sacral nerve stimulation (SNS) for constipation, 966 for fecal incontinence, 972–973, 973f sacroiliitis, 797 SAE. See splenic artery embolization Salameh, J. R., 536 Salerno, F., 1133 Salminen, P., 737 Salmonella spp. gallbladder cancer and, 1223 infectious colitis from, 297 splenic cysts and, 1404 UC and, 824 salpingitis, appendicitis and, 734 Salvia, R., 1334, 1335 Sammour, T., 117 sample size, performance measurement and, 47–48, 50 SANT. See sclerosing angiomatoid nodular transformation SAPE. See sentinel acute pancreatitis event sarcoidosis, 1217 sarcoma, 567–568 cholangiocarcinoma as, 1231 sarcopenia, ERPs and, 32–33 Sato, K., 1104 Sauer, R., 1010 Sawhney, M. S., 1330 SBO. See small bowel obstruction SBS. See short bowel syndrome scalpels, introduction, 6

Scarpa’s layer, 195 SCC. See squamous cell carcinoma Schauer, P. R., 648 Schiffman, S. C., 115, 1105 Schlatter, 551 Schmidt, C. M., 1337 Schmidt, S. C., 1212 Schnelldorfer, T., 112 Scholten, A., 1433 Schwab, C. W., 182 schwannoma, esophagus, 378 schwannomas, 1437 scintigraphy for carcinoids, 718 for FNH, 1067 for gastroparesis, 538–539 for GI bleeding, 285 for liver resection, 1118 for Roux stasis syndrome, 522 for SI-NETs, 707 SCJ. See squamocolumnar junction scleroderma gastroparesis and, 535 SBS and, 757–758 sclerosing angiomatoid nodular transformation (SANT), 1404, 1405f sclerosing mesenteritis, 303–304 SCNs. See serous cystic neoplasms SDH. See succinate dehydrogenase Secca procedure, for fecal incontinence, 969–970 secnidazole, 1043 secondary bile duct stones, 1171 second-look laparotomy, 183, 352–353 secretogogues, 965 sedation, for delirium, 11

SEER. See Surveillance, Epidemiology, and End Results Seeto, R. K., 1036 segmental colitis, Crohn’s disease and, 814–815 selective adhesion molecule inhibitors, for UC, 827 selective internal radiation therapy (SIRT), 1101–1104, 1102f–1104f selective referral, for performance measurement, 50–51, 51t selective serotonin reuptake inhibitors (SSRIs), 11 GI bleeding and, 283 PUD and, 287 selective shunts, 1137–1139 selective vagotomy (SV), 607, 607f, 1376, 1376t self-expanding metallic stent (SEMS), 69–70, 470, 470f ERCP for, 82–83, 82f, 83f for LBO, 92, 92f for pancreatic necrosis, 1284 SEMS. See self-expanding metallic stent Sengstaken-Blakemore tube, 292, 1136f Senokot, 965 Senthilnathan, P., 1196 sentinel acute pancreatitis event (SAPE), 1306 sentinel node navigation, laparoscopy for, 636 separated ileostomy, 245–246 separation of components, for incisional hernia, 222 Seprafilm, 233 for intestinal stoma colostomy, 237 sepsis benign biliary strictures and, 1207 delirium and, 11 enterocutaneous fistulas and, 263, 268 with parenteral nutrition, for JIA, 152–153 pyrogenic liver abscesses and, 1040 splenic cysts and, 1404 TDS and, 1180 serial transverse enteroplasty (STEP)

for Crohn’s disease, 758 for intestinal lengthening, 761, 761f for JIA, 153 for SBS, 137, 755 seroma, 188 after inguinal hernia repair, 208 seromyotomy, 633–634, 634f seronegative polyarteritis, 797 serotonin, 723 serous cystic neoplasms (SCNs), 1323, 1324–1328, 1325t, 1326f, 1327f SG. See sleeve gastrectomy Shakir, M., 1354 SHARP. See Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol Sheedy, S. P., 691 Shigella spp., infectious colitis from, 297 Shike, M., 542 Shim, L. S., 965 Shinya, H., 85 Shires, G. Thomas, 6 shock anaphylactic, 1052, 1117, 1403 cardiogenic, 11 GI bleeding and, 282t hypovolemic, 1062 malrotation and, 141 resuscitation from, 6 upper GI bleeding and, 288 Shorb, Paul, 79 short bowel syndrome (SBS), 755–765 intestinal lengthening for, 759–761, 760f, 761f ITx for, 761–765, 762f–764f JIA and, 152–153 pediatrics, 137

radiation enteropathy and, 699 RYGB for, internal hernia after, 756, 757f Shouldice technique, 193–194, 199–201, 200f, 215 Si System, 121 sickle cell disease, 1157, 1408–1409 side-to-side isoperistaltic strictureplasty, 806–807, 806f, 807f sigmoid colectomy HALS for, 907–909, 908f, 909f robotic surgery for, 919–920, 919t sigmoid diverticula, 769f sigmoid diverticulitis, 772f sigmoid volvulus, 686, 686f, 785, 786–788, 786t, 787f, 788f sigmoidectomy, 909 sigmoidopexy, 788 sigmoidoscopy, 979 flexible, 284, 827, 875 sigmoidostomy, 789 sildenafil, 384 SILS. See single-incision laparoscopic surgery Silva-Velazco, J., 836 silver nitrate, 1050 SI-NETs. See small intestinal neuroendocrine tumors single anastomosis gastric bypass, 666 single photon emission computed tomography (SPECT), 1101, 1118 single-incision laparoscopic surgery (SILS), 1168 SIR. See Society of Interventional Radiology SIRS. See systemic inflammatory response syndrome SIRT. See selective internal radiation therapy Sjögren syndrome, 535, 1305 Sjoquist, K. M., 476 skin cancer, 850 Skinner, D. B., 460, 501 sleep delirium and, 11

obesity and, 17 UC and, 823 sleeve gastrectomy (SG), 526, 536, 649, 650f, 653, 656–658, 656f, 657f, 670, 671 endoscopic, 643, 644t, 668 sleeve gastroplasty, 75, 77f sleeve stenosis, endoscopic dilation for, 69 SMA. See superior mesenteric artery small bowel adenocarcinoma, 705, 710–711, 711f bile acids and, 705 Crohn’s disease and, 705, 803, 807 FAP and, 705 bacterial translocations in, 681–682 benign tumors, 709–710 cancer, 710–715 HNPCC and, 849 carcinoids, 705, 717, 718f, 721–722, 721f Crohn’s disease, 796, 811–813, 811f, 812f, 842 diverticula, 748–751 endoscopic bariatric therapies for, 75, 78f enteroscopy, 85 fistulas, 265 GISTs, 705, 714–715, 714t hamartomas, 706 lymphoma, 705, 706 metastases, 715 NHL, 706, 711–712, 712f penetrating trauma, 334 second-look laparotomy for, 353 trocar injury to, 101 tumors, 705–715 small bowel obstruction (SBO), 429, 677–700 adhesions and, 682–683, 697

cancer and, 700, 700f Crohn’s disease and, 684–685, 688, 802 diagnosis, 687–692 epidemiology, 679–680 gastroparesis and, 536 hernias and, 683–684, 683f, 684f intussusception and, 685 ischemia and, 691–692 laparoscopy for, internal hernia after, 683–684 management, 692–700, 692f, 694f, 700f metastases and, 684, 685f pathophysiology, 680–682 radiation enteropathy and, 687, 687f, 699–700 radiographs for, 688–690, 689f, 690f recurrence, 696–697 after RYGB, 698–699 RYGB for, internal hernia after, 683–684 strangulation and, 691–692 volvulus, 679, 686–687, 686f WSCA for, 694, 694f small cell cancer, 1231 small duct disease, 1318–1320 small intestinal neuroendocrine tumors (SI-NETs), 705, 707, 712–715, 713f small left colon, 156 SmartPill, 963–964 smoking alkaline reflux gastritis and, 521 anal SCC and, 1017 chronic pancreatitis and, 1304 COPD and, 17 CRC and, 860 Crohn’s disease and, 794 diverticulitis and, 776 enterocutaneous fistulas and, 264

GC and, 551 GERD and, 393, 404 incisional hernia and, 220 inguinal hernias and, 196 JIA and, 151 PUD and, 511, 513 rectal cancer and, 978 RYGB and, 653 UC and, 823 SMPV. See superior-mesenteric-portal vein SMV. See superior mesenteric vein SNS. See sacral nerve stimulation Society of American Gastrointestinal and Endoscopic Surgeons, 386 Society of Interventional Radiology (SIR), 1133 SOD. See sphincter of Oddi Soffer, E. E., 536 Sohn, T. A., 1341, 1386 solitary rectal ulcer syndrome, 800, 940–942 somatostatin, 714, 1134 for carcinoid, 724 for enterocutaneous fistulas, 270 for gastric carcinoids, 562 for gastrinoma, 1368 for SBS, 756 for upper GI bleeding, 292 somatostatinoma, 720, 1365, 1370 sorafenib, 591 Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP), 1086 source control, for abscesses, 261–263, 262t space of Retzius, 205, 207, 224 Spallanzani, L., 531 SPECT. See single photon emission computed tomography sphincter of Oddi (SOD), 1175, 1179

benign biliary strictures and, 1213 biofeedback for, 965 choledochal cysts and, 1193 chronic pancreatitis and, 1306 gallbladder cancer and, 1223 pancreatic pseudocyst and, 1276 sphincterotomy and, 81 stenosis, 1216 sphincteroplasty for choledocholithiasis, 1173–1174, 1180 for fecal incontinence, 971–972, 971f, 972f sphincterotomy, 948–951, 950f–952f for anorectal abscess, 952 for choledocholithiasis, 1173–1174 ERCP for, 81, 81f, 82f for SOD stenosis, 1216 Spigelian hernia, 223–224, 223f splanchnic artery aneurysm, 364–366, 364t spleen, 1392–1428 abscess, 1404 anatomy, 1393–1394, 1394f–1396f bacteria in, 692 benign tumors, 1404–1405 blood supply, 1394–1397, 1397f blunt trauma to, 322–324, 323f cancer, 1405–1406, 1407f cysts, 1402–1403, 1402f, 1403t, 1428 hamartomas, 1405 histology, 1397, 1397f inflammatory pseudotumors, 1405 lymphomas, 1413 penetrating trauma, 334 physiology, 1397–1398 trauma to, 1398–1400, 1398f, 1399t, 1400f

splenectomy, 1416t, 1417f for anemia, 1406–1410 antibiotics with, 1414–1415 for blunt trauma, 324 CRC and, 1398 for gastrinoma, 1369f for immune thrombocytopenia, 1411 infections after, 1398 for insulinoma, 1367, 1367f laparoscopy for, 1414, 1416–1423, 1418f, 1420f–1421f for PHTN, 1413 robotic surgery for, 123 for SMA trauma, 357 splenic artery and, 344 for splenic cancer, 1406 for splenic cysts, 1403 for splenoptosis, 1394 splenic artery, 344, 1394, 1396, 1396f aneurysm, 364–365, 364t, 1400–1401, 1401f splenic artery embolization (SAE), 1399–1400, 1417–1418 splenic capsule injury, 434 splenic flexure, 789–790 splenic vein, 357, 1139f splenic-portal vein thrombosis (SPVT), 1422–1423, 1423f splenomegaly, 1398, 1405, 1417, 1421–1422, 1421f, 1422f splenopneumopexy, 1140, 1140f splenoptosis, 1394 splenorrhaphy, 324, 1424 sporadic colon cancer, 863 sports hernias, 216–217 S-pouch, 840 Springer, S., 1328 SPVT. See splenic-portal vein thrombosis squamocolumnar junction (SCJ), 70, 71f

squamous cell carcinoma (SCC). See also anus; esophagus cholangiocarcinoma as, 1231 choledochal cysts and, 1195 SSIs. See surgical site infections SSRIs. See selective serotonin reuptake inhibitors Stadler, R. F., 1024 staged reduction, for omphalocele, 140–141 stapled transanal rectal resection (STARR), 940, 967 staplers. See also double-staple technique for gastrectomy, 635 introduction, 6 for IPAA, 832 for J-pouch, 897 PF and, 1383 for right colectomy, 925 for robotic TME for CRC, 928 for tri-incisional esophagectomy, 482–485, 483f, 484f for UC, 840 for Zenker diverticulum, 375 Starling, E., 532 STARR. See stapled transanal rectal resection Starzl, Thomas, 6, 755, 1125 Stattner, S., 1108 steatorrhea, 1387 stem cells, 863 stenosis intestinal stomas, 250 sphincter of Oddi, 1216 STEP. See serial transverse enteroplasty “step-up approach,” for pancreatic necrosis, 1283–1284 stereotactic body radiation therapy (SBRT), 1110–1112 steroids for Crohn’s disease, 296 for Cushing syndrome, 1434

for pouchitis, 835 Stevenson, A. R., 1007 Stewart, L., 1206 STG. See subtotal gastrectomy stitch abscess, 188 Stocchi, L., 747 Stokes, K. R., 1176 stomach. See also gastric adenomas, 525 adhesions, 482 benign disorders, 507–527 motility, 531–533 penetrating trauma, 334 wedge resection, 613–615, 615f Stone, H. H., 328, 330 STOP-IT. See Study to Optimize Peritoneal Infection Therapy Stoppa, Rene, 221–222 Stoppa technique, 215 strangulation early postoperative bowel obstruction and, 698 inguinal hernias, 196, 197, 209–210 mechanical bowel obstruction, 677–678 PEH and, 423, 432–433 SBO and, 691–692 Strasberg, S. M., 1200 Street, D., 743 Streptococcus spp., 15, 188, 1404, 1409.1414 stress gastritis, 289 stress ulcers, 17–18, 523–524, 524t Stretta, 70–72–71f strictureplasty for Crohn’s disease, 805–807, 805f–807f, 841 for IBD, 893 strictures, 835

benign biliary cholecystectomy for, 1212 from laparoscopic cholecystectomy, 1199–1213, 1204f–1210f, 1212t, 1213t from pancreatitis, 1213–1214, 1214f QoL with, 1213 esophageal, 396 stroke, 639 Strong, V. E., 1438 ST-segment, 12, 105 Study to Optimize Peritoneal Infection Therapy (STOP-IT), 738 Sturgeon, C., 1436 subepithelial gastric tumors, 525 subtotal colectomy for constipation, 965–966 for HNPCC, 847 for UC, 829 subtotal fenestrating cholecystectomy, 1252–1253 subtotal gastrectomy (STG), 556, 557f, 558f succinate dehydrogenase (SDH), 581 “suck-and-cut,” EMR, 64 “suck-and-ligate,” EMR, 65 sucralfate, 404, 524 Sugiura, M., 1125 Sugiyama, M., 1185 sulfasalazine, 825–826 sunitinib malate, 588, 591 superior mesenteric artery (SMA), 344 acute mesenteric insufficiency, 349–352, 350f–352f aneurysm, 364t, 365–366 angiography, 349, 350f colon and, 872 computed tomography angiography for, 349, 350f, 351f exposure, 346, 347f

IPAA and, 832 lazy C loop, 351, 351f malrotation and, 141 pancreatic adenocarcinoma and, 1376–1377, 1376t periampullary adenocarcinoma of pancreas and, 1349 trauma to, 357 superior mesenteric vein (SMV) malrotation and, 141 pancreatic adenocarcinoma and, 1376t periampullary adenocarcinoma of pancreas and, 1349 PHTN and, 1129, 1132f superior rectal artery, 934 superior-mesenteric-portal vein (SMPV), 1375 superobesity, 639 supraceliac aorta, 342–344, 343f suprarenal aorta, 354–355 suprarenal IVC, 355 Surgical Care Improvement Project (SCIP), 35 surgical site infections (SSIs), 24–25, 24t, 830 CDC on, 186t–187t MBP and, 33 rectal cancer and, 988 wound management, postoperative and, 184–185, 185t Surveillance, Epidemiology, and End Results (SEER), 581, 717, 722, 857 anal melanoma and, 1027 Sutcliffe, R. P., 537 Suter, M., 1180 sutureless closure, 138, 139f, 202, 203f sutures for bleeding PUD, 514 endoscopy for, 62, 63f for esophagoesophagostomy, 145 for femoral hernia repair, 211 for hemorrhoidectomy, 947

for inguinal hernia, 193 for intestinal stoma colostomy, 236, 237 for laparoscopy, 104, 105, 106f for rectal prolapse, 938–939 for loop ileostomy, 242–243 for PEH repair, 429, 429f PF and, 1383 resorption, 180, 180f robotic surgery for, 923 SV. See selective vagotomy Swanson, S. J., 494 Sweet, R., 486 Swenson procedure, 157 sympathectomy, 681 syphilis, 958–959 systemic inflammatory response syndrome (SIRS), 1257, 1262, 1288–1289 systemic vascular resistance, 105 T TAC. See total abdominal colectomy TACE. See transarterial chemoembolization tachycardia, 13, 520, 730 TAE. See transarterial embolization TAH. See total abdominal hysterectomy TAH-BSO. See total abdominal hysterectomy and bilateral salpingooophorectomy Takahashi-Monroy, T., 969, 995 Talamini, M., 126 TAMIS. See transanal minimally invasive surgery tamponade, 308, 361, 434, 1045 Tan, M. C., 1334 Tanner, N. C., 443 TAP. See transversus abdominis plane TAPP. See transabdominal preperitoneal Tarasconi, J. C., 7

Targarona, E. M., 1185 targeted therapies, for PNETs, 1372 Taylor, T. V., 633 TDF. See Theoretical Domains Framework TDS. See transduodenal sphincteroplasty TEF. See tracheoesophageal fistula Teicher, I., 731 Telling, W. H., 767 TEM. See transanal endoscopic microsurgery Temple, C. L., 729 TEMPO, 72 temporary closure, 182–183 TEP. See total extraperitoneal Tepper, J. E., 475 terminal ileus disease, 813 testicular injury, from inguinal hernia repair, 209 Testoni, P. A., 72 tetracycline, 959 Teubner, A., 271 TG. See Tokyo Guidelines TGF-β. See tumor growth factor beta Thal fundoplication, 147–148 thalassemia, 1408 THE. See transhiatal esophagectomy Theoretical Domains Framework (TDF), 39 thiazide diuretics, 1257 thiopurines, 826–827 Thompson retractor system, 172 thoracoscopy, 454 thoracotomy, 147 Thornblade, L. W., 33 Thorotrast, 1089, 1231 thrombocytopenia, 59, 136, 1398, 1409 thromboembolectomy, 361

thrombopoietin receptor (TPO-R) agonists, 1411 thrombosis acute mesenteric, 349 with acute pancreatitis, 1287 DVT, 11, 98, 827, 996, 1160 hemorrhoids, 946, 947–948 mesenteric venous, 352 PVT, 1110, 1125, 1129, 1145–1147 pyrogenic liver abscesses and, 1041 SPVT, 1422–1423, 1423f thrombotic thrombocytopenic purpura (TTP), 1411–1412 through-the-scope stents (TTS), 69–70 thyroid cancer, 844 TIAs. See transient ischemic attacks TIF. See transoral incisionless fundoplication TIGAR-O system, 1304, 1304t Tilepro, 123 tincture of opium, 248 tinidazole, 1043 TIPS. See transjugular intrahepatic portosystemic shunt Tirumani, S. H., 588 tissue plasminogen activator (TPA), 349 TKI. See tyrosine kinase inhibitor TLESR. See transient lower esophageal sphincter relaxation TME. See total mesorectal excision TNF-α. See tumor necrosis factor-alpha TNM. See tumor-node-metastasis staging system TNT. See total neoadjuvant therapy Tocchi, A., 1182 Todani classification, for choledochal cysts, 1192, 1192f Tokyo Guidelines (TG), for cholecystitis, 1251, 1251t, 1252t Toldt’s line, 344, 345f topoisomerase I inhibitor, 469 TORe. See transoral outlet reduction

Torek, F., 475, 476f total abdominal colectomy (TAC), 829, 845, 846, 847 total abdominal hysterectomy (TAH), 849, 850 total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO), 978 total colonic HD, 156, 156f total extraperitoneal (TEP), 206, 211, 216 total gastrectomy, 556 total mesorectal excision (TME), 123, 128, 128t, 129, 575, 881 for CRC, 923 for CRC robotic surgery, 925–928, 926f–928f for rectal cancer, 977 total neoadjuvant therapy (TNT), 1012 total pancreatectomy, 1382 total pancreatectomy with autologous islet transplantation (TPAIT), 1319– 1320 total parenteral nutrition (TPN), 137, 756 for acute pancreatitis, 1261 for PF, 1383 total proctocolectomy (TPC), 831–832, 833, 845, 846, 850, 897 Toupet, A., 404 Toupet fundoplication, 408, 409f, 414 Toussaint, E., 542 toxic megacolon, 829, 829f TPA. See tissue plasminogen activator TPAIT. See total pancreatectomy with autologous islet transplantation TPC. See total proctocolectomy TPN. See total parenteral nutrition TPO-R. See thrombopoietin receptor agonists tracheoesophageal fistula (TEF), 447. See also esophageal atresia/tracheoesophageal fistula tracheomalacia, 147, 148 transabdominal preperitoneal (TAPP), 205–206, 211, 216 transanal endoscopic microsurgery (TEM), 724, 993–999, 996f, 997f, 999f

transanal minimally invasive surgery (TAMIS), 724 transarterial chemoembolization (TACE), 1086, 1088f, 1089f–1090f for HCC, 1112 for liver metastases, 1097–1100, 1098f for PNETs, 1372 transarterial embolization (TAE), 1102, 1372 transduodenal sphincteroplasty (TDS), 1180–1181 transesophageal echocardiography, 12 transfusions for CRC surgery, 877 damage control and, 183 for GI bleeding, 282–283 introduction, 6 for liver blunt trauma, 328 platelets, 22 for PPH, 1386 RBCs, 22 for GI bleeding, 282 transhiatal esophagectomy (THE), 458, 478–480, 487–488, 487f, 488f transient ischemic attacks (TIAs), 15 transient lower esophageal sphincter relaxation (TLESR), 395 transjugular intrahepatic portosystemic shunt (TIPS), 293 injection sclerotherapy and, 62 for PHTN, 1125, 1127, 1129, 1133, 1135, 1141–1145, 1141t, 1143f–1144f, 1144t PPI and, 72–74, 74f transoral incisionless fundoplication (TIF), 70, 72–74, 73f, 411, 411f transoral outlet reduction (TORe), 667 transpyloric stenting, 543 transthoracic esophagectomy (TTE), 458, 478–480 transverse colectomy, 910, 910f transverse incisions, 169–170 transversus abdominis plane (TAP), 10, 35 Trastulli, S., 129

trastuzumab (Herceptin), 469 trauma, 315–338, 320t. See also blunt trauma; penetrating trauma arteriovenous fistula from, 356–357 DPL for, 317 fecal incontinence from, 967 grades, 319t to IMA, 357 initial management, 315–317 kidney injury from, 320t to mesenteric veins, 357 to SMA, 357 to spleen, 1398–1400, 1398f, 1399t, 1400f stress ulcers and, 523 US for, 317–318, 318f vascular emergencies from, 353–354 traumatic brain injury, 11 traumatic liver cysts, 1057, 1057f trazodone, 11 Trede, Michael, 1381 Trendelenburg position, 926, 927, 996. See also reverse Trendelenburg position Triadafilopoulos, G., 70 tricuspid regurgitation, 14 tricyclic antidepressants, 388, 389, 538 tri-incisional esophagectomy, 480–486, 480f–486f trocars, 99–100, 99f, 100f, 178 for Crohn’s disease, 808–809 hernia and, 684 injury from, 101 for robotic TME for CRC, 928 for splenectomy, 1419 truncal vagotomy (TV), 505f, 517, 520, 603, 605–607, 606f Trypanosoma cruzi, 382 trypsinogen, 154, 1304–1305

Tseng, J. F., 1328, 1387 TSH. See 2-stage hepatectomy TTE. See transthoracic esophagectomy TTP. See thrombotic thrombocytopenic purpura TTS. See through-the-scope stents tuberculosis, 4, 685, 957 tumor growth factor beta (TGF-β), 1306 tumor necrosis factor-alpha (TNF-α), 257, 271, 826. See also anti-TNF therapies acute pancreatitis and, 1257 Crohn’s disease and, 841 tumor-node-metastasis staging system (TNM) for carcinoids, 719, 719t for cholangiocarcinoma, 1233, 1233t, 1234t for CRC, 870, 870t for esophageal cancer, 447–448, 448t for gallbladder cancer, 1225, 1225t for GC, 552, 553t for HCC, 1081–1083, 1082t for rectal cancer, 986, 987t tumors. See also benign tumors; cancer; specific types colon, 857–885, 858t small bowel, 705–715 Tuxun, T., 1052 TV. See truncal vagotomy 2-stage hepatectomy (TSH), 1118–1119 type 1 errors, 47 type 2 errors, 47–28 tyrosine kinase inhibitor (TKI), 567, 586–588, 591, 599, 600–602 U UC. See ulcerative colitis UDCA. See ursodeoxycholic acid UES. See upper esophageal sphincter UFH. See unfractionated heparin

UGI. See upper gastrointestinal study UICC. See International Union Against Cancer ulcerative colitis (UC), 823–837, 824f, 825f, 839–841 acute, 828–830 anal SCC and, 1017 chronic, 830–833 Crohn’s disease and, 797, 800 diagnosis, 824–825 end ileostomy and, 240 endoscopy for, 826f IPAA for, 832–836 J-pouch for, 831–832, 831f, 832f laparoscopic IPAA for, 830 PSC and, 1216–1217 rectal cancer and, 977, 978 toxic megacolon and, 829, 829f US for, 824, 824f ulcers. See also peptic ulcer disease aphthous, 794 duodenal, 285–288, 287f, 288f, 508, 514, 733 gastric, 289, 733 marginal, 523 rectum, 296 solitary rectal ulcer syndrome, 800, 940–942 stress, 17–18, 523–524, 524t Ultraflex stent, 470 ultrasonic shears, 105, 123 ultrasound (US). See also endoscopic ultrasound; focused abdominal sonography for trauma for abscesses, 258–259 for acute mesenteric lymphadenitis, 303 for amebic liver abscess, 1043 for appendicitis, 731–732, 731f, 732t for cholangitis, 1183–1183

for choledochal cysts, 1194 for choledocholithiasis, 1172–1173 for congenital liver cysts, 1053 for cystadenoma, 1055–1056, 1056f EEU, 1281 for esophageal benign tumors, 378 for esophageal cancer, 451–453 for fecal incontinence, 968–969 for FNH, 1067 for gallbladder cancer, 1224, 1224f for gallstones, 1156, 1156f for gastrinoma, 1368 for hepatolithiasis, 1185 IOUS, 1178, 1242 for IRE, 1113 for liver hemangiomas, 1064f for local anesthesia, 10 LUS, 110, 110f, 111, 112, 113, 1163 for mesenteric cysts, 304 for PEG, 67 for PHTN, 1128–1129 for pyrogenic liver abscesses, 1036, 1037f for recurrent pyogenic cholangitis, 1215 for SBO, 691 for splenic cysts, 1402 for trauma, 317–318, 318f for UC, 824, 824f umbilical hernia, 219–220, 683 unfractionated heparin (UFH), 16, 23, 1160 upper esophageal sphincter (UES), 373 upper gastrointestinal study (UGI) for bezoars, 526 for chronic gastric stasis, 521 for duodenal atresia, 149

endoscopy for, 60–66 for gastric epithelial polyps, 524 for hernia, 684 for HPS, 135 for JIA, 152 for malrotation, 141 for meconium ileus, 153 for PEH, 412 for Roux stasis syndrome, 522 upper GI bleeding, 286–293, 286f–292f, 286t carcinoids and, 717 Dieulafoy lesions and, 526 from gastroesophageal varices, 291–292, 292f Mallory–Weiss tears and, 527 portal hypertension and, 291–292, 292f PUD and, 513–514 rebleeding, 293 from PUD, 513–514 Urba, S. G., 475 urinary urea nitrogen (UUN), 27 urine output, 106, 282 Urografin, 693 urokinase, 349 Urschel, J. D., 476 ursodeoxycholic acid (UDCA), 1218 US. See ultrasound ustekinumab, 801 UUN. See urinary urea nitrogen V VAC. See vacuum-assisted closure VACTERL. See vertebral defects, anal atresia, cardiac anomalies, TEF, EA, renal defects, and limb abnormalities vacuum-assisted closure (VAC), 183, 269, 957 vaginectomy, 1005–1006, 1005f

vagotomy anterior proximal, 633–634, 634f Bookwalter retractor for, 605f DGE and, 603 for duodenal ulcers, 514 gastric acid and, 6 gastric emptying and, 6, 518 gastroparesis and, 521, 535–536 highly selective, 515, 517–518, 518f, 603, 607–610, 608f–610f, 633 incision for, 604–605 laparoscopy for, 629–634, 632f–634f for perforated PUD, 513 SV, 607, 607f, 1376, 1376t TV, 505f, 517, 520, 603, 605–607, 606f vagus nerve, 397, 518, 604 Vailati, C., 72 Vakili, C., 101 ValenTx, 75 valvular disease, 13–14 Van Aalten, S. M., 1070 van der Wal, J. B., 697 van Hagen, P., 476 van Helmont, J. B., 531 van Lent, A. U., 1184 vancomycin, 15 Varadhachary, G. R., 1375 VARD. See video-assisted retroperitoneal debridement varices anorectal, 296 esophageal, 62, 283, 1126, 1126t, 1133–1145, 1134, 1134f, 1135f gastric, 62, 1133–1145 gastroesophageal, 291–292, 292f vas deferens injury, 209 vasa recta, 768, 768f

Vasan, H. A., 476 vascular emergencies, 341–367, 342f diagnosis, 341–342 exposure and control, 342–348, 343f, 345f–348f management, 349–354 from trauma, 353–354 vascular endothelial growth factor (VEGF), 567, 591, 724, 885 vasoactive intestinal polypeptide-secreting tumors (VIPomas), 1365, 1369 vasodilators, 12 vasopressin, 1134 vatalanib, 591 VATER, 144, 158 VATS. See video-assisted thoracoscopic surgery VBG. See vertical banded gastroplasty VBLOC system, 644 VCE. See video capsule endoscopy vedolizumab, 801, 827 VEGF. See vascular endothelial growth factor velusetrag, 539 Venderbosch, S., 1007 venous thromboembolism (VTE), 15, 22–24, 654, 655, 1099 ventral hernias, 141 ventral rectopexy, 967 ventricular tachycardia, 13 Veress needles/technique, 99–100, 100f, 109, 177, 926 Verner, J. V., 1366 vertebral defects, anal atresia, cardiac anomalies, TEF, EA, renal defects, and limb abnormalities (VACTERL), 144, 158 vertical banded gastroplasty (VBG), 649, 648f vertical incisions, 168–169 vestibular fistula, 158, 159 VHL. See von Hippel-Lindau disease Vibrio cholerae, 4 Vicryl, 138, 180, 236, 237, 993

video capsule endoscopy (VCE), 691, 707–708 video-assisted retroperitoneal debridement (VARD), 1265, 1285, 1285f, 1296–1297, 1297f video-assisted thoracoscopic surgery (VATS), 459 vinorelbine, 469 VIPomas. See vasoactive intestinal polypeptide-secreting tumors Virchow, Rudolph, 6 visceral aorta, 344 visceral artery aneurysms, 363–367, 364t vitamin A, 444, 850 vitamin B12, 523, 655 vitamin C, 444, 850 vitamin D, 523, 653 vitamin E, 444, 850 vitamin K, 16 Vogelstein, Bert, 847 volvulus cecal, 686, 686f, 785, 786, 786t, 787f, 788–789 colonic, 785–790, 786t, 787f, 788f gastric, 412, 423, 527 midgut, 141, 142, 142f, 143, 756 SBO, 679, 686–687, 686f sigmoid, 686, 686f, 785, 786–787, 786t, 787–788, 787f, 788f splenic flexure, 789–790 transverse colon, 789 von Hippel-Lindau disease (VHL), 1323 MEN-1 and, 1379 pheochromocytoma and, 1346 PNETs and, 1365 SCNs and, 1327 von Recklinghausen, Friedrich, 6 von Recklinghausen syndrome, 1365 von Willebrand disease, 308 von Willebrand factor (vWF), 22, 1412

Vons, C., 736 Vortmeyer, A. O., 1327 VTE. See venous thromboembolism vWF. See von Willebrand factor W Wagner, J. M., 732 Wakelin, S. J., 111 Waldeyer’s fascia, 980, 982 walled-off pancreatic necrosis (WON), 1263, 1272 pancreatic necrosis and, 1280 VARD for, 1285, 1285f Walsh, T. N., 467, 475 Walz, M. K., 1438 Wangensteen, O. H., 728 warfarin, 23 Warren, J. R., 507, 532 Warren, John Collins, 3 watchful waiting (WW), for inguinal hernia, 213–214 water-soluble contrast agents (WSCA), 694, 694f Watkins, P. J., 544 WAVESS. See Worldwide Anti-Vomiting Electrical Stimulation Study Weber, P. A., 919–920 wedge gastroplasty, 408 wedge resection for CRC, 879 for duodenal ulcers, 289 for esophageal lengthening, 431 in gastrectomy, 408, 409f, 634, 635f for GISTs, 585 for highly selective vagotomy, 607 of liver, 1119–1120 for perforated peptic ulcer, 513 stomach, 61ff, 613–615

weight loss chronic pancreatitis and, 1306 endoluminal devices for, 74–78, 75f–79f, 643–644, 644t after gastrectomy, 523 gastroparesis and, 526 for obesity, 642–644, 643t, 644t SCNs and, 1327 UC and, 824 Wells, Thomas Spencer, 1406 West, N. P., 1005 Wexner, S. D., 973 Whipple, Allen O., 1365, 1381 Whipple procedure, 544, 711f, 1198, 1313, 1351–1352, 1352f Whipple triad, 1367, 1367t Whitcomb, D. C., 1304, 1387 Whiteway, J., 768 WHO. See World Health Organization Wick, E. C., 34 Wilmore, D. W., 755 Wilson, Louis, 6 Wilson disease, 1126 Wind, J., 275 windsock deformity, 149 Winter, 1337–1338 Wittgrove, A. C., 648 Witzel-type closure, 1315 Wolff, W. I., 85 WON. See walled-off pancreatic necrosis work of breathing, 17 World Health Organization (WHO), 36, 1412 on GERD, 396 on hyperplastic polyps, 868 on pancreatic cystic neoplasms, 1324, 1324t Worldwide Anti-Vomiting Electrical Stimulation Study (WAVESS), 541

Worrell, S. G., 500–501 wound classification, 24–25, 24t, 185t wound management, postoperative for dehiscence, 181–182, 188–189, 274 dressing for, 183–184 for evisceration, 188–189 for hematoma, 188 for necrotizing wound infections, 185–188 for seroma, 188 SSIs and, 184–185, 185t for stitch abscess, 188 W-pouch, 840 WSCA. See water-soluble contrast agents WW. See watchful waiting X Xeloda. See capecitabine Xi System, 121, 527 Xiong, J., 38 Y Yamamoto, T., 817 Yamashita, M. H., 1354 Yeh, R. W., 70 Yeo, Charles, 1381 Yersinia spp., 799 Z Zacarelli, Adrian, 1414 Zani, A., 751 Zehetner, J., 544 Zeng, Q., 697 Zenker diverticulum, 373–375, 374f ZES. See Zollinger-Ellison syndrome Zeus Robotic Surgical System, 121

Zielinski, M. D., 691 Zimmerman, A., 1062 Zofran. See ondansetron Zollinger-Ellison syndrome (ZES), 561, 1366, 1367–1368, 1368f, 1378 zona fasciculata, 1433 zona glomerulosa, 1433 zona reticularis, 1433 Zureikat, A. H., 115