Oxford Textbook of Plastic and Reconstructive Surgery [1 ed.] 0199682879, 9780199682874

Table of contents :
cover
Series
Oxford Textbook of 
Plastic and Reconstructive Surgery
Copyright
Contents
Section editors
Contributors
Symbols and abbreviations
Section 1 General principles and techniques
1.1 General principles and techniques
1.2 Tissue healing
1.3 Infections
1.4 Structure and function of the skin
1.5 Vascular anatomy
1.6 Anaesthesia
1.7 Skin grafts
1.8 Skin flaps
1.9 Microsurgery
1.10 Benign skin conditions and tumours
1.11 Non-​melanoma skin cancer and premalignant conditions
1.12 Pigmented lesions and melanoma including premalignant conditions
1.13 Wound dressings
1.14 Sarcoma
1.15 Vascularized composite allotransplantation
Section 2 Burns surgery
2.1 Mechanisms of burn injury: thermal, chemical, electrical, and radiation
2.2 The burned patient: physiology and pathology
2.3 Adult thermal burns
2.4 The burnt child
2.5 Electrical injury and burns and their management
2.6 Chemical burns
2.7 Cold-​induced injury to the skin and deep tissues
2.8 Radiation injury to the skin and deep tissues
Section 3 Nerve surgery
3.1 Surgical anatomy and physiology of the intact peripheral nervous system including cranial nerves
3.1.1 Macroscopic and microscopic anatomy of the peripheral nervous system
3.1.2 Blood supply of the peripheral nerve
3.1.3 The Schwann cell
3.1.4 Physiological requirements for action potential conduction, sensory awareness, and motor control
3.1.5 Tactile sensory control of the human hand
3.2 Neurobiology of injury (compression, traction, laceration) and repair, and grading of injuries
3.3 Clinical features of nerve injuries and their diagnosis
3.3.1 Clinicopathological correlates with theoretical grades
3.3.2 Tinel–​Hoffman sign
3.3.3 Neurophysiological assessments for peripheral nerve injury
3.3.4 Adult brachial plexus injury
3.3.5 Brachial plexus injury in the child
3.4 Surgical management of the divided nerve and nerve grafts and transfers
3.4.1 Surgical management of the divided nerve
3.4.2 Nerve grafts and transfers
3.5 Hand therapy after peripheral nerve injury
3.6 Chronic postsurgical pain and complex regional pain syndrome
3.7 Compression or mechanical neuropathy
3.7.1 Pathophysiology
3.7.2 Compression neuropathies
3.7.3 Thoracic outlet syndrome
3.8 Mass lesions of the peripheral nervous system
Section 4 Upper limb
4.1 Clinical assessment and imaging of the upper limb
4.2 Anthropological, behavioural, and cultural characteristics of the human hand
4.3 Applied biomechanics of the hand, wrist, and forearm
4.4 Soft tissue infections of the hand and upper limb
4.5 Dupuytren’s disease
4.6 Soft tissue reconstruction of the hand
4.7 Microsurgical reconstruction of the upper limb
4.8 Hand therapy, rehabilitation, and rehabilitation following tendon injury
4.9 Amputations
4.10 Fractures of the hand and wrist
4.11 Ligamentous injuries of the hand and wrist
4.12 Osteoarthritis of the wrist and hand
4.13 Soft tissue inflammatory disorders of the hand
4.14 Inflammatory arthritis of the hand and wrist
4.15 The flexor tendons
4.16 The extensor tendons
4.17 Tendon transfers in the hand and wrist
4.18 Reanimation in the upper limb: free functioning and pedicled muscle transfer
4.19 Pain syndromes
4.20 Embryology of the upper limb
4.21 Management of children’s hand disorders
4.22 Traumatic injury to the child’s hand
4.23 Upper limb spasticity
4.24 Soft tissue swellings of the hand and upper limb
4.25 Bone lesions in the upper limb and hand
4.26 Systemic disorders reflected in the hand
Section 5 Lower limb
5.1 Classification of lower limb trauma
5.2 Principles of acute management of lower limb trauma
5.3 The devascularized limb
5.4 Management of soft tissue loss without microsurgery
5.5 Microvascular cover in the lower limb: indications and timing, flap types, and technique
5.6 Management of bone loss
5.7 Lower limb replantation
5.8 Amputations in the lower limb
5.9 Lower limb trauma outcome measures: limb salvage and amputation
5.10 Lower limb osteomyelitis
5.11 Management of congenital limb deficiency
5.12 Orthopaedic management of congenital pseudarthrosis of the tibia
5.13 How the foot and ankle works (mechanics of the foot)
5.14 The skeletal consequences of meningococcal septicaemia
Section 6 Craniofacial and cleft
6.1 Classification of craniofacial anomalies
6.2 Embryology of craniofacial skeleton
6.3 Genetics of craniofacial anomalies
6.4 Assessment of patients with craniosynostosis
6.5 Non-​syndromic craniosynostosis
6.6 Syndromic craniosynostosis
6.7 Hypertelorism and orbital dystopia
6.8 Orofacial clefts: embryology, epidemiology, and genetics
6.9 Classification, evaluation, and management of the neonate with a cleft
6.10 Primary management of cleft lip and palate
6.11 Outcome assessment in cleft lip and palate surgery
6.12 Secondary surgery in cleft lip and palate
6.13 Velopharyngeal dysfunction
Section 7 Maxillofacial trauma
7.1 Assessment of the maxillofacial patient: maxillofacial trauma and ATLS®
7.2 Fractures of the mandible
7.3 Zygomatic complex fractures
7.4 Orbital fractures
7.5 Fractured nasal bones
7.6 Management of midface fractures: maxilla
7.7 Frontal sinus and nasoethmoidal injuries
7.8 Sequencing of panfacial fracture repair
7.9 Introduction to orthognathic surgery, the assessment of facial disproportion, and orthognathic treatment planning
7.10 First and second branchial arch anomalies
7.11 Common orthognathic procedures
Section 8 Head and neck surgery
8.1 The head and neck multidisciplinary team
8.2 Anatomy and embryology of the head and neck
8.3 Tumours of the oral cavity
8.4 Tumours of the nasopharynx, oropharynx, and hypopharynx
8.5 Tumours of the larynx
8.6 Tumours of the thyroid gland
8.7 Tumours of the salivary glands
8.8 Tracheostomy
8.9 Assessment and management of metastatic neck disease
8.10 Scalp, forehead, and calvarial reconstruction
8.11 Eyelid reconstruction
8.12 Lip reconstruction
8.13 Cheek reconstruction
8.14 Nasal reconstruction
8.15 Reconstruction of the pharynx
8.16 Reconstruction of the mandible and maxilla
8.17 Anatomy and physiology of the facial nerve and aetiology of facial nerve palsy
8.18 Management of facial palsy
8.19 Radiology of the head and neck
8.20 Adjuvant therapy for head and neck cancers
Section 9 The chest and breast
9.1 Embryology and development of the chest wall and breast
9.2 Deformities of the chest
9.3 Surgical anatomy of the breast
9.4 Congenital deformities of the breast
9.5 Preoperative imaging for autologous breast reconstruction
9.6 Breast malignancy: diagnosis and management
9.7 Breast reconstruction: patient assessment
9.8 Tissue expander and implant breast reconstruction
9.9 Latissimus dorsi breast reconstruction
9.10 TRAM flap breast reconstruction
9.11 DIEP flap breast reconstruction
9.12 Alternative flaps for microsurgical breast reconstruction
9.13 The tissue-​engineered breast
9.14 Management of complications of microvascular abdominal flap breast reconstruction
9.15 The nipple–​areolar complex
9.16 Ancillary considerations in breast surgery
9.17 Anaesthesia and analgesia considerations in breast surgery
9.18 Measuring outcomes in plastic surgery of the breast
Section 10 Abdomen
10.1 Functional anatomy of the abdominal wall
10.2 The open abdomen
10.3 The principles of complex abdominal hernia repair
10.4 Local and free flap abdominal wall repair
10.5 Necrotizing fasciitis of the abdomen
10.6 Functional anatomy of the pelvis and gluteal region
10.7 Pilonidal disease
10.8 Pressure ulcers
10.9 Perineal reconstruction following anorectal excision
10.10 Vulval and vaginal reconstruction
Section 11 Urogenital surgery and gender dysphoria
11.1 Hypospadias
11.2 Bladder exstrophy and epispadias: functional and surgical challenges
11.3 Penile reconstruction
11.4 Differences in sex development: surgical challenges
11.5 Gender reassignment
Section 12 Cosmetic surgery
12.1 Psychological assessment
12.2 Avoiding patient dissatisfaction: the consultation, preoperative preparation, and postoperative care
12.3 Lasers and flashlamps in the treatment of skin disorders
12.4 Botulinum toxins
12.5 Lipomodelling
12.6 Fillers and dermabrasive therapies
12.7 Treatment of large and ptotic breasts
12.8 Hair restoration
12.9 Periorbital, lower face, and neck
12.10 Primary aesthetic rhinoplasty
12.11 Modification of the facial skeleton in aesthetic facial surgery
12.12 Gynaecomastia
12.13 Treatment of small breasts and inverted nipples
12.14 Asymmetry of the breast
12.15 Abdominal wall anatomy
12.16 Anatomy, physiology, and pathology of body fat
12.17 Abdominoplasty
12.18 Liposculpture
12.19 Buttock augmentation
12.20 Aesthetic surgery of the genitalia
12.21 Bariatric surgery
12.22 Upper trunk and breast surgery after massive weight loss
12.23 Lower body lift and abdominal surgery after massive weight loss
12.24 Thigh lift
12.25 Brachioplasty
12.26 Aesthetic surgery of the leg
12.27 The ageing breast
Section 13 The legal, ethical, and behavioural components of plastic surgery
13.1 The ethics of gender reassignment surgery
13.2 Psychological consequences of the birth of a child with a congenital hand anomaly
13.3 Psychological assessment of cosmetic surgery patients
13.4 Factitious injury and related conditions
13.5 Legal aspects of consent to treatment and the nature of malpractice claims in the United Kingdom
13.6 Consulting with children
Index

Citation preview

Oxford Textbook of 

Plastic and Reconstructive Surgery

OXFORD TEXTBOOKS IN SURGERY SERIES Published Oxford Textbook of Trauma and Orthopaedics Edited by Christopher Bulstrode, James Wilson-​MacDonald, Deborah M. Eastwood, John McMaster, Jeremy Fairbank, Parminder J. Singh, Sandeep Bawa, Panagoitis D. Gikas, Tim Bunker, Grey Giddins, Mark Blyth, and David Stanley Oxford Textbook of Fundamentals of Surgery Edited by William E. G. Thomas, Malcolm W. R. Reed, and Michael G. Wyatt Oxford Textbook of Vascular Surgery Edited by Matthew M. Thompson, Robert Fitridge, Jon Boyle, Matt Thompson, Karim Brohi, Robert J. Hinchliffe, Nick Cheshire, A. Ross Naylor, Ian Loftus, and Alun H. Davies Oxford Textbook of Urological Surgery Edited by Freddie C. Hamdy and Ian Eardley Oxford Textbook of Neurological Surgery Edited by Ramez W. Kirollos, Adel Helmy, Simon Thomson, and Peter J. Hutchinson Oxford Textbook of Plastic and Reconstructive Surgery Edited by Simon Kay, Daniel Wilks, and David McCombe

Oxford Textbook of 

Plastic and Reconstructive Surgery EDITED BY

Simon Kay Consultant Plastic Surgeon, Plastic and Reconstructive Surgery Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK

Daniel Wilks Consultant Plastic Surgeon, Plastic and Maxillofacial Surgery Department, The Royal Children’s Hospital, Melbourne, Australia

David McCombe Clinical Associate Professor, Plastic and Maxillofacial Surgery Department, The Royal Children’s Hospital, Melbourne, Australia

1

3 Great Clarendon Street, Oxford, OX2 6DP, United Kingdom Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries © Oxford University Press 2021 The moral rights of the authors have been asserted First Edition published in 2021 Impression: 1 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by licence or under terms agreed with the appropriate reprographics rights organization. Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this work in any other form and you must impose this same condition on any acquirer Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America British Library Cataloguing in Publication Data Data available Library of Congress Control Number: 2020945296 ISBN 978–​0–​19–​968287–​4 DOI: 10.1093/​med/​9780199682874.001.0001 Printed in Great Britain by Bell & Bain Ltd., Glasgow Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-​to-​date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-​pregnant adult who is not breast-​feeding Links to third party websites are provided by Oxford in good faith and for information only. Oxford disclaims any responsibility for the materials contained in any third party website referenced in this work.

To Rowan, Cyrus, and Jacob, and to my teachers, especially my patients. To Anna and Emmeline for joining me on the journey and my family, friends, and colleagues for helping me find the way. To Georgie, Lachie, Finn, and Stella, to my mentors and to those willing to learn.

Series preface This is a new development in surgical publishing; the first two editions of the Oxford Textbook of Surgery are to be replaced by a series of specialty-​specific textbooks in surgery. This change was precipitated by the ever-​increasing size of a single textbook of surgery which embraced all specialties (the second edition of the Oxford Textbook of Surgery was three volumes), and a decision to adapt the textbooks to meet the needs of the audience; firstly, to suit the requirements of Higher Surgical trainees and, secondly, to make it available online. Thus, we have produced a key book to deal with the fundamentals of surgery, such as Anatomy, Physiology, Biochemistry, Evaluation of Evidence, and so forth. Then there are to be separate volumes covering individual specialties, each appearing as an independent textbook and available online via the Oxford University Press Academic Platform. It is planned that each textbook in each specialty will be independent although there obviously will be an overlap between different specialties and, of course, the core book on fundamentals of surgery will underpin the required scientific knowledge and practice in each of the other specialties.

This ambitious programme will be spread over several years, and the use of the online platform will allow for regular updates of the different textbooks. Each textbook will include the proposed requirements for training and learning as defined by the specialist committees (SACs) of surgery recognized by the four Colleges of Surgery in Great Britain and Ireland, and will continue to be applicable to a global audience. This ambitious programme will be spread over several years, and the use of the online platform will allow for regular updates of the different textbooks. When completed, the Oxford Textbooks in Surgery series will set standards for a long time to come. Professor Sir Peter J. Morris Nuffield Professor of Surgery Emeritus, and former Chairman of the Department of Surgery and Director of the Oxford Transplant Centre, University of Oxford and Oxford Radcliffe Hospitals, UK

Introduction The word ‘text’ is derived from the Latin texere meaning to weave, to join, fit together, or braid. This is particularly apt in this case as the editors have attempted with a broad loom to assemble a comprehensive description of Plastic Surgery. As will be described in the following chapters, Plastic Surgery is a specialty that encourages the practitioner to apply its principles and techniques to resolve, repair, and reconstruct across all the domains of the body. Consequently, the breadth of the specialty can be simultaneously inspiring and intimidating to the surgeon, as they may be presented with a diversity of challenges that can be addressed with principle-​based decision making but require nuanced knowledge of the issues that relate to the individual problem. The genesis of this text owes much to its ancestor, the Oxford Textbook of Surgery, edited in 2000 by Sir Peter Morris and William Wood. This comprehensive and authoritative reference was designed to meet the demands of specialists and trainees addressing general surgery and several other specialties. Its evolution into what is now a series of 11 multivolume texts, overseen by Sir Peter, detailing the entirety of surgery is testament to the innovation and dedication that typifies his remarkable career. Our purpose is to offer the aspiring surgeon a comprehensive guide to Plastic Surgery as well as provide a reference for those who are established in their practice. We have attempted to encompass the curriculum of the Royal College of Surgeons fellowship in Plastic Surgery and have added further chapters where necessary to arm the surgeon with knowledge. We have enlisted a range of authors from around the globe and are grateful for the incisive knowledge and enthusiasm that they have brought to this project. A multiauthor text such as this relies upon the generosity of experts in their individual fields in being prepared to educate all of us with their hard-​won knowledge to the benefit of all of

our patients and their families and we are grateful for this. The editors are also grateful to the section editors who have assembled their individual teams of authors and shepherded them all through the process of chapter development to submission and have been invaluable in their efforts to produce the inaugural edition of this text. The organisation and production of this textbook relies upon the specialist knowledge and the strength of a publisher and the editors thank Oxford University Press for their support and expertise in helping to bring this project to fruition. The editors would like to thank Caroline Smith, Jamie Oates, and Helen Liepman of Oxford University Press in particular for their support, coaching and coaxing throughout the gestation and birth of this work. The continuing development of an innovative discipline such as Plastic Surgery means that what is written in these pages today inevitably will have evolved by tomorrow. That does not make this text obsolete or redundant. Such progress is only possible on a solid foundation of knowledge, summarised and consolidated from time to time, which this text provides. We are grateful that you as a reader are using this work as your foundation in your own areas of development. Simon Kay Daniel Wilks David McCombe

Preface Healing after injury is a remarkable biological phenomenon found in all vertebrates, given the opportunity. To hasten or improve healing by surgical repair may have been practiced throughout the history of our species, but to go one step further and to reconstruct damaged anatomy has been only a dream until the last few hundred years. It was a miracle that Jesus could reattach the ear of one of his captors, and the legend of Saints Cosmos and Damien transplanting a lower limb was of course fantastical also. Things began to change when flap surgery for nasal reconstruction, passed down by artisan surgeons in the east, emerged in the west, first in Sicily, before being reported from British colonial India. Free grafting was slower to be investigated and understood, even though the corresponding horticultural practices were well established. Paul Bert’s experiments on skin grafting in sheep were early examples of science in reconstructive surgery, possibly influencing Reverdin in clinical practice a short time later. The advents of asepsis and anaesthesia allowed more and more empirical experience, rather than laboratory experiment, on the repair and reconstruction of the integument. This moved from simply closing the difficult wound to consideration of aesthetics. The First World War, the first industrialised conflict employing high-​explosive and trench warfare, produced the pabulum of facial and head injuries on which the innovations of surgeons like Morestin, Esser, Valadier and Gillies were nourished. The Second World War saw another great step forward for surgical practice with the development of antimicrobial drugs. That conflict left us the legacy of extensive skin grafting and burns reconstruction, as well as the prompt evacuation of field casualties. The Korean and Vietnamese conflicts especially capitalized on these protocols and saw step advances in vascular surgery, cavity surgery and neurosurgery. The Second World War heralded an era of proliferating surgical spin-​offs, and plastic surgery took its place amongst the major acute disciplines. Many of the facial trauma bone fixation techniques of the first conflict were now applied to hand and limb surgery. Scientific enquiry took a firm hold of our burgeoning specialty, wonderfully exemplified by the collaboration between Gibson and Medawar whose investigation into the “second set” skin grafting phenomenon started the modern understanding of immunology and transplantation. Since then the efflorescence of scientific and empirical reconstructive surgical developments has been remarkable, from the cornfields of Kentucky to the highways of Slovenia, the People’s

Hospitals of China, the clinics of Europe and throughout the world. Every surgical discipline has contributed to the growth of plastic surgery, and every surgical specialty has learned and benefited from it. Our boundaries are wonderfully indistinct and porous and yet we preserve a distinct identity at the focal point of the reconstructive web. But something else has happened. We moved from asking only “how?” to asking “why?”, and to examining our outcomes more rigorously and within wider frames of reference. Surgeons moved gradually to consider not just the form, or appearance of restored anatomy, but also the activity or function of the reconstructed part. Many metrics were designed and recorded to reflect this urge to restore activity and function. But physiological function was not the final goal. Forty years ago or more, craniofacial units, for example, started to realise that the best judges of surgical aesthetic outcomes might be a child’s peers, not the surgeon or even the parents. At about the same time surgeons began to include the concept of participation as an outcome. How closely did the patient integrate back into the normal activities of life and partake in their society? How did a patient feel about themselves? How did they behave? Finally we saw the “why?” of surgery emerge into stark scrutiny. What worth has a sophisticated and successful suite of surgery to restore form or function if the patient is no better psychologically or socially? The human body transports and nourishes the acme of evolution that is the human brain, which in turn holds the mystical entities that are the mind and spirit. It is remarkable, through the intercession of social mechanisms, how a defect in the body can adversely influence the expression of these latter two. More and more we realise that our success in treating the physical, the appearance and function of the body, can only be interpreted through the prism of behavior. Each of us must be empathetic to our patients’ minds and collaboration in psychology should be the norm. Perhaps Harvey Cushing knew this when he said “I would like to see the day when somebody would be appointed surgeon somewhere who had no hands, for the operative part is the least part of the work”. This wide-​ranging text reflects the breadth and the depth of our craft, and throughout it we see the traces of our past and the directions of our future as we strive to restore ever more effectively and more comprehensively the human beings in front of us. Its existence is a tribute to Sir Peter Morris who first proposed it to me, and to the considerable roll call of fellow editors and authors whose patience and hard work are only now rewarded by the final text. I was

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Preface

delighted when David McCombe agreed to join me to bring the energy and perspective of the Southern Hemisphere to the task. We then reasoned that textbooks are aimed in great part at young surgeons who are too often unrepresented in the editorship, and so and we were both grateful when Dan Wilks accepted my invitation to be a co-​editor whilst still a surgical trainee. But of course it is the enthusiasm, experience and continuing quest for refinement of all our contributors that powers our specialty. That and the patients

that place their trust in us and whom we keep as the focus of all our endeavours. Simon Kay

REFERENCE Endpiece. No hands. BMJ. 2004; 329(7462): 374. https://www.ncbi. nlm.nih.gov/pmc/articles/PMC509378/pdf/bmj3290374a.pdf

Brief contents Contents  xv Section editors  xxiii Contributors  xxv Symbols and abbreviations  xxix

SECTION 7 Maxillofacial trauma 

SECTION 1 General principles and techniques 

SECTION 8 Head and neck surgery 

Section editor: Lachlan M. Carter

1

Section editors: Simon Kay, David McCombe, and Daniel Wilks

SECTION 2 Burns surgery 

Section editor: Jeremy Rawlins

Section editor: Maniram Ragbir

SECTION 9 The chest and breast 

983

SECTION 10 Abdomen  1173 Section editor: Andrew Fleming

227

Section editors: Simon Kay, Mikael Wiberg, and Andrew Hart

SECTION 4 Upper limb  321

SECTION 11 Urogenital surgery and gender dysphoria  Section editor: Oliver Fenton

Section editors: Vivien Lees and James Haeney

SECTION 5 Lower limb  575

SECTION 12 Cosmetic surgery 

1333

Section editors: Nigel Mercer and Mark Soldin

Section editor: Umraz Khan

SECTION 6 Craniofacial and cleft 

851

Section editors: Rodney Cooter, Nicola R. Dean, and Kieran Horgan

127

SECTION 3 Nerve surgery 

787

669

Section editors: Hiroshi Nishikawa, Felicity V. Mehendale, and David C.G. Sainsbury

SECTION 13 The legal, ethical, and behavioural components of plastic surgery  1571 Section editor: Simon Kay

Index  1609

1273

Contents Section editors  xxiii Contributors  xxv Symbols and abbreviations  xxix

1.12 Pigmented lesions and melanoma including premalignant conditions  79 Michael Henderson, John Spillane, David Gyorki, and Christopher McCormack

1.13 Wound dressings  91

SECTION 1 General principles and techniques Section editors: Simon Kay, David McCombe, and Daniel Wilks 1.1 General principles and techniques  3

David Stewart

1.14 Sarcoma  95 Ian M. Smith and Vinay Itte

1.15 Vascularized composite allotransplantation  105 Daniel Wilks and Simon Kay

Simon Kay and David McCombe

1.2 Tissue healing  7 Gus McGrouther

1.3 Infections  13 Donald Dewar

1.4 Structure and function of the skin  21 Mark Goodfield

1.5 Vascular anatomy  25 Amanda Murphy, Steven F. Morris, and G. Ian Taylor

1.6 Anaesthesia  31 Chetan Srinath and Alan Yates

1.7 Skin grafts  35 Siobhan O’Ceallaigh and Mamta Shah

1.8 Skin flaps  39 Donald Dewar

1.9 Microsurgery  51 David McCombe and Wayne Morrison

1.10 Benign skin conditions and tumours  61 Rajib Rahim and Graeme Stables

1.11 Non-​melanoma skin cancer and premalignant conditions  69 Barbara Jemec and Gregor B.E. Jemec

SECTION 2 Burns surgery  Section editor: Jeremy Rawlins 2.1 Mechanisms of burn injury: thermal, chemical, electrical, and radiation  129 Ravi F. Sood and Nicole S. Gibran

2.2 The burned patient: physiology and pathology  139 Fiona Wood and Keith Judkins

2.3 Adult thermal burns  155 Jeremy Rawlins and Isabel Jones

2.4 The burnt child  179 Suzanne Rea and Sian Falder

2.5 Electrical injury and burns and their management  193 David C.G. Sainsbury and Joel Fish

2.6 Chemical burns  205 Alexandra Murray

2.7 Cold-​induced injury to the skin and deep tissues  215 Marc-​James Hallam, Johann A. Jeevaratnam, Christopher H.E. Imray, and Tania Cubison

xvi

Contents

2.8 Radiation injury to the skin and deep tissues  221 Johann A. Jeevaratnam, Marc-​James Hallam, and Tania Cubison

3.4.2 Nerve grafts and transfers  275

Robert Bains and Simon Kay

3.5 Hand therapy after peripheral nerve injury  283 Birgitta Rosén and Christina Jerosch-​Herold

SECTION 3 Nerve surgery

3.6 Chronic postsurgical pain and complex regional pain syndrome  289 Lesley A. Colvin and Sebastian Bourn

Section editors: Simon Kay, Mikael Wiberg, and Andrew Hart

3.7 Compression or mechanical neuropathy  293

3.1 Surgical anatomy and physiology of the intact peripheral nervous system including cranial nerves  229

3.7.1 Pathophysiology  293

3.1.1 Macroscopic and microscopic anatomy of the peripheral nervous system  229

Lev N. Novikov and Mikael Wiberg 3.1.2 Blood supply of the peripheral nerve  231

Andrew Hart

Andrew Hart 3.7.2 Compression neuropathies  294

Lars B. Dahlin and Niels Thomsen 3.7.3 Thoracic outlet syndrome  302

Anna Barnard and Simon Kay

3.8 Mass lesions of the peripheral nervous system  309 Thomas J. Wilson, Carlos E. Restrepo, and Robert J. Spinner

3.1.3 The Schwann cell  234

Paul J. Kingham and Mikael Wiberg 3.1.4 Physiological requirements for action potential

conduction, sensory awareness, and motor control  235 Staffan Johansson 3.1.5 Tactile sensory control of the human hand  239

Roland S. Johansson and Per F. Nordmark

3.2 Neurobiology of injury (compression, traction, laceration) and repair, and grading of injuries  243 Andrew Hart

3.3 Clinical features of nerve injuries and their diagnosis   253 3.3.1 Clinicopathological correlates with theoretical grades  253

Robert Bains and Simon Kay 3.3.2 Tinel–​Hoffman sign  260

Simon Kay 3.3.3 Neurophysiological assessments for peripheral nerve injury  261

Arup Mallik 3.3.4 Adult brachial plexus injury  263

Simon Kay and Robert Bains

3.3.5 Brachial plexus injury in the child  266

Robert Bains and Simon Kay

3.4 Surgical management of the divided nerve and nerve grafts and transfers  269 3.4.1 Surgical management of the divided nerve  269

Duncan A. McGrouther

SECTION 4 Upper limb  Section editors: Vivien Lees and James Haeney 4.1 Clinical assessment and imaging of the upper limb  323 Anuj Mishra

4.2 Anthropological, behavioural, and cultural characteristics of the human hand  339 James Haeney

4.3 Applied biomechanics of the hand, wrist, and forearm  345 Vivien Lees

4.4 Soft tissue infections of the hand and upper limb  351 Sophie Collier and Barbara Jemec

4.5 Dupuytren’s disease  361 Richard Milner

4.6 Soft tissue reconstruction of the hand  375 David Elliot

4.7 Microsurgical reconstruction of the upper limb  385 Alex E. Hamilton

4.8 Hand therapy, rehabilitation, and rehabilitation following tendon injury  393 Fiona Peck

Contents

4.9 Amputations  403 Robert Winterton

4.10 Fractures of the hand and wrist  409 David J. Shewring

4.11 Ligamentous injuries of the hand and wrist  435 Carlos Heras-​Palou

4.12 Osteoarthritis of the wrist and hand  443 Manu Sood

4.13 Soft tissue inflammatory disorders of the hand  459 Sohail Akhtar

4.14 Inflammatory arthritis of the hand and wrist  467 Peter Burge

4.15 The flexor tendons  479 Fortune Iwuagwu

4.16 The extensor tendons  495 Sanjib Majumder

4.17 Tendon transfers in the hand and wrist  501 Cath Hernon

4.18 Reanimation in the upper limb: free functioning and pedicled muscle transfer  509 Simon Kay

4.19 Pain syndromes  515 David Elliot

4.20 Embryology of the upper limb  523 Wee-​Leon Lam and Megan G. Davey

4.21 Management of children’s hand disorders  533 Grainne Bourke, Ian Grant, and Gill Smith

4.22 Traumatic injury to the child’s hand  547 David McCombe

4.23 Upper limb spasticity  553 Paul McArthur

4.24 Soft tissue swellings of the hand and upper limb  557 Vikram Devaraj

4.25 Bone lesions in the upper limb and hand  563 Geoffrey Hooper

4.26 Systemic disorders reflected in the hand  569 Stewart Watson

SECTION 5 Lower limb  Section editor: Umraz Khan 5.1 Classification of lower limb trauma  577 Umraz Khan

5.2 Principles of acute management of lower limb trauma  583 Michael Kelly

5.3 The devascularized limb  585 Kaz M.A. Rahman and Shehan Hettiaratchy

5.4 Management of soft tissue loss without microsurgery  593 Thomas C. Wright

5.5 Microvascular cover in the lower limb: indications and timing, flap types, and technique  601 Zoran M. Arnež

5.6 Management of bone loss  611 Mark Jackson

5.7 Lower limb replantation  617 Moazzam N. Tarar and Ata Ul Haq

5.8 Amputations in the lower limb  625 Umraz Khan and Alan Gordon

5.9 Lower limb trauma outcome measures: limb salvage and amputation  635 David Wallace

5.10 Lower limb osteomyelitis  643 Umraz Khan

5.11 Management of congenital limb deficiency  651 Fergal Monsell

5.12 Orthopaedic management of congenital pseudarthrosis of the tibia  655 Fergal Monsell

5.13 How the foot and ankle works (mechanics of the foot)  661 Ian Winson

5.14 The skeletal consequences of meningococcal septicaemia  665 Fergal Monsell

xvii

xviii

Contents

SECTION 6 Craniofacial and cleft  Section editors: Hiroshi Nishikawa, Felicity V. Mehendale, and David C.G. Sainsbury 6.1 Classification of craniofacial anomalies  671 Jagajeevan Jagadeesan and Hiroshi Nishikawa

6.2 Embryology of craniofacial skeleton  685 Mark S. Lloyd

6.3 Genetics of craniofacial anomalies  691 Andrew O.M. Wilkie

6.4 Assessment of patients with craniosynostosis  697 Nicholas White

6.5 Non-​syndromic craniosynostosis  705 Christian Duncan and Hiroshi Nishikawa

6.6 Syndromic craniosynostosis  713 Stephen Dover and Martin Evans

6.7 Hypertelorism and orbital dystopia  721 Aina V.H. Greig and David J. Dunaway

6.8 Orofacial clefts: embryology, epidemiology, and genetics  729 David R. FitzPatrick

6.9 Classification, evaluation, and management of the neonate with a cleft  737

7.2 Fractures of the mandible  793 Lachlan M. Carter

7.3 Zygomatic complex fractures  801 A. Nicholas Brown

7.4 Orbital fractures  807 Trevor Teemul

7.5 Fractured nasal bones  815 A. Nicholas Brown

7.6 Management of midface fractures: maxilla  817 Jiten D. Parmar and Lachlan M. Carter

7.7 Frontal sinus and nasoethmoidal injuries  821 Nabeela Ahmed, Lachlan M. Carter, and Rabindra P. Singh

7.8 Sequencing of panfacial fracture repair  827 Jiten D. Parmar and Lachlan M. Carter

7.9 Introduction to orthognathic surgery, the assessment of facial disproportion, and orthognathic treatment planning  831 Claire Bates, Trevor Hodge, Christopher J. Mannion, and Lachlan M. Carter

7.10 First and second branchial arch anomalies  841 Claire Bates, Trevor Hodge, and Lachlan M. Carter

7.11 Common orthognathic procedures  845 Claire Bates, Christopher J. Mannion, and Lachlan M. Carter

David C.G. Sainsbury

6.10 Primary management of cleft lip and palate  745 Jason Neil-​Dwyer

6.11 Outcome assessment in cleft lip and palate surgery  761 Marc C. Swan, Conrad J. Harrison, and Tim E.E. Goodacre

6.12 Secondary surgery in cleft lip and palate  767 Peter D. Hodgkinson

6.13 Velopharyngeal dysfunction  777 David C.G. Sainsbury, Caroline C. Williams, and Felicity V. Mehendale

SECTION 8 Head and neck surgery  Section editor: Maniram Ragbir 8.1 The head and neck multidisciplinary team  853 Kristian Sørensen

8.2 Anatomy and embryology of the head and neck  855 Charles Y.Y. Loh and Christopher G. Wallace

8.3 Tumours of the oral cavity  859 Jonathan A. Dunne and Paolo L. Matteucci

SECTION 7 Maxillofacial trauma 

8.4 Tumours of the nasopharynx, oropharynx, and hypopharynx  867 Isma Z. Iqbal, Anusha Balasubramanian, and Vinidh Paleri

Section editor: Lachlan M. Carter

8.5 Tumours of the larynx  875

7.1 Assessment of the maxillofacial patient: maxillofacial trauma and ATLS®  789

8.6 Tumours of the thyroid gland  879

Christopher J. Mannion

Mark Puvanendran and Vinidh Paleri Ramesh Gurunathan and Vinidh Paleri

Contents

8.7 Tumours of the salivary glands  885 James Wokes and Neil McLean

8.8 Tracheostomy  893 Peter Kalu and Maniram Ragbir

8.9 Assessment and management of metastatic neck disease  897 Vinidh Paleri and Maniram Ragbir

8.10 Scalp, forehead, and calvarial reconstruction  903 Kaz M.A. Rahman

8.11 Eyelid reconstruction  907 Mogdad Alrawi

8.12 Lip reconstruction  919 David C.G. Sainsbury

8.13 Cheek reconstruction  931 Matthew Potter

8.14 Nasal reconstruction  937 Michael D. Kernohan and Kelly Thornbury

8.15 Reconstruction of the pharynx  945 Jonathan Pollock and Maniram Ragbir

8.16 Reconstruction of the mandible and maxilla  951 Colonel Douglas G Bryant, Alex P. Jones, and Maniram Ragbir

8.17 Anatomy and physiology of the facial nerve and aetiology of facial nerve palsy  963 Onur Gilleard and Kallirroi Tzafetta

8.18 Management of facial palsy  969 Omar A. Ahmed and Richard Chalmers

8.19 Radiology of the head and neck  973 Ivan Zammit-​Maempel

8.20 Adjuvant therapy for head and neck cancers  977 Charles Kelly

9.3 Surgical anatomy of the breast  1001 Amy E. Jeeves

9.4 Congenital deformities of the breast  1007 Michelle L. Lodge

9.5 Preoperative imaging for autologous breast reconstruction  1017 Mark Ashton and Iain Whitaker

9.6 Breast malignancy: diagnosis and management  1025 Kieran Horgan, Barbara Dall, Rebecca Millican-​Slater, Russell Bramhall, Fiona MacNeill, David Dodwell, Indu Chaudhuri, and Sebastian Trainor

9.7 Breast reconstruction: patient assessment  1053 Nicola R. Dean

9.8 Tissue expander and implant breast reconstruction  1063 Melissa A. Mueller, Emily G. Clark, and Gregory R.D. Evans

9.9 Latissimus dorsi breast reconstruction  1069 Mark A. Lee

9.10 TRAM flap breast reconstruction  1081 Janek S. Januszkiewicz

9.11 DIEP flap breast reconstruction  1093 Mark Ashton

9.12 Alternative flaps for microsurgical breast reconstruction  1107 Hinne A. Rakhorst

9.13 The tissue-​engineered breast  1115 Wayne Morrison

9.14 Management of complications of microvascular abdominal flap breast reconstruction  1121 Marc A.M. Mureau

9.15 The nipple–​areolar complex  1133 Garry Buckland

SECTION 9 The chest and breast  Section editors: Rodney Cooter, Nicola R. Dean, and Kieran Horgan 9.1 Embryology and development of the chest wall and breast  985 Quoc Lam

9.2 Deformities of the chest  991 Harvey Stern

9.16 Ancillary considerations in breast surgery  1145 Emily G. Clark, Melissa A. Mueller, and Gregory R.D. Evans

9.17 Anaesthesia and analgesia considerations in breast surgery  1151 Glenda Rudkin and Sarah Gardiner

9.18 Measuring outcomes in plastic surgery of the breast  1159 Nicola R. Dean, Rod Cooter, and Andrea L. Pusic

xix

xx

Contents

SECTION 10 Abdomen  Section editor: Andrew Fleming 10.1 Functional anatomy of the abdominal wall  1175 Kezia Echlin

10.2 The open abdomen  1179 Omar A. Khan, Emma Rose McGlone, and Marcus Reddy

10.3 The principles of complex abdominal hernia repair  1185 Kezia Echlin and Andrew Fleming

10.4 Local and free flap abdominal wall repair  1195 Jonathan W.G. Lohn and Martin J.J. Vesely

10.5 Necrotizing fasciitis of the abdomen  1203 Anthony Barabás and Andrew Fleming

10.6 Functional anatomy of the pelvis and gluteal region  1209 Donald Hudson and Sean Moodley

10.7 Pilonidal disease  1213 Kezia Echlin and Andrew Fleming

10.8 Pressure ulcers  1223 Donald Hudson and Sean Moodley

10.9 Perineal reconstruction following anorectal excision  1247 Alexandra Crick

10.10 Vulval and vaginal reconstruction  1259 Lucy Cogswell

11.5 Gender reassignment  1321 Oliver Fenton

SECTION 12 Cosmetic surgery  Section editors: Nigel Mercer and Mark Soldin 12.1 Psychological assessment  1335 Nichola Rumsey and Nicole Paraskeva

12.2 Avoiding patient dissatisfaction: the consultation, preoperative preparation, and postoperative care  1341 Nigel Mercer and Mark Soldin

12.3 Lasers and flashlamps in the treatment of skin disorders  1347 Richard J. Barlow

12.4 Botulinum toxins  1355 Sherina Balaratnam, Sami Stagnell, and Tamara W. Griffiths

12.5 Lipomodelling  1359 John Dickson and Nigel Mercer

12.6 Fillers and dermabrasive therapies  1363 Brett Archer

12.7 Treatment of large and ptotic breasts  1367 Adam Searle, Albert de Mey†, and Christophe Zirak

12.8 Hair restoration  1373 Nagham Darhouse and Greg Williams

12.9 Periorbital, lower face, and neck  1379 Norman Waterhouse, Naresh Noshi, Niall Kirkpatrick, and Lisa Brendling

SECTION 11 Urogenital surgery and gender dysphoria 

12.10 Primary aesthetic rhinoplasty  1399

Section editor: Oliver Fenton

12.11 Modification of the facial skeleton in aesthetic facial surgery  1425

11.1 Hypospadias  1275 Simon Wharton, Khurram Khan, and David Coleman

11.2 Bladder exstrophy and epispadias: functional and surgical challenges  1295 Dan Wilby and Dan Wood

11.3 Penile reconstruction  1303 Giulio Garaffa and David J. Ralph

11.4 Differences in sex development: surgical challenges  1313 Dan Wood

Lucian Ion

Paul Johnson and David Tighe

12.12 Gynaecomastia  1429 John Dickson and Nigel Mercer

12.13 Treatment of small breasts and inverted nipples  1435 Marion Grob and Elliott Smock

12.14 Asymmetry of the breast  1449 Farida Ali

12.15 Abdominal wall anatomy  1461 Nicholas Wilson Jones

Contents

12.16 Anatomy, physiology, and pathology of body fat  1465

12.27 The ageing breast  1567 Donald Hudson

Isabel Teo and Mark Soldin

12.17 Abdominoplasty  1473 Christopher Abela and Mark Soldin

12.18 Liposculpture  1481 Marco Gasparotti, Isabel Teo, Andrea Maria Florio, Davide Lazzeri, and Mark Soldin

12.19 Buttock augmentation  1491 Lina Triana and Mildred Martínez Millán

12.20 Aesthetic surgery of the genitalia  1499 Maleeha Mughal and Mark Soldin

12.21 Bariatric surgery  1505 Alberic Fiennes

12.22 Upper trunk and breast surgery after massive weight loss  1513 Mohammed Akhavani and Mark Soldin

12.23 Lower body lift and abdominal surgery after massive weight loss  1523 Dirk F. Richter and Nina Schwaiger

12.24 Thigh lift  1543 Anthony Barabás and Mark Soldin

12.25 Brachioplasty  1551 Charles J. Bain and Mark Soldin

12.26 Aesthetic surgery of the leg  1557

SECTION 13 The legal, ethical, and behavioural components of plastic surgery Section editor: Simon Kay 13.1 The ethics of gender reassignment surgery  1573 Oliver Fenton

13.2 Psychological consequences of the birth of a child with a congenital hand anomaly  1577 Maggie Bellew

13.3 Psychological assessment of cosmetic surgery patients  1583 Maggie Bellew

13.4 Factitious injury and related conditions  1591 Simon Kay and Maggie Bellew

13.5 Legal aspects of consent to treatment and the nature of malpractice claims in the United Kingdom  1597 Mark Ashley

13.6 Consulting with children  1605 Simon Kay and Maggie Bellew

Athanasios Papas and Mark Soldin

Index  1609

xxi

Section editors Lachlan M. Carter  Department of Oral and

Maxillofacial Surgery, Leeds Teaching Hospitals, Leeds, UK Section 7: Maxillofacial trauma Rodney Cooter  Waverley House Plastic Surgery

Centre, Adelaide, Australia Section 9: The chest and breast

Nicola R. Dean  Department of Plastic and

Reconstructive Surgery, Flinders Medical Centre; and College of Medicine and Public Health, Flinders University, South Australia, Australia Section 9: The chest and breast Oliver Fenton  Department of Plastic Surgery,

Pinderfields Hospital, Wakefield, UK Section 11: Urogenital surgery and gender dysphoria Andrew Fleming  Department of Plastic Surgery,

St Georges NHS Trust, London, UK Section 10: Abdomen

Andrew Hart  Canniesburn Plastic Surgery Unit,

Glasgow Royal Infirmary; and College of Medical Veterinary and Life Sciences, The University of Glasgow, Glasgow, UK Section 3: Nerve surgery James Haeney  Department of Plastic Surgery, Castle

Hill Hospital, Cottingham, Hull, UK Section 4: Upper limb

Kieran Horgan  Department of Breast Surgery,

Leeds Teaching Hospitals NHS Trust, Leeds, UK Section 9: The chest and breast Simon Kay  Plastic and Reconstructive Surgery

Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK Section 1: General principles and techniques Section 3: Nerve surgery Section 13: The legal, ethical, and behavioural components of plastic surgery Umraz Khan  Department of Reconstructive Plastic

Surgery, North Bristol NHS Trust, Bristol, UK Section 5: Lower limb Vivien Lees  Department of Plastic Surgery,

Wythenshawe Hospital, Manchester, UK Section 4: Upper limb

David McCombe  Plastic and Maxillofacial Surgery

Department, The Royal Children’s Hospital, Melbourne, Australia Section 1: General principles and techniques

Felicity V. Mehendale  Cleft Lip and Palate Service,

East of Scotland, Royal Hospital for Sick Children, Edinburgh, UK Section 6: Craniofacial and cleft

Nigel Mercer  The Cleft Unit of the South West of

England, Frenchay Hospital, Bristol, UK Section 12: Cosmetic surgery

Hiroshi Nishikawa  Department of Plastic and

Reconstructive Surgery, Birmingham Children’s Hospital, Birmingham, UK Section 6: Craniofacial and cleft Maniram Ragbir  Department of Plastic Surgery,

University of Newcastle, Freeman, Hospital, Newcastle upon Tyne, UK Section 8: Head and neck surgery

Jeremy Rawlins  Plastic, Reconstructive, and Burns

Surgery, Royal Perth Hospital, Perth, Australia Section 2: Burns surgery David Sainsbury  Cleft Lip and Palate Service,

Birmingham Children’s Hospital, Birmingham, UK Section 6: Craniofacial and cleft Mark Soldin  Department of Plastic Surgery, St

Georges Hospital, London, UK Section 12: Cosmetic surgery

Mikael Wiberg  Departments of Integrative Medical

Biology and Surgical and Perioperative Science, Faculty of Medicine, Umeå University; Umeå University Hospital Regional NHS Trust; and University Hospital, Sweden Section 3: Nerve surgery Daniel Wilks  Plastic and Maxillofacial Surgery

Department, The Royal Children’s Hospital, Melbourne, Australia Section 1: General principles and techniques

Contributors Nabeela Ahmed  Oral and Maxillofacial

Surgery Department, Queens Medical Centre, Nottingham, UK Omar A. Ahmed  Department of Plastic and Reconstructive Surgery, Royal Victoria Infirmary, Newcastle upon Tyne, UK Mohammed Akhavani  Department of Plastic Surgery, Royal Free Hospital, London, UK Sohail Akhtar  Department of Upper Limb Surgery, Wrightington Hospital, Wigan, UK Farida Ali  Department of Plastic Surgery, St George’s University Hospital, London, UK Mogdad Alrawi  Department of Plastic Surgery, Royal Victoria Infirmary, Newcastle upon Tyne, UK Brett Archer  Southbank Plastic Surgery Centre, Southbank, Victoria, Australia Zoran M. Arnež  Plastic, Reconstructive and Aesthetic Surgery, Department of Medicine, Surgery and Health Sciences, University of Trieste, Italy Mark Ashley  DAC Beachcroft LLP, Bristol, UK Mark Ashton  Department of Plastic and Reconstructive Surgery, Royal Melbourne Hospital, Melbourne, Australia Charles J. Bain  Department of Plastic Surgery, Guys and St Thomas’ NHS Foundation Trust, London, UK Robert Bains  Department of Plastic and Reconstructive Surgery, Leeds Teaching Hospital NHS Trust, Leeds, UK Sherina Balaratnam  S-Thetics Clinic, Beaconsfield, Buckinghamshire, UK Anusha Balasubramanian  Surrey and Sussex Healthcare NHS Trust, Redhill, Surrey, UK Anthony Barabás  Department of Plastic Surgery, Hinchingbrooke Hospital, Cambridgeshire, UK Richard J. Barlow  Department of Surgery and Laser Unit, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Anna Barnard  Department of Plastic and Reconstructive Surgery / Discovery Hand Unit, James Cook University Hospital, Middlesbrough, UK Claire Bates  Leeds Teaching Hospitals, Leeds, UK Maggie Bellew  Department of Plastic Surgery, Leeds General Infirmary, Leeds, UK Grainne Bourke  Great North Air Ambulance Service; and Department of Plastic Surgery, Leeds General Infirmary, Leeds, UK

Sebastian Bourn  Great North Air Ambulance

Service; and Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK Russell Bramhall  Department of Plastic Surgery, Glasgow Royal Infirmary, Glasgow, UK Lisa Brendling  Department of Dermatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK A. Nicholas Brown  Maxillofacial Surgery Department, York Tweaching Hospital NHS Foundation Trust, York, UK Colonel Douglas G Bryant Department of Oral and Maxillofacial Surgery, James Cook University Hospital, Middlesbrough, UK Garry Buckland  Plastic and Reconstructive Surgery Department, Prince of Wales Private Hospital, Randwick, Sydney, Australia Peter Burge  Nuffield Orthopaedic Centre, Oxford, UK Lachlan M. Carter  Department of Oral and Maxillofacial fSurgery, Leeds Teaching Hospitals, Leeds, UK Richard Chalmers  Department of Plastic Surgery, University Hospital of North Durham, Durham, UK Indu Chaudhuri  Department of Breast Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Christopher Abela  Department of Plastic Surgery, Chelsea and Westminster Hospital, Bariatric Multidisciplinary Team, London, UK Emily G. Clark  Department of Aesthetic and Plastic Surgery, University of California, Irvine, CA, USA Lucy Cogswell  Department of Plastic Surgery, Oxford University Hospital NHS Trust, Oxford, UK David Coleman  Department of Plastic Surgery, Oxford University Hospitals, John Radcliffe Hospital, Oxford, UK Sophie Collier  Department of Microbiology, Royal Free London NHS Foundation Trust, London, UK Lesley A. Colvin  University Department of Anaesthesia, Glasgow Royal Infirmary, Glasgow, UK Rod Cooter  Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia Alexandra Crick  Plastic Surgery Department, Salisbury NHS Trust, Salisbury, UK Tania Cubison  Department of Burns and Plastic Surgery, Queen Victoria Hospital, East Grinstead, UK

Lars B. Dahlin  Department of Hand Surgery, Lund

University, Skåne University Hospital, Malmö, Sweden

Barbara Dall  Department of Breast Imaging, Leeds

Teaching Hospitals NHS Trust, Leeds, UK

Nagham Darhouse   Department of Plastic Surgery,

Chelsea and Westminster Hospital, London, UK

Megan G. Davey  The Roslin Institute, University of

Edinburgh, Edinburgh, UK

Albert de Mey†  Department of Plastic Surgery,

Brugmann University Hospital, Brussels, Belgium

Nicola R. Dean  Department of Plastic and

Reconstructive Surgery, Flinders Medical Centre; and College of Medicine and Public Health, Flinders University, South Australia, Australia Vikram Devaraj  Department of Plastic Surgery, Royal Devon and Exeter Hospital, Exeter, UK Donald Dewar  Plastic Surgery Department, James Cook University Hospital, Middlesbrough, UK John Dickson  Plastic Surgery Department, Derriford Hospital, Plymouth, UK David Dodwell  Nuffield Department of Population Health, University of Oxford, Oxford, UK Julie Doughty Department of Surgery, Gartnavel General Hospital, Glasgow, UK Stephen Dover  West Midlands Craniofacial Unit, Birmingham Children’s Hospital, Birmingham, UK David J. Dunaway  Department of Craniofacial Surgery, Great Ormond Street Hospital, London, UK Christian Duncan  Plastic and Craniofacial Surgery, Alder Hey Hospital, Liverpool, UK Jonathan A. Dunne  Department of Plastic Surgery, Imperial College Healthcare NHS Trust, London, UK Kezia Echlin  Department of Plastic Surgery, St Georges NHS Trust, London, UK David Elliot  St Andrew’s Centre for Plastic Surgery and Burns, Broomfield Hospital, Chelmsford, UK Martin Evans  Oral, Maxillofacial, and Craniofacial Surgery, Birmingham Children’s and Queen Elizabeth Hospitals, Birmingham, UK Gregory R.D. Evans  Department of Plastic Surgery, University of California, Irvine, CA, USA Sian Falder  Plastic Surgery Department, Alder Hey Children’s NHS Foundation Trust, Liverpool, Merseyside, UK Oliver Fenton  Department of Plastic Surgery, Pinderfields Hospital, Wakefield, UK Alberic Fiennes  International Federation for the Surgery of Obesity and Metabolic DiseaseEuropean Chapter, Surrey, UK

xxvi

Contributors

Joel Fish  Department of Surgery, Hospital for Sick

Children, Toronto, Ontario, Canada David R. FitzPatrick  MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK Andrew Fleming  Department of Plastic Surgery, St Georges NHS Trust, London, UK Andrea Maria Florio  Department of Plastic Surgery, Ars Medica Clinic, Rome, Italy Giulio Garaffa  St Peter’s Andrology and the Institute of Urology, University College London Hospitals, London, UK Sarah Gardiner  Plastic Surgery Department, Christchurch Hospital, Christchurch, New Zealand Marco Gasparotti  University of Camerino, Camerino; and Department of Plastic Surgery, Ars Medica Clinic, Rome, Italy Nicole S. Gibran  Department of Surgery, University of Washington, Seattle, WA, US Onur Gilleard  Plastic and Reconstructive Surgery, Barts Health NHS Trust, Chelmsford, UK Tim E.E. Goodacre  Nuffield Department of Surgery, University of Oxford, Oxford, UK Mark Goodfield  The Centre for Dermatology, Chapel Allerton Hospital, Leeds, UK Alan Gordon  Academy Prosthetist, Ottoblock, Bristol, UK Ian Grant  Department of Plastic Surgery, Addenbrooke’s Hospital, Cambridge, UK Aina V.H. Greig  Department of Plastic Surgery, Guy’s and St Thomas’ NHS Trust, London, UK Tamara W. Griffiths  Dermatology Department, Spire Manchester Hospital, Manchester; and Spire Manchester Clinic Hale, Altrincham, UK Marion Grob  Department of Plastic and Reconstructive Surgery, Rothenbaum Clinic, Hamburg, Germany Ramesh Gurunathan  Department of Head and Neck Surgery, County Durham and Darlington NHS Foundation Trust, Durham, UK David Gyorki  Melanoma and Skin Unit, Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne; and University of Melbourne, Melbourne, Australia James Haeney  Department of Plastic Surgery, Castle Hill Hospital, Cottingham, Hull, UK Marc-​James  Hallam  Department of Plastic Surgery, The Christie NHS Foundation Trust, Manchester, UK Alex E. Hamilton  Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Sheffield, UK Andrew Hart  Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary; and College of Medical Veterinary and Life Sciences, The University of Glasgow, Glasgow, UK Conrad Harrison Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK Ata Ul Haq Department of Plastic Surgery, Jinnah Burn and Reconstructive Surgery Centre, Allama Iqbal Medical School, Lahore, Pakistan Michael Henderson  Melanoma and Skin Unit, Division of Cancer Surgery, Peter MacCallum Cancer Centre Melbourne; and University of Melbourne, Melbourne, Australia

Carlos Heras-​Palou  Pulvertaft Hand Centre, Derby

Royal Hospital, Derby, UK Cath Hernon  Department of Plastic Surgery, Leeds General Infirmary, Leeds, UK Shehan Hettiaratchy  Department of Plastic and Reconstructive Surgery, Imperial College Healthcare NHS Trust, London, UK Trevor Hodge  Leeds Dental Institute; and Leeds Teaching Hospitals, Leeds, UK Peter D. Hodgkinson  Cleft Lip and Palate Service, Royal Victoria Infirmary, Newcastle, UK Geoffrey Hooper  Retired Consultant Orthopaedic Surgeon, St John’s Hospital, Livingstone, UK Kieran Horgan  Department of Breast Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK Donald Hudson  Department of Plastic Surgery, Groote Schuur Hospital, Cape Town, South Africa Christopher H.E. Imray  Vascular and Renal Transplant Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry UK Lucian Ion  Plastic and Cosmetic Surgeon, Aveling House, London, UK Isma Z. Iqbal  Otorhinolaryngologist and Skull Base Surgeon, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Northumberland, UK Vinay Itte  Department of Plastic and Reconstructive Surgery, Leeds General Infirmary, Leeds, UK Fortune Iwuagwu  St Andrew’s Centre for Plastic Surgery and Burns, Broomfield Hospital, Chelmsford, UK Mark Jackson  Department of Orthopaedics, University Hospital Bristol, Bristol, UK Jagajeevan Jagadeesan  Department of Plastic Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK Janek S. Januszkiewicz  New Zealand Institute of Plastic and Cosmetic Surgery, Auckland, New Zealand Johann A. Jeevaratnam  Department of Plastic Surgery, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Amy E. Jeeves  Department of Plastic and Reconstructive Surgery, Royal Adelaide and Women’s and Children’s Hospital, Adelaide, Australia Barbara Jemec  Department of Plastic Surgery, Trillium Health Partners, Toronto, Ontario, Canada Gregor B.E. Jemec  Department of Dermatology, Zealand University Hospital, Roskilde, Denmark Christina Jerosch-​Herold  Rehabilitation Research, School of Health Sciences, University of East Anglia, Norwich, UK Roland S. Johansson  Department of Integrative Medical Biology, Umeå University, Umeå, Sweden Staffan Johansson  Department of Integrative Medical Biology (Physiology), Umeå University, Umeå, Sweden Paul Johnson  Oral, Maxillofacial, and Facial Plastic Surgeon, Royal Surrey County Hospital, Guildford, UK

Alex P. Jones  Plastic and Reconstructive Head and

Neck Surgeon, James Cook University Hospital, Middlesbrough, UK Isabel Jones  Plastic and Reconstructive Surgery (Burns), Chelsea and Westminster Hospital, London, UK Keith Judkins  Department of Anaesthesia and Critical Care, Pinderfields Hospital, Wakefield, West Yorkshire, UK Peter Kalu  Department of Plastic Surgery, Oxford University Hospitals, John Radcliffe Hospital, Oxford, UK Simon Kay  Plastic and Reconstructive Surgery Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK Charles Kelly  Bobby Robson Cancer Institute, Freeman Hospital, Newcastle upon Tyne, UK Michael Kelly  Department of Reconstructive Plastic Surgery, North Bristol NHS Trust, Bristol, UK Michael D. Kernohan  Department of Plastic and Reconstructive Surgery, St Vincent’s Private Hospital Sydney, New South Wales, Australia Omar A. Khan  Department of General Surgery, St Georges NHS Trust, London, UK Umraz Khan  Department of Reconstructive Plastic Surgery, North Bristol NHS Trust, Bristol, UK Khurram Khan, Department of Plastic Surgery, Birmingham Children’s Hospital, West Midlands, UK Paul J. Kingham  Department of Integrative Medical Biology, Umeå University, Umeå, Sweden Niall Kirkpatrick  Craniofacial Unit, Chelsea and Westminster Hospital, London, UK Quoc Lam  Waverley House Plastic Surgery Centre, Adelaide, Australia Wee-​Leon Lam  Department of Plastic Surgery, Royal Hospital for Sick Children, Edinburgh, UK Davide Lazzeri  Plastic, Reconstructive, and Cosmetic Surgery, Villa Salaria Clinic, Rome, Italy Mark A. Lee  Department of Plastic Surgery, St John of God Hospital, Subiaco, Australia Vivien Lees  Department of Plastic Surgery, Wythenshawe Hospital, Manchester, UK Mark S. Lloyd  Department of Plastic Surgery, Texas Children’s Hospital, Houston, TX, USA Michelle L. Lodge  Department Plastic and Reconstructive Surgery, Women’s and Children’s Hospital, Adelaide, Australia Charles Y.Y. Loh  Department of Plastic Surgery, Chang Gung Memorial Hospital, Taiwan Jonathan W.G. Lohn  Department of Plastic Surgery, St Georges NHS Trust, London, UK Fiona MacNeill  Department of Breast Surgery, The Royal Marsden Hospital, London, UK Sanjib Majumder  Department of Plastic Surgery, Pinderfields Hospital, Wakefield, UK Arup Mallik  Department of Clinical Neurophysiology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK

Contributors

Christopher J. Mannion  Oral and Maxillofacial

Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK Mildred Martínez Millán  Rostrum Surgery Center; and University of Valle, Corpus, Colombia Paolo L. Matteucci  Department of Plastic and Reconstructive Surgery, Hull University Teaching Hospitals, Hull, UK Paul McArthur  Department of Plastic Surgery, Whiston Hospital, Liverpool, UK David McCombe  Plastic and Maxillofacial Surgery Department, The Royal Children’s Hospital, Melbourne, Australia Christopher McCormack  Melanoma and Skin Unit, Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne; and University of Melbourne, Melbourne, Australia Emma Rose McGlone  Department of General Surgery, St Georges NHS Trust, London, UK Duncan A. McGrouther  Plastic and Reconstructive Surgery Research, University of Manchester, Manchester, UK Gus McGrouther  Plastic and Reconstructive Surgery, University of Manchester, Manchester, UK Neil McLean  Faculty of Health and Medical Sciences, Department of Surgery, University of Adelaide, South Australia Felicity V. Mehendale  Cleft Lip and Palate Service, East of Scotland, Royal Hospital for Sick Children, Edinburgh, UK Nigel Mercer  Bristol Plastic Surgery, Bristol, UK Rebecca Millican-​Slater  Department of Breast Pathology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Richard Milner  Department of Plastic Surgery, Royal Victoria Infirmary, Newcastle, UK Anuj Mishra  Department of Plastic Surgery, Whiston Hospital, Liverpool, UK Fergal Monsell  Department of Paediatric Orthopaedic Surgery, Bristol Royal Hospital for Children, Bristol, UK Sean Moodley  Department of Plastic Surgery, Groote Schuur Hospital, Cape Town, South Africa Steven F. Morris  Division of Plastic Surgery, Dalhousie University, Halifax, Nova Scotia, Canada Wayne Morrison  Plastic Surgery Department, St Vincent’s Hospital; and Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia Melissa A. Mueller  Department of Aesthetic and Plastic Surgery, University of California, Irvine, CA, USA Maleeha Mughal  Plastic and Reconstructive Surgery Department, Guy’s and St Thomas Hospital, London, UK Marc A.M. Mureau  Department of Plastic and Reconstructive Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands Amanda Murphy  McGill University Faculty of Medicine Jewish General Hospital, Montreal, Quebec, Canada

Alexandra Murray  Burns and Plastic Surgery,

Nottingham University Hospitals NHS Trust, Nottingham, UK Jason Neil-​Dwyer  Department of Plastic Surgery, Nottingham University Hospitals NHS Trust, Nottingham, UK Hiroshi Nishikawa  Department of Plastic and Reconstructive Surgery, Birmingham Children’s Hospital, Birmingham, UK Per F. Nordmark  Department of Hand and Plastic Surgery, Umeå University Hospital, and Department of Integrative Medical Biology, Umeå University, Sweden Naresh Noshi  Oculoplastic Surgeon, BUPA Cromwell Hospital, London, UK Lev N. Novikov  Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Umeå, Sweden Siobhan O’Ceallaigh  Department of Plastic and Reconstructive Surgery, Manchester University NHS Foundation Trust, Manchester, UK Vinidh Paleri  Head and Neck Surgery, The Royal Marsden NHS Foundation Trust, London, UK Athanasios Papas  Department of Plastic Surgery, St Georges Hospital, London, UK Jiten D. Parmar  Oral and Maxillofacial Surgeon, Leeds Teaching Hospitals, Leeds, UK Nicole Paraskeva  Centre for Appearance Research (CAR), University of West of England, Bristol, UK Fiona Peck  Department of Plastic Surgery, Wythenshawe Hospital, Manchester, UK Jonathan Pollock  Department of Plastic Surgery, Nottingham University Hospitals NHS Trust, Nottingham, UK Matthew Potter  Plastic and Reconstructive/​Head and Neck Surgeon, Oxford University Hospital NHS Trust, Oxford, UK Andrea L. Pusic  Plastic and Reconstructive Surgery, Memorial Sloan-​Kettering Cancer Center, New York, NY, USA Mark Puvanendran  Department of Surgery, Mid and South Essex NHS Foundation Trust, Chelmsford, UK Maniram Ragbir  Department of Plastic Surgery, University of Newcastle, Freeman Hospital, Newcastle upon Tyne, UK Rajib Rahim  Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds, UK Kaz M.A. Rahman  Department of Plastic and Reconstructive Surgery, Aberdeen Royal Infirmary, NHS Grampian; and University of Aberdeen, Aberdeen, UK Hinne A. Rakhorst  Plastic and Reconstructive Hand Surgery, Medisch Spectrum Twente, Enschede, The Netherlands David J. Ralph  St Peters Hospital and the Institute of Urology, University College London, London, UK Jeremy Rawlins  Plastic, Reconstructive, and Burns Surgery, Royal Perth Hospital, Perth, Australia Suzanne Rea  Burns Service of Western Australia, Princess Margaret Hospital, Perth, Australia Marcus Reddy  Department of General Surgery, St Georges NHS Trust, London, UK

Carlos E. Restrepo  Department of Surgery, Mayo

Clinic, Rochester, MN, USA

Dirk F. Richter  Department of Plastic Surgery, Holy

Trinity Hospital, Wesseling, Koln, Germany

Birgitta Rosén  Hand Surgery Research Group,

Lund University, Malmö, Sweden

Glenda Rudkin  Specialist Anaesthetic Services,

Adelaide, Australia

Nichola Rumsey  Centre for Appearance Research

(CAR), University of West of England, Bristol, UK David C.G. Sainsbury  Department of Cleft and Plastic Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK Nina Schwaiger  Department of Plastic Surgery, Dreifaltigkeitskrankenhaus, Wesseling, Germany Adam Searle  Plastic and Reconstruction Surgery, HCA Hospitals, UK Mamta Shah  Burns and Plastic Surgery, Royal Manchester Children’s Hospital and University of Manchester, Manchester, UK David J. Shewring  Department of Hand Surgery, University Hospital of Wales, Cardiff, UK Rabin Singh  Department of Oral and Maxillofacial Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK Caroline C. Williams  Newcastle Cleft Lip and Palate Service, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK Gill Smith  Department of Plastic Surgery, Great Ormond Street Hospital, London, UK Ian M. Smith  Department of Plastic Surgery, Leeds Teaching Hospital Trust, Leeds, UK Elliott Smock  Christine M Kleinert Institute for Hand and Microsurgery, Louisville, KY, US Mark Soldin  Department of Plastic Surgery, St Georges Hospital, London, UK Manu Sood  St Andrew’s Centre for Plastic Surgery and Burns, Broomfield Hospital, Chelmsford, UK Ravi F. Sood  Department of Surgery, University of Washington, Seattle, Washington, US Rabindra P. Singh Department of Oral and Maxillofacial Surgery, University Hospital Southampton, UK Kristian Sørensen  Plastic and Reconstructive Surgery, Cairns Hospital, Department of Surgery, Cairns, Queensland Australia John Spillane  Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne; and University of Melbourne, Melbourne, Victoria, Australia Robert J. Spinner  Departments of Neurologic Surgery, Mayo Clinic; and Department of Orthopedics, Mayo Clinic, Rochester, MN, USA Chetan Srinath  Department of Anaesthetics, Leeds Teaching Hospitals NHS Trust, Leeds, UK Graeme Stables  The Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds; and University of Leeds, UK Sami Stagnell  Specialist Oral Surgeon; and Honorary Clinical Lecturer, University of Manchester School of Medicine, Manchester, UK

xxvii

xxviii

Contributors

Harvey Stern  Plastic and Reconstructive Surgery,

Royal Prince Alfred and Strathfield Private Hospitals, Sydney, Australia David Stewart  Hand and Peripheral Nerve Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia Marc C. Swan  Spires Cleft Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Moazzam N. Tarar  Department of Reconstructive Plastic Surgery, Jinnah Hospital, Lahore, Pakistan G. Ian Taylor  Jack Brockhoff Reconstructive Plastic Surgery Research Unit, Department of Anatomy and Neuroscience, University of Melbourne, Melbourne; and Plastic and Reconstructive Surgery Unit, Royal Melbourne Hospital, Melbourne, Australia Trevor Teemul  Department of Trauma and Deformity, Hull University Teaching Hospitals NHS Trust, UK Isabel Teo  Plastic Surgery Unit, Ninewells Hospital, Dundee, UK Niels Thomsen  Department of Hand Surgery, Skåne University Hospital, Malmö, Sweden Kelly Thornbury  Aesthetic Day Surgery, Sydney, Australia David Tighe  Department of Oral and Maxillofacial Surgery, East Kent Hospitals University NHS Foundation Trust, UK Sebastian Trainor  Department of Breast Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Lina Triana  University of Valle, Corpus and Rostrum Surgery Center, Cali, Colombia

Kallirroi Tzafetta  St Andrew’s Centre of Plastic

Surgery and Burns, Broomfield Hospital, Chelmsford, UK Martin J.J. Vesely  Department of Plastic Surgery, St Georges NHS Trust, London, UK Christopher G. Wallace  Royal Devon and Exeter Hospital, Exeter, UK David Wallace  Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK Norman Waterhouse  Plastic Surgery Department, The Aesthetic Plastic Surgeons, London, UK Stewart Watson  Department of Plastic Surgery, Wythenshawe Hospital, Manchester, UK Simon Wharton Dudley Group of Hospitals NHS Foundation Trust, Dudley, West Midlands, UK Iain Whitaker  Reconstructive Surgery and Regenerative Medicine Research Group (ReconRegen), Institute of Life Science, Swansea University Medical School, Swansea; and The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, UK Nicholas White  Department of Craniofacial and Plastic Reconstructive Surgery, Birmingham Children’s Hospital, Birmingham, UK Mikael Wiberg  Section for Hand and Plastic Surgery, Umeå University and Umeå University Hospital, Sweden Dan Wilby  Department of Urology, Portsmouth Hospitals University NHS Trust, Queen Alexandra Hospital, Hampshire, UK Andrew Wilkie  MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

Daniel Wilks  Plastic and Maxillofacial Surgery

Department, The Royal Children’s Hospital, Melbourne, Australia Greg Williams  Farjo Hair Institute, London, UK Nicholas Wilson Jones  The Welsh Centre for Burns and Plastic Surgery, Swansea, Canada Thomas J. Wilson  Centre for Peripheral Nerve Surgery, Stanford University, Palo Alto, CA, USA Ian Winson  Department of Orthopaedic Surgery, North Bristol NHS Trust, Bristol, UK Robert Winterton  Department of Plastic Surgery, Manchester University Foundation Trust, Manchester, UK James Wokes  Department of Plastic and Reconstructive Surgery, University Hospital North Durham, Durham, UK Dan Wood  Department of Urology, University College Hospital, London, UK Fiona Wood  Burn Service, University of Western Australia, Perth, Western Australia, Australia Thomas C. Wright  Department of Reconstructive Plastic Surgery, North Bristol NHS Trust, Bristol, UK Alan Yates  Paediatric Anaesthetist, Leeds Teaching Hospitals NHS Trust, Leeds, UK Ivan Zammit-​Maempel  Department of Radiology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK Christophe Zirak  Plastic Surgery Department, CHU Brugmann-Site Victor Horta, Brussels, Belgium

Symbols and abbreviations ~ approximately > greater than < less than 2PD two-​point discrimination 3D three-​dimensional 5FU fluorouracil ABPI ankle–​brachial pressure index AC alternating current ACh acetylcholine ACPGBI Association of Coloproctology of Great Britain and Ireland ACS abdominal compartment syndrome ADM acellular dermal matrix AER apical ectoderm ridge AGB adjustable gastric banding AKA above-​knee amputation ALCAR acetyl-​ l-​carnitine ALT anterolateral thigh AMH anti-​Müllerian hormone AP action potential APB abductor pollicis brevis APC antigen-​presenting  cell APE abdominoperineal excision APL abductor pollicis longus AR acute rejection ASCO American Society of Clinical Oncologists ASIS anterior superior iliac spine ATLS® Advanced Trauma Life Support® BAPRAS British Association of Plastic, Reconstructive and Aesthetic Surgeons BCC basal cell carcinoma BCS body contouring surgery or breast-​conserving surgery BDD body dysmorphic disorder BKA below-​knee amputation BMI body mass index BMP bone morphogenetic protein BOA British Orthopaedic Association BoNT botulinum toxin BPD biliopancreatic diversion BPD-​BS biliopancreatic diversion by duodenal switch BWL body weight loss CCJ calcaneocuboid joint CEA cultured epithelial autograft CFNS craniofrontonasal syndrome CI confidence interval

CL(P) cleft lip with or without cleft palate CLP cleft lip with cleft palate CMAP compound muscle action potential CMCJ carpometacarpal joint CMV cytomegalovirus CN cranial nerve CNS central nervous system CO carbon monoxide COX cyclooxygenase CPSP chronic post-​surgical pain CR chronic rejection CRPS complex regional pain syndrome CRT chemoradiotherapy CSF cerebrospinal fluid CSN cleft specialist nurse CST component separation technique CT computed tomography CTA computed tomography angiography CTS carpal tunnel syndrome DASH Disability of the Arm, Shoulder and Hand DAT deep adipose tissue DC direct current DCIA deep circumflex iliac artery DHT dihydrotestosterone DIE deep inferior epigastric DIEA deep inferior epigastric artery DIEP deep inferior epigastric perforator DIPJ distal interphalangeal joint DISI dorsal intercalated segment instability pattern DRG dorsal root ganglion DRUJ distal radioulnar joint DSA donor-​specific anti-​HLA antibodies DSD disorder of sex development DSEA deep superior epigastric artery DSM Diagnostic and Statistical Manual of Mental Disorders DVT deep vein thrombosis EBC early breast cancer EBV Epstein–​Barr  virus ECM extracellular matrix ECRB extensor carpi radialis brevis ECRL extensor carpi radialis longus ECU extensor carpi ulnaris EDM extensor digiti minimi EIP extensor indicis proprius ELAPE extralevator abdominoperineal excision

xxx

Symbols and abbreviations

EMG electromyography EMSB Emergency Management of Severe Burns END elective neck dissection EORTC European Organisation for Research and Treatment of Cancer EPB extensor pollicis brevis EPL extensor pollicis longus EPUAP European Pressure Ulcer Advisory Panel ESPEN European Society for Parenteral and Enteral Nutrition EWL excess weight loss FCR flexor carpi radialis FCU flexor carpi ulnaris FDG fluorodeoxyglucose FDP flexor digitorum profundus FDS flexor digitorum superficialis FFA free fatty acid FFMT free functional muscle transfer FGF fibroblast growth factor FNAC fine-​needle aspiration cytology FND frontonasal dysostosis FPB flexor pollicis brevis FPHL female pattern hair loss FPL flexor pollicis longus FTSG full-​thickness skin graft FUE follicular unit extraction GA general anaesthetic GAP glans approximation procedure GDFT goal-​directed fluid therapy GHJ glenohumeral joint GIC gender identity clinic GMC General Medical Council GRS gender reassignment surgery H&E haematoxylin and eosin HA hyaluronic acid hCG human chorionic gonadotrophin HF hydrofluoric acid HIV human immunodeficiency virus HLA human leucocyte antigen HNPP hereditary neuropathy with pressure palsies HPV human papillomavirus IAP intra-​abdominal pressure IASP International Association for the Study of Pain ICP intracranial pressure ICU intensive care unit IGAP inferior gluteal artery perforator IJV internal jugular vein IL interleukin IMF inframammary fold or intermaxillary fixation IMRT intensity-​modulated radiation therapy IPJ interphalangeal joint IR inflammatory response IV intravenous IVV intravelar veloplasty KTP potassium titanyl phosphate K-​wire Kirschner  wire LA local anaesthetic LCNT lateral cutaneous nerve of the thigh

LEAP Lower Extremity Assessment Project LRINEC Laboratory Risk Indicator for Necrotizing Fasciitis LRTI ligament reconstruction and tendon interposition MAGPI meatoplasty and glanuloplasty MAP mitogen-​activated protein MCPJ metacarpophalangeal joint MDT multidisciplinary team MESS Mangled Extremity Severity Score MFD mandibulofacial dysostosis MHC major histocompatibility complex MMF mycophenolate mofetil MPHL male pattern hair loss MPNST malignant peripheral nerve sheath tumour MRA magnetic resonance angiography MRC Medical Research Council MRI magnetic resonance imaging MRSA methicillin-​resistant Staphylococcus aureus MSDS material safety data sheet MSSA methicillin-​sensitive Staphylococcus aureus MTZ microthermal treatment zone MWL massive weight loss NAC N-​acetyl-​cysteine or nipple–​areolar complex NACT neoadjuvant chemotherapy NAM nasoalveolar moulding NCS nerve conduction study Nd:YAG neodymium-​doped yttrium aluminium garnet NF neurofibromatosis NHS National Health Service NICE National Institute for Health and Care Excellence NISSSA Nerve injury, Ischaemia, Soft tissue injury, Skeletal injury, Shock, and Age NK natural killer NMDA N-​methyl-​d-​aspartate NMSC non-​melanoma skin cancer NOE naso-​orbitoethmoid NPUAP National Pressure Ulcer Advisory Panel NPWT negative pressure wound therapy NSAID non-​steroidal anti-​inflammatory  drug OAVS oculo-​auriculo-​vertebral spectrum OBPP obstetric brachial plexus palsy OM occipitomental OMT Oberg, Manske and Tonkin OPSCC oropharyngeal squamous cell cancer OPT orthopantomogram OR odds ratio ORIF open reduction and internal fixation ORL oblique retinacular ligament PA posteroanterior PAP profunda artery perforator PCR polymerase chain reaction PDL pulsed dye laser PDT photodynamic therapy PET positron emission tomography PIA posterior interosseous artery PIN posterior interosseous nerve PIPJ proximal interphalangeal joint PL palmaris longus PNF percutaneous needle fasciotomy

Symbols and abbreviations

PNS PONV PROM PRUJ PSIS PUPS PVB PVL QOL RA RCL RCM RCT REE RFFF ROOF RR RRA SA SAT SCIA SCIV SCPRT SEAP SEPA SF-​36 SGAP SIEA SIEV SIP SIRS SLAC SLE SMA SMAS SMCP SNAP SNB SND SOOF SOT SSG

peripheral nervous system postoperative nausea and vomiting patient-​reported outcome measure proximal radioulnar joint posterior superior iliac spine periumbilical perforator-​sparing paravertebral block Panton–​Valentine leucocidin quality of life regional anaesthetic or retinoic acid radial collateral ligament reflectance confocal microscopy randomized controlled trial resting energy expenditure radial forearm free flap retro-​orbicularis oculi fat relative risk radioiodine remnant ablation Staphylococcus aureus superficial adipose tissue superficial circumflex iliac artery superficial circumflex iliac vein short-​course preoperative radiotherapy superior epigastric artery perforator superficial external pudendal artery 36-​Item Short Form Survey superior gluteal artery perforator superficial inferior epigastric artery superficial inferior epigastric vein Sickness Impact Profile systemic inflammatory response syndrome scapholunate advanced collapse systemic lupus erythematosus smooth muscle actin superficial musculoaponeurotic system submucous cleft palate sensory nerve action potential sentinel node biopsy selective neck dissection suborbicularis oculi fat solid organ transplantation split-​skin  graft

SSRO sagittal split ramus osteotomy STSG split-​thickness skin graft STT scaphotrapeziotrapezoid STTJ scaphotrapeziotrapezoid joint T2DM type 2 diabetes mellitus TAC temporary abdominal closure TAP transversus abdominis plane TB tuberculosis TBSA total body surface area TDAP thoracodorsal artery perforator TFCC triangular fibrocartilage complex TFL tensor fascia lata TIP tubularized incised plate TKA through-​knee amputation TMG transverse myocutaneous gracilis TMJ temporomandibular joint or trapeziometacarpal joint TMTJ tarsometatarsal joint TNF tumour necrosis factor TNJ talonavicular joint TORS transoral robotic surgery TOS thoracic outlet syndrome TRAM transverse rectus abdominis myocutaneous TUG transverse upper gracilis UADT upper aerodigestive tract UBL upper body lift UCL ulnar collateral ligament UICC Union for International Cancer Control UV ultraviolet VCA vascularized composite allotransplantation VIN vulval intraepithelial neoplasia VISI volar intercalated segmental instability VPD velopharyngeal dysfunction VRAM vertical rectus abdominis musculocutaneous VTE venous thromboembolism WHO World Health Organization WLE wide local excision WPATH World Professional Association for Transgender Health ZF zygomaticofrontal suture ZPA zone of polarizing activity

xxxi

SECTION 1

General principles and techniques Section editors: Simon Kay, David McCombe, and Daniel Wilks

1.1 General principles and techniques  3 Simon Kay and David McCombe

1.9 Microsurgery  51 David McCombe and Wayne Morrison

1.2 Tissue healing  7 Gus McGrouther

1.10 Benign skin conditions and tumours  61 Rajib Rahim and Graeme Stables

1.3 Infections  13 Donald Dewar

1.11 Non-​melanoma skin cancer and premalignant conditions  69 Barbara Jemec and Gregor B.E. Jemec

1.4 Structure and function of the skin  21 Mark Goodfield 1.5 Vascular anatomy  25 Amanda Murphy, Steven F. Morris, and G. Ian Taylor

1.12 Pigmented lesions and melanoma including premalignant conditions  79 Michael Henderson, John Spillane, David Gyorki, and Christopher McCormack

1.6 Anaesthesia  31 Chetan Srinath and Alan Yates

1.13 Wound dressings  91 David Stewart

1.7 Skin grafts  35 Siobhan O’Ceallaigh and Mamta Shah

1.14 Sarcoma  95 Ian M. Smith and Vinay Itte

1.8 Skin flaps  39 Donald Dewar

1.15 Vascularized composite allotransplantation  105 Daniel Wilks and Simon Kay

1.1

General principles and techniques Simon Kay and David McCombe

Introduction Plastic surgery pursues the amelioration of acquired or congenital defects, to restore both function and form. Uniquely among surgical specialties, plastic surgery is defined by concept rather than by tissue or anatomical region. The concepts and techniques that are its foundation may be applied throughout the body irrespective of tissue type, to reconstruct or repair deficiencies resulting from trauma, disease, or birth defects. To the uninformed, it appears a solely technical specialty, but in truth, the interactions between form, function, and human behaviour are so intimate that diagnosis and treatment must consider each of these aspects. In particular, it requires a detailed understanding of human behaviour and its variants in a wide variety of circumstances to treat the individual effectively. These words of Harvey Cushing were prescient for the newly emerging discipline of plastic surgery: ‘A physician is obligated to consider more than a diseased organ, more than even the whole man, he must view the man in his world’ (Dubos, 1965, p. 342).

General principles Basic principles of technical practice underpin plastic surgery, and once grasped allow a structured and individualized approach to a great diversity of clinical problems. Ambroise Paré proposed the following principles in the sixteenth century: ‘There are five duties of surgery: to remove what is superfluous, to restore what has been dislocated, to separate what has grown together, to reunite what has been divided, and to redress the defects of nature’ (Porter, 1999, p. 188). Almost five hundred years later, despite advances in techniques, these principles still offer a succinct approach to each reconstructive challenge. Plastic surgery techniques have been garnered from many allied disciplines and many nations. The First World War (1914–​1918) was the first mechanized war, deploying high explosives and prodigious armament by newly emerged military–​industrial complexes. Trench warfare created the unique new injuries of high-​velocity facial wounds. Following on from the then-​recent developments in the knowledge of skin grafting in the late nineteenth century, these injuries proved fertile pabulum for the incubation of new techniques

of tissue repair and restoration. In Paris, Hippolyte Morestin at the Val de Grace Hospital established a specialized unit for managing these wounds with innovative flap and grafting procedures. So prevalent were these facial injuries that the patients became known as Gueules Casseés, and at the Congrés de la Paix in Versailles were on show as emblematic of the damage France’s young men had suffered (Monestier, 2009). This exposure served greatly to draw popular attention to the role of reconstructive surgery, and this public fascination has scarcely waned since, perhaps in part because of the arresting nature of the imagery, the empathy that mutilation induces, and the novelty of surgical ingenuity. Morestin inspired Harold Gillies, a New Zealander and otolaryngologist in the British Army, who was faced with the challenge of these post-​traumatic deformities in Allied soldiers. Gillies had been charged with the supervision of Auguste Valadier, a Franco-​American dental surgeon in Paris, who had taken upon himself the treatment of facial wounds in Allied troops at camps near Boulogne. It is likely that Valadier introduced Gillies to Morestin, by then already a legend in Parisian surgery. Although Gillies and Morestin met only briefly (and parted, it seems, with some rancour), Gillies was so inspired by Morestin’s skill and courage in facial surgery that he immediately set himself to learn and advance such techniques. He appreciated the need for specialized centres and expertise to treat these wounded combatants, and promoted many principles of reconstruction during these years. These were codified by his paying student, the American surgeon Ralph Millard (Gillies and Millard, 1957), into 33 principles grouped into Preparational, Executional, Innovational, Contributional, and Inspirational categories (Box 1.1.1). It is axiomatic in all medical intervention that before treatment can be prescribed, a diagnosis must be made and that with that diagnosis the natural history of the condition be understood in order that a prognosis can be estimated. Only then can the benefits and demerits of a proposed treatment be weighed against the consequences of inaction. Surprisingly, this is no different for plastic surgery and many new surgeons underestimate the value of this fundamental discipline, believing these steps to be self-​evident in matters of appearance, for instance. Some reflection will reveal that even in the ‘obvious’ cases of an elderly male with a rodent ulcer of the face or a teenager with a prominent nose, the sequence of diagnosis, prognosis, and treatment planning can create some unexpected considerations.

4

SECTION 1  General principles and techniques

Box 1.1.1  Gillies’ principles of plastic surgery Preparational principles • Correct the order of priorities. • Aptitude should determine specialization. • Mobilize auxiliary capabilities. • Acknowledge your limitations so as to do no harm. • Extend your abilities to do the most good. • Seek insight into the patient’s true desires. • Have a goal and a dream. • Know the ideal beautiful normal. • To be familiar with the literature • Keep an accurate record. • Attend to physical condition and comfort of position. • Do not underestimate the enemy. Executional principles • Diagnose before treating. • Return what is normal to normal position and retain it there. • Tissue losses should be replaced in kind. • Reconstruct by units. • Make a plan, a pattern, and a second plan (a lifeboat). • Invoke a Scot’s economy—​don’t discard tissue until it is certain that it won’t be needed. • Use Robin Hood’s tissue apportionment—​use excess tissue from one area to reconstruct deficits in another area. • Consider the secondary donor site. • Learn to control tension. • Perfect your craftsmanship. • When in doubt, don’t. Innovational principles • Follow up with a critical eye. • Avoid the rut of routine. • Imagination sparks innovation. • Think while down and turn a setback into a victory. • Research basic truths by laboratory experimentation. Contributional principles • Gain access to other specialties’ problems. • Teaching our specialty is its best legacy. • Participate in reconstructive missions. Inspirational principles • Go for broke. • Think principles until they become instinctively automatic in your modus operandi. Source data from Gillies HM, Millard DR. The Principles and Art of Plastic Surgery. Boston, MA: Little, Brown and Co., 1957.

At the core of the principles of plastic surgery is the formulation of an individual management plan for the patient. Plastic surgery often offers several possible solutions for a problem. The process of matching a technique to a patient requires assessment of the relevant characteristics of the patient, the pathology, and the treatment options available. Two further valuable axioms all plastic surgeons learn eventually is that the indication for surgery of appearance is related to the extent of distress of the patient, and that the extent of that distress is not necessarily proportional to the degree of deformity: a potential hazard for the unwary! To elaborate further, when a patient requests surgery to improve appearance (larger breasts, more symmetrical ears, a less haggard face, for example) only the

inexperienced surgeon will accept the presence of that characteristic together with the patient’s request as the indication for surgery. Instead, an experienced surgeon will direct herself to discover how much the appearance distresses the patient, and perhaps why, for how long, and what it is that has provoked this reaction. Surprising answers are often revealed, answers which may redirect the therapeutic effort, may draw in other expert advice, and may serve to understand how likely the expectations of the patient are to be met.

The patient From the foregoing it can be appreciated that an apparently simple request may disguise a complex behavioural problem that has lain unaddressed often for many years. For the patient also, plastic surgery solutions for appearance may be misleadingly simple, belying the technical complexity needed to achieve the desired result and the concomitant potential for an unexpected outcome. Much of plastic surgery is surface surgery, and every patient is an expert in the appearance of their surface, or at the very least has a strong opinion on their appearance. Errors by the surgeon and complications in the surgical area are all on view in contrast to cavity surgery. For these reasons, much effort must be put into understanding the patient’s request and expectations and then into conveying the surgeon’s proposals, likely outcomes, and what will by agreement define success. Patient motivation and compliance during the recovery and rehabilitation period are less tangible but equally important characteristics. Given that a significant proportion of plastic surgery is elective and aimed at improving quality of life, the motivation of the patient and likelihood of acceptance of the proposed treatment and its outcome is a specific and important part of the analysis of the patient and planning of treatment. The field of plastic surgery is strewn with technical successes that are viewed by the patient as failures. The patient’s capacity and enthusiasm for the demanding rehabilitation often required after complex reconstructive procedures is necessary to achieve the desired result. The surgeon may seek help in determining whether the patient has the capacity to understand what is proposed, to cooperate with care, and to cope with an unintended outcome. Where the patient is a child, and consent to care lies with those with parental responsibility, this determination becomes yet more demanding and often multidisciplinary input is required (see Chapter 13.6). Patient comorbidities can compromise wound healing and/​or tissue regeneration, and hence the outcome of surgery. These can be grouped into congenital and acquired conditions. Congenital conditions that affect wound healing are rare but include conditions affecting the connective tissues and skin such as Ehlers–​ Danlos syndrome, pseudoxanthoma elasticum, progeria, cutis laxa, Werner syndrome, and epidermolysis bullosa. Acquired conditions that affect wound healing are far more common. It is necessary to address these conditions if the comorbidity is reversible and the timing of treatment allows. If not, then the effect of these conditions upon wound healing and likely success of the proposed treatment needs to be considered. The following are the more common of these conditions to consider: advanced age, obesity, malnutrition, immobility, diabetes, autoimmune diseases, disorders of immunity, advanced cancer, smoking, and specific pharmacotherapy such as immunosuppression, chemotherapy, and glucocorticoids.

1.1  General principles and techniques

The pathology

Non-​operative techniques

Plastic surgery repairs tissues or reconstructs defects, each of which may result from pathology or trauma, or may be generated by the extirpation of a pathological condition. Here, the concept of a defect also applies to congenital differences, and is extended to encompass the exchange of a natural but unwanted form for a more desired or self-​affirming form in aesthetic surgery. Local factors need to be considered in planning treatment. The surgeon has to consider the site of the pathology and the possible adverse influence of local tissue conditions that may include:

Non-​operative techniques can be used either to heal the wound or to prepare the wound for surgery. Wound dressings are active forms of treatment of open wounds and aim to prevent or reduce wound contamination and to provide an ideal environment for the biology of healing. The plastic surgeon’s expertise and regular involvement is required in wound assessment and formulating a plan for specific dressing regimens, rather than abdicating responsibility for this to nursing staff and wound consultants (mystically named tissue viability consultants in some systems). The choice of wound dressing will depend on the characteristics of the wound and is discussed in detail in Chapter 1.13. Hyperbaric oxygen therapy involves the exposure of the patient to increased oxygen levels at elevated pressure to increase the arterial oxygen concentration. The usual indication for hyperbaric oxygen therapy is the treatment of decompression sickness or Caisson disease; however, benefit has been shown in the treatment of radiation-​ induced injury such as osteoradionecrosis. It has also been applied in the treatment of both acute and chronic wounds, particularly complex wounds where there is an element of ischaemia. The mechanisms of action of hyperbaric oxygen include improved fibroblast and leucocyte function, mediated in part at least by increased concentrations of oxygen free radicals.

• ​ The anatomical site—​areas in the distal lower limb and areas subject to pressure or shear in the immobilized patient may show impaired healing. • ​ Coexistent peripheral vascular disease—​arterial disease, chronic venous insufficiency or lymphoedema all compromise tissue perfusion and wound healing. • ​ Previous radiotherapy—​due to the alteration of local vascularity and impaired healing and angioneogenesis. • ​ Significant wound contamination or local crush or shearing injury in traumatic wounds predisposes the wound to local tissue ischaemia and infection. • ​ Coexistent infection or quiescent infection such as osteomyelitis. • ​ Denervation—​wounds in denervated tissue are slow to heal and given the lack of protective sensation, are prone to pressure necrosis, local ischaemia, and infection.

The treatment options The initial phase of treatment may include resection of a lesion or debridement of a wound. It may also require recreation of an original defect by the release of contracted scar, or repositioning of the components of a congenital or post-​traumatic deformity. In times past, selecting a wound closure technique meant working sequentially through a hierarchy based on complexity, beginning with direct wound closure, escalating through use of a graft, and culminating in the choice of a local flap, a regional flap, or a distant flap including flaps transferred by microvascular surgery—​free flaps. This is referred to as the reconstructive ladder and was originally conceived to incline surgeons towards the simplest effective option in order to avoid the attendant risks of more complex procedures. Now that many of the risks can be mitigated, the procedures are more and more reliable, and the concept of choice has given patients a firm role in decision making. Nonetheless, the ladder is useful to remind one that it pays to consider simple options first, only moving up the ladder if the benefits outweigh other considerations. When the surgical goal is reconstruction rather than repair, the ladder is less useful as considerations of tissue matching, structure, and form assume priority. The treatment plan concludes with establishing postoperative management and rehabilitation programmes and the facility for assessment and documentation of the outcome of treatment.

Wound management The practice of plastic surgery requires understanding and skill in the application of both non-​operative and operative techniques.

Operative techniques The creation and repair of complex wounds defines plastic surgery. The techniques of wound incision, wound debridement, and wound closure must be mastered by all plastic surgeons. Wound incisions in elective procedures are designed to allow adequate exposure of the underlying structures, to minimize the risk of postoperative contracture and to optimize the appearance of the scar. The determinants of scar quality include intrinsic factors such as racial heritage, any inherited tendency to adverse scarring (e.g. keloid), the anatomical site (e.g. the volar forearm and the presternal and preclavicular regions are prone to hypertrophic scarring), and surgical factors including the orientation of the scar, the tension on the wound as it heals, the choice of suture material, and avoiding complications such as wound dehiscence, wound edge necrosis, and infection. Scars are minimized if placed in the lines of relaxed skin tension (Borges, 1984), which correspond to skin creases, or if placed in the junctions of facial subunits. Wound debridement is required in the traumatic wound to remove contamination and non-​viable tissue to convert the wound to a clean wound amenable to closure. Where the traumatic wound has been heavily contaminated or there is a crush injury with questionable viability of the tissues, a second-​look procedure may be required 24 hours after the initial debridement to reassess tissue viability and the adequacy of debridement. In this situation, the use of vacuum-​assisted closure dressings (see Chapter 1.13) are a useful adjunct to wound management. Wound closure aims to bring the wound edges together without tension with obliteration of underlying dead space where present. This can be achieved either by direct closure or importation of tissue by grafting, tissue expansion, or flap transfer. Regardless of the technique employed, it is ultimately important to close the skin accurately by everting the wound margins to appose the dermis. A variety of suture techniques and adjuncts such as skin staples, skin adhesive, and tapes can be applied according to site and skin type.

5

6

SECTION 1  General principles and techniques

Beyond these steps, reconstruction requires the repositioning or replacement of tissues. Differentiated autologous tissue of any type—​ skin, bone, nerve, fat, or fascia—​may be imported as either a graft or a flap. A graft is detached from its donor site and attached to the recipient site. There the graft survives (see Chapter 1.7) by a common process of tissue nutrition, initially by imbibition of oxygen and nutrients from the wound bed, and concurrent inosculation—​the ingrowth of new blood vessels which link with the micro-​vessels in the graft to establish a circulation. This process is common to all free grafts, and any interference with any of these steps results in graft failure. Thus, a graft will not survive if the wound bed is unable to support angioneogenesis and the process of inosculation (e.g. if the wound bed is avascular, or irradiated, or if infection or haematoma intercede between the bed and the graft). By contrast, tissue may also be transferred with its blood supply intact at the end of surgery. The first such transfers were of flaps of skin, and so the transferred tissue is commonly referred to as a flap, whatever its origin or architecture. Such flaps may never have their blood flow interrupted, or may be transferred in a temporary arrangement (pedicled flaps) and

have their donor blood supply divided when the recipient site has established a new alternative source of blood supply. In microsurgical free tissue transfer, the re-​establishment of this recipient alternative blood supply is complete by the end of surgery, so shortening the process of transfer and ensuring robust tissue viability. Exogenous biological tissue or alloplastic material can also be implanted to restore structure or volume with individual characteristics attributable to the various materials available.

REFERENCES Borges AF. Relaxed skin tension lines (RSTL) versus other skin lines. Plast Reconstr Surg 1984;73:144–​50. Dubos RJ. Man Adapting. New Haven, CT: Yale University Press, 1965. Gillies HM, Millard DR. The Principles and Art of Plastic Surgery. Boston, MA: Little, Brown and Co., 1957. Monestier M. Les Gueules Cassées. Paris: Le Cherche Midi, 2009. Porter R. The Greatest Benefit to Mankind:  A Medical History of Humanity. New York: WW Norton and Company, 1999.

1.2

Tissue healing Gus McGrouther

Tissues heal, unless there is a reason not to! In managing wounds, an understanding of the biology that promotes healing and the pathology which limits it will allow a more logical and scientific approach to intervention. Healing is a natural process which the body has evolved to do and the skill of the surgeon is to understand and anticipate events and intervene to improve the functional and aesthetic outcome. The knowledge base of the science of wound healing has now so advanced that the time has come to review the traditional concept of the three stages of wound healing, namely inflammation, proliferation, and remodelling.

Stages of wound healing What do we mean by inflammation? Inflammation is in fact a whole sequence of events at molecular and cellular levels giving some explanation of the cardinal signs described by Celsus: calor, dolor, rubor, and tumour. The first event within seconds to minutes is neural inflammation which can be demonstrated by firm stroking of the skin—​the author refer to Lewis’s triple response of erythema, surrounding blanching, and then a wheal (Lewis and Grant, 1924; Reed et al., 1961), thought by Lewis himself to be an axon-​mediated reflex, involving what he termed H substance (suspecting it to be histamine release) but not yet fully explained in terms of local cellular response to trauma. Heavy-​handed use of the marking pen at operation may be enough to set this off. As the scalpel blade passes in to the dermis, it reaches the critical level beyond a scratch where bleeding occurs. Superficial dermal injury at this depth such as in a scald may heal without a scar as shown by Dunkin and colleagues (2007) who made scratches of graduated depth in volunteers. Passing on down through the dermis, bleeding is more apparent and platelets attracted to the scene release cytokines which start a whole sequence of events with endothelial adhesion, capillary permeability, and leucocyte, predominantly neutrophil, trafficking in to tissue (Sumagin and Sarelius, 2013). Neutrophils are important players at this stage as they degranulate showing little respect for tissue integrity as their enzymes soften connective tissue matrix (Fields, 2013). The different microcompartments of

our body tissues, cells, and organelles contain countless molecules which will cause reactive changes when released from their proper containment. The main players are the neutrophils which have apparently evolved for the limited role of protecting us from surface wounds and bacterial infection of airways or gut, and certainly not for twenty-​first-​century surgery. Although often considered beneficial, much inflammatory activity is redundant for elective wounds and can even be potentially fatal in large wounds (Kaukonen et al., 2015). As the surgeon’s blade proceeds through the various layers of a wound, it must be appreciated that unwanted inflammation can be limited by careful tissue handling, minimal invasiveness, avoiding blood and fluid collection, and minimizing the coagulation of electrocautery. Moreover, the desiccating effect of the heat of the theatre lights on the entire surface of the wound is to be avoided by keeping the wound moist. Inflammation is generally excessive for any contribution to the healing of surgical wounds as shown by mice lacking the transcription factor PU.1 which lack leucocytes yet still are able to heal wounds (Martin et al., 2003). Much is now known about the factors that promote inflammation in wound healing (Eming et al., 2014) but to date, it is not clear if inflammation eventually fades due to a lack of promoting factors or whether there are specific mechanisms that reverse it (Headland and Norling, 2015).

Proliferation—​what and where? The second healing stage, proliferation, has become a significant misnomer as the old-​fashioned belief that wounds heal by just proliferation of marginal cells has been turned over by modern understanding of stem cells. The key is that only some cells have an ability to mount a proliferative (healing) response and these stem or precursor cells may come from a local ‘niche’ (Marthiens et al., 2010) or alternatively by haematogenous transport from bone marrow. Epidermis appears to have stem cells in its basal layer which certainly proliferate as a physiological process but apparently to a greater extent adjacent to wound margins under the control of cytokines (Daniels et al., 2003) and we have long known that periosteum is a source for cellular repair for bone. There is less certainty about the location of the stem cell niche for healing of tendon muscle and fascia but the pericytes in vascular adventitia have been a considerable focus of attention as a stem cell source (Bobryshev et al., 2015),

8

SECTION 1  General principles and techniques

although bone marrow-​derived mesenchymal stem cells also participate in tissue healing (Rodriguez-​Menocal et al., 2015). When a break is established in skin, keratinocytes will move to fill the gap by pseudopodial creeping. And so what of the potential space between epithelium and bone? This is perhaps the most interesting evolutionary trick as all exposed, but vascularized, tissues in the ‘wound bed’ will rapidly mount an angiogenic response to produce granulation tissue, visible within 24–​48 hours. This has two principal components—​vessel loops and fibroblasts—​and the fight for dominance between these components will determine whether there is more fibroblast dominance resulting in wound contraction or more vascular tissue resulting in an outgrowth of pyogenic granuloma. Fibroblasts are very sensitive to physical forces (Eastwood et  al., 1998) and after wounding they will lay down collagen in a pattern determined by the strain on individual fibroblastic cells. This was well illustrated in a study of the stretched scar by Sommerlad and Creasey (1977) who demonstrated that the initial fibrin provisional matrix was laid down along the wound but on suture removal the wound tended to gap and subsequent collagen deposition was transverse. This was an excellent model of the scar architecture resulting from healing by primary intention. The cellular response to strain has been confirmed by Starborg and colleagues (2013) who have shown the mechanisms of collagen deposition at a molecular level, each fibroblast laying down collagen along the lines of strain experienced by that individual cell.

Remodelling—​according to the map of physical forces on the wound and scar Remodelling is a later event in tissue healing and is most apparent when wounds either heal and scar or fail to heal and become chronic. These seemingly diverse outcomes have certain common characteristics as the prolonged time frame brings in to play mechanical influences. The wound bed events are more complex in a wound which is described as healing by secondary intention, a term which confused me as a young houseman but effectively means a requirement to bridge a gap. In this situation the wound bed can be visualized as a battlefield between forces tending to close the wound and forces tending to open it. The closing force is predominantly fibroblastic contraction although joint positioning may help. By contrast, unfavourable joint positioning may become an opening force but the major opening force is that of the skin’s elastic retraction. This elastic behaviour was noticed by Baron Dupuytren, involved in a medico-​ legal discussion of an assault case where it was alleged that an assailant was accused of inflicting a wound with a round instrument but presented a defence that the wound was in fact a longitudinal slit. Dupuytren noted that such a slit wound could be inflicted by a round instrument as the skin had a preferred fibre and elastic orientation. Karl Langer went on to describe the lines of skin ‘cleavability’ in cadaveric studies which have been adopted as lines of surgical election (translated by Gibson, 1978). The exact direction of these lines has been controversial with different orientations being illustrated by different authors. Bush and colleagues (2007) have investigated the dynamic movement of these lines on skin movements such as different facial expressions where the lines may change direction by up to 90 degrees. It is suggested that in the areas where Langer’s lines rotate through a large angle in different postures, that it is most difficult to obtain a good (minimal) scar from surgery. Bush’s technique was to punch out a round hole and then to look at the amount

of gape in various directions (Bush et al., 2008). Curiously, it was found that punching out a small defect (135

0

110–​135

1

135

0

1.4). 3. Severe systemic infection or infection at the site of the block. 4. Untreated hypovolaemia.

Complications of regional anaesthesia 1. Post-​dural puncture headache. 2. Nerve injuries—​temporary or permanent. 3. High spinal and total spinal:  spinal anaesthesia ascending to higher levels can result in hypotension, bradycardia, apnoea, and unconsciousness. 4. Epidural haematoma: this is very rare after spinal/​epidural anaesthesia and the majority of the reported cases are in patients with coagulopathy. 5. LA toxicity.

Peripheral nerve blocks These involve the deposition of LA around a nerve plexus or individual nerve(s) to provide anaesthesia or analgesia to a specific area of the body. Multiple nerve blocks and approaches have been described which include the commonly performed blocks shown in Table 1.6.4. Ultrasound-​ guided nerve blocks are the accepted standard for regional anaesthesia (National Institute for Health and Care Excellence, 2009). The main advantages of ultrasound-​guided nerve blocks are seeing the needle in real time and confirmation of spread of the LA around the nerve(s). Ultrasound-​guided nerve block lowers the mean volume of LA required to produce an effective block and can result in faster onset and longer duration of blockade. Ultrasound also decreases the block performance time and reduces the incidence of vascular puncture.

General anaesthesia This is a state of unconsciousness achieved by drugs for the purpose of performing an operative procedure. Preoperatively the anaesthetist assesses the patient and explains the anaesthetic procedure, side effects, and risks. High-​risk patients may require special investigations to stratify risk and minimize them. Induction of general anaesthesia can be achieved by intravenous or inhalational agents. Intravenous induction is the more common, inhalational induction being more often used in children. Either an endotracheal tube or a laryngeal mask airway is used to maintain the airway during anaesthesia. Anaesthesia is then maintained by inhalational agents where depth of anaesthesia can be assessed by the minimum alveolar concentration value (vapour concentration needed to prevent movement in 50% of subjects in response to surgical stimulation). Alternatively, intravenous agents can also

1.6 Anaesthesia

Table 1.6.3  Central neuraxial blockade techniques Technique

Spinal

Epidural

Caudal

Site of drug injection

Within the cerebrospinal fluid (intrathecal)

Extradural (outside the dura)

Extradural

Indications

Surgical procedures below the level of umbilicus

Thoracic, abdominal, and lower limb procedures

Abdominal and lower limb procedures in children

Uses

Anaesthesia and analgesia

Mainly analgesia—​usually with general anaesthetic

Analgesia in children—​with general anaesthetic

Advantages

Quick onset (2–​5 min) Dense block Small volume of drug required (2–​4 mL)

Used as an infusion—​long duration Less motor block Large volume of the drug required (20–​30 mL)

Less effects on cardiovascular system and respiratory system

Disadvantages

Limited duration (2–​3 hours)

Slow onset (20–​30 min)

Slow onset

maintain anaesthesia as in total intravenous anaesthesia. Analgesia is provided mainly by opioids and supplemented by paracetamol and non-​steroidal anti-​inflammatory drugs. Regional anaesthesia can be combined with general anaesthesia to minimize the need for opioids. In the immediate postoperative period, patients are managed in a recovery area until fit for discharge to the ward. Further analgesia, antiemetics, and fluids are given as needed.

Anaesthesia for free tissue transfer The authors are of the strong opinion that the primary determinant of the success or failure of free tissue transfer is the surgical design and technique of vascular anastomosis and whereas good anaesthesia optimizes patient physiology, it can do little to rescue suboptimal surgical technique. The converse of course also applies. Free tissue transfers are subject to at least one ischaemic episode. Primary ischaemia occurs due to vessel clamping as part of flap harvesting while secondary ischaemia occurs after the flap is transferred either due to arterial or venous hypoperfusion. The venous outflow particularly is susceptible to obstruction as a result of kinking, haematoma formation, tissue oedema, or tight dressings. For successful surgery it is essential to optimize blood flow through the flap and the determinants of flow are given by the Hagen–​ Poiseuille equation: Laminar flow = πPr 4 /8nl where P is pressure, r is radius, n is viscosity, and l is length. This would suggest that the anaesthetic technique should deliver a good perfusion pressure, vasodilatation, and a low plasma

viscosity and this should direct appropriate fluid management. The precise level of perfusion pressure is very patient specific but it goes without saying that prolonged periods of hypotension should be avoided. Numerous anaesthetic techniques have been described for free tissue transfer, the importance being that the actual anaesthetic technique and monitoring used should be individualized to the free flap proposed and any comorbidity of the patient. In addition to standard monitoring, arterial and central venous pressure, core/​ peripheral temperature gradient, and urine output are often monitored. The development of increasingly accurate non-​invasive cardiac output monitors, tissue perfusion monitors, and miniaturized Doppler probes has questioned the need for invasive lines and may improve regional perfusion assessment. Regional anaesthesia is a useful supplement to general anaesthesia as it provides excellent analgesia extending well into the postoperative period, promotes vasodilatation by sympathetic blockade, and encourages blood flow. Prevention of cold-​induced vasoconstriction is essential. The immediate postoperative period is the critical time for detection of any free tissue transfer that appears to be getting into trouble. Patients should be monitored closely in a specialized unit by staff familiar with free tissue transfer surgery. It is as important to monitor and safeguard the haemodynamic state of the patient as it is to monitor the transferred tissue, ensuring they maintain optimum fluid balance, are warm, and free of pain and fear. A low threshold for re-​exploration is warranted in the suspected flap failure, but must of course be balanced against the risks of further prolonged anaesthesia in each case. Postoperative thromboprophylaxis and non-​ steroidal anti-​ inflammatory drug usage are both two-​ edged swords in that while they may inhibit platelet aggregation, they may also promote bleeding, and their use should be risk assessed for individual patients.

Table 1.6.4  Commonly performed peripheral nerve blocks Nerve blocks

Indications

Brachial plexus—​interscalene approach

Shoulder, clavicle, or upper arm surgery

Brachial plexus—​supraclavicular or axillary approach

Elbow, forearm, and hand surgery

Sciatic nerve block

Knee and lower limb surgery

Ankle nerve block

Foot and toe surgery

FURTHER READING Butterworth J, Wasnick JD, Mackey DC (eds). Morgan and Mikhail’s Clinical Anesthesiology, 6th ed. New  York:  McGraw-​Hill Medical, 2018. Lin T, Smith T, Pinnock C (eds). Fundamentals of Anaesthesia, 4th ed. Cambridge: Cambridge University Press, 2016.

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SECTION 1  General principles and techniques

REFERENCES American Society of Plastic Surgeons. Evidence-​ based patient safety advisory:  liposuction. 2009. http://​www.plasticsurgery.org/​ Documents/​medical-​professionals/​health-​policy/​evidence-​safety/​ Liposuction.pdf Association of Anaesthetists of Great Britain and Ireland. AAGBI safety guideline:  management of severe local anaesthetic toxicity. 2010. http://​www.aagbi.org/​sites/​default/​files/​la_​toxicity_​2010_​ 0.pdf

National Institute for Health and Care Excellence. Ultrasound-​guided regional nerve block [IPG285]. 2009. https://​www.nice.org.uk/​guidance/​ipg285 Ostad A, Kageyama N, Moy RL. Tumescent anesthesia with a lidocaine dose of 55mg/​kg is safe in liposuction. Dermatol Surg 1996;22:921–​7. Pace MM, Chatterjee A, Merill DG, et al. Local anesthetics in liposuction: considerations for new practice advisory guidelines to improve patient safety. Plast Reconstr Surg 2013;131:820–​6. Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 2004;29:564–​75.

1.7

Skin grafts Siobhan O’Ceallaigh and Mamta Shah

Introduction

Graft take

Skin grafts are an option for closing skin defects that cannot be closed primarily. A skin graft consists of epidermis and a portion of the underlying dermis that is detached from its blood supply and transferred to another location, usually on the same individual (an autograft). Skin grafts can also be used from cadaver donors (allografts) in extensive burn injuries, but as the recipient’s immune system will eventually reject this foreign tissue, this is only a temporary measure.

Skin graft types A skin graft may either be full or split thickness, depending on how much dermis is included with the graft. Split-​thickness skin grafts contain varying thicknesses of dermis while a full-​thickness skin graft contains the entire dermis including adnexal structures such as sweat glands, sebaceous glands, hair follicles, and capillaries (Fig. 1.7.1). Thin split-​thickness skin grafts ‘take’ under conditions less favourable than required by full-​thickness or thicker split-​skin grafts, but tend to shrink considerably, and are more susceptible to trauma.

Epidermis (5%) Thin Split-thickness skin graft

Medium

Dermis (95%) Sebaceous gland

100%

Thick Hair follicle

Full-thickness skin graft

Subcutaneous tissue

Sweat gland

Fig. 1.7.1  Diagram illustrating the structures included in split-​skin and full-​thickness skin grafts this figure is From Grabb, 1979.

Initially the graft adheres to its new bed with the fibrin that forms in the acute wound, and survives by the process of plasmatic imbibition of nutrients from the graft bed. Within 48 hours, the fibrin starts to break down and revascularization of the graft occurs. This is usually well advanced by the third day and corresponds with a change in the colour of the graft from blue to pink. Adhesion of the graft to its bed is maintained by the proliferation and migration of fibroblasts, with the deposition of collagen replacing the fibrin (McGregor and McGregor, 2000). The strength of this attachment increases rapidly, anchoring the graft within 4 days. Plasmatic imbibition was initially described by Hübscher (1888). He theorized that in the early period after grafting, skin grafts were nourished by fluid from the host and termed this process ‘plasmatic circulation’. Studies by Converse and colleagues (1957) in animal models confirmed that grafts increased in weight by imbibition from as early as 1 hour after application to a vascular bed. Later, between 48 and 72 hours after grafting, as visible circulation is established within the graft, there is further weight gain due to increased filling of the graft vascular system, and inadequate venous drainage (probably a product of venous engorgement and interstitial oedema). With the improved venous drainage, the graft regained its original weight by the eighth or ninth day post grafting. The authors argued that the term ‘plasmatic circulation’ is a misnomer because the absorption of fluid is a passive, one-​way process and that the term ‘phase of serum imbibition’ more truly expresses the absorption of serum from the host bed which occurs (Converse et al., 1969). It was argued that this is for the purpose of keeping the graft moist in a state of ‘in vivo tissue culture’, or maintaining the patency of the graft vessels until revascularization from the host can assure the permanent survival of the graft. The phenomenon of skin graft revascularization has been proposed to occur by the connection of graft and host vessels (anastomosis) or by the ingrowth of new vessels (angiogenesis). The anastomosis theory was proposed by Thiersch (1874) on the basis of vascular injection studies in canine models of full-​thickness grafts. He concluded that the contrast seen in the graft vascular bed within 18 hours was evidence of the development of communicating vessels between the graft and bed vascular networks, a process he described as inosculation. Further studies by Clemmesen (1964) in

36

SECTION 1  General principles and techniques

a pig model with split-​skin grafts and India ink injection showed no ink within the graft in the first post-​graft day, but on day two, a number of dye-​filled vessels were seen in the graft in the deep part of the dermis, without filling in the papillary or subpapillary dermal vessels. After the second day, the vessels of the graft and the bed were well connected and large-​diameter vascular channels termed ‘sinusoids’ were seen connecting the vessels of the recipient bed with those of the graft. The microcirculation of grafts was studied by Haller and Billingham (1967) by serial observation, photography, and histology. Although most of the original graft vessels contained blood by the second postoperative day, blood flow was not seen until the fifth postoperative day. They also found that the vessel patterns in the healed graft were of the same pattern as before grafting and were of such size and maturity to exclude the possibility of an invasion from the capillary bed of the host in such a short period of time. If the original vessels were blocked by injected silicone rubber before graft transfer, the graft necrosed. These authors concluded that the intrinsic vessels of the graft were used for circulation and were necessary for its survival. The process of anastomosis appears to be an active one with the vessels of the recipient bed growing towards and anastomosing with open vessels in the graft in the early phase of revascularization (Smahel, 1967) and gradual remodelling of the vascular pattern of the graft occurring with the re-​establishment of graft circulation with a combination of anastomotic connections and invasion of capillaries from the graft bed to the deep dermis and periphery of the graft (Birch and Brånemark, 1969). Birch and colleagues (1969) explained that the capillary invasion from the periphery of the graft occurs because granulation tissue forms at the periphery of the graft to obliterate any gap present between skin and the graft or because some of the peripheral vessels of the graft are unable to form anastomoses because of injury or desiccation. Careful apposition between the edge of the graft and the recipient bed, and minimizing graft trauma and desiccation, results in more anastomoses forming with pre-​existing vessels at the graft margin and less granulation tissue and capillary invasion. The alternative theory of graft revascularization suggests that the graft is perfused through new vessels migrating from the recipient bed into the transplanted graft, the process of angiogenesis. Medawar’s (1944) studies on allografting included control experiments using autografts. Grafts were removed every 4 days up to the twenty-​fourth day after grafting and analysed with histology. On the fourth day, there were dilated vessels in the graft filled with red cells he named ‘wound vessels’, interpreting them as a sign of mild traumatic inflammation. These wound vessels firstly stagnated (an inference which the author drew from the presence of pyknotic or otherwise degenerate leucocytes within them), then the endothelial lining was disrupted and the lumen of the vessels obliterated. They disappeared by the eighth day. Medawar observed that the graft vessels underwent endothelial disruption and occluded while ingrowth of new vessels occurred by the fourth day and showed differentiation into arterioles and venules. Converse and Rappaport (1956) studied full-​thickness grafts by direct stereomicroscopy and later with histochemistry using nicotinamide adenine dinucleotide (NADH) diaphorase (a marker of viable endothelium), and determined that while an early connection of graft and host vessels might occur, this was followed by active invasion of the graft by vessels from the graft bed, which go on to form the definitive vasculature of the skin graft. This was further corroborated by Wolff and Schellander (1965)

who measured cellular enzymes to evaluate the return of circulation in porcine split-​thickness skin grafts. While pre-​existing vascular channels within the graft did not exhibit enzymatic reactions during graft take and appeared to undergo involution, markers of cellular turnover activity such as ATP correlated well with a pattern of new vessel in-​growth, leading the authors to conclude that the new graft vasculature consisted entirely of ingrown vessels. Studies with a transparent chamber model by Zarem and colleagues (1967) showed that for at least 3 days after grafting, angiogenic activity was largely confined to the recipient bed. New vessels became progressively dilated and tortuous with proliferation of smaller vessels from the arterioles and venules in the direction of the graft. The graft’s native vessels appeared initially empty of cellular elements, but subsequently became infiltrated with leucocytes and the ingrowing blood vessels appeared to use the white blood cell-​filled channel as conduits. The process of graft take by the combination of angiogenesis and revascularization appears to be similar in both full-​thickness and split-​thickness grafts. Table 1.7.1 summarizes the studies of the process of skin graft revascularization, and highlights the lack of consensus regarding the exact mode of revascularization and the precise timing of this process. Allografts are commonly used in patients with major burn injury to allow early excision of the burn wound and protection of the wound bed from desiccation and fluid, electrolyte, and protein loss. This is particularly useful where the donor sites are limited. Allografts are derived either from cadavers and cryopreserved or glycerolized, or from living human donors. Allografts will ‘take’ similar to autografts but due to the immunogenicity of the skin, allografts are usually rejected after 2–​3 weeks post grafting. The rejection phenomenon is widely studied but not fully understood. Cytotoxic T-​cell-​derived immune response as well as macrophage-​ derived delayed-​type hypersensitivity have both been implicated in this rejection phenomenon (Mason et al., 1984).

Vascularization and incorporation of tissue-​engineered skin equivalents While autologous skin grafts are ideal for closure of extensive defects such as large burns or other soft tissue trauma, donor sites are often limited and harvesting grafts can have considerable cosmetic sequelae. For patients with extensive burns, wound coverage with a skin substitute comprising both dermis and epidermis should be the best alternative to a split-​thickness graft. Unlike human skin, engineered skin equivalents lack an intrinsic vasculature and the process of vascular incorporation remains unclear. Moeimen and colleagues (2001) studied the use of an artificial bilaminar dermal regenerative template (Integra®) in post-​burn reconstruction. They described the cellularization and neovascularization of the dermal template followed by remodelling and maturation of the neodermis. Until recently, the poor potential for vascularization in reconstructed skin limited the success of grafting a composite with a thick dermis, as the time necessary for its revascularization reduced the chance of survival of the overlying epidermis due to prolonged ischaemia (Germain et al., 2000). However, experimental work with human umbilical vein endothelial cells (HUVECs) seeded with fibroblasts in a collagen-​glycosaminoglycan sponge has shown promise in the formation of an intrinsic vascular network within an engineered

1.7 Skin grafts

Table 1.7.1  Studies of the process of skin graft revascularization Method

Author

Model

Graft depth

Onset of circulation

Adequate circulation

Method of circulation

Histology

Medawar (1944) Peer and Walker (1951) Henry et al. (1961)

Rabbit Rat and human Human

Subpannicular Subpannicular –​

4th day 3rd day 2nd day

8th day Not described 5th–​6th day

Ingrowth Anastomosis Anastomosis

Histochemical

Converse and Ballantyne (1962)

Rat

Suprapannicular

2nd–​3rd day

3rd–​4th day

Ingrowth

Dye injection

Smahel (1969) Clemmesen (1964)

Rat Pig

Subpannicular Suprapannicular (split-​skin graft)

2nd day 2nd day

6th–​7th  day 6th–​7th day

Anastomosis Anastomosis

Transparent chamber

Conway (1957) Zarem (1967) Birch and Brånemark (1969)

Mouse Mouse Rabbit

Suprapannicular Suprapannicular Suprapannicular

2nd day 3rd day 2nd day

7th day 5th–​8th  day 5th–​7th day

Anastomosis Ingrowth Anastomosis

Cheek pouch

Haller and Billingham (1967)

Hamster

Suprapannicular

2nd day

5th day

Anastomosis

Microangiography

Bellman and Velander (1957)

Rabbit

Suprapannicular

2nd day

14th day

Birch and Brånemark (1969)

Rabbit

Suprapannicular

2nd day

5th–​7th day

Anastomosis and ingrowth Anastomosis and ingrowth

Stereo-​microscopy

Converse and Rappaport (1956) Marckmann (1966)

Human Rat

–​ Subpannicular

2nd day 2nd–​3rd day

5th–​6th  day Not described

Ingrowth Anastomosis

Corrosion casting

Okada (1986)

Rabbit

Suprapannicular

3rd day

5th–​7th  day

Goretsky et al. (1995)

Rat

Subpannicular

3rd day

7th day

Anastomosis and ingrowth Ingrowth

In situ hybridization

Young et al. (1996)

Human/​athymic mouse

Subpannicular

2nd–​4th day

Not described

Anastomosis

Immunocytochemistry

Demarchez et al. (1987)

Human/​athymic mouse

Subpannicular

Not described

Not described

Anastomosis and ingrowth

skin substitute (Black et al., 1998). In addition, angiogenesis can be augmented within a tissue-​engineered construct seeded with keratinocytes modified to overexpress vascular endothelial growth factor (VEGF), a proangiogenic growth factor (Supp et al., 2002). Skin grafts are a useful technique for resurfacing skin defects and understanding the mechanism of ‘take’ helps formulate the next generation of skin substitutes. Future research into development of skin substitutes involving both dermis and epidermis with preformed blood vessels along with the potential of regenerating epidermal appendages will be the challenge.

REFERENCES Bellman S, Velander E. Vascular reaction following experimental transplantation of free full thickness skin grafts. In:  Transactions of the International Society of Plastic Surgeons, First Congress, Stockholm and Uppsala, 1955, p. 493. Baltimore, MD: Williams and Wilkins, 1957. Birch J, Brånemark PI. The vascularization of a free full thickness skin graft. I. A vital microscopic study. Scand J Plast Reconstr Surg 1969;3:1–​10. Birch J, Brånemark PI, Lundskog J. The vascularization of a free full thickness skin graft. II. A  microangiographic study. Scand J Plast Reconstr Surg 1969;3:11–​17. Black AF, Berthod F, L’heureux N, et al. In vitro reconstruction of a human capillary-​like network in a tissue-​engineered skin equivalent. FASEB J 1998;12:1331–​40.

Clemmesen T. The early circulation in split skin grafts: restoration of blood supply to split-​skin grafts. Acta Chir Scand 1964;127:1–​8. Converse JM, Ballantyne DL, Jr. Distribution of diphosphopyridine nucleotide diaphorase in rat skin autografts and homografts. Plast Reconstr Surg Transplant Bull 1962;30:415–​25. Converse JM, Ballantyne DL Jr, Rogers BO, et al. Plasmatic circulation in skin grafts. Transplant Bulletin 1957;4:154–​6. Converse JM, Rappaport FT. The vascularisation of skin autografts and homografts:an experimental study in man. Ann Surg 1956;143:306–​15. Converse JM, Uhlschmid GK, Ballantyne DL Jr. ‘Plasmatic circulation' in skin grafts. The phase of serum imbibition. Plast Reconstr Surg 1969;43:495–​9. Conway H, Griffith BH, Shannon JE Jr, et al. Re-​examination of the transparent chamber technique as applied to the study of circulation in autografts and homografts of the skin. Plast Reconstr Surg 1957;20:103–​16. Demarchez M, Hartmann DJ, Prunieras M. An immunohistological study of the revascularization process in human skin transplanted onto the nude mouse. Transplantation 1987;43:896–​903. Germain L, Remy-​Zolghadri M, Auger F. Tissue engineering of the vascular system: from capillaries to larger blood vessels. Med Biol Eng Comput 2000;38:232–​40. Goretsky MJ, Breeden M, Pisarski G, et al. Capillary morphogenesis during healing of full-​thickness skin grafts: an ultrastructural study. Wound Repair Regen 1995;3:213–​20. Grabb WC. Basic Techniques of Plastic Surgery. In Plastic Surgery, 1979, 3rd, (Grabb W.C. and Smith J.W.) Boston: Little Brown.

37

38

SECTION 1  General principles and techniques

Haller JA Jr, Billingham RE. Studies of the origin of the vasculature in free skin grafts. Ann Surg 1967;166:896–​901. Henry L, Marshall DC, Friedman EA, et al. A histological study of the human skin graft. Am J Pathol 1961;39:317–​32. Hübscher C. Beitrage zur Hautverpflanzung nach Thiersch. Beitr Klin Chir 1888;4:345–​51. Marckmann A. Autologous skin grafts in the rat:  vital microscopic studies of the microcirculation. Angiology 1966;17:475–​82. Mason DW, Dallman MJ, Arthur RP, et  al. Mechanisms of allograft rejection: role of cytotoxicity T-​cells and delayed-​type hypersensitivity. Immunol Rev 1984;77:167–​84. McGregor IA and McGregor AD. Free skin grafts. In Fundamental Techniques of Plastic Surgery, 2000, 10th Ed, 35–59. Edinburgh: Churchill Livingstone. Medawar PB. The behaviour and fate of skin autografts and skin homografts in rabbits. J Anat 1944;78:176–​99. Moeimen NS, Staiano JJ, Ojeh NO, et al. Reconstructive surgery with a dermal regenerative template: a clinical and histological study. Plast Reconstr Surg 2001;108:93–​103. Okada T. Revascularisation of free full thickness skin grafts in rabbits: a scanning electron microscope study of microvascular casts. Br J Plast Surg 1986;39:183–​9.

Peer LA, Walker J. The behaviour of autogenous human tissue grafts, I. Plast Reconstr Surg 1951;7:6–​23. Smahel J. The revascularization of a free skin autograft. Acta Chirurgica Plasticae 1967;9:76–​7. Smahel J. The problem of revascularization of free skin autografts. Acta Chirurgica Plasticae 1969;11:78–​84. Supp DM, Wilson-​Landy K, Boyce ST. Human dermal microvascular endothelial cells form vascular analogs in cultured skin substitutes after grafting to athymic mice. FASEB J 2002;16: 797–​804. Thiersch K. Finer anatomic changes in skin healing over granulations. Langenbecks Arch Klin Chir 1874;17:318–​45. Wolff K, Schellander FG. Enzyme-​histochemical studies on the healing process of split-​skin grafts. I. Aminopeptidase, diphosphopyridine-​ nulceotide-​ diaphorase and succinic dehydrogenase. J Invest Dermatol 1965;45:38–​45. Young DM, Greulich KM, Weier HG. Species-​specific in situ hybridization with fluorochrome-​labeled DNA probes to study vascularization of human skin grafts on athymic mice. J Burn Care Rehabil 1996;17:305–​10. Zarem HA, Zweifach BW, McGehee JM. Development of microcirculation in full thickness autogenous skin grafts in mice. Am J Physiol 1967;212:1081–​5.

1.8

Skin flaps Donald Dewar

Introduction to flaps Flaps can reconstruct defects of the integument, resurface mucosal defects, as well as contribute to contour. They are used where grafting is not feasible because of the nature of the defect and/​or where the aims of reconstruction would be better served by vascularized tissue with both cutaneous and subcutaneous components. A  skin flap can also be combined with fascia, muscle, or bone to reconstruct a complex or composite defect, and to provide tissue to restore function. Flaps may be classified according to the origin of the flap: local skin flaps are raised from tissue adjacent to the defect (usually deriving their blood supply from the subcutaneous tissue and subdermal plexus), and distant flaps are raised on dedicated vascular pedicles from a non-​contiguous region. A distant flap may be moved to the defect maintaining the continuity of the pedicle (a ‘regional’ or ‘pedicled’ flap) or as a free flap, where the flap is elevated from its remote donor site and the pedicle is divided to allow the flap to be transported ‘free’ to the defect and then the vascular continuity is re-​established by anastomosis to a recipient vessel in the defect. This chapter focuses on local flaps. The features and use of various regional and free flaps are discussed throughout the remainder of the text.

Local flaps Local flaps are indispensable for the reconstruction of the defects that result from skin tumour excision. They are most often used because they provide skin of the same colour and contour as that excised, yielding a more aesthetically satisfactory result than can be achieved with a skin graft. Conversely, a poorly designed flap may distort important structures, or yield unfavourable scarring. Occasionally, a flap is needed because the defect is not suitable for grafting due to exposed cartilage, tendon, or bone. Therefore, being able to plan and execute local flaps successfully is a core plastic surgery skill. Despite their widespread use, the design of the commonly used local flaps remains the subject of debate among plastic surgeons. Opinions are often strongly held despite the lack of published

evidence comparing different designs (see Cho and Kim (2006) for one of the very few comparative studies, in cadavers). Furthermore, much of the literature on flap design is beset by line diagrams and complex two-​dimensional geometry that bear little relation to the three-​dimensional, elastic reality of human skin. This chapter seeks to explore both the theory of flap design, and its ‘real-​life’ application in clinical practice.

General principles Classification of local flaps Flaps may be classified according to their contiguity, composition, circulation, and method of movement. Local flaps are, by definition, adjacent to the defect to be reconstructed. Most commonly, they are composed of skin and a variable amount of subcutaneous tissue. The circulation is provided by the skin and subcutaneous tissue, with the greatest contribution from the subdermal plexus. Some local flaps contain a known blood supply at their base, defining them as axial, and allowing larger flaps to be raised. Examples include the dorsonasal advancement flap (see Fig. 1.8.13 in the ‘Advancement flap’ section) which contains branches of the supratrochlear artery at its base. Some local flaps include fascia and derive their blood supply from fasciocutaneous or septocutaneous perforating vessels, although these are rarely formally dissected. The different modes of flap movement—​transposition, rotation, advancement, and interpolation—​ have confused generations of trainee plastic surgeons. It is important to understand the differences between these modes of movement because they influence flap design, but the nomenclature is partly a matter of convention. Transposition flaps move over nearby skin to reach a defect (Fig. 1.8.1). They are most commonly moved into the defect by transposing the flap through an arc and this is commonly misinterpreted as making them a type of rotation flap. A transposition flap is usually the same size as the defect to be reconstructed (or just slightly smaller). Thus, a secondary (donor) defect is created, which needs to be dealt with by direct closure, a skin graft, or a second flap. In this sense, transposition flaps simply swap the defect from one place

40

SECTION 1  General principles and techniques (a) F

F E

G

B C

A D (b)

H

J

J

C

B X A A

(c) A C

B (d)

Fig. 1.8.1  Transposition flaps. (a) Left: an elliptical defect A–​B–​C–​D is reconstructed with a transposition flap E–​F–​G–​H–​J. The width of the flap E–​G is the same as the width of the defect B–​D. The length of the flap is designed so that point F will reach point A after transposition. This can be planned by measuring A–​H and copying this length to F–​H (light grey lines). The shaded areas are excised. Right: the flap after transposition and direct closure of the donor site. As this flap has been transposed through 90 degrees, a large dog-​ear may result at point J. This usually has to be corrected secondarily to avoid compromising flap blood supply. The donor site scar may be extended at F to remove the dog-​ear there. (b) Scalp transposition flap. Left: a large defect is positioned such that there is not sufficient scalp available for a rotation flap. A transposition flap is designed, with X–​C equal to X–​B to ensure that the flap will reach the far edge of the defect. The light shaded area may be excised, but a large dog-​ear tends to form at point A nonetheless. Right: the flap after transposition. The donor defect is covered with a skin graft (dark shading). (c) Transposition flap for reconstruction of an extensive lower eyelid defect. Left: the flap is designed with a small perforator within its base, allowing a long (axial) flap to be raised. A–​B and A–​C must be equal to allow the flap to reach the far edge of the defect (arc of transposition shown for clarity). Right: the flap after transposition, with the lax cheek skin allowing direct closure of the donor site. (d) Transposition flap from the side of the finger to fill volar skin shortage. Top: the shaded area represents the skin defect. Bottom: the flap after transposition.

1.8 Skin flaps

to another—​in and of themselves they do not recruit any new skin. In the same way, closure of a properly executed transposition flap should be tension free as the flap skin does not need to stretch to fill the defect. Rotation flaps, by contrast, are designed by first triangulating the defect then constructing a semicircle around that triangle, which delineates the flap (see Fig. 1.8.8a in the ‘Rotation flap’ section). It is this semicircular flap which rotates into the defect, as if rotating about the centre of the semicircle, giving the flap its name. Thus, the flap is designed to be several times the size of the defect (in the classical design, the flap area is five times the area of the defect), with the flap being stretched across both donor site and defect to allow direct closure of both, without creating a secondary defect. Closure will often be tight at all edges of the flap, as the flap skin must stretch to fill this larger area. The absence of a donor defect accounts for the popularity of rotation flaps in reconstructing scalp defects, where grafting a donor site yields undesirable alopecia. True advancement flaps are less common. In this type of flap, the flap moves directly forwards into the defect without turning, or passing over adjacent skin. The flap is usually the same size as (or slightly larger than) the defect and stretches to cover both defect and donor site. A good clinical example is the double opposing advancement flaps of an ‘H flap’ reconstruction (see Fig. 1.8.12 in the ‘Advancement flap’ section). Interpolation involves leaving an intervening skin bridge intact between the defect and the flap, with the skin paddle of the flap being islanded on a subcutaneous or de-​epithelialized pedicle. This technique is less commonly used in reconstructing small excisional defects, due to its complexity and the fragility of the subcutaneous pedicle, but such flaps have a role in reconstructing defects at the alar base using nasolabial tissue (Fig. 1.8.14b in the ‘Interpolation flap’ section).

Simple transposition flap The simplest transposition flap is a rectangular, or tongue-​like, flap which is transposed through an arc to reach the defect. Transposition flaps are usually the same size as the defect to be reconstructed, and the typical geometry is shown in Fig. 1.8.1a. The flap may be raised adjacent to the defect and turned through a short arc, or be raised further away and transposed through up to 180 degrees. Larger angles of transposition are associated with significant dog-​ear formation, and shortening of the reach of the flap due to tethering of the back corner (see Fig. 1.8.1a for an illustration of the extra flap length needed to compensate for this).

Applications Clinical applications include the scalp transposition flap, which is used to cover non-​graftable areas of skull, where the defect is too large or awkwardly sited to allow a scalp rotation flap to be used (Fig. 1.8.1b). A large dog-​ear usually forms at the flap base, and the resultant donor site must be skin-​grafted, so the aesthetic result is often poor.

Reconstruction of extensive lower eyelid defects can be accomplished using a transposition flap from the cheek (Fig. 1.8.1c). A  small perforating vessel just lateral to the orbicularis oculi axializes this flap and allows for a length:breadth ratio of at least 3:1. Care must be taken to suspend the flap carefully to avoid ectropion. After release of a finger contracture through a mid-​lateral incision, the skin may be found to be short on the palmar aspect of the finger. The lateral laxity produced by a long-​standing contracture allows a small transposition flap to be raised from the side of the digit and transposed to the volar defect (Fig. 1.8.1d).

Rhomboid flap A rhomboid flap is a rhombus-​shaped transposition flap designed to fit an adjacent defect of the same size and shape (Fig. 1.8.2a). It was first described by Limberg (1966), and is commonly referred to as a Limberg flap. The flap is designed to recruit tissue from a nearby area of lax skin, allowing the donor defect to close directly. Where possible, the linear scar resulting from closure of the donor site is placed in a line of relaxed skin tension. The rhomboid flap has many advantages and may be used anywhere on the body where sufficient lax skin is available to close the donor defect, and to raise the flap without compromising other structures. The main limitation on the size of flap which can be raised is finding sufficient adjacent lax skin for the donor site to close. Thus, the flap works well on the temple, where lax skin is usually available just below, in front of the sideburn. Similarly, in closing defects of the natal cleft, the adjacent buttock usually provides lax skin for even large flaps to be raised with direct closure of the donor site. On the centre of the back, by contrast, the skin adjacent to the defect is usually as tight as the defect itself, and it will be just as difficult to close the donor site as it would have been to close the original wound. Once the flap is raised, the donor defect should be closed prior to flap inset, and satisfactory donor site closure predicts a successful flap. Properly designed rhomboid flaps have a 1:1 length:breadth ratio and so should survive on the subdermal plexus. On the back and on the limbs, however, larger flaps may struggle unless a perforator is incorporated into the base, axializing the flap. The rhomboid flap lends itself particularly well to elliptical defects, in which the amount of normal skin discarded to create a rhomboid defect is minimal. For circular defects, a larger amount of normal tissue must be discarded to make the defect rhomboid, and this is one of the criticisms of the classical design. For any given rhomboid defect, there are four possible rhomboid flaps which can be used (see Fig. 1.8.4b in the ‘Rhomboid flap—​ variations’ section). The choice of flap is dictated by skin laxity sufficient to close the donor site, the need to avoid adjacent structures such as the hairline, and the aim of leaving a favourable donor site scar. A geometrical approach to planning the flap (Fig. 1.8.2a, left) ensures that the donor defect will end up in a line of relaxed skin tension. While this is a useful concept which can guide the novice

41

42

SECTION 1  General principles and techniques

x

x

(a) LRST

r

D

D

r

60°

x A

A 90°

Q

D

C

x A

120°

x C

B

B x

(b)

Fig. 1.8.2  Rhomboid flaps. (a) Left: the lines of relaxed skin tension (LRST) are drawn next to a circular defect with radius r. A line perpendicular to the LRST, and tangential to the edge of the defect is drawn Q–​A–​D. Point A is marked directly below the centre of the defect, and point D is marked directly level with the centre of the defect. A–​D forms one side of the rhomboid flap. Centre: using A–​D as a base, the rest of the defect is marked to form a rhombus, with sides of length x. Adjacent to the defect, a rhomboid flap is designed, with the same dimensions as the defect. Right: the flap is raised and transposed (point C passing over point A), with the donor defect (A–​B) closing directly. The linear donor site scar lies within the LRST because points A and B both move as the donor site is closed. (b) The final result in a clinical case, showing the obliquely oriented donor site scar.

surgeon, and a much-​loved exam question, it is rarely drawn out this way in practice.

Rhomboid flap—​variations Rhomboid flap for a square defect In this variation (Fig. 1.8.3), a circular defect is converted to a square with angles of 90 degrees, rather than a rhombus with angles of 60 and 120 degrees. This results in a smaller amount of normal skin being discarded with the excision. The flap is designed as an adjacent rhombus, with all sides of the flap being equal in length to the width of the defect. However, the angles on the rhombus are now 45 degrees and 125 degrees, requiring the flap skin to stretch to fill the defect, and making the tip of the flap narrow. Furthermore, the flap transposes through 90 degrees, rather than 60, and so is more likely to produce a prominent dog-​ear.

and Sommerlad (1987) proposed that a flap the same size as the primary defect is unnecessary, as skin laxity will allow a smaller flap to fill the defect. Using a flap slightly smaller than the defect allows a smaller donor site which can be closed more easily. They proposed a flap up to a third smaller. This allows the flap to be used for larger defects, where the standard design would leave a donor site too big to close. Furthermore, most excisional defects are round or elliptical, so the excision of the corners of the standard rhomboid wastes normal skin and is unnecessary. Unlike the standard rhomboid flap, this design allows the flap to be designed in any direction around the defect, providing useful flexibility (Fig. 1.8.4b, right). By relying on skin laxity to compensate for a smaller flap, this modification necessitates tight closure, and this can lead to wound healing problems. Wide undermining of the edges of the defect will go some way to reducing wound tension.

Square peg in a round hole

Dufourmontel flap

This modification (Fig. 1.8.4a) is now so widely used that it is rare to see an actual rhomboid drawn, much less excised. Quaba

This modification of Limberg’s design (Dufourmontel, 1962) uses a narrower angle of transposition of the flap, and a different orientation

1.8 Skin flaps

(a)

F

F

D

E

E A

x

A B

B C

x 45°

C

x

Fig. 1.8.3  Rhomboid flap for a square defect. The shaded area is excised and discarded. The flap sides are the same length as the width of the defect. This modification produces a 45-​degree angle at the tip of the flap, which may increase the risk of necrosis.

of the limbs (Fig. 1.8.5). The narrower angle is intended to reduce the tendency for a dog-​ear to form as the flap is transposed. The reoriented flap shortens the distance that the tip of the flap (point E in Fig. 1.8.5) has to travel to reach the far corner of the defect. Many surgeons have found this area to be under tension during inset of a standard rhomboid flap and, at least in theory, Dufourmontel’s design should reduce that tension. The downside of this design is that a larger area of normal skin is excised and discarded than in the standard rhomboid flap, and the design is more complex (see Lister and Gibson (1972) for a comparison). For these reasons, it is rarely used in practice.

Bilobed flap The history and development of the bilobed flap is reviewed by Zimany (1946), who acknowledges a paper by Esser (1918, in German) as the likely first description of a bilobed flap. Zimany discusses modifications to the size of the lobes of the flap, and the debate about the exact dimensions and design of this flap has continued ever since. Zitelli’s series of 20 bilobed flaps among 400 skin cancer cases (Zitelli, 1989) is perhaps the most quoted description of the flap, leading many to assume (incorrectly) that Zitelli is the flap’s inventor. McGregor and Soutar (1981) reviewed 80 bilobed flaps and concluded that the flap is best confined to the face and the sole of the foot, with the risk of complications much higher at other sites. Rhomboid and bilobed flaps are both types of transposition flap. For a rhomboid flap, the donor defect closes directly, but for a bilobed flap, the donor defect is closed by a secondary flap and the donor site for this secondary flap closes directly (Fig. 1.8.6). It is useful to consider why rhomboid flaps are widely used except on the nose, whereas bilobed flaps are commonly used on the nose, but rarely elsewhere. Basal cell carcinoma commonly affects those parts of the nasal tip, alae, and the lower part of the nasal dorsum where adjacent lax skin is not available for reconstruction. There is, however, usually adequate donor skin around the upper third of the nasal dorsum. This skin is too far from most defects to be transposed using a rhomboid flap, and a straightforward transposition from the upper to lower

(b)

Fig. 1.8.4  Square peg in a round hole. (a) Left: in the standard rhomboid flap, extra skin is excised (and wasted) to make the defect rhomboid-​ shaped. This allows the tip of the flap (marked C) to fit into the defect at point D, and eliminates the dog-​ear at point E. The donor defect A–​B is the same width as the primary defect (A–​F), so the flap can only be successful if the skin in the donor area is more lax than the skin at the site of the defect. Centre: in the ‘square peg in a round hole’ modification, no additional skin is excised, and the flap is designed slightly smaller than the defect, so A–​B is approximately 15% shorter than A–​F. This means that less laxity is needed at the donor site, allowing larger defects to be reconstructed with the flap. Right: the flap after transposition. The edges of the defect may be undermined to aid in insetting the deliberately smaller flap (grey arrows). Excess skin at point C, and any dog-​ear at point E, may be trimmed. (b) Left: for any given rhombus-​shaped defect, there are four possible rhomboid flaps which can be used. Right: using the ‘square peg in a round hole’ modification, an infinite number of flaps are possible.

B x

x C

A D x

P E

60° x

F

Q

Fig. 1.8.5  The Dufourmontel flap (right), with a rhomboid flap (left) for comparison. The circular defect is converted to a rhombus with sides of length x, and the angle B–​C–​D between 40 and 60 degrees. The short axis of the rhombus B–​D is extended, as is the long side C–​D. The resulting angle P–​D–​Q is bisected to form one side of the flap E–​D, with length x. The second side of the flap E–​F is drawn parallel to the long axis of the rhomboid A–​C , and with length x.

43

44

SECTION 1  General principles and techniques

(a) F

G

F 90°

B E

A

r

G B

D

C

H

E

(b)

C

D

E

D E

C

B r

r

J

C

r

B r

r A

r

r

r

A

Fig. 1.8.6  Bilobed flaps—​design. (a) McGregor and Soutar’s design for a bilobed flap (1981). Left: for a circular defect with radius r, C–​D is drawn with C approximately half r from the edge of the defect, and length equal to r. C–​B is drawn as a tangent to the defect, and D–​F is drawn parallel to C–​B, and length equal to D–​E (the arc E–​F–​G has been drawn in for clarity). D–​G is then drawn at 90 degrees to and the same length as D–​F. Centre: the primary flap is drawn around D–​F, with width equal to 2r. C–​F and H–​F are equal. The secondary flap is drawn around D–​G, with width 50–​60% of the primary flap. H–​G and J–​G are equal. The shaded area at C is excised to prevent formation of a dog-​ear. Right: the flap after transposition and closure. (b) Zitelli’s design (1989). Left: for a circular defect with radius r, point A is drawn at distance r from the edge of the defect. Concentric arcs are drawn as shown, centred on A and with radius 2r, 3r, and 4r. A–​C is drawn at an angle of 60 degrees to A–​B, and A–​E is drawn at an angle of 60 degrees to A–​C . Centre: the primary flap is marked at C, the same size (or slightly smaller) than the defect. The secondary flap is drawn at D, half the width of the defect. The shaded area at D is trimmed as necessary, and a dog-​ear is usually excised near point A. Right: the flap after transposition and closure.

(a)

(b)

A

B

B

C

C

Fig. 1.8.7  Bilobed flaps—​application. (a) Left: sticking rigidly to a design will, in this case, lead to the secondary flap (and subsequent donor site scar) crossing the junction between the dorsal and lateral subunits. Right: modifying the length of the primary flap and the angle between the flaps brings the donor scar to lie in the junction between aesthetic subunits (dashed grey line). (b) Left: a large cheek defect is too big for a cheek rotation flap. A bilobed flap is designed, using a transposition flap from the cheek and a second flap from behind the ear. Right: after transposition, the flaps are sutured together, and both are used to reconstruct the defect.

1.8 Skin flaps

D

(a)

(d)

5x

C x E

E2

B

A

2x

(b)

E

F D

C

P

B

A

(c)

H

F

G

P

E

C

B D

A

Fig. 1.8.8  Rotation flaps. (a) The classical rotation flap is designed by triangulating the defect to give a triangle with short side A–​C of length x and long sides A–​B of length 2x. Using A–​B as the radius, a semicircular flap is drawn, giving a flap C–​D–​E of which the length is approximately 5x. A back-​cut may be used as shown (dotted line), and a Z-​plasty may be added to help closure of the base of the flap (dashed line). Although the pivot point of the flap is often given as point B, the critical length to check when designing the flap is that E–​C will reach to point A. A back-​cut moves point E, rather than moving the pivot point. (b) Ahuja’s modified rotation flap (Ahuja, 1988). After triangulation (A–​B–​C), the triangle is copied (B–​C–​P) to create a new centre of rotation P. P–​A is then used as the radius of the flap, giving a much larger flap D–​E–​F than the standard rotation flap with radius A–​B. The position of the end of the flap F can be chosen intraoperatively, using a ‘cut-​as-​you-​go’ approach (dashed line). (c) Sandhir’s divine rotation flap (Sandhir, 1997). The defect is triangulated into an isosceles triangle A–​B–​C . A rectangle A–​D–​E–​C is drawn around this, and then a square C–​E–​F–​G is drawn alongside. Bisecting side E–​F derives point P, which becomes the centre of rotation of the flap, with P–​C as its radius. The end of the flap may be extended at H as necessary. (d) A clinical example of a classical rotation flap. The arc has been adjusted to leave the final scar at the junction between aesthetic subunits, and favourable skin laxity has permitted the overall flap length to be less than five times the width of the defect.

part of the nose involves moving a flap through nearly 180 degrees, with a resultant large dog-​ear. Esser, therefore, conceived the bilobed flap as a means to recruit the lax upper nasal skin by means of a secondary flap used to close the donor site of a primary flap raised adjacent to the defect (Esser 1918). When the flap is deployed outside the nose, it may be used with a similar principle in mind, that is, to assist in transfer of skin from an available donor site that is not ideally positioned to a defect without

sufficient tissue available adjacently. A second application, however, is to use two smaller flaps to fill a larger defect, where there is not adequate lax skin for a single flap large enough for the defect. The commonest application of this is using a retroauricular flap in addition to a cheek flap to fill a large cheek defect (Fig. 1.8.7). Both the primary and secondary flaps are transposed into the defect, and are sutured together—​the resultant ‘seam’ is one of the disadvantages of this approach.

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Practical considerations A technical, geometrical approach to flap design, as proposed by some authors (McGregor and Soutar, 1981; Zitelli, 1989), does not take into account the three-​dimensional nature of the skin surface, nor variations in its elasticity. Furthermore, scars should be placed in favourable lines, and surrounding structures should not be distorted. On the nose, the key principles are: (1) to design flaps that are still long enough after transposition to avoid alar retraction, (2) to avoid flaps crossing the nasolabial groove, and (3)  to place scars along the junctions between cosmetic subunits (Burget and Menick, 1985) (Fig. 1.8.7). However good the design, some stretching of the flap skin is needed, and there will always be a tendency for dog-​ears to form. Wide undermining around the edges of the defect and the base of the flap (taking care to protect the blood supply) helps to distribute the tension evenly around the flap edges, and minimizes the formation of dog-​ears.

Rotation flap The design of a classical rotation flap begins with triangulation of the defect. That is, drawing a triangle with sides tangential to the defect, with the short side just longer than the width of the defect and each of the long sides twice as long as the width of the defect (Fig. 1.8.8a). The acute angle of this triangle is then taken as the centre of a semi-​ circular flap, with its radius as long as the long side of the triangle. Taking π as three, this gives a flap with a length and area five times that of the triangle to be excised. This large flap area, relative to the size of the defect, allows the skin to be stretched to cover both defect and donor site. The skin is closed by differential suturing and there is no secondary defect.

Practical applications Rotation flaps are commonly used on wide, featureless surfaces such as the cheek, scalp, and buttock, where there is enough skin for the large flap dimensions that are needed. Furthermore, the shape of a rotation flap allows scars to be hidden at the edges, for example, in the preauricular or gluteal creases. The lack of a secondary donor defect is particularly useful in reconstructing the hair-​bearing skin of the scalp.

Flap design The length of the long side of the flap should be planned to be approximately five times the width of the defect but, in practice, lax skin will sometimes allow a flap as short as three times the width of the defect and, conversely, tight skin may necessitate a flap up to nine times as long as the defect. It is best to plan for a large flap in advance, and then raise as much as proves necessary during dissection to reach the defect—​this is sometimes referred to as a ‘cut-​as-​you-​go’ approach. The key measurement in designing the flap is from the base of the flap (point E in Fig. 1.8.8a) to the tip of the defect. Some have advised extending the tip of the flap, which makes closure at the tip less tight. However, the donor site closure then becomes correspondingly tighter at the site of the extra flap length. If the front edge of the flap closure is tight, then a back cut may be made at the base of the flap, moving point E closer to the tip of the defect (E2 in Fig.

Fig. 1.8.9  The effect of skull convexity on scalp rotation flaps. Top: a simulated rotation flap resting on a flat surface with the tip reaching the far corner of the defect, showing the distance A–​B which will require tight closure around the flap edge. Bottom: the same simulation laid over a spherical surface to simulate the skull. Note that A–​B is now significantly longer.

1.8.8a). A longer back cut will lessen the tension across the flap, but also reduces the width of the flap base—​too ambitious a back cut will compromise the blood supply. On the scalp, the convexity of the skull may lengthen the distance a rotation flap needs to stretch to reach the defect (Fig. 1.8.9). It is, therefore, essential to plan the flap larger than might be expected to leave room for manoeuvre. The galea on the underside of the flap may be scored to allow the flap to stretch further, but this needs to be done with care, as the blood supply to the flap lies just superficial to the galea and is easily damaged. A back cut of the galea at the base of the flap is often equally effective and usually safer. Variations on the standard rotation flap design have been described by Ahuja (1988) and Sandhir (1997). Ahuja’s modified rotation flap (Fig. 1.8.8b) is much larger than the standard rotation flap, and this allows a greater margin of error, as the distance the flap needs to reach is proportionally smaller if the flap is large (since the flap skin needs to stretch, a larger flap is better in principle). Sandhir’s divine rotation flap (Fig. 1.8.8c) is more geometrically complex. It is slightly larger than the standard design, and

1.8 Skin flaps

lengthens the front edge of the flap (where closure is often tight) at the expense of discarding a small area of normal skin. Although these designs have been compared using in vitro simulation (Lo and Kimble, 2008), the applicability of this work to in vivo flap design (especially when reconstructing in three dimensions on the scalp) is debatable. While most rotation flaps are closed with differential suturing, a dog-​ear may result at the base of the flap. This can be dealt with by using a back cut to create a V-​Y, or using a Z-​plasty (Fig. 1.8.8a).

Rotation flap—​variations Hatchet flap Although sometimes considered to be an advancement flap, a hatchet flap (so called because it resembles the head of an axe) may be better understood as a rotation flap on which the edge has been straightened. This is because the design of the flap, like a standard rotation flap, begins with triangulation of the defect, and the long edge of the flap should measure at least five times the width of the defect (unless the skin is particularly lax). A large

(a)

(b)

A

(c)

B

B

A

A

B

B

A

(d)

Fig. 1.8.10  Variations on rotation flaps. (a) Top: a hatchet flap to reconstruct a defect over the distal interphalangeal joint of the finger (shaded area). The defect is triangulated, and the flap length is five times the width of the defect. The dashed line indicates where a back cut may be placed if needed. Bottom: A similar defect at the proximal interphalangeal joint (shaded area) is sited where there is not enough skin to allow a single hatchet flap, but two smaller hatchet flaps may be used, each reconstructing half of the defect. (b) Double opposing rotation flaps—​an ‘O to T’ plasty. (c) Double opposing rotation flaps—​an ‘O to Z’ plasty. (d) A clinical example of an ‘O to T’ plasty, in this case allowing the donor scars to lie inconspicuously along the hairline.

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SECTION 1  General principles and techniques

(a)

(a)

(b)

(c)

(d)

r 2r

(b)

2r

(c) 4r

Fig. 1.8.11  Advancement flaps. (a) A simple rectangular advancement flap, with sides equal to the width of the defect (2r). The flap partly stretches into the defect, and partly advances through excision of Burow’s triangles at either side of the base. The shaded areas are excised and discarded. (b) Two opposing rectangular advancement flaps are used to reconstruct a defect. Differential suturing deals with the excess skin at the flap base. Burow’s triangles may be used but are rarely needed in practice, as each flap only needs to stretch to cover half of the defect. The shaded areas are excised and discarded. (c) A V-​Y advancement. The flap should be at least twice the width of the defect (i.e. 4r). The shaded areas are excised and discarded. Once the flap is islanded and advanced, the donor area closes directly.

back-​cut completes the flap, and allows V-​Y closure of the donor defect (Fig. 1.8.10a).

(e)

Fig. 1.8.12  Double opposing advancement flaps—​the ‘H flap’. (a) The lesion to be excised. (b) The defect after excision. (c) The flaps raised in the subcutaneous plane. (d) After flap advancement and wound closure. (e) The result at 3 months.

Pairs of rotation flaps: O-​T and O-​Z Local anatomy sometimes prevents a single rotation flap from covering a defect—​either where there is not sufficient skin for a single flap which is large enough, or where raising a single large flap would put the donor scar in an unsatisfactory position. In these situations, the defect may be reconstructed with a pair of opposing rotation flaps, each of which fills half the defect. The two flaps may be raised on the same side of the defect, making an ‘O-​T plasty’ (Figs. 1.8.10b and Fig. 1.8.10d), or on opposite sides of the defect, making an ‘O-​Z plasty’ (Fig. 1.8.10c).

Advancement flap True advancement flaps consist of rectangular or triangular flaps which move directly forwards into a defect without turning or passing over adjacent skin. A  rectangular flap may be stretched to fill both defect and donor site, but excess skin at the base of the flap is prone to form a dog-​ear. In practice, differential suturing may deal with this excess skin (Fig. 1.8.11b), but if necessary it may be excised as Burow’s triangles (Fig. 1.8.11a). For triangular

advancement flaps, the donor site is usually closed as a V-​Y (Fig. 1.8.11c). Rectangular advancement flaps based on a subcutaneous pedicle may struggle if designed longer than a 1:1 length:breadth ratio. At some sites (such as the forehead), longer flaps may be used if they are planned so as to incorporate a known vessel in the base. Another approach is to use two standard-​ sized opposing advancement flaps, each of which fills half the defect. This is commonly known as an ‘H flap’ due to the shape of the resulting scars (Fig. 1.8.11b and Fig. 1.8.12). V-​Y advancement flaps are by definition islanded, and so derive their blood supply from perforating vessels reaching the deep surface of the flap. Most often, the perforators are not formally dissected, and this means that larger flaps are preferred, as this increases the chance of incorporating a suitable perforator. If there is doubt about the existence of suitable perforators, a hand-​held Doppler may be used to identify perforators prior to marking out the flap. For clinical applications of advancement flaps, see Fig. 1.8.13.

1.8 Skin flaps

(a)

(b)

Interpolation flap

x

x

x

A B

Fig. 1.8.13  Clinical applications of advancement flaps. (a) A dorsal nasal advancement flap. The edges of the flap follow the junction between the dorsal and lateral subunits. Branches of the supratrochlear artery enter the base of the flap, axializing it, and allowing a long flap. (b) A crescentic advancement flap for reconstruction of a defect of the upper lip. Left: the defect is extended to make a square, and the flap is planned the same size. Large crescent-​shaped areas are excised (hatched areas) as Burow’s triangles to permit the advancement. Right: after advancement and inset, careful planning should leave the donor scars hidden in the alar groove and nasolabial fold. A–​B should lie along the philtral column.

(a)

(b)

Fig. 1.8.14  Interpolation flaps. (a) Left: the flap consists of the white circle (designed to fit the nearby defect) and the light grey area, which is de-​epithelialized and forms the pedicle. The dark grey areas are dog-​ears which may be excised. Right: the flap after transposition, the dashed grey lines delineate the subcutaneous tunnel through which the flap is passed, and within which the pedicle lies. (b) The typical clinical application of an interpolated flap is for reconstructing a defect of the alar base, where a standard nasolabial transposition flap would pass across the nasolabial groove, distorting the contour. Here, the dark grey area is the de-​ epithelialized pedicle, and the light grey area is the subcutaneous tunnel.

In some circumstances, local anatomy precludes the use of a standard transposition flap, where the pedicle is likely to distort, or add scarring to, important structures. In such cases, an interpolation flap may be used. The design is the same as a standard transposition flap, but the skin/​subcutaneous pedicle is de-​epithelialized and passed through a subcutaneous tunnel to reach the defect being reconstructed (Fig. 1.8.14). This allows the pedicle to be hidden from view. In theory, a flap may also be interpolated by passing the pedicle over an intervening skin bridge, but this necessitates a secondary division of the flap pedicle and so this approach is rarely used in practice for local flaps.

REFERENCES Ahuja RB. Geometric considerations in the design of rotation flaps in the scalp and forehead region. Plast Reconstr Surgery 1988;81: 900–​6. Burget GC, Menick FJ. The subunit principle in nasal reconstruction. Plas Recon Surg 1985;76:239–​47. Cho M, Kim D. Modification of the Zitelli bilobed flap:  a comparison of flap dynamics in human cadavers. Arch Facial Plast Surg 2006;8:404–​9. Dufourmontel C. Le fermeture des pertes de substance cutanee limitees “Le lambeau de rotation en L pour losange” dit “LLL”. Annales de Chirurgie Plastique 1962;7:61–​6. Esser JFS. Gestielte lokale Nasenplastik mit Zweizipfligem lappen, Deckung des Sekundaren Defektes vom ersten Zipfel duch den Z weiten. Dtsch Zschr Chir 1918;143:385–​90. Limberg AA. Modern trends in plastic surgery. Design of local flaps. Mod Trends Plast Surg 1966;2:38–​61. Lister GD, Gibson T. Closure of rhomboid skin defects:  the flaps of Limberg and Dufourmentel. Br J Plast Surg 1972;25:300–​14. Lo CH, Kimble FW. The ideal rotation flap: an experimental study. J Plastic Reconstr Aesthet Surg 2008;61:754–​61. McGregor JC, Soutar DS. A critical assessment of the bilobed flap. Br J Plast Surg 1981;34:197–​205. Quaba AA, Sommerlad BC. “A square peg into a round hole”:  a modified rhomboid flap and its clinical application. Br J Plast Surg 1987;40:163–​70. Sandhir RK. Divine rotation flap. Ann Plast Surg 1997;38:194–​5. Zimany A. The bi-​lobed flap. Plast Reconstr Surg 1946;11:424–​34. Zitelli JA. The bilobed flap for nasal reconstruction. Arch Dermatol 1989;125:957–​9.

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1.9

Microsurgery David McCombe and Wayne Morrison

Introduction Microsurgery for the plastic surgeon is the technique of surgery performed under magnification that allows for accurate dissection and repair of microvascular structures and peripheral nerves. Proficient microsurgery expands the realm of reconstructive surgery by allowing reliable revascularization of tissues, nerve repair, and the repair of other tubular structures such as the vas deferens. This chapter will focus on microvascular surgery, with peripheral nerve surgery covered in detail in Chapter 3.4.1.

History The techniques of vascular surgery pioneered by Alexis Carrel and others including the triangulation suture technique of vessel repair (Fig. 1.9.1) and the importance of including the intima within the suture (Carrel and Guthrie, 1906; Guthrie, 1912), form the basis

Fig. 1.9.1  Triangulation suture technique of anastomosis promoted by Carrel and Guthrie with sutures at three equidistant points around the anastomosis and then a continuous suture between each of these points. The division of the anastomosis into segments limits stenosis by gathering of the continuous suture and allows for the back wall of the anastomosis to fall away from the anterior suture line. Reproduced from Guthrie, G. 1912. Blood-​vessel surgery and its application. London, Edward Arnold, 44–​54.

of the microvascular surgery performed today over one hundred years later. Carrel, a French surgeon who emigrated to Canada and thence to the United States in 1903, was later recognized for his work when awarded the Nobel Prize in Physiology or Medicine in 1912. His oeuvre included many vascularized transplants in animals. Macrovascular repair progressed during the Korean and Vietnam conflicts and in civilian practice repair of the smaller vessels of the extremity allowed revascularization of the hand (Kleinert et  al., 1963), and replantation of amputated limbs (Chen et al., 1963; Malt and McKhann, 1964). Free tissue transfer with vascular anastomosis was also performed during this period with Seidenberg and co-​ workers performing a jejunal transfer for oesophageal reconstruction in 1957 (Seidenberg et al., 1959), and while this patient died from a stroke 7 days after surgery, the jejunal segment was examined postmortem and considered to have been viable. While magnification with an operating microscope was being used in other fields of surgery in the early twentieth century, Jacobson and Suarez were the first to publish about the use of the technology for anastomosis of small vessels in the 1960s and developed instrumentation and a double binocular microscope to allow for the surgeon and assistant to share the optical field (Jacobson and Suarez, 1962). The technique of microvascular surgery was further refined by Buncke and colleagues with experimental work in primates including a toe to thumb transplant (Buncke et  al., 1966). Clinically, microvascular surgery began to find application with replantation of a digit first performed in 1965 (Komatsu and Tamai, 1968). Subsequently, Cobbett performed a toe to thumb transfer to reconstruct a woodworker’s hand in 1968 (Cobbett, 1969). His report details the travails of microsurgery but ultimately the transferred toe survived and became a functioning digit. The further history of ‘free’ transfer of tissue, following the initial vascularized transfers of jejunal and gastric segments in the 1950s, was marked by McLean and Buncke’s (1972) report of the transfer of the omentum to a scalp defect following resection of a neurofibroma in 1971 with the microscope used for the vascular anastomoses. Daniel and Taylor (1973), Harii and colleagues (1974) and O’Brien and co-​workers (1973) all reported free vascularized skin flap transfers in quick succession, and these reports heralded an exciting era of the expansion of microsurgery from these early steps to the transfer of vascularized muscle, fascia, nerve, bone, joints, as well as composite flaps of these tissues allowing customized

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SECTION 1  General principles and techniques

reconstruction of defects. Ongoing development with application of the expanding knowledge of vascular anatomy (see Chapter  1.5) has led to the refinement of flap transfer to perforator-​based flaps, minimizing donor site morbidity. Microvascular surgery has also evolved to address lymphoedema, to promote angiogenesis within prefabricated or tissue-​engineered constructs, and most recently composite tissue allotransplantation.

Principles of microvascular surgery Vascular injury and repair The haematological and vascular responses to injury are important factors in the patency of anastomoses and the consequent perfusion of replanted or transferred tissues. The mechanism of injury, the type of vessel, and pre-​existing vascular disease will influence the response of the vessel. Crush and particularly avulsion injuries damage segments of the vessel wall, the arteries being more severely affected than the veins. Vascular injury can be exacerbated by the surgeon with traumatic handling of the vessel, particularly the intimal surface, desiccation of the vessel, high-​pressure hydrodilation, excessive clamp pressure, and tension across the anastomosis all contributing to injury. Pre-​existing disease of the artery such as arteriosclerosis, radiation injury, or inflammation will make microvascular anastomosis more difficult due to the presence of subintimal calcific plaques, delamination of the intima, oedema, or fibrosis or friability of the artery wall. Even after appropriate debridement of damaged vessel and meticulous microvascular repair the damaged intimal surface at the anastomosis will provoke the formation of platelet thrombus through the activation of platelets stabilized by a fibrin lattice that forms as a consequence of the intrinsic and extrinsic clotting pathways. Following anastomosis of healthy vessels where there has been no or minimal intimal injury, the platelet aggregates forming at the anastomosis are limited and disappear by 24–​72 hours. They are replaced by a pseudo-​intima within 5  days and normal endothelium by 3 weeks. Intimal hyperplasia typically develops at the anastomosis, peaking at 3 months post anastomosis (Lidman et al., 1984). On the other hand, occlusive thrombus can form at the anastomosis where there is significant abnormality of flow or extensive intimal injury that is either present before or resulting from the anastomosis. Hypercoagulable states can also contribute to occlusion. Further vascular injury can occur within the flap, digit, or limb itself distal to the anastomosis due to a period of ischaemia and then subsequent reperfusion once blood flow has been re-​established (ischaemia reperfusion injury). The effect of ischaemia is to increase intracellular calcium, reduce pH, and increase xanthine oxidase production, and with reperfusion into this environment, reactive oxygen species (oxygen free radicals) are formed within the mitochondria. These free radicals lead to cellular membrane injury and subsequent necrosis and apoptosis. Leucocytes, complement, mast cells, and immune complexes are also activated. This complex process leads to endothelial oedema and dysfunction, with vasoconstriction, an increase in postcapillary venule permeability, and thrombosis within the capillary bed of the revascularized flap, digit, or limb (Khalil et al., 2006; Wang et al., 2011). The reperfusion injury

is dependent on the duration of ischaemia, the tissue temperature, and the tissue type, with muscle being more sensitive than skin, soft tissue, or bone. At its most marked, the capillary bed thrombosis and retrograde vascular occlusion leads to what is recognized as the ‘no reflow phenomenon’ where despite an apparently successful arterial anastomosis re-​establishing inflow to the tissue, the venous outflow is poor and progressively declines to the point where it ceases (a phenomenon recognized initially with areas of persistent defects of cerebral perfusion following transient ischaemia (Majno et  al., 1967)). The most effective treatment is prevention and includes limiting the duration of ischaemia and cooling the ischaemic part. Other strategies of prevention include administration of antioxidants perioperatively, intra-​arterial perfusion of the ischaemic tissue with preservatives such as University of Wisconsin solution or heparin, and ischaemic preconditioning of the flap. Ischaemic preconditioning of the flap can be achieved acutely by intermittent short-​duration arterial occlusion prior to definitive pedicle division, which alters cellular metabolism and reduces production of the reactive oxygen species responsible for the ischaemia reperfusion injury. These techniques have been researched at length but have yet to be accepted into standard practice (Khalil et al., 2006; Wang et al., 2011). If the ‘no reflow phenomenon’ becomes established, revision of the anastomoses and perfusion with a fibrinolytic agent such as tissue plasminogen activator can lyse thrombi and assist in salvage (Chang et al., 2011).

Equipment Microvascular surgery requires magnification, either by operating loupes or operating microscope, specialized instruments, and sutures or coupling devices that allow the surgeon to dissect and to anastomose vessels of diameters as small as 0.3 mm (Masia et al., 2014). While operating loupes have advantages in cost and flexibility, magnification is limited practically to the range of 2.5–​4.5×. For most surgeons, loupes are used for dissection of flaps and pedicles but optimally an operating microscope is used for vessel preparation and anastomosis. Magnification up to 40× can be achieved, with high-​quality illumination and a shared optical field for the surgeon and assistant. Also, an attached video camera and display facilitates more active participation by the operating room nurses and students. Microsurgeons should familiarize themselves with the microscopes available to them and personalize settings for interpupillary distance, eyepiece dioptre settings, and operating distance so as to optimize the conditions for surgery. The instruments used for most microsurgery include a range of forceps, scissors, needle holders, and vascular clamps. The forceps are modified jewellers’ forceps with flat fine tips to minimize trauma while holding tissues and vessel dilator forceps with specialized rounded tips can be introduced within the lumen for manipulation or to gently dilate the vessel lumen. Straight and curved scissors are needed for vessel dissection, arteriotomy or venotomy, and for cutting sutures. Vascular clamps in a range of sizes matched to vessel diameter and available as both single and linked double clamps are essential. The clamp closing pressure must be sufficient to maintain occlusion and vessel positioning but not exceed 30 g/​mm2 to avoid trauma. Additional equipment such as fine-​calibre cannulas for irrigation, suction or cellulose sponges or ‘spears’ for clearing excess local fluid, microclips, and

1.9 Microsurgery

microbipolar diathermy for haemostasis should be available. Specialized sutures used for microvascular surgery are designed with fine-​calibre suture material (8-​0 to 11-​0 nylon) and usually curved taper-​point needles of 75–​135 μm diameters though there are some finer suture and needle combinations available for super microsurgery. Heparin diluted in saline or Ringer’s solution (100 units/​mL) should be available for irrigation of the vessel ends during anastomosis. Heparin is a glycosaminoglycan that is produced by mast cells and basophils. It activates antithrombin III, leading to inactivation of thrombin and factor Xa preventing thrombus formation and allowing unopposed thrombolysis. Reduced anastomotic thrombosis has been demonstrated with heparin irrigation in animal models (Cox et al., 1992), and it is widely used in clinical practice. Other drugs that should be available for topical application include vasodilators. There are a number of these available with varying evidence of efficacy for each (Vargas et al., 2015). The commonly used drugs include: • Papaverine: a phosphodiesterase inhibitor that inhibits vascular smooth muscle contractility as well as collagen-​induced platelet aggregation. Papaverine is acidic and can injure the endothelium if used as an intraluminal irrigant. • Lidocaine: the mechanism of its vasoactive effect is unclear with inhibition of sodium channels, stabilization of cell membrane preventing calcium influx, and its effect on autonomic nerves all proposed as responsible. The effect is dose dependent with topical application of lower concentrations of 1–​2% being found in animal models to be vasoconstrictive, compared to the vasodilation seen with use of 4% or greater solutions. • Calcium channel blockers (e.g. verapamil): these agents act to inhibit the influx of calcium which inhibits muscle contraction. Further vasodilators that have been used experimentally include prostaglandin E1, phentolamine, chlorpromazine, and magnesium sulfate among many others.

Microvascular surgery—​preparation While minimizing ischaemia time is important to avoid the complications of ischaemia reperfusion injury and flap or replant failure, rather than operating in haste, careful preparation is required to ensure there is an adequate environment for surgery and postoperative care, and that there has been appropriate patient and procedure selection. The environment The important environmental considerations include having adequate equipment and a microsurgical team, including anaesthetists who are familiar with the procedure and its requirements. The operating theatre should be warm to avoid cooling the patient intraoperatively and avoid the physiological peripheral vasoconstriction that maintains core temperature. Hypothermia is also associated with an increase in haematocrit and plasma viscosity (Hagau and Longrois, 2009), which increase the risk of thrombosis. The postoperative environment should also be warm to limit shivering and vasoconstriction. Experienced ward staff are essential to ensure monitoring of the patient’s haemodynamic status, analgesia requirements, and perfusion of the flap or replanted tissue. Despite the multiple modalities of postoperative monitoring that are available, and

will be discussed in later sections, clinical experience of direct assessment of flap or replant perfusion is invaluable. Patient selection The indications for microvascular surgery have broadened as the technique has evolved and now patients considered for microsurgery include those with significant comorbidities and at the extremes of age. Although complications are higher in such groups including smokers, they relate to wound healing and medical complications rather than microvascular patency (Vandersteen et al., 2013). Age itself does not seem to influence outcomes independent of the accrued patient comorbidities (MacLeod and Cleland, 1994; Peters et al., 2015). The patient characteristics that do appear to affect the success of microvascular surgery include preoperative radiotherapy, obesity, peripheral vascular disease, concurrent immunosuppressive therapy, and thrombophilia due to either congenital or acquired causes (Chang et al., 2000; Mehrara et al., 2006; Benatar et al., 2013; Kolbenschlag et al., 2014; Masoomi et al., 2014; Sbitany et al., 2014). While many of these factors are not reversible, those that can be should be addressed and should be considered in patient and procedure selection and in informing the patient of the risks of surgery. Procedure selection The fundamental requirements for successful microvascular surgery are that the flap or amputated tissue has a vascular pedicle that perfuses the part, that the recipient vessels are of good calibre and flow, and that the arterial and venous anastomoses remain patent. The surgeon’s choices of flap, recipient pedicle, and anastomotic technique influence each step. For free tissue transfer, the choice of flap is determined by the specific requirements of the reconstruction and by donor site availability or suitability. Choice is also influenced by the suitability of the flap pedicle for the likely recipient site, particularly pedicle length and calibre and whether the flap can be harvested simultaneously with the dissection of the recipient site to avoid repositioning of the patient during surgery. While knowledge and experience of a range of flaps is important to the surgeon, making the right choices about the recipient pedicle and meticulous preparation of these vessels is paramount. A pedicle of adequate length and calibre is chosen and mobilized to bring the site of anastomosis into an accessible part of the wound. Every effort should be made to align the vessels for repair at right angles to the operator and in the horizontal plane to ensure maximum visualization of both lumens during anastomosis. If, despite planning, these conditions aren’t possible, the surgeon must consider the elective use of vein grafts to lengthen the pedicle, rather than proceed with a suboptimal anastomosis and then be forced to salvage the situation with vein grafts later. For replantation or revascularization, the surgeon’s choice of microvascular procedure is limited by the nature and site of injury; however, the principles of preparation of the vessels and site of anastomosis still apply.

Microvascular surgery—​technique The initial steps of a microvascular free tissue transfer are elevation of the flap tissue including its pedicle as well as dissection of the vessels at the recipient site. In the case of replantation, debridement of the wounds and identification of appropriate vessels are required. This is followed by inset of the flap or replant and then vascular

53

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SECTION 1  General principles and techniques

anastomosis. The final step is completion of the inset and dressing the wounds. Flap and vascular pedicle dissection The design and elevation of a flap for free tissue transfer requires a thorough knowledge of anatomy, a template or understanding of the defect to be reconstructed, and care to preserve the continuity of the vascular pedicle of the flap. With perforator flaps, the vascular pedicle dissection is continued beyond the main trunk of the pedicle to include the relevant perforating branch(s), and particular care must be taken with these smaller-​calibre and often-​fragile vessels. Unwanted side branches are ligated with clips or bipolar diathermy away from the main pedicle to limit injury and care taken to avoid excessive tension, torsion, or shearing of the pedicle during mobilization of the flap which may result in avulsion of the pedicle or pedicle injury. Once the flap pedicle is dissected back to its origin or a point where the flap vessels are of adequate length and calibre, the flap can be temporarily secured in its donor site for safety while the recipient site dissection is completed. It is important not to divide the pedicle until the recipient vessels are fully prepared to minimize the ischaemia time of the flap. The adequacy of the perfusion of the flap should also be confirmed at this point prior to division of the pedicle. The recipient vessels are prepared and mobilized to ensure that the subsequent anastomosis will be tension free and accessible within the field of an operating microscope and care taken to ensure the proximal arterial and venous recipient pedicles are uninjured, particularly in a combined case where another surgeon may have inadvertently traumatized the proximal pedicle without realizing the importance of these vessels to the microsurgeon. At this point, and still prior to division of the flap pedicle, the authors prefer to divide the recipient artery to confirm adequate flow and an appropriately sized microvascular clamp is applied. The flap pedicle is then divided and the proximal stump of the donor pedicle ligated. The authors prefer not to clip or clamp the flap side of the pedicle to limit trauma, and will in small-​calibre pedicles with venae comitantes mark the artery with a pen so as to avoid the embarrassment of confusing the veins and artery at the subsequent anastomosis. This is not always necessary as often it is self-​evident.

surgeon preference. If access to the anastomosis is difficult because it lies deep in the wound, a small swab placed beneath the vessels to elevate them into a more superficial plane is helpful. A low-​pressure suction system can also be useful to prevent the anastomosis being submerged in blood and irrigation fluid. At this point, the surgeon should check the pedicles for twists, malposition, and tension-​free apposition. Under the microscope, the vessels are inspected for luminal injury. Further dissection using micro-​scissors to isolate and mobilize the pedicle artery or veins can be performed at this point, taking advantage of the assistant’s ability to provide gentle counter traction on the vessel. The vessels should be handled by grasping the adventitia only, rather than the full thickness of the vessel or the intima. The adventitia should be trimmed from the end of the artery to prevent it prolapsing into the anastomosis where it may be a thrombogenic stimulus. This may not be necessary for the veins as these are thin walled and the adventitial layer less significant. The end of the vessel should be trimmed if there is any evidence of irregularity or crush injury from the original flap dissection (Fig. 1.9.2a). In the case of an arteriosclerotic artery, it is preferable to find a soft segment of the artery without plaques if possible. Some arteriosclerotic or irradiated arteries tend to delaminate with trimming and in this situation it helps to cut around the circumference of the vessel from the inside of the lumen so as to try to compress the intima against the medial layer rather than trying to cut across the whole vessel with a single stroke of the scissor blades (Fig. 1.9.2b). With the vessel ends prepared, the authors usually check the flow in the recipient artery and irrigate all the vessels with heparinized saline to clear the vessels of thrombus. The decision as to whether to perform the venous or arterial anastomosis first depends on which anastomosis will be deeper in the wound and which pedicle is shortest, so that the other pedicle can be trimmed to this length and avoid kinking of the longer vessel. Anastomoses are either performed end to end or end to side, and they are secured with interrupted sutures or in the case of end-​to-​ end venous anastomosis, a coupling device can be used. Alternative methods using tissue adhesives and lasers have been described but remain experimental (Pratt et al., 2012). When using sutures,

Flap inset The extent of inset of the flap required prior to microvascular anastomosis varies according to circumstance. Toe transfer for digit reconstruction requires osteosynthesis and tendon repair prior to anastomosis because of the risk to the anastomosis if these steps were to be performed after the digit was revascularized. On the other hand, for soft tissue coverage or breast reconstruction, it is often preferable to only tether the flap in a temporary position adjacent to the defect so as to allow access to the recipient pedicle which would otherwise be buried under the inset flap. It is important to consider this step carefully so as to set up the microvascular anastomosis in as favourable position as possible. Time spent at this stage is a good investment in the overall success of the surgery. Microvascular anastomosis The flap and recipient vascular pedicles can now be brought into proximity, secured in position with a double microvascular clamp and elevated into the superficial part of the wound. Background contrast material may be placed behind the vessels according to

(a)

(b)

Vessel wall intact Delamination of the vessel wall

Fig. 1.9.2  Preparing the vessel ends prior to anastomosis. (a) Where the structure of the vessel wall is intact, the end can be trimmed with sharp scissors to remove any crushed or irregular margin. (b) If the vessel wall is stiffened due to arteriosclerosis or radiation injury, cutting the vessel end can crush the rigid vessel wall and lead to delamination. This effect can be reduced by cutting around the circumference of the vessel with the blades of the scissors compressing the wall together as they cut.

1.9 Microsurgery

the path of the needle should be perpendicular to the vessel wall to avoid the further trauma of an oblique needle path and to produce an everted suture line. The suture ‘bite’ size should be regular to avoid bunching and inverting the vessel wall and presenting the thrombogenic adventitia to the lumen. Experience is important in assessing the tension of the suture. Excess tension produces ischaemia of the vessel wall and intimal injury, but inadequate tension leads to gapping and leaking. Similarly, the number of sutures can be judged with experience with too many sutures leading to an ischaemic vessel wall and ultimately thrombosis and too few, leaking and haematoma. Where the vessel is diseased and prone to delamination, it can be useful to arrange the anastomosis so the suture is passed from luminal surface out through the diseased vessel, so as to compress the fragile vessel wall with the suture rather than push the lamina of the vessel apart with the needle coming from the external surface inwards. For veins, it is best to avoid anastomosis at the level of a valve so the lumen can be defined clearly as often the vein wall is thin and difficult to delineate from the valve. Before completing the anastomoses, both vessel lumens should be irrigated to remove any blood or thrombogenic debris. The final sutures of an anastomosis may be difficult to place particularly with the more rigid artery, as the view of the lumen can be obscured. At this point, the penultimate suture can be inserted but not tied, allowing enough of a gap for the lumen to be irrigated and the final suture to be inserted before tying both sutures (Harashina, 1977; Foucher and Schuind, 1984). The end-​to-​end anastomosis is usually performed using a double clamp to immobilize the vessels although in small spaces that do not easily accommodate their bulk, separate single clamps on each vessel allows for easier manipulation of the recipient and flap vessels. The clamp is positioned so that the vessels are not twisted relative to each other, the anastomosis won’t be under tension, and that there is enough free vessel length to allow their manipulation. Interrupted sutures are preferred by the authors over continuous to avoid producing a stenosis and to allow more precise suture placement, though continuous techniques have their proponents, citing equivalent patency rates and reduced operating time (Alghoul et al., 2011). The sequence of suture depends upon the circumstance of the anastomosis. Where the clamp can be turned over easily, placing sutures at 120-​degree (triangulation) or 180-​degree intervals allows the anastomosis to be broken up into segments with greater precision of matching the suture intervals in each vessel and hence avoiding bunching up of one of the vessel ends relative to the other. It also encourages the ‘back’ or deep wall of the anastomosis to fall away from the superficial interval being sutured, reducing the risk of capturing the back wall inadvertently with the suture and occluding the anastomosis. With this technique, the initial sutures are placed and then each segment is closed and to close the back wall, the clamp is rotated to bring this into the superficial wound. The lumen can be checked at this point to ensure it is patent before completing the closure. This technique is particularly useful where there is mismatch of the diameter of the vessels as it allows the difference in relative length of circumference of each vessel to be taken up gradually. Where the clamp cannot be turned over, the anastomosis can be performed by beginning the suturing at the deep surface and working sequentially up each side of the anastomosis until the suture is completed anteriorly. Mismatch of vessel diameter at an end-​ to-​end anastomosis can either lead to excessive turbulence of flow or leaking. There are several strategies that can be used to manage this

problem. A mismatch of up to two to one can be addressed with differential suture interval in the two vessels to produce an even anastomosis. Where the mismatch is greater, either cutting the smaller vessel obliquely or spatulating its end with a longitudinal incision increases its circumference. Another technique reported for this situation is the sleeve anastomosis (Lauritzen, 1984), though this is not used by the authors. The end-​to-​end anastomosis can also be performed with a coupling device (Fig. 1.9.3). Originally developed by Nakayama and colleagues (1962), the coupling device consists of a pair of rings with pins that are held on a frame in an open position like on the opposing leaves of an open book. A handle spindle at the leaf hinge is rotated to open or close the rings. The coupling rings are available in a range of sizes and a template is used to estimate the size required. Each vessel end is brought through its ring in turn, the mobile or less fixed one first to allow it to be brought to the fixed one. The vessel end is everted and anchored circumferentially by the pins and the rings are then rotated into apposition and the pins interlock, securing the everted anastomosis. The handle with its frame support then disengages and can be withdrawn. Equivalent patency rates and reduced operating times compared to hand-​ sewn anastomoses are reported (Ardehali et al., 2014). Some vessel diameter mismatch is tolerated by the technique but care has to be taken to avoid either stretching the small vessel excessively or bunching the larger vessel and leaving gaps that will leak. While use in arterial and end-​to-​side anastomoses is reported, the coupling devices are most commonly used for venous anastomoses, as veins are pliable and can be everted more easily. Another option for securing the anastomosis is the Vascular Closure Stapler device (VCS-​Anastoclip®, Le Maitre). The non-​penetrating staples are applied to the margins of the anastomosis once three or four stay sutures have been placed to allow the assistant to elevate the intervening segments of the anastomosis so the staples can be applied. Again, equivalent patency rates and reduced operating time are reported (Reddy et al., 2012). The end-​to-​side anastomosis is used where the recipient pedicle artery or vein cannot be divided or where there is significant mismatch in vessel diameter that cannot be effectively addressed with the techniques discussed previously. The key steps in the end-​to-​side anastomosis (Fig. 1.9.4) are the arteriotomy or venotomy, the placement of the initial sutures at one of the apices of the anastomosis, securing the vessel, and then the repair of the rear wall and then anterior wall of the anastomosis. The recipient vessel is mobilized and side branches ligated so a double clamp can be applied to an isolated segment. The arteriotomy or venotomy is sited so that the flap pedicle will lie flat in the wound without a kink or fold. An appropriately sized oval disc of the recipient vessel wall is resected. This is relatively straightforward for a venotomy, but the thicker wall of the artery makes this more difficult and there are risks of resecting an excessive amount of the artery wall or leaving a ragged margin that is difficult to repair neatly. Arterial punches can be used or the authors use a suture placed into the wall of the artery at the site of the arteriotomy to place traction on the wall and use sharp scissors to cut below this to form the arteriotomy. The margins are trimmed if necessary, the lumen irrigated, and then an apical suture placed to begin the anastomosis. The deep or back wall is then sutured toward the other apex of the anastomosis. The anterior or superficial wall of the anastomosis is then completed.

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(a)

(b)

(d)

(c)

(e)

Fig. 1.9.3  Venous anastomosis using a microvascular anastomotic coupler (Synovis, Birmingham, AL). (a) The diameter of the vein is estimated using the measuring gauge. A mismatch in diameter of 1 mm is tolerated by the coupling device. The size of the smaller vein should be chosen for the coupler. If the coupling ring is too large for the vein, there is a risk of tearing the vein as it stretches around the circumference of the ring, too small and the vein will be infolded into the lumen of the anastomosis. (b) The coupling ring is mounted on an anastomotic device. Note the pins on the opposing surfaces of the ring. (c) The vein is brought through the ring and everted over the pins, gently forcing the vein wall over the pin to hold the vein in place. Care needs to be taken to site the vein so the pins pierce the full thickness of the vein wall at equidistant intervals to limit infolding and produce an intima-​to-​intima anastomosis. (d) The coupling rings are brought together by winding the anastomotic device, and the ring is disengaged from the device once closed. The ring can be further compressed at this point by a haemostat forcep. (e) The completed venous anastomosis. The arterial anastomosis is a sutured anastomosis.

Once the arterial and venous anastomoses are complete, the clamps can be removed carefully using some irrigation fluid to lubricate the arms of the clamp. Vasodilating drugs (see ‘Equipment’) may be applied if there is concern regarding vasospasm. The anastomoses and the distal flap perfusion are observed. It is usually wise at this point to avoid handling the vessels to limit vasospasm and optimize flow, as this time is the highest risk for anastomotic thrombosis. A warm pack is placed over the flap or replant and left for 15 to 20 minutes to allow the circulation to normalize prior to completing the inset of the flap and wound closure. The distal pedicle should be observed for pulsation, the flap for perfusion and the vein for congestion. If there is concern about the patency of the anastomosis, a ‘patency test’ can be performed where the artery distal to the anastomosis is gently compressed with a forcep to occlude flow, a second forcep is applied distal to this and drawn a short distance further distally along the artery to empty this segment. Then, with the second forcep still occluding the distal end of this empty segment to

prevent back flow, the proximal forcep is released. If the anastomosis is patent, the segment should fill rapidly from proximal to distal and both forceps can be released. This test should be applied judiciously to avoid excessive handling of the pedicle. The surgeon may proceed with a second venous anastomosis if an accessory flap vein and recipient are available. There is evidence that this may reduce pedicle thrombosis and the need to return to theatre (Ross et al., 2008; Chen et al., 2014; Silverman et al., 2016) but a contrary argument is that having two venous anastomoses reduces venous blood flow velocity in each vein and hence increases risk of thrombosis (Hanasono et al., 2010). Despite this latter evidence, the authors will perform more than one venous anastomosis if there is any concern about venous congestion and the second anastomosis does not distort either the initial venous or arterial anastomosis. Vein grafts are used either electively to extend the flap or replant pedicle where no local recipient vessels are available or to salvage a thrombosed pedicle where resection and replacement of a length

1.9 Microsurgery

(a)

(b) First interrupted suture

(c)

(d)

Fig. 1.9.4  End-​to-​side anastomosis. (a) A full-​thickness traction suture is inserted in the wall of the vessel to raise a dome. The base of this dome is incised with sharp scissors to create an elliptical arteriotomy. (b) The first suture is placed at one of the apices of the ellipse. (c) The ‘back’ (less accessible) wall of the anastomosis is completed and the other apex of the ellipse is secured. (d) The ‘front’ (more accessible) wall of the anastomosis is completed.

of pedicle and anastomosis is required. Vein grafts can be harvested from the saphenous vein system or locally, depending on the length and calibre required. Side branches are ligated carefully and the length of the graft measured in situ before the elevation of the graft, as the graft will contract when free and then re-​elongate when perfused. This elongation can lead to kinking of the pedicle if too long a graft is inset. The graft should be irrigated and dilated with heparinized saline to ensure the graft is of adequate calibre, the side branches have been ligated, and the graft is not twisted. When used as an arterial conduit, the graft is reversed to account for the direction of the valves. Vein grafts are susceptible to early loss of the endothelium and subsequent neointimal hyperplasia, which may cause late occlusion. Whether this is clinically significant depends upon whether the transferred flap has gained an adequate circulation from its inset. This late occlusion is more relevant in replantation or revascularization (Morrison et al., 1998). Antiplatelet agents are used routinely in coronary artery grafting to prevent late occlusion of vein grafts and may have a role here as well. Flap inset, wound closure, and dressing Once the patency of the anastomoses have been established, haemostasis is secured and the course of the pedicle should be checked after the flap is in its definitive position, ensuring there are no kinks or twists. The flap inset is completed with care, being sure that the wound closure does not compress the vascular pedicle and taking into account the likely postoperative swelling. Drains, if used, should be secured away from the pedicle and anastomoses. Dressings and splints are applied to protect the flap or replant taking care to prevent compression.

Postoperative care and monitoring After the procedure is completed, it is important to keep the patient warm during transfer to the recovery room and ward to limit the risk of peripheral vasoconstriction. The patient should be kept comfortable and haemodynamically stable with adequate fluid replacement to drive peripheral perfusion. The patient’s haemodynamic

parameters should be carefully monitored including the differential between core and peripheral temperature to ensure the circulatory volume is maintained. The perfusion of the flap or replant itself can be monitored in a number of ways. Direct clinical observation is the mainstay of monitoring but requires experience. Tissue warmth, colour, turgor, and capillary return should be assessed regularly and documented. An objective measure of flap perfusion is flap temperature as measured by a surface probe or adhesive thermal sensor. This can be compared to adjacent skin for relative perfusion. Pedicle or flap perforator blood flow can be assessed by Doppler ultrasound using an external probe. There is the potential to mistake an adjacent vessel for the flap artery and to be deluded especially with buried flaps by a continuing arterial signal long after the flap pedicle has occluded. A potentially more reliable method is to use an implantable Doppler probe placed within a cuff adjacent to the venous pedicle at the time of surgery, connected to a monitor with a percutaneous fine wire electrode. At 3–​5 days the implanted electrode is withdrawn and it disengages from the cuff. This technique is particularly useful for buried flaps. Other techniques of non-​invasive continuous monitoring include colour Duplex sonography which measures velocity and direction of flow, near infrared spectroscopy which measures haemoglobin oxygen saturation in the tissues of the flap, and laser Doppler flowmetry which measures blood flow in the microcirculation. All of these techniques have been shown to be effective in clinical application (Smit et  al., 2010). The reliability of any of these techniques is dependent on the experience of the surgeon and nursing staff and correlating their readings with clinical observations. The important step is to recognize and act upon the observations. When the circulation of the flap appears to be deteriorating, it is critical to act and return the patient to theatre to assess the anastomoses and address any issues. Delay at this point often condemns the flap or replant to failure because of the consequence of prolonging the ischaemic injury.

Outcomes and complications Outcomes in microvascular surgery as measured by flap survival have reached the level where at least 95% of flaps employed in a broad range of reconstructions will survive (Damen et  al., 2013; Fischer et al., 2013; Wu et al., 2014). Beyond this figure, however, is a significant incidence of flap-​related complications such as arterial or venous thrombosis which require re-​exploration and revision of the affected anastomosis, partial flap necrosis due to either extending the flap beyond the region of reliable perfusion or due to the consequence of ischaemia reperfusion, and wound-​related complications such as haematoma, wound dehiscence, or infection. These complications will require return to theatre, prolongation of recovery, and will likely impact functional and aesthetic outcomes. While microvascular surgery has become a routine tool for the plastic surgeon, it is not for the faint-​hearted and is best performed in units with high caseloads so that expertise in the procedure, postoperative care, and management of complications can be maintained.

Arterial occlusion Intraoperatively, arterial insufficiency is recognized by the failure of the flap or replant to flush pink, an absence of capillary refill, and no bleeding from the cut tissue edge. There will also be absence

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of pulsatile flow within the arterial pedicle. Theoretically, this may represent vasospasm, arterial anastomotic thrombosis, or pedicle obstruction from kinks, twists, or technical damage during dissection. Vasospasm can be excluded by performing a patency test on the recipient artery proximal to the anastomosis. If there is no forward flow to the level of the anastomosis then it may be due to vasospasm or proximal vessel damage but the latter should have been excluded prior to anastomosis. Vasospasm is likely where there has been inadequate fluid replacement, hypothermia, or hypotension. This can be compounded by administration of vasoconstrictors to maintain blood pressure. Vasodilators such as lidocaine, verapamil, or papaverine can be applied topically and the adventitia of the proximal vessel can be gently stripped, and systemic causes must be simultaneously corrected. Occlusion of the arterial pedicle or anastomosis may be due to thrombus secondary to mechanical obstruction by misplacement of sutures, dissection and clamp damage, or most likely vessel wall injury associated with the original pathology (trauma, radiation, etc.). Arterial inflow may stop during insetting of the flap due to compression of the pedicle or the failure to maintain adequate perfusion through the anastomosis. If, after ensuring local vasospasm has been treated, pulsatile flow does not return or the flap does not perfuse within 15 minutes, the anastomosis should be revised after all clot is removed and damaged vessel ends resected. The lumen is thoroughly irrigated with heparinized saline and an adequate flow in the proximal artery is reconfirmed. Postoperatively, if arterial thrombosis is suspected because of deterioration in flap perfusion, temperature, or Doppler signal, immediate return to theatre is required and the anastomosis needs to be evaluated and revised if occlusion is suspected. Where the intra-​arterial thrombus is extensive or adherent to the intima, resection of the pedicle and replacement of the affected segment with a vein graft may be required. Systemic heparin, platelet inhibitors, or fibrinolytics may be administered to minimize risk of recurrent thrombosis, but the associated risk of haematoma needs to be considered in the individual case. If perfusion can be re-​established,

(a)

ischaemia reperfusion injury may still complicate the surgery and lead to either partial or total flap necrosis. The mechanism and treatment of ischaemia reperfusion injury has been discussed earlier in this chapter.

Venous congestion The revascularized flap or replant will become congested if the venous pedicle is thrombosed, compressed, or inadequate to cope with the arterial perfusion. This will lead to swelling, congestion, and bleeding from the flap or replant and progresses to thrombosis throughout the flap and ultimately arterial occlusion (Fig. 1.9.5). Venous thrombosis is more common than arterial thrombosis (Bui et al., 2007; Wu et al., 2014); however, flap salvage rates are higher if the primary problem is venous congestion. The initial steps that can be taken to relieve flap or replant congestion are to relieve extrinsic compression by releasing bandages or dressings and to elevate the surgical site. If the flap remains congested, return to theatre is required to ensure there are no kinks or compression of the pedicle as well to evacuate haematoma and revise the anastomosis if there is thrombus present. If congestion persists despite these steps, venous drainage can be improved by anastomosis of additional veins. If no recipient veins are available, relief of venous congestion can be achieved by bleeding the flap or replant until enough angiogenesis at the flap or replant inset has occurred to allow adequate venous drainage. It is most effective in small volumes of tissue such as replants rather than large flaps and is not a substitute for re-​exploration and ensuring the patency of the primary venous pedicle. The bleeding of the flap or replant can be achieved by cannulation of an accessory flap vein and controlled venesection or via ‘leeching’ either with medicinal leeches (Hirudo medicinalis) or by creating a wound and local or systemic heparinization to encourage bleeding (Talbot and Pribaz, 2010). If medicinal leeches are applied, appropriate prophylactic antibiotics are required to prevent wound infection with the Aeromonas hydrophila and other organisms potentially transmitted by the leech (Kruer et al., 2015). While

(b)

Fig. 1.9.5  (a) Venous congestion in an anterolateral thigh free flap resurfacing an unstable prepatellar scar. The venous pedicle had twisted with inset of the flap and occluded. (b) The flap was successfully salvaged following revision of the venous anastomosis with thrombectomy and repositioning of the venous pedicle.

1.9 Microsurgery

salvage of flaps and replants has been reported with these adjunctive techniques (Nguyen et al., 2012), care must be taken with managing blood loss. The risks of bleeding, leech treatment, and blood transfusion need to be balanced against the likelihood and importance of flap salvage. In general, pedicle occlusion occurs typically within the first 3 days and salvage rates during this period are high. Late occlusion is associated with a poor outcome (Chen et al., 2007). The critical point here is the importance of early recognition of the compromise of perfusion and the preparedness to re-​explore the vascular pedicle and deal with the issues described.

Flap necrosis Flap necrosis may be partial or total. The management depends upon the extent of necrosis and the consequence of the resulting defect. There may be a need for debridement and further flap repair using either another free flap or regional flap, or the defect may result in a graftable defect or a contour defect that can be dealt with by repositioning of the surviving flap or addition of further tissue. While performing a further free flap to replace a failed flap is a daunting scenario, and the surgeon has to take into account the potential for a paucity of recipient vessels and a compromised bed to inset the flap, successful outcomes can be achieved (Wei et al., 2001).

Conclusion Microvascular surgery offers the plastic surgeon a powerful tool for repair and reconstruction. Replantation, revascularization, and free tissue transfer are reliably achieved but success requires attention to detail in preparation, performance, and postoperative care in these cases.

REFERENCES Alghoul MS, Gordon CR, Yetman R, et al. From simple interrupted to complex spiral: a systematic review of various suture techniques for microvascular anastomoses. Microsurgery 2011 ;31:72–​80. Ardehali B, Morritt AN, Jain A. Systematic review: anastomotic microvascular device. J Plast Reconstr Aesthet Surg 2014;67:752–​5. Benatar MJ, Dassonville O, Chamorey E, et al. Impact of preoperative radiotherapy on head and neck free flap reconstruction: a report on 429 cases. J Plast Reconstr Aesthet Surg 2013;66:478–​82. Bui DT, Cordeiro PG, Hu QY, et  al. Free flap reexploration:  indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg 2007;119:2092–​100. Buncke HJ, Jr, Buncke CM, Schulz WP. Immediate Nicoladoni procedure in the Rhesus monkey, or hallux-​to-​hand transplantation, utilising microminature vascular anastomoses. Br J Plast Surg 1966;19:332–​7. Carrel A, Guthrie CC, III. The reversal of the circulation in a limb. Ann Surg 1906;43:203–​15. Chang DW, Wang B, Robb GL, et al. Effect of obesity on flap and donor-​ site complications in free transverse rectus abdominis myocutaneous flap breast reconstruction. Plast Reconstr Surg 2000;105:1640–​8. Chang EI, Mehrara BJ, Festekjian JH, et  al. Vascular complications and microvascular free flap salvage: the role of thrombolytic agents. Microsurgery 2011;31:505–​9.

Chen CW, Chien YC, Pao YS. Salvage of the forearm following complete traumatic amputation:  report of a case. Chin Med J 1963;82:633–​8. Chen KT, Mardini S, Chuang DC, et al. Timing of presentation of the first signs of vascular compromise dictates the salvage outcome of free flap transfers. Plast Reconstr Surg 2007;120:187–​95. Chen WF, Kun Kung YP, Kang YC, et al. An old controversy revisited-​ one versus two venous anastomoses in microvascular head and neck reconstruction using anterolateral thigh flap. Microsurgery 2014;34:377–​83. Cobbett JR. Free digital transfer. Report of a case of transfer of a great toe to replace an amputated thumb. J Bone Joint Surg Br 1969;51:677–​9. Cox GW, Runnels S, Hsu HS, et al. A comparison of heparinised saline irrigation solutions in a model of microvascular thrombosis. Br J Plast Surg 1992;45:345–​8. Damen TH, Morritt AN, Zhong T, et al. Improving outcomes in microsurgical breast reconstruction: lessons learnt from 406 consecutive DIEP/​TRAM flaps performed by a single surgeon. J Plast Reconstr Aesthet Surg 2013;66:1032–​8. Daniel RK, Taylor GI. Distant transfer of an island flap by microvascular anastomosis. Plast Reconstr Surg 1973;52:11–​17. Fischer JP, Wink JD, Nelson JA, et al. A retrospective review of outcomes and flap selection in free tissue transfers for complex lower extremity reconstruction. J Reconstr Microsurg 2013;29:407–​16. Foucher G, Schuind F. A new trick for end-​to-​end anastomosis in microvascular surgery. Modified Harashina procedure. J Reconstr Microsurg 1984;1:49–​51. Guthrie G. Anastomosis of the vessels. In: Blood-​Vessel Surgery and its Application, pp. 44–​54. London: Edward Arnold, 2012. Hagau N, Longrois D. Anesthesia for free vascularized tissue transfer. Microsurgery 2009;29:161–​7. Hanasono MM, Kocak E, Ogunleye O, et al. One versus two venous anastomoses in microvascular free flap surgery. Plast Reconstr Surg 2010;126:1548–​57. Harashina T. Use of the united suture in microvascular anastomoses. Plast Reconstr Surg 1977;59:134–​5. Harii K, Ohmori K, Torii S. Free gracilis muscle transplantation, with microneurovascular anastomoses for the treatment of facial paralysis. Plast Reconstr Surg 1976;57:133–​43. Jacobson JH, 2nd, Suarez EL. Microvascular surgery. Dis Chest 1962;41:220–​4. Khalil AA, Aziz FA, Hall JC. Reperfusion injury. Plast Reconstr Surg 2006;117:1024–​33. Kleinert HE, Kasdan ML, Romero JL. Small blood-​vessel anastomosis for salvage of severely injured upper extremity. J Bone Joint Surg Am 1963;45A:788–​96. Kolbenschlag J, Daigeler A, Lauer S, et  al. Can rotational thromboelastometry predict thrombotic complications in reconstructive microsurgery? Microsurgery 2014;34:253–​60. Komatsu S, Tamai S. Successful replantation of a completely cut off thumb. Plast Reconstr Surg 1968;42:374–​7. Kruer RM, Barton CA, Roberti G, et  al. Antimicrobial prophylaxis during Hirudo medicinalis therapy: a multicenter study. J Reconstr Microsurg 2015;31:205–​9. Lauritzen CG. The sleeve anastomosis revisited. Ann Plast Surg 1984;13:145–​9. Lidman D, Lyczakowski T, Daniel RK. The morphology and patency of arterial and venous microvascular anastomoses throughout the first post-​operative year. A histological study. Scand J Plast Reconstr Surg 1984;18:187–​92.

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MacLeod AM, Cleland H. Free flaps in the aged and infirm. Med J Aust 1994;160:679–​81. Majno G, Ames A, III, Chiang J, et al. No reflow after cerebral ischaemia. Lancet 1967;2:569–​70. Malt RA, McKhann CF. Replantation of severed arms. JAMA 1964; 189:716–​22. Masia J, Olivares L, Koshima I, et  al. Barcelona consensus on supermicrosurgery. J Reconstr Microsurg 2014;30:53–​8. Masoomi H, Clark EG, Paydar KZ, et  al. Predictive risk factors of free flap thrombosis in breast reconstruction surgery. Microsurgery 2014;34:589–​94. McLean DH, Buncke HJ, Jr. Autotransplant of omentum to a large scalp defect, with microsurgical revascularization. Plast Reconstr Surg 1972;49:268–​74. Mehrara BJ, Santoro TD, Arcilla E, et al. Complications after microvascular breast reconstruction:  experience with 1195 flaps. Plast Reconstr Surg 2006;118:1100–​9. Morrison WA, Mitchell GM, Hickey MJ. Late occlusion of microvascular vein grafts in replantation. J Hand Surg Am 1998;23:1106–​11. Nakayama K, Yamamoto K, Tamiya T. A new simple apparatus for anastomosis of small vessels. Preliminary report. J Int Coll Surg 1962;38:12–​26. Nguyen MQ, Crosby MA, Skoracki RJ, et al. Outcomes of flap salvage with medicinal leech therapy. Microsurgery 2012;32:351–​7. O’Brien BM, MacLeod AM, Miller GD, et al. Clinical replantation of digits. Plast Reconstr Surg 1973;52:490–​502. Peters TT, Post SF, Van Dijk BA, et al. Free flap reconstruction for head and neck cancer can be safely performed in both young and elderly patients after careful patient selection. Eur Arch Otorhinolaryngol 2015;272:2999–​3005. Pratt GF, Rozen WM, Westwood A, et  al. Technology-​assisted and sutureless microvascular anastomoses:  evidence for current techniques. Microsurgery 2012;32:68–​76. Reddy C, Pennington D, Stern H. Microvascular anastomosis using the vascular closure device in free flap reconstructive surgery: a 13-​year experience. J Plast Reconstr Aesthet Surg 2012;65:195–​200.

Ross GL, Ang ES, Lannon D, et al. Ten-​year experience of free flaps in head and neck surgery. How necessary is a second venous anastomosis? Head Neck 2008;30:1086–​9. Sbitany H, Xu X, Hansen SL, et al. The effects of immunosuppressive medications on outcomes in microvascular free tissue transfer. Plast Reconstr Surg 2014;133:552e–​8e. Seidenberg B, Rosenak SS, Hurwitt ES, et al. Immediate reconstruction of the cervical esophagus by a revascularized isolated jejunal segment. Ann Surg 1959;149:162–​71. Silverman DA, Pryzlecki WH, Arganbright JM, et al. Revisiting the argument for one versus two-​vein outflow in head and neck free tissue transfers: a review of 317 microvascular reconstructions. Head Neck 2016;38:820–​3. Smit JM, Zeebregts CJ, Acosta R, et  al. Advancements in free flap monitoring in the last decade: a critical review. Plast Reconstr Surg 2010;125:177–​85. Talbot SG, Pribaz JJ. First aid for failing flaps. J Reconstr Microsurg 2010;26:513–​15. Vandersteen C, Dassonville O, Chamorey E, et  al. Impact of patient comorbidities on head and neck microvascular reconstruction. A  report on 423 cases. Eur Arch Otorhinolaryngol 2013;270: 1741–​6. Vargas CR, Iorio ML, Lee BT. A systematic review of topical vasodilators for the treatment of intraoperative vasospasm in reconstructive microsurgery. Plast Reconstr Surg 2015;136:411–​22. Wang WZ, Baynosa RC, Zamboni WA. Update on ischemia-​ reperfusion injury for the plastic surgeon: 2011. Plast Reconstr Surg 2011;128:685e–​92e. Wei FC, Demirkan F, Chen HC, et  al. The outcome of failed free flaps in head and neck and extremity reconstruction:  what is next in the reconstructive ladder? Plast Reconstr Surg 2001; 108: 1154–​60. Wu CC, Lin PY, Chew KY, et al. Free tissue transfers in head and neck reconstruction:  complications, outcomes and strategies for management of flap failure:  analysis of 2019 flaps in single institute. Microsurgery 2014;34:339–​44.

1.10

Benign skin conditions and tumours Rajib Rahim and Graeme Stables

Introduction Benign lesions of the skin can be classified according to their nature (cystic lesions or solid neoplasms) and their tissue of origin. Clinical characteristics assist in diagnosis and distinguishing these benign lesions from more aggressive lesions. Treatment is dictated by this assessment.

Cysts

Trichilemmal cyst (pilar cyst) Pilar cysts are common and primarily affect the scalp. The cyst wall derives from the external root sheath of the hair follicle and the content is keratin and keratin-​breakdown material. Clinically, lesions present as firm nodules on the scalp but can be lobulated. Unlike epidermoid cysts, a punctum may not be visible. Multiple cysts are common and this may be a genetic condition (autosomal dominant inheritance). Females are more commonly affected than males and the incidence increases from middle age onwards. Lesions

Epidermoid cyst (epidermal cyst, epidermal inclusion cyst) This is the most common cutaneous cyst. It is often referred to as a ‘sebaceous cyst’, a term which is incorrect and should be avoided. The cyst contains keratin and lipids; the cyst wall is epithelium and is usually contained within the dermis. An epidermoid cyst may be caused either by traumatic displacement of some epidermis into the dermis or subcutaneous tissue (an ‘inclusion cyst’) or inflammation around the follicle. These lesions present as dome-​shaped nodules (Fig. 1.10.1). A punctum can usually be identified from which the keratin can often be expressed. Lesions may be pigmented, especially in patients with darker skin. They are most commonly seen in young adults and are usually solitary though multiple lesions can be seen. Lesions can vary in size from a few millimetres to a few centimetres. Common sites for these cysts include the face, neck, upper body and scrotum; however, they may occur at any site. Inclusion cysts are seen on limbs and buttocks. Males are affected more than females. Lesions may become symptomatic due to rupture, which may be associated with a local inflammatory response, or they may also become infected. A  variety of techniques have been described for removal. An uninflamed cyst can either be excised or incised and the cyst contents and wall expressed. Recurrence of the cyst can occur if the cyst wall is not completely removed. Inflamed cysts can be more difficult to remove acutely and are often incised and drained to allow them to settle before definitive excision. Intralesional steroid can be of benefit to help settle the inflammation.

Fig. 1.10.1  Preauricular epithelial cyst.

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can be tender and as with epidermoid cysts, they may become infected or inflamed. Spontaneous resolution may occur. Treatment is by excision, particularly for proliferating pilar cysts, a subtype associated with proliferating cells that result in locally aggressive cyst development.

Milium This is a common cyst that can be likened to a very small epidermoid cyst. Clinically, milia present as 1–​2  mm smooth, firm, white or yellow papules most commonly on the face. Lesions are particularly common on the upper cheeks and eyelids. Milia can also be induced by trauma (e.g. burns) or inflammation and are associated with blistering disorders (e.g. porphyria cutanea tarda, bullous pemphigoid). In these situations, milia occur more commonly at extra-​facial sites. All ages are affected including early infancy. Lesions are commonly seen in newborns. A milium may be confused with basal cell carcinoma or benign syringoma and trichoepithelioma. Treatment is cosmetic. Milia may be easily removed by simple incision of the overlying epidermis with a needle or scalpel and expression of contents (Thami et al., 2002). Laser ablation, electrosurgery, or dermabrasion can also be used. Milia may spontaneously resolve, particularly in childhood and infant cases.

Epidermal neoplasms Seborrhoeic keratosis (seborrhoeic wart) This is a very common benign epithelial tumour. Lesions are seen in either sex and occur increasingly with age. Typically seborrhoeic keratoses present as ‘stuck-​on’, well-​defined, pigmented plaques or nodules with a ‘greasy’ appearance varying in size from a few millimetres to centimetres in diameter. They are most commonly seen on the trunk but can be found elsewhere including the face, neck, and limbs. While for most the concern is cosmetic, they can become traumatized, inflamed, or may bleed. Spontaneous resolution is unlikely. A pigmented variant is dermatosis papulosa nigra. This condition occurs in darker skins and presents as small papules over the upper face including the cheeks and periorbital region. These lesions are commonly pedunculated. Classic seborrhoeic keratoses are clinically distinctive; however, a flat seborrhoeic keratosis can be confused with a solar lentigo, lentigo maligna, lentigo maligna melanoma, or a pigmented actinic keratosis. Nodular lesions may be confused with pigmented basal cell carcinomas or malignant melanomas. Seborrhoeic keratoses may also occur together with another neoplasm, including naevi, in so-​called collision lesions. The sign of Leser–​Trélat describes the development of multiple seborrhoeic keratoses within a short time frame and is associated with a concurrent underlying malignancy such as a gastrointestinal or haematological malignancy (Schwartz, 1996). This is very rare, but if suspected, a full screening for malignancy is recommended. Treatment is considered when lesions are symptomatic or of cosmetic concern. Options include curettage, electrodessication, shave excision, liquid nitrogen cryotherapy, and laser therapy. If

there is diagnostic uncertainty then appropriate histology should be obtained with excision or incisional/​punch biopsy.

Stucco keratosis These are benign, small keratotic plaques or papules with a similar ‘stuck-​on’ appearance to seborrhoeic keratoses. Indeed, lesions can be easily picked off. Lesions may appear as white, grey, or lightly pigmented papules predominantly located on the lower legs, commonly on the dorsa of feet and ankles. Hands and forearms are also affected. They occur in middle-​aged to elderly individuals and predominantly in Caucasians. Lesions are similar to seborrhoeic keratoses but are smaller (1–​4 mm) and lack significant pigmentation. Treatment is cosmetic, and curettage or cryotherapy are options. Lesions can be softened with use of emollients containing urea, lactic acid, or salicylic acid or with use of topical retinoids.

Keratoacanthoma Keratoacanthoma presents as a rapidly growing solitary nodule. During the initial phase of rapid development, a keratoacanthoma can be difficult to differentiate from a squamous cell carcinoma but it is not malignant. Following a growth phase lasting from a few weeks to a few months, lesions tend to regress and spontaneously resolve. Clinically, the presentation is of a solitary dome-​shaped nodule. The texture can be firm or fleshy with a central keratin plug. Lesions rarely grow large and typically regression should be complete within 6 months. Lesions are most commonly seen on the face and upper limbs. They occur in the age group older than 50 years, and more frequently in males than females. Sun exposure is a risk factor and they can also occur following injury and an association with biological medications such as sorafenib and vemurafenib has been reported (Kong et al., 2007; Sinha et al., 2012). Multiple keratoacanthomas have been described and can be associated with immunodeficiency and Torre’s syndrome (Poleksic, 1974). The main differential diagnosis is squamous cell carcinoma; however, lesions can be confused with hypertrophic actinic keratoses or viral warts. Some consider keratoacanthoma to be a self-​healing form of squamous cell carcinoma. Lesions should be treated as invasive squamous cell carcinoma (keratoacanthomatous type) (Weedon et al., 2008) because of the risk of misdiagnosis. The treatment of choice for keratoacanthoma is surgical excision (as with squamous cell carcinoma). Although curettage may be used, importantly it may not allow exclusion of a squamous cell carcinoma. If a keratoacanthoma is allowed to spontaneously resolve, a crateriform scar typically remains. Cosmetically, excision or curettage may offer a preferred outcome. Radiotherapy may be considered and there is some evidence for the use of 5-​fluourouracil and imiquimod. Systemic retinoids may be considered for multiple lesions.

Skin tag (acrochordon, fibroepithelial polyp) Skin tags present as small, fleshy, soft, and often pedunculated lesions (Fig. 1.10.2). While usually skin coloured, they may also be pigmented. Typically, skin tags are only a few millimetres in size although some are larger. Flexural or intertriginous areas such as the neck, axillae, groin, and inframammary regions are commonly affected as well as the abdomen and back. Lesions are more numerous in obese individuals and are seen more commonly in females than

1.10  Benign skin conditions and tumours

more commonly in females than males. The recommended treatment is excision and in view of the desmoplastic growth pattern, Mohs micrographic surgery may be of benefit.

Pilomatrixoma

Fig. 1.10.2  Fibroepithelial polyp.

males and with increasing age. Small regressing intradermal naevi may resemble skin tags. Skin tags are usually asymptomatic. If treatment is desired then options include snip excision, shave excision, simple excision, cryotherapy, and electrosurgery/​electrodessication.

Adnexal neoplasms Trichoepithelioma Trichoepitheliomas are benign adnexal tumours that show follicular differentiation. Lesions usually present as solitary smooth papules on the central face but may also occur on the scalp and trunk. Young adults are most commonly affected and lesions may be multiple. Familial cases with an autosomal dominant inheritance pattern are seen with multiple lesions presenting in childhood. Malignant transformation is very rare (Lee et  al., 2008). Trichoepitheliomas may, however, commonly be confused with basal cell carcinomas and if diagnosis is uncertain, then histological confirmation is required. Trichoepitheliomas are seen in association with Brooke–​Spiegler syndrome. This autosomal dominant condition displays a number of cutaneous neoplasms including cylindromas, spiradenomas, and trichoepitheliomas (Hu et al., 2003; Uede et al., 2004). Treatment can be considered cosmetic. Excision, curettage, dermabrasion, laser therapy, and cryotherapy are recognized techniques. If diagnosis is uncertain or malignancy considered, then excision would be recommended.

Desmoplastic trichoepithelioma Desmoplastic trichoepithelioma can be difficult to distinguish both clinically and histologically from basal cell carcinomas. Presenting as a gradually expanding plaque usually on facial sites, the appearance can be similar to a morphoeic basal cell carcinoma. A central depression may be present. Desmoplastic trichoepitheliomas occur

Pilomatrixoma is the most common benign hair follicle neoplasm. They arise from the hair follicle matrix. Clinically, lesions present as a firm dermal or subcutaneous nodule. They may be skin coloured or have a blue-​red appearance. Stretching of the skin over the lesion produces an angulated appearance known as the ‘tent’ sign. The head and neck are most commonly affected but lesions may be seen on the trunk and extremities. Usually a solitary nodule, multiple lesions have been described (Demircan et al., 1997). Individual lesions are usually no greater than a few centimetres but larger, so-​called giant pilomatrixomas have been described. Pilomatrixomas usually present in childhood to early adulthood with females more commonly affected than males. Lesions are generally asymptomatic unless inflamed or ulcerated. Lesions can be associated with myotonic dystrophy and Turner’s syndrome (Chiaramonti et al., 1978; Noguchi et al., 1999). Malignant transformation is very rare but has been reported (van der Walt and Rohlova, 1984). Treatment with local excision is sufficient unless malignant transformation is suspected, when wide excision is recommended.

Syringoma Syringoma is a benign adnexal tumour of the eccrine ducts. Typically, lesions are 1–​2 mm, firm, skin-​coloured or yellow papules, and are often multiple. These are most commonly seen on the face, particularly the periorbital region, but are also seen on the neck, chest, axillae, and abdomen. Females are more affected than males with lesions appearing from teenage years. These lesions may be confused with small basal cell carcinomas. Lesions are generally asymptomatic. If treated, then electro­ dessication, curettage, and excision can be used. Laser and cryotherapy have also been described.

Poroma A benign adnexal tumour that displays ductal differentiation. Lesions usually present as a solitary papule or plaque, most commonly on the palms or soles but any body site may be affected. A typical lesion has a red or pink vascular appearance or may sometimes be pigmented. Lesions are slow growing, reaching up to 2 cm in size, and are generally asymptomatic. Multiple lesions are rare. Males and females may be affected. Important differential diagnoses include squamous cell carcinoma and amelanotic melanoma. Lesions may be mistaken for pyogenic granulomas. Malignant change within lesions has been reported (porocarcinoma) (Robson et al., 2001). Poromas are usually treated with surgical excision. Shave excision or electrosurgery can also be helpful.

Sebaceous hyperplasia This is a common benign growth of the sebaceous unit. Lesions are typically small, measuring up to a few millimetres, and present as soft, yellow papules. Telangiectasia may be present. These features can lead to confusion with basal cell carcinomas. Central umbilication may be present in sebaceous hyperplasia. Lesions are most typically located on the nose, forehead, temples, and upper

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cheeks and are usually seen from middle-​age onwards. An increase in sebaceous hyperplasia can be associated with medications such as ciclosporin (Boschnakow et al., 2003). Treatment is not usually required for this. If treatment is desired, then a variety of options including electrosurgery/​cautery, shave excision, excision, cryotherapy, laser, photodynamic therapy, and camouflage may be considered.

as a solitary, firm, skin-​coloured papule or nodule with a characteristic rim of scale at the base. Lesions may develop on palmar or volar aspects. Usually lesions are asymptomatic. Clinically, the differential diagnosis may include a viral wart, actinic keratosis, dermatofibroma, or a rudimentary supernumerary digit in younger patients. Treatment is usually with excision.

Sebaceous adenoma

Dermatofibromas are common dermal lesions that typically present as firm papules on the lower limbs but can occur at other sites. While it has been thought that dermatofibromas occur as a reaction to penetrating trauma to the skin, such as an insect bite or thorn, the aetiology remains unknown. Lesions vary from skin-​ coloured to pink, yellow, or brown papules or nodules (Fig. 1.10.3). The overlying skin can be scaly or have a depressed appearance. Lesions classically demonstrate the ‘dimple’ or ‘button’ signs. As the skin surrounding the lesion is pinched, a depression or ‘dimple’ is formed. While dermatofibromas are usually small lesions, ‘giant’ dermatofibromas greater than 5 cm have been described (Requena et al., 1994). Lesions may regress spontaneously but commonly persist for many years. Dermatofibromas may affect any age group with females more commonly affected than males and be asymptomatic, pruritic, or tender. Cases of eruptive dermatofibromas have been described and have been associated with underlying immunosuppression, systemic

This is a benign tumour originating from incompletely differentiated sebaceous cells. Clinically, lesions present as yellow or pink papules or nodules, usually less than a centimetre in diameter. Lesions may be pedunculated and can be ulcerated. Treatment is with local excision. Importantly, sebaceous adenomas may be associated with Muir–​Torre syndrome (an association of sebaceous adenomas, epitheliomas, or carcinomas with internal malignancy, most commonly gastrointestinal, genitourinary, or haematological) (Hare et al., 2008; Ingram et al., 2009).

Naevus sebaceous This is a congenital hamartoma derived from an epidermal, sebaceous, follicular, and apocrine background. Lesions are typically seen on the scalp but can be found on the face or neck. Plaques thicken with age, developing a rough, warty surface and orange appearance. Lesions appear in both males and females. Naevus sebaceous is most usually solitary in nature. Adnexal tumours are known to commonly develop within naevus sebaceous including syringocystadenoma papilliferum, and trichoblastoma most commonly. Apocrine cystadenoma, trichilemmoma, and keratoacanthoma may also develop (Cribier et  al., 2000; Jaqueti et  al., 2000; Idriss et  al., 2014). Lesions are also associated with increased basal cell carcinoma development. Historically, this has been estimated to be as high as 10–​15%; however, recently there have been suggestions that the rate of basal cell carcinoma development is much lower than this. In view of the perceived risk of basal cell carcinoma, complete excision of naevus sebaceous has been recommended. While this risk may have been overestimated, treatment may still be desirable for cosmetic purposes for which shave excision or laser may also be considered in addition to local excision.

Dermatofibroma (fibrous histiocytoma)

Fibrous and fibrohistiocytic neoplasms Fibrous papule of nose This is a common benign lesion that presents as a firm, domed papule on the nose of a middle-​aged individual. Lesions can also arise on the upper face including the forehead and cheeks. Usually skin coloured, fibrous papules may be pink or occasionally pigmented. Lesions are often confused with small basal cell carcinomas or naevi. As lesions are asymptomatic, treatment is generally for cosmetic purposes or to exclude malignancy. Treatments include shave excision, curettage, and excision.

Acquired digital fibrokeratoma (acral fibrokeratoma) This is a benign lesion usually found on fingers or toes that is thought to be a consequence of minor trauma to the site. Lesions may present

Fig. 1.10.3  Dermatofibroma—​note the pigmentation associated with the lesion.

1.10  Benign skin conditions and tumours

disease, or familial presentations (Niiyama et al., 2002; Yazici et al., 2006; Zaccaria et al., 2008). Several variants of dermatofibromas exist including cellular, aneurysmal, and atypical dermatofibroma. The variants are associated with an increased risk of local recurrence. The atypical and cellular variants have also been reported to rarely metastasize to distant sites (Colome-​Grimmer et  al., 1996; Kaddu et  al., 2002; Kimyai-​ Asadi et  al., 2008). For large and/​or atypical dermatofibromas, dermatofibrosarcoma protuberans is an important differential diagnosis. Other important differential diagnoses include desmoplastic melanoma and amelanotic melanoma. The common dermatofibroma does not require treatment unless for symptomatic or cosmetic purposes. Excision or cryotherapy are useful treatments. For the dermatofibroma variants, complete excision is recommended in view of the increased risk of local recurrence and the rare risk of metastasis.

Vascular, adipose, and neural neoplasms Cherry angioma (Campbell De Morgan spot) These are very common benign vascular neoplasms. Lesions develop in adulthood and increase in number over time. Lesions may appear initially as small red macules and develop into vascular domed papules rarely greater than a few millimetres in diameter. The trunk and limbs are usually affected. Lesion number may increase during pregnancy. Very rarely a sudden eruption of angiomas may be associated with an underlying malignancy (Pembroke et al., 1978). As lesions are asymptomatic, treatment is primarily cosmetic. Laser can be helpful for multiple lesions. Shave excision, electrodessication, and cryotherapy are effective treatments.

Pyogenic granuloma (lobular capillary haemangioma) Pyogenic granulomas are benign vascular lesions often originating at a site of trauma and typically presenting as a red or blue nodule on the finger or hand (Fig. 1.10.4). Lesions may also occur on the lips, head, and feet or in the oral cavity. The nodules are commonly small, soft, pedunculated, and tend to develop rapidly. They are sometimes

pigmented. Crusting and ulceration of the surface of the lesion may be present. Lesions are generally solitary but multiple lesions have been described. Pyogenic granulomas are seen in all age groups and in both sexes but are more common in the young and are often seen to develop during pregnancy. The diagnosis is usually clinical but important differentials include amelanotic melanoma and Kaposi’s sarcoma, and benign lesions such as viral wart and seborrhoeic keratosis. Lesions tend to bleed easily and are troublesome for the individual. Treatment options include excision, shave or curettage and cautery. Cryotherapy can be helpful too (Ghodsi et al., 2006; Mirshams et al., 2006). Other treatments described but less commonly utilized include laser therapy, intralesional steroid, and imiquimod (Tritton et al., 2009).

Lipoma Lipomas (benign tumours of mature fat cells) are common and may affect any age group but are more often found in adults. Lesions may affect all races and are more frequently seen in overweight patients. Most are asymptomatic and usually develop as a slow-​ growing lump. Typically, they present as a soft, mobile, subcutaneous lobulated mass with normal overlying skin. Although mostly subcutaneous, lipomas may develop in any adipose tissue including subfascial and intramuscular fat. The common sites include the trunk, neck, upper limbs, and thighs. The size can vary from a few millimetres to a few centimetres most commonly although larger lesions are also seen. Multiple lipomas may be associated with a lipomatosis (e.g. familial multiple lipomatosis) or systemic disorders (e.g. Proteus syndrome, Gardner syndrome). Multiple painful lipomas are seen with Dercum’s disease (adiposis dolorosa) (Reece et al., 1999). Treatment for small solitary lipomas is usually surgical excision. This includes ‘shelling out’ of well-​circumscribed lesions. Frontalis-​ associated lipomas occur more deeply either within or below frontalis and this should be considered when treating a lipoma in this area. Larger lipomas are more likely to recur. Liposuction can be an effective treatment (Kaneko et al., 1994).

Angiolipoma Angiolipomas are clinically very similar to lipomas, with a significant vascular component. Lesions are more commonly seen in young adults and are usually more painful or tender than lipomas. The arms are a common site but lesions are also seen on the abdomen and legs. Typically, lesions are well circumscribed and amenable to surgical excision. Angiolipomas are one of a number of lesions that should be considered in the presence of painful cutaneous tumours. A  helpful mnemonic to remember these tumours is BENGAL (Blue rubber bleb naevus, Eccrine spiradenoma, Neuroma, Glomus tumour, Angiolipoma, and Leiomyoma).

Neurofibroma (solitary type)

Fig. 1.10.4  Pyogenic granuloma—​pedunculated vascular lesion, often with a collarette of epithelium around the base of the lesion.

This is a common neural hamartoma particularly affecting young adults. Males and females are equally affected. Lesions typically present as slow-​growing, skin-​coloured, soft papules or nodules. Lesions may be polypoid or pedunculated and can grow to a couple of centimetres. Lesions are generally solitary and can occur at any site. Multiple neurofibromas together with the other typical signs are

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seen in neurofibromatosis. While usually asymptomatic, excision of the neurofibroma is recommended if treatment is required. Plexiform neurofibroma is a distinct lesion to the solitary lesion and considered pathognomonic for neurofibromatosis type 1. This typically presents in children or young adults with a ‘bag-​like’ appearance and carries a small risk of malignant transformation.

Neuroma A neuroma is a benign growth of neural tissue. Cutaneous neuromas are uncommon. Traumatic (amputation) neuromas result as a response to physical injury of nerve fibres. Lesions present as skin-​coloured or red papules at the site of injury (e.g. surgical scar/​amputation). Lesions may be painful. Treatment is with surgical excision (with careful apposition of nerve ends). Solitary palisaded encapsulated neuromas (solitary circumscribed neuroma) occur spontaneously without a history of injury. Lesions are asymptomatic and typically appear as a small papule on the face. If treated, surgical excision is effective.

Other benign cutaneous conditions Chondrodermatitis nodularis helicis chronica Chondrodermatitis is a benign but painful condition affecting the ear. Patients develop a tender, firm nodule on the ear on the side they usually sleep on. It is thought that the problems arise due to focal pressure on the ear, particularly over the calcified auricular cartilage of the older patient and impaired vascular supply in the setting of skin atrophy or actinic injury. For men, this is most commonly on the outer helix; however, lesions may arise on the antihelix, tragus, anti-​tragus, and concha. For women, the distribution is more varied and antihelical lesions more common. The condition usually arises from the fifth decade onwards. Cases may arise earlier particularly in the presence of traumatic injury, cold injury, or anatomical abnormality. Clinically, an inflamed nodule is seen that can be ulcerated or crusted. Lesions are usually present on a prominent aspect of the ear. Bilateral lesions may be seen but are often the consequence of an altered sleep position due to tenderness of the initial lesion. The differential diagnosis includes actinic keratosis, basal cell carcinoma, squamous cell carcinoma, or calcification. It is common for patients with chondrodermatitis to have evidence of actinically damaged skin or a history of skin cancer. Lesions can disrupt sleep. For symptomatic lesions, treatments include pressure-​ relieving strategies, intralesional steroid, cryotherapy, or surgical excision. Surgical excision may be performed with removal of cartilage only (Lawrence, 1991). Pressure-​relieving strategies include the use of foam or sponge pillows specifically cut or shaped to spare pressure on the ear. However, patients should be counselled with regard to the risk of recurrence associated with all treatments.

Hypertrophic and keloid scars These entities represent an excessive fibrous reaction that results in a larger scar than would normally be anticipated. A hypertrophic scar remains within the original site of injury. A keloid scar extends beyond the original site of injury. Both hypertrophic and keloid scars can occur after any traumatic injury to the skin, including surgery.

Scars may also form following inflammatory lesions such as acne. Spontaneous keloid scars describe keloid scar formation in which there is no clear history of injury to the skin. The most commonly affected site is the upper torso including the upper back, chest, neck, and shoulders. The ear is another commonly affected site and this is usually piercing related. All ages may be affected but young adults in particular. Darker skin is more commonly affected. Clinically, the lesion initially represents the original injury and can be papules, nodules, or linear. As keloid scars develop, this initial shape may change. Scars can appear more red and vascular but can be pigmented too. Although usually asymptomatic in nature, keloid scars can be tender. Keloid scars may also produce contractures and functional impairment. The diagnosis is usually clinical. An important differential in an expanding scar-​ like lesion is dermatofibrosarcoma protuberans. Biopsy should be avoided unless diagnosis is uncertain as this can lead to worsening of the scar. Keloid scars can continue to develop and hence treatment is often sought. On the other hand, hypertrophic scars improve over time, often becoming flatter. Successful treatment may be difficult with unsatisfactory results not uncommon. Intralesional steroid (triamcinolone) can be effective (Darzi et al., 1992). This may be combined with pre-​injection cryotherapy or laser treatment. Topical treatments include silicone, imiquimod, and 5-​ fluorouracil (Fitzpatrick, 1999; Berman and Villa, 2003; O’Brien and Pandit, 2006). Surgical excision of the scar can be helpful but risks enlarging the eventual scar and recurrence of the keloid scar. If used, then combination treatment such as with triamcinolone injection is advised (Berman and Flores, 1997). In refractory cases, excision followed by radiotherapy may be considered (Klumpar et al., 1994). Importantly, individuals with a history of keloid scar should be counselled with regard to an increased risk of further similar scar formation and recommended to avoid unnecessary procedures.

Molluscum contagiosum A common benign skin lesion caused by the molluscum contagiosum pox virus. Lesions usually present in childhood as firm, shiny, white papules. A central umbilication is seen. Lesions may be seen on a variety of body sites including the neck, face, and trunk. Lesions may also be seen in the genital area. The presence of multiple lesions is common. Lesions can be inflamed and may be associated with an eczematous rash. The virus is spread by direct contact. Individual lesions may last from a few months to a few years but tend to resolve spontaneously. However, a scar may be evident on clearance. Lesions may also be seen in immunocompromised individuals. The diagnosis is usually clinical although it may be confused with other types of warts. Single lesions may cause diagnostic difficulties. As lesions are self-​limiting, treatment in children is not usually required. Treatment may be considered for cosmetic purposes, slow resolving lesions, or multiple lesions. Secondary bacterial infection may increase the risk of scarring and require treatment. Topical treatments include potassium hydroxide, benzoyl peroxide, and imiquimod. Cryotherapy, curettage, or laser therapy may also be considered.

Pyoderma gangrenosum This is an uncommon neutrophilic dermatosis characterized by recurrent ulceration. Lesions typically present on the lower limbs but can occur at any site including around stomas and mucosal

1.10  Benign skin conditions and tumours

Fig. 1.10.5  Pyoderma gangrenosum—​an ulcerated lesion with the typical violaceous margin.

sites. Initially developing from a red papule or pustule, pyoderma gangrenosum progresses to a deeply ulcerated lesion with irregular, violaceous, or necrotic undermined margins (Fig. 1.10.5). Lesions are painful and development is rapid. Pustular, bullous, and atypical forms are recognized. Pyoderma lesions may display pathergy. This describes the formation of new areas of disease at sites of trauma or injury including surgical procedures. Pyoderma gangrenosum is often associated with systemic disease including inflammatory bowel disease, arthritis, and haematological disorders. All ages may be affected but it is more common in young to middle-​aged adults. Although these clinical features may lead to suspicion of pyoderma gangrenosum, diagnosis requires exclusion of other causes of ulceration including malignancy, infection, vascular disease, or vasculitis and a dermatology opinion should be sought. Pyoderma lesions may be mistaken for any of these conditions but suspicions should be raised in ulcerated conditions that worsen following interventions such as wound debridement. Due to the risk of pathergy, surgery should be avoided if possible as this is likely to extend ulceration. Therapy is usually with anti-​inflammatory and immunosuppressant agents. If surgery is required then this ideally should be delayed until adequate treatment has been initiated.

REFERENCES Berman B, Flores F. Recurrence rates of excised keloids treated with postoperative triamcinolone acetonide injections or interferon alfa-​ 2b injections. J Am Acad Dermatol 1997; 37(5 Pt 1):755–​7. Berman B, Villa A. Imiquimod 5% cream for keloid management. Dermatol Surg 2003;29:1050–​1. Boschnakow A, May T, Assaf C, et  al. Ciclosporin A-​induced sebaceous gland hyperplasia. Br J Dermatol 2003;149:198–​200. Chiaramonti A, Gilgor RS. Pilomatricomas associated with myotonic dystrophy. Arch Dermatol 1978;114:1363–​5.

Colome-​Grimmer MI, Evans HL. Metastasizing cellular dermato­ fibroma: a report of two cases. Am J Surg Pathol 1996;20: 1361–​7. Cribier B, Scrivener Y, Grosshans E. Tumors arising in nevus sebaceus: a study of 596 cases. J Am Acad Dermatol 2000;42(2 Pt 1):263–​8. Darzi MA, Chowdri NA, Kaul SK, et al. Evaluation of various methods of treating keloids and hypertrophic scars: a 10-​year follow-​up study. Br J Plast Surg 1992;45:374–​9. Demircan M, Balik E. Pilomatricoma in children: a prospective study. Pediatr Dermatol 1997;14:430–​2. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-​FU. Dermatol Surg 1999;25:224–​32. Ghodsi SZ, Raziei M, Taheri A, et al. Comparison of cryotherapy and curettage for the treatment of pyogenic granuloma: a randomized trial. Br J Dermatol 2006;154:671–​5. Hare HH, Mahendraker N, Sarwate S, et al. Muir-​Torre syndrome: a rare but important disorder. Cutis 2008;82:252–​6. Hu G, Onder M, Gill M, et al. A novel missense mutation in CYLD in a family with Brooke-​ Spiegler syndrome. J Invest Dermatol 2003;121:732–​4. Idriss MH, Elston DM. Secondary neoplasms associated with nevus sebaceus of Jadassohn:  a study of 707 cases. J Am Acad Dermatol 2014;70:332–​7. Ingram JR, Griffiths AP, Roberts DL. All patients with sebaceous gland neoplasms should be screened for Muir-​Torre syndrome. Clin Exp Dermatol 2009;34:264–​6. Jaqueti G, Requena L, Sanchez Yus E. Trichoblastoma is the most common neoplasm developed in nevus sebaceus of Jadassohn:  a clinicopathologic study of a series of 155 cases. Am J Dermatopathol 2000;22:108–​18. Kaddu S, McMenamin M, Fletcher CD. Atypical fibrous histiocytoma of the skin: clinicopathologic analysis of 59 cases with evidence of infrequent metastasis. Am J Surg Pathol 2002;26:35–​46. Kaneko T, Tokushige H, Kimura N, et  al. Treatment of multiple angiolipomas by liposuction surgery. J Dermatol Surg Oncol 1994;20:690–​2. Kimyai-​Asadi A, Goldberg LH, Greenberg C, et  al. Cellular, atypical, and indeterminate dermatofibromas:  benign or malignant? Dermatol Surg 2008;34:1264–​71. Klumpar DI, Murray JC, Anscher M. Keloids treated with excision followed by radiation therapy. J Am Acad Dermatol 1994;31(2 Pt 1):225–​31. Kong HH, Cowen EW, Azad NS, et al. Keratoacanthomas associated with sorafenib therapy. J Am Acad Dermatol 2007;56:171–​2. Lawrence CM. The treatment of chondrodermatitis nodularis with cartilage removal alone. Arch Dermatol 1991;127:530–​5. Lee KH, Kim JE, Cho BK, et al. Malignant transformation of multiple familial trichoepithelioma:  case report and literature review. Acta Derm Venereol 2008;88:43–​6. Mirshams M, Daneshpazhooh M, Mirshekari A, et al. Cryotherapy in the treatment of pyogenic granuloma. J Eur Acad Dermatol Venereol 2006;20:788–​90. Niiyama S, Katsuoka K, Happle R, et al. Multiple eruptive dermato­ fibromas: a review of the literature. Acta Derm Venereol 2002; 82:241–​4. Noguchi H, Kayashima K, Nishiyama S, et al. Two cases of pilomatrixoma in Turner’s syndrome. Dermatology 1999;199:338–​40. O’Brien L, Pandit A. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev 2006;1:CD003826.

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Pembroke AC, Grice K, Levantine AV, et al. Eruptive angiomata in malignant disease. Clin Exp Dermatol 1978;3:147–​56. Poleksic S. Keratoacanthoma and multiple carcinomas. Br J Dermatol 1974;91:461–​3. Reece PH, Wyatt M, O’Flynn P. Dercum’s disease (adiposis dolorosa). J Laryngol Otol 1999;113:174–​6. Requena L, Farina MC, Fuente C, et al. Giant dermatofibroma. J Am Acad Dermatal 1994;30(5 Pt 1):714–​18. Robson A, Greene J, Ansari N, et  al. Eccrine porocarcinoma:  a clinicopathologic study of 69 cases. Am J Surg Pathol 2001;25:710–​20. Schwartz R. Sign of Leser-​Trélat. J Am Acad Dermatol 1996;35:88–​95. Sinha R, Edmonds K, Newton-​ Bishop JA, et  al. Cutaneous adverse events associated with vemurafenib in patients with metastatic melanoma: practical advice on diagnosis, prevention and management of the main treatment-​related skin toxicities. Br J Dermatol 2012;167:987–​94. Thami GP, Kaur S, Kanwar AJ. Surgical pearl: enucleation of milia with a disposable hypodermic needle. J Am Acad Dermatol 2002;47:602–​3.

Tritton SM, Smith S, Wong LC, et  al. Pyogenic granuloma in ten children treated with topical imiquimod. Pediatr Dermatol 2009; 26:269–​72. Uede K, Yamamoto Y, Furukawa F. Brooke-​Spiegler syndrome associated with cylindroma, trichoepithelioma, spiradenoma, and syringoma. J Dermatol 2004;31:32–​8. van der Walt JD, Rohlova B. Carcinomatous transformation in a pilomatrixoma. Am J Dermatopathol 1984;6:63–​4. Weedon D, Marks R, Gao GF, et al. Keratoacanthoma. In: Le Boit PE, Burg G, Weedon D, et al. (eds) World Health Organization Classification of Tumours. Pathology and Genetics:  Skin TumoursOrganization Classification of Tumours, pp. 44–​7. Lyon: IARC Press, 2008. Yazici AC, Baz K, Ikizoglu G, et al. Familial eruptive dermatofibromas in atopic dermatitis. J Eur Acad Dermatol Venereol 2006;20:90–​2. Zaccaria E, Rebora A, Rongioletti F. Multiple eruptive dermatofibromas and immunosuppression: report of two cases and review of the literature. Int J Dermatol 2008;47:723–​7.

1.11

Non-​melanoma skin cancer and premalignant conditions Barbara Jemec and Gregor B.E. Jemec

Introduction Non-​melanoma skin cancer (NMSC) is one of the most common diagnoses encountered in any plastic surgery clinic. Most lesions end up being excised either for pathological or cosmetic reasons (Bystrzonowski et al., 2013), but pre-​surgical diagnosis is important to optimize management. This chapter provides aids for diagnosis and an overview of the most common and some more obscure NMSCs including their classifications.

Diagnosis The sensitivity and specificity of the clinical diagnosis of NMSC is dependent on many factors, but experienced plastic surgeons can achieve considerable accuracy in determining whether the lesion is malignant. The overall diagnostic sensitivity based on clinical examination or assessment of an image alone ranges from 56% to 90% with a specificity of 75% to 90% (Jemec et al., 2010). While histopathology is the definitive diagnostic method, an accurate pre-​excision diagnosis is of importance for planning the operation. This is especially the case with multiple or anatomically complex tumours. Preoperative assessment is most often done using multiple 2  mm punch biopsies to map the extent of the lesion; however, there are limitations such as sampling error and the provision of inadequate material for subclassification of basal-​cell carcinomas (BCCs), due to the common intratumour variation. In addition, patient preference is usually for non-​invasive diagnostic methods (Wolberink et al., 2013). Many methods are being developed for the in vivo non-​ invasive diagnosis of NMSC, but three methods appear particularly suitable for preoperative assessment of skin cancer:  dermoscopy, optical coherence tomography, and reflectance confocal microscopy (RCM). Their use obviously depends on the practical availability and operator skills of those providing the service. For the detection of metastasis or local spread, for instance, to underlying bone, conventional methods such as positron emission

tomography/​computed tomography, computed tomography, and magnetic resonance imaging are appropriate.

Dermoscopy Dermoscopy permits the low magnification (10–​100×) of anatomical details of the lesion after alteration of the reflective indices of the skin surface. Surface reflection is eliminated either through the use of polarized light or an optical coupling medium such as oil or alcohol gel, between the magnifying lens and the skin surface. The combination of better visualization of the skin and magnification assists the diagnosis of many conditions. Dermoscopy can be made using either a hand-​held dermoscope (10× magnification) or videodermoscopy (40+× magnification), and has become a standard method for the assessment of pigmented lesions. The melanocytes or melanin in the basal layer of the epidermis normally form a pigment network. This network is made up of dense pigment rings, which are projections of rete pegs or ridges and paler ‘holes’, which are due to projections of dermal papillae. For pigmented BCC, in contrast to melanocytic lesions, uniform accumulations of pigment and the absence of a pigmented network are usually found. Dermoscopy can also be used for the diagnosis of non-​pigmented NMSC, particularly BCC (Rosendahl et  al., 2011). For superficial BCC, diagnostic features include short fine superficial telangiectasia, maple leaf-​like areas, shiny white-​red structureless areas, and multiple small erosions; while other types of BCC predominantly show arborizing vessels, blue-​grey ovoid nests, and ulceration (Lallas et al., 2014). Reported diagnostic sensitivity for BCC ranges from 87% to 96% and the corresponding specificity from 71% to 92% (Jemec et  al., 2010). The technique is limited to visualizing structures superficial to the papillary dermis.

Optical coherence tomography Optical coherence tomography is based on interferometry. Interferometry is the measurement of the interference of waves (in this case, laser) as they travel a different path through the tissue due to reflections and are recombined before going through a detector. The difference in the path distance travelled by each wave (as they

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are reflected) creates a phase difference, which in turn creates an interference pattern. Interferometry is often likened to ultrasound, only with light, and is used for high-​resolution imaging. Optical coherence tomography generates greyscale micrometre-​resolution images (3–​7 micrometres depending on type) of the superficial 2 mm of the skin. Preliminary data suggest it can be used to diagnose recurrent or residual tumour tissue and identify tumour margins better than clinical examination alone or dermoscopy (De Carvalho et al., 2018), including decreasing the number of sessions necessary in Mohs’ surgery (Hussain et al., 2016). Its potential for diagnosing subtypes of BCC and differentiating BCC from other NMSCs is being explored (Boone et al., 2015; Hussein et al., 2015; Wahrlich et al., 2015; Iftimia et al., 2017).

Risk factors

Reflectance confocal microscopy

Clinical appearance

RCM uses a microscope to focus light on an area micrometres in diameter within the tissue and reduces the scattering of the reflected light by using a pinhole aperture in a screen focused on the area of interest. This system allows cellular imaging (resolution = 1 micrometre) of skin lesions to a depth of approximately 250 micrometres and offers the possibility of in vivo histology with accurate diagnosis of the most superficial portion of tumours. Numerous proof-​ of-​concept studies have been published describing RCM features of rarer NMSC types. RCM diagnostic criteria for all types of BCC have been proposed and one study found these to have a sensitivity of 95.7% and a specificity of 82.9% (Nori et al., 2004). Previous reports of the use of RCM to identify BCC margins preoperatively are supported by these findings (Pan et al., 2012). Recent randomized controlled multicentre trials showed non-​inferiority utilizing RCM in the treatment of BCCs (Kadouch et al., 2017; Manfredini et al., 2017; Dinnes et al., 2018).

Seventy per cent of all BCCs are found on the head and neck. The clinical appearance varies with a number of identifiable subtypes (Table 1.11.1). See Fig. 1.11.1.

Other diagnostic methods A host of experimental techniques for non-​invasive preoperative diagnosis of NMSC are being developed to cope with the big volume of new cases. These include, for example, opto-​acoustic imaging as well as qualitative methods such as spectroscopy or Raman spectroscopy capable of identifying specific proteins in the tissue (Attia et al., 2019; Chang et al., 2020; Hult et al., 2020; Romano et al., 2020; Yaroslavsky et al., 2020). The development of new non-​invasive diagnostic methods combined with artificial intelligence may be expected to reduce the need for diagnostic biopsies in the future.

Interfollicular epithelium-​derived skin malignancies Basal cell carcinoma Epidemiology Approximately 80% of all skin cancers in the white population are BCCs, and the estimated lifetime risk in the white population is 35% for men and 25% for women (with a lifetime risk of 65% in high-​risk countries such as Australia). The incidence doubles every 25 years. Non-​white ethnicity provides some protection for BCCs, though BCCs are reported in Asians as well as Africans (Munyao and Othieno-​Abinya, 1997; Tan et al., 2015).

By far the most common cause is sun exposure, but the extrinsic risk factors include exposure to arsenic, coal tar, raw paraffin, certain types of industrial oil, radiation, welding light, long-​standing unstable scars as in burns, and immunosuppression (>200-​fold increase in skin cancer). Intrinsic risk factors can be general, such as Fitzpatrick skin type 1 or more specific genetic diseases such as xeroderma pigmentosum or Gorlin syndrome. These specific diseases are rare, but should be considered in young patients or patients without obvious general or extrinsic risk factors. Hedgehog signalling pathway abnormalities play a role in sporadic as well as genetic BCC (e.g. Gorlin syndrome).

Morbidity and mortality Patients who are diagnosed with BCC have a 35% risk of developing a subsequent new BCC within 3 years and a 50% chance of developing yet another BCC (not recurrent lesions) within 5 years (McLoone et al., 2006). While the risk of metastatic spread of a BCC is less than 0.1%, neglected BCCs can be locally destructive with subsequent high morbidity. Management Superficial BCCs can be treated topically with a variety of modalities (Table 1.11.2). Surgery is recommended in nearly all other types of BCC, and includes excision, electrodesiccation and curettage, Mohs’ surgery (the specimen’s margins are examined intraoperatively, ensuring clear margins upon completion), and cryosurgery. The recurrence rate for Mohs’ surgery is less than 1%; all other modalities, including excision, average 8%, though excision for primary BCCs only carries a less than 2% recurrence rate (Walker and Hill, 2006) and is much more practical and readily available in most circumstances. The specific indications for Mohs’ surgery depend upon tumour site (especially the central face:  periorbital, the nose and Table 1.11.1  Basal cell carcinoma subtypes Nodular

Commonest BCC: cystic, pigmented, presents as a round, pearly, flesh-​coloured papule with telangiectasis

Infiltrative

Less apparent clinical margins, infiltrates the dermis in thin strands between collagen fibres

Micronodular

Yellow-​white when stretched, is firm to the touch, and may have a seemingly well-​defined border, not usually ulcerated

Morphoeic

White or yellow, waxy, sclerotic plaque that rarely ulcerates; is flat or slightly depressed, fibrotic, and firm

Superficial

Erythematous, well-​circumscribed patch or plaque, often with a whitish scale Pigmented: may be mistaken for a naevus/​melanoma

Basosquamous

With some features of squamous cell carcinoma, and best treated as the latter

Ulcerated

With ulcer (Fig. 1.11.1)

Pigmented

With uniform pigment (use dermoscopy to differentiate from melanoma)

1.11  Non-melanoma skin cancer and premalignant conditions

recommended for high-​risk lesions (Weinstein et al., 2012). A study of 2016 BCCs by Breuninger and Dietz (1991), using horizontal sections to accurately detect BCC at any part of the surgical margin, found that excision of small (2  cm), histological subtype (especially morphoeic, infiltrative, micronodular, and basosquamous subtypes), poor clinical definition of tumour margins, recurrent lesions, and perineural or perivascular involvement (Telfer et al., 2008). The recommended margin for excision of a low-​ risk BCC is 4  mm, 4–​6  mm for a medium-​risk BCC, and Mohs’ surgery is

Nodular BCCs which are completely excised are usually discharged after their 3-​month follow-​up, but patients with tumours in high-​risk areas (face), or with tumours showing perineural invasion, or with recurrent or multiple BCCs should be followed up for 3 years according to guidelines from the British Association of Dermatologists (Telfer et al., 2008). It is unlikely that a recurrence is visible at 3 months, and therefore an annual visit seems more logical in parallel with patient education and patient self-​examination if possible. In Australia, the recommendations are annual surveillance if the patient has had more than one skin cancer, and closer follow-​up for 3 years if non-​surgical treatment modalities were used. Patient education aimed at limiting UV exposure and patient self-​monitoring for recurrence/​de novo tumour development, is generally recommended.

Squamous cell carcinoma Epidemiology Cutaneous SCC is the second most common form of skin cancer seen in Caucasians, Asians, and Hispanics, and the most common form seen in black people and Asian Indians. Only 10–​20% of all skin

Table 1.11.2  Topical treatment options Active ingredient

Principle

Indication

Treatment duration

Response rate after 1 year

5-​fluouracil, 5% cream

Inhibition of DNA/​RNA synthesis

Low-​risk superficial BCC or premalignant lesions

Twice daily for 4–​6 weeks

80.1% (74.7–​85.9%) (Lecluse and Spuls, 2015)

Imiquimod, 5% cream

Activation of Toll-​like receptor and release of proinflammatory cytokines

Low-​risk superficial BCC or premalignant lesions

Once daily for 5 days per week for 6 weeks

83.4% (78.2–​88.9%)*

Photodynamic therapy with ointment containing 16.0% of methyl aminolevulinate or 10% aminolevulinic acid hydrochloride as a nanoemulsion

Semi-​selective accumulation of protoporphyrin-​IX and phototoxic reaction and induction of apoptosis

Low-​risk superficial BCC or premalignant lesions

3-​hour incubation of ointment followed by red light illumination, repeated after 1 week

72.8% (66.8–​79.4%)

Ingenol mebutate, 0.015–​0.05% cream

Induces necrosis and protein kinase C activation

Premalignant lesions only

Once daily for 3 days in the face (0.015%) or 2 days on the body (0.05%)

Unknown. 42% after 57 days (Lebwohl et al., 2012)

Diclofenac, 3% gel

Cyclooxygenase inhibitor. Reduced angiogenesis and increased apoptosis

Premalignant lesions only

Twice daily for 60–​90 days

39.6% (30.8–​49.1%) after 75 days (Pirara et al., 2005)

Adapalene, 0.1–​0.3% gel

Binding to retinoid receptors

Premalignant lesions only

Twice daily for 9 months

Reduced number of actinic keratosis between 0.5 and 2.5 per patient (Kang et al., 2003)

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SECTION 1  General principles and techniques

cancers are squamous cell carcinomas (SCCs), but these cause the majority of deaths attributed to NMSC. Incidence increases markedly in patients older than 40 and has doubled over the last 40 years. The male:female ratio is 2–​3:1 and 80% occur in sun-​exposed skin. The cumulative risk of another SCC within 3  years is 18%. Solid organ transplant patients have a significantly increased risk of SCC, though this has reduced following a change in the use of immunosuppressive drugs (Rizvi et al., 2017). Tumour incidence and clinical course is affected by the degree of immunosuppression. Heart transplant patients carry the greatest risk, two to three times greater than renal transplants, and liver transplants carry the lowest risk. Risk factors Cumulated sun exposure is the most significant extrinsic risk factor. Ultraviolet (UV) radiation induces mutations, especially UVB (290–​ 320 nm wavelength), which is a 1000 times more potent mutagen than UVA (320–​400 nm) which predominates in the UV contained in sunlight. UVA can, however, also act as a tumour promotor through modulation of protein kinase C and suppresses the immune response via interleukin-​10 and suppressor T cells. Exposure to polycyclic aromatic hydrocarbons, tar, pitch, shale and mineral oil, arsenic (Leonardi et al., 2012), smoking (for lower lip SCCs), and human papilloma virus (especially human papilloma virus, subtypes 6 and 11:  Buschke–​Löwenstein tumour) are other recognized risk factors. Immunosuppressive agents especially azathioprine and ciclo­ sporin and immunosuppressive illnesses such as acquired immunodeficiency syndrome, lymphoma, and chronic lymphocytic leukaemia are associated with an increased risk of SCC as is BRAF inhibitor monotherapy with vemurafenib, dabrafenib, or encorafenib in patients with metastatic melanoma (Peng et al., 2017). Chronic ulcers (Marjolin’s ulcer), hidradenitis suppurativa, skin damage from ionizing radiation, chronic thermal exposure or inflammation (discoid lupus, lichen sclerosus, lymphoedema), and chronic infection (osteomyelitis, chronic fungal infections, lupus vulgaris, granuloma inguinale) may also be associated with SCC. Mutations in p53 (a tumour suppressor gene that arrests defect cell in G1 or induces apoptosis) are present in 40–​60% of all SCCs. Intrinsic risk factors include constitutional skin pigmentation (Fitzpatrick skin type 1) as well as specific genetic syndromes such as xeroderma pigmentosum (a genetic DNA repair defect), albinism, dystrophic epidermolysis bullosa, Fanconi’s anaemia, chronic mucocutaneous candidiasis, and KID syndrome (keratitis, ichthyosis, deafness) are associated with an increased incidence of SCC. Clinical presentation See Tables 1.11.3–​1.11.5 and Fig. 1.11.2.

Table 1.11.3  Squamous cell carcinoma and related lesions Actinic keratosis

Rough keratotic papules or macules that are an early precursor to SCC. 25% of actinic keratoses regress with sun protective measures, but thicker ones need treatment: especially in immunocompromised patients. Pain, rapid growth, and induration suggest malignant transformation

Actinic cheilitis

A precursor for lower lip SCC. The lower lip becomes dry with an indistinct vermillion border and the lesion is atrophic and irregularly hypopigmented. These lesions are especially aggressive when they appear at the commissure, with 20% presenting with lymphadenopathy

Verrucous carcinoma

Verrucous carcinoma is a low-​grade subtype of SCC that presents as a verrucous plaque or nodule (cauliflower growth). It is referred to as a Buschke–​Löwenstein lesion in the anogenital region, an Ackerman tumour of the oral mucosa, and epithelioma cuniculatum of the feet. These are associated with human papilloma virus 6 and 11, betel nut or tobacco chewing, and persistent trauma or inflammation and can become more anaplastic after radiation, even though radiotherapy is a recognized and effective treatment option

Keratoacanthoma (KA)

KA appears after rapid growth over weeks and is a dome-​shaped lesion that involutes over months or years. Multiple KAs are found in familial Ferguson–​Smith syndrome, the Gryzbowski variant, and Muir–​Torre syndrome in which KAs are found with cutaneous sebaceous tumours and visceral cancers (most common colonic adenocarcinoma)

Bowen’s disease

An intra-​epidermal carcinoma of SCC, which presents as a well-​defined thin red plaque. On the penis this lesion is called erythroplasia of Queyrat

Marjolin’s ulcer

This is SCC of chronically scarred or inflamed skin. Any erosion, breakdown, nodule, or change in old and stable scar should be biopsied. Latency period is 20 years, though is less in radiation damaged skin

SCC

Presents as a firm, adherent, nodular or ulcerated lesion, with pain and exudate (Fig. 1.11.2). Paraesthesia, dysaesthesia, and motor nerve palsies are late manifestations due to perineural spread. Anogenital SCC—​irritation, pruritus, pain, erythema, erosions and intermittent bleeding, penile SCC usually found on the glans, associated with balanitis xerotica obliterans (lichen sclerosus et atrophicans)

Periungual SCC

Red, indurated, painful periungual swelling. Non-​resolving chronic paronychia, which does not respond to treatment, should be biopsied to exclude malignancy

Morbidity and mortality Compared with BCC, SCC has a significantly higher risk of metastasis (2–​6%) and death. SCCs that occur in a radiation field, in chronic ulcers, on a mucosal membrane, or in immunosuppressed patients have a poorer prognosis. Recipients of solid organ transplants have a 60–​250-​fold increased risk of developing SCC compared with the general population and these lesions tend to be multiple and aggressive, with a resultant mortality of 13–​46% over 2–​4 years (Lindelöf et al., 2000; Kim et al., 2016; Ducroux et al., 2017).

Several studies have reported decreases in the rate of skin cancers after conversion to, or supplementation with, sirolimus, a bacterial macrolide antibiotic, which is used primarily as an immunosuppressant in organ transplant patients (Le Blanc et al., 2011). The ear, lip, and genitals are high-​risk primary sites due to their thin skin and rich vasculature, as well as to the frequency of desmoplasia in the corresponding tumours. In one study, 50% of all

1.11  Non-melanoma skin cancer and premalignant conditions

Table 1.11.4  High-​risk features for primary tumour (T) staging for non-​eyelid carcinoma Depth/​invasion

>2 mm thickness (Breslow thickness)a

Clark level

≥IV

Perineural invasion

+

Anatomical

Primary site ear

Location

Primary site hair-​bearing lip

Differentiation

Poorly differentiated or undifferentiated

a

Note that in the AJCC eighth edition system, a depth of 6 mm (or perineurial invasion) automatically upstages the tumour from T1 or T2 to T3. Data from Matthiesen C, Thompson S, Ahmad S, Syzek E, Zhao D, Herman T, Bogardus C. A comparison of the sixth and seventh editions of the AJCC TNM systems for T classification and predicting the outcomes of advanced (T2–​T4) non-​melanoma skin cancers treated with radiotherapy. Journal of Radiation Oncology, 2013;2:79–​85.

deaths from cutaneous SCC were from genital primaries (Lewis and Weinstock, 2004). If SCC metastasizes, it is mainly to the regional lymph nodes, though patients with solid organ transplants and chronic lymphocytic leukaemia can have in-​transit cutaneous metastases prior to lymphatic involvement. Most metastases occur within 3 years of diagnosis and the 5-​year survival after lymph node spread is 25%. Risk factors that predispose to a higher rate of recurrence and metastatic spread are similar and both include thickness and invasion beyond subcutaneous fat, perineural invasion, diameter greater than 20 mm, location on temple, and poor differentiation, but metastatic spread is also more likely in tumours present on the ear and the lip and in immunosuppression. Of note, SCCs of the vulva and penis have average 5-​year survivals of 88% for local, 56% for regional, and 14% for distant disease. Human papilloma virus increases the risk for these forms of cancer,

Table 1.11.5  Tumour-​, host-​, and environment-​related prognostic factors for skin cancer Prognostic factors

Tumour related

Host related

Environment related

Essential

TNM, histopatho­ logical type, location, thickness, PNI (clinical)

Immune suppression, recurrent disease

Surgical margins, previous radiotherapy

Additional

Tumour borders, differentiation, rate of growth, LVSI, PNI (incidental)

Genetic factors, Gorlin syndrome, age, chronic inflammation, scars, burns

Smoking (SCC)

New and promising

Sentinel lymph node biopsy, perturbed pathways

Viral aetiology, highly conformal radiotherapy, chemoradiotherapy, targeted therapies, intralesional therapy

LVSI, lymphovascular space invasion; PNI, peripheral nerve invasion. Reproduced from  UICC Manual of Clinical Oncology, Ninth Edition. Edited by Brian O’Sullivan, James D. Brierley, Anil K. D’Cruz, Martin F. Fey, Raphael Pollock, Jan B. Vermorken and Shao Hui Huang. © 2015 UICC. Published 2015 by John Wiley & Sons, Ltd.

Fig. 1.11.2  Squamous cell carcinoma.

and hence a vaccination programme for girls and boys has commenced in many countries. Death directly caused by SCC correlates with a diameter greater than 20 mm, poor differentiation, location on ear or lip, invasion beyond subcutaneous fat, and perineural invasion (Thompson et al., 2016). Management Definitive diagnosis and management options are determined by a biopsy that includes the dermis so as to evaluate the depth of the tumour, and evaluates thickness and perineural invasion. Topical treatment with imiquimod or 5-​fluorouracil can be used for in situ SCC. Alternatively, a carbon dioxide laser can be used with curettage for in situ SCC, but none of these treatments treat follicular extension adequately. For invasive SCC, excision is advised. Locally destructive measures such as cryotherapy, curettage, electrodessication, carbon dioxide laser, photodynamic therapy, or intralesional interferon/​bleomycin do not provide control, as opposed to surgery with margin control (particularly Mohs’ surgery). Radiotherapy can be used for early-​stage cancers with effective local control, particularly if used as a primary treatment and also for smaller lesions. A note of caution with regard to radiotherapy and SCCs situated on the hand, especially the digits or thumb or in the web space: radiotherapy can render the digits stiff and the recurrent tumour seems to spread locally via tissue planes including tendons and muscles. For patients with SCC with perineural invasion, prognosis is related to the presence of symptoms and to the radiographic extent of disease (poorer prognosis as the tumour extends centrally towards the central nervous system). Patients with incidental perineural disease have a local control rate of 80–​90% compared with about

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SECTION 1  General principles and techniques

50–​55% for those with clinical perineural disease. For clinical perineural disease, treatment is by resection of the lesion together with the affected nerve as far proximally as possible and then adjuvant radiation to the field. The treatment for patients with nodal disease is surgery and postoperative radiotherapy, with a likely cure of approximately 70–​80% for those with positive parotid nodes (Mendenhall et  al., 2009). Chemotherapy with cisplatin, 5-​ fluorouracil, bleomycin, doxorubicin, and cetuximab is used for advanced cases of SCC, or as primary treatment (also for BCCs) with electrochemotherapy (Gargiulo et  al., 2012). Electrochemotherapy utilizes electroporation (an electrical field applied to cells increases the permeability of the cell membrane) to allow more of the chemotherapeutic agent into the tumour and though it can be used primarily, it is mostly used for advanced cases, which are not suitable for surgery with an 80% response rate in SCC (Di Monta et al., 2017). Margins for SCC excision In their study, Brodland and Zitelli (1992) showed a 95% clearance for low-​risk tumours if excised with a 4 mm margin (2 cm, invading fat, poorly differentiated, central face, ear, lip, pre-​and postauricular, temples, scalp, genitalia, hands, and feet). The European interdisciplinary guidelines suggest a 6–​10  mm margin for high-​risk tumours, and 5  mm for low-​risk tumours (Stratigos et al., 2020).  Follow-​up Patients who develop one SCC have a 40% risk of developing additional SCCs within the next 2 years and this risk only increases with time. Follow-​up with complete skin examination should be done every 6–​12 months. For patients with high-​risk tumours, skin and lymph node examination is required at 3-​to 6-​month intervals for at least 2 years after diagnosis (British Association of Dermatologists’ guidelines (Motley et al., 2009)).

Merkel cell carcinoma Epidemiology The incidence of Merkel cell carcinoma is low relative to BCC and SCC, though a recent Australian study (Garbutcheon-​Singh et al., 2020) showed an incidence of 3.9 per 100,000 for men and 1.5 per 100, 000 for women. Risk factors Risk factors include sun exposure and viral infection. Most Merkel cell carcinomas contain Merkel cell polyomavirus DNA, assumed to play a pivotal role in tumour pathogenesis (Waltari et al., 2011). Clinical presentation Merkel cell carcinoma usually presents as a solitary, painless, smooth, shiny, non-​ulcerated, red-​to violet nodule on the head, neck, or extremities of Caucasian patients (Fig. 1.11.3). Clinical diagnosis requires a high index of suspicion, and it is estimated that locoregional metastases are already present in approximately 30% of patients at primary diagnosis (Becker et al., 2017).

Fig. 1.11.3  Merkel cell carcinoma.

Subtypes are differentiated by histology and include trabecular (rare and less aggressive), intermediate (most common), and small-​ cell types (most aggressive). Mortality and morbidity Merkel cell carcinoma has a propensity for early metastasis to regional lymph nodes and often presents at an advanced stage with corresponding poor outcomes. The primary lesion is usually small, but the definitive staging and treatment is often delayed because of difficulties in clinical diagnosis. In a recent study with a median follow-​up of 16  months (0–​ 157), the 5-​year overall  survival  was 70%, with a 5-​year disease-​ specific survival of 84% (Farley et al., 2020). Management Surgery is preferred for primary lesions with excision with 3 cm margins and frozen section confirmation of negative excision margins. Mohs’ surgery may be used in difficult areas such as the face where 3 cm margins may not be feasible. Elective lymph node dissection is controversial. Radiotherapy is used as either primary treatment in disseminated disease or as adjuvant treatment in localized disease as Merkel cell carcinoma is radiosensitive. Chemotherapy is used in disseminated disease. Follow-​up The recommended follow-​up is intensive with monthly review for 6 months, 3-​monthly for 2 years, and then 6-​monthly on an ongoing basis because of the risk of local or regional recurrence.

1.11  Non-melanoma skin cancer and premalignant conditions

Adnexal (pilosebaceous, eccrine, and apocrine)-​derived skin malignancies Pilosebaceous lesions These lesions are extremely rare but often aggressive. Pilomatrix carcinoma: presents as a subcutaneous nodule, covered with normal skin or superficial red/​blue nodule possibly with ulceration. These arise by malignant transformation or de novo and are locally aggressive, with a high recurrence rate and can metastasize to the lungs. Wide local excision and close follow-​up are required. Malignant proliferating trichilemmal tumour: presents as a lobulated mass that can ulcerate. There is 3:1 female-​to-​male predominance. These lesions are locally aggressive but metastasis is unusual. Trichilemmal carcinoma: presents on the face of the elderly in sun-​ exposed areas. They have an indolent course and excision is usually curative. Trichoplastic carcinoma:  an exceedingly rare tumour that arises from trichoblastoma. They present as a rapidly growing, painful deep dermal nodule and are highly aggressive lesions.

Eccrine gland lesions These rare lesions may arise from their benign counterparts. Porocarcinoma/​ malignant eccrine poroma:  the most common eccrine carcinoma and 50% arise from benign counterpart. These lesions can be ulcerated, nodular, or verrucous in appearance and occur on the lower legs and feet of elderly people. They can metastasize regionally and systemically and treatment is wide local excision with regional lymphadenectomy if necessary. Several options for adjuvant treatment exist, but cure has been reported with chemoradiotherapy including cisplatin and docetaxel combination (Mandaliya and Nordman, 2016). Malignant eccrine spiradenoma: usually arise from long-​standing pre-​existing benign spiradenoma in 60–​70-​year-​olds. These lesions present with pain and growth of an existing intradermal nodule and can metastasize. Wide local excision is required with close follow-​ up. Adjuvant chemoradiotherapy has been recommended (Rebegea et al., 2016). Malignant nodular hidradenoma: a rare lesion. Most arise de novo and are highly aggressive lesions. They present as an intradermal nodule on the head, trunk, and extremities, mostly in middle age. Treatment is wide local excision and possibly elective lymph node dissection. Malignant chondroid syringoma: arises mostly de novo on the torso and extremities in middle age. There is a female-​to-​male preponderance (2:1). The lesion grows rapidly and 50% of patients have regional metastases and 50% distant metastases at presentation (Barnett et al., 2000). Wide local excision, regional lymphadenectomy, and radiotherapy for distant metastases are recommended. Syringoid eccrine carcinoma: presents as an asymptomatic nodule or plaque on the head or extremities in middle age. The differential diagnosis is a cutaneous manifestation of adenocarcinoma or adenoid BCC, though carcinoembryonic antigen expression differentiates it from the latter. Wide local excision and close follow-​up is required. Microcystic adnexal carcinoma: a locally aggressive lesion that infiltrates the dermis, subcutaneous tissue, and skeletal muscle and is associated with perineural invasion. The tumour is a pale yellow

nodule/​plaque with ill-​defined borders, mostly seen in nasolabial and periorbital areas, and can take up to 30  years to evolve. It is treated with Mohs’ surgery. Mucinous adenocystic (eccrine) carcinoma:  a superficial raised nodule or subcutaneous lesion, most commonly found in eyelids, but also on scalp and face in 50–​70-​year-​old males. It can recur locally, but rarely metastasizes. It is treated with wide local excision and close follow-​up. Mammography and colonoscopy are recommended to rule out the differential diagnoses of cutaneous metastases from breast or colon carcinoma. Adenoid cystic carcinoma: is exceedingly rare (5 cm), the resection margin is less than 1 cm, it is poorly differentiated, or if there are more than four positive lymph nodes.

Sebaceous gland lesions Sebaceous carcinoma (Fig. 1.11.4) is a rare and aggressive lesion. It arises from the adnexal epithelium of the sebaceous gland. There are two types: 75% are ocular (aggressive lesions with metastatic potential) and 25% are extraocular (still found in the head and

Fig. 1.11.4  Sebaceous carcinoma.

75

76

SECTION 1  General principles and techniques

neck). They present as a pink-​red nodule, which may ulcerate (similar to a nodular BCC). They can metastasize to regional lymph nodes or systemically. Wide local excision is required and lymphadenectomy, radiotherapy, and chemotherapy can be used for metastatic disease.

Other non-​melanoma skin malignancies Haematological malignancies Haematological malignancies may present with erythematous skin tumours, for example cutaneous T-​cell lymphoma or cutaneous leukaemia. Diagnosis is provided by histology and management is by dermato-​oncologists or haematologists using drugs such as, for example, retinoids, and irradiation.

Cutaneous metastasis Skin metastasis occurs in up to 10% of all cancer patients and constitutes approximately 2% of all skin tumours undergoing histological examination (Alcaraz et al., 2012). In addition to histopathological examination of the excised tumour, additional investigations are indicated to find the metastasizing cancer.

The terminology of the histopathology report The management of skin malignancy hinges on the histopathological report and it is therefore important to understand it completely. There is a specific descriptive terminology that has prognostic significance for the individual tumour. Acantholytic: this means a loss of intercellular connections, such as desmosomes, and expression of adhesion markers, resulting in loss of cohesion. It is usually taken to indicate a more aggressive tumour (Griffin et al., 2013), particularly in SCC, though this is controversial (Ogawa et al., 2017). Degree of differentiation:  tumours with cells which almost look like normal cells are low grade and well differentiated, while tumours with very abnormal cells are high grade, poorly differentiated, or non-​d ifferentiated. Poorly differentiated especially refers to tumours in which the products of differentiation, such as keratin or desmostromal attachments, are poorly expressed. Immunohistochemistry techniques for keratin subsets are often used to identify such tumours, basosquamous and metatypical carcinoma, for example. Sometimes tumours may be encountered that show histological features intermediate between BCC and SCC. These generally behave more like SCC and in practice should be considered to be forms of SCC. Desmoplasia: the growth of fibrous or connective tissue associated with the tumour is the most important histological feature for local recurrence (local recurrence is 24% in desmoplastic SCCs vs 1% for similar but non-​desmoplastic SCC (Brantsch et  al., 2008)). Desmoplasia is more commonly associated with BCC than SCC. Diameter: larger tumours, particularly in SCC, have an increased risk of recurrence and metastasis. The risk of recurrence doubles for tumours greater than 2 cm in diameter compared to smaller lesions

(15.2% vs 7.4%) and the risk of metastasis trebles (30.3% vs 9.1%) (Farasat et al., 2011). Lymphatic invasion: dermal lymphatic spread in the primary tumour as well as in satellite nodules may be seen separate from the primary lesion and is a poor prognostic sign. Mitotic rate: this describes the frequency of cell division within the lesion. Higher mitotic rates are associated with more rapidly dividing cells and therefore larger lesions, with greater potential for metastasis and poorer prognosis. Perineural invasion: in SCCs (Haug et al., 2020) correlates with local recurrence, spindle cell histology, and increasing tumour size. It is an indication that the tumour has spread to deeper tissues, is particularly important in facial lesions, and is an indication that further measures are required for tumour clearance, such as nerve resection and postoperative radiotherapy. Regression: this describes an area within the tumour where it appears there had been cancer cells, but these have been destroyed by the immune system and replaced with inflammation or scar tissue. When regression is present, the original size of the lesion is hard to define because it is difficult to determine its extent before the regression occurred. Thickness: tumour thickness greater than 6 mm (measured as the Breslow thickness, which measures the distance between the upper layer of the epidermis (granular layer) and the deepest point of tumour penetration) automatically upstages the tumour from T1/​T2 to T3 in SCC, which has consequences for treatment and follow-​up. Ulceration: this is thought to reflect rapid tumour growth, leading to the death of cells in the centre of the tumour. It also causes the Breslow thickness to be underestimated. Vascular invasion: this finding indicates the lesion has the potential to metastasize and is a poor prognostic sign.

Classifications and staging The American Joint Committee on Cancer (AJCC) was started in 1959 and the first AJCC manual was published in 1977. For most of these years, tumour staging was heavily influenced by the ability of surgery to treat the particular cancer, but now advances in medical and radiation oncology have improved their efficacy to the point where they also influence staging. Prior to the seventh edition of the AJCC staging manual, cutaneous malignancies were divided into only two categories: melanoma and NMSC. Since the seventh edition, Merkel cell carcinoma has been assigned its own staging protocol in keeping with its aggressive biological behaviour, and the main changes in the eighth edition is the significant changes in N categorization and stratification of stages I–​IV, with the clinical and pathological staging separated. Head and neck cutaneous SCC (including the lower lip) has been separated in the eighth edition of the AJCC, which includes the thickness on prognosis, the involved nerve branch that infiltrates the tumour, and the depth of invasion of the SCC for the stratification of the T category. The N stratification is based on the same system of other head and neck tumours.  This edition, however, does not define any system for classification of SCCs located on the eyelid, vulva, penis, and perineal regions, which is a drawback and means, for example, that such a tumour on

1.11  Non-melanoma skin cancer and premalignant conditions

the dorsum of the hand cannot be classified according to the eighth edition of the AJCC TNM staging manual. Neither is there a specific staging system for basal cell carcinoma or for other forms of NMSC (Cañueto and Román-​Curto, 2017). It may therefore be easier for the clinician to use the TNM classification (Brierley et al., 2016).

REFERENCES Alcaraz I, Cerroni L, Rütten A, et al. Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol 2012; 34:347–​93. Allen PJ, Bowne WB, Jaques DP, et al. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 2005;23:2300–​9. Attia ABE, Balasundaram G, Moothanchery M, et al. A review of clinical photoacoustic imaging: current and future trends. Photoacoustics 2019;16:100144. Barnett MD, Wallack MK, Zuretti A, et  al. Recurrent malignant chondroid syringoma of the foot:  a case report and review of the literature. Am J Clin Oncol 2000;23:227–​32. Becker JC, Stang A, DeCaprio JA, et al. Merkel cell carcinoma. Nat Rev Dis Primers 2017;3:17077. Boone MA, Suppa M, Pellacani G, et al. High-​definition optical coherence tomography algorithm for discrimination of basal cell carcinoma from clinical BCC imitators and differentiation between common subtypes. J Eur Acad Dermatol Venereol 2015;29:1771–​80. Bouwes Bavinck JN, Hardie DR, Green A, et al. The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-​up study. Transplantation 1996;61:715–​21. Brantsch KD, Meisner C, Schönfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous-​cell carcinoma:  a prospective study. Lancet Oncol 2008;9:713–​20. Breuninger H, Dietz K. Prediction of subclinical tumor infiltration in basal cell carcinoma. J Derm Surg Oncol 1991;17:574–​8. Brierley JD, Gospodarowicz MK, Wittekind C (eds). TNM Classification of Malignant Tumours, 8th ed. Hoboken, NJ:  Wiley-​ Blackwell,  2016. Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermal 1992;27:241–​8. Bystrzonowski N, Gardiner M, Rice S, et al. Differences in outcome for patients referred to dermatology or plastic surgery with suspected skin cancer. Int J Surg 2013;11:684. Cañueto J, Román-​Curto C. Novel additions to the AJCC’s new staging systems for skin cancer. [Article in English, Spanish] Actas Dermosifiliogr 2017;108:818–​26. Chang H, Jang WH, Lee S, et  al. Moxifloxacin labeling-​ based multiphoton microscopy of skin cancers in Asians. Lasers Surg Med 2020;52:373–​82. de Bree E, Volalakis E, Tsetis D, et al. Treatment of advanced malignant eccrine poroma with locoregional chemotherapy. Br J Dermatol 2005;152:1051–​5. De Carvalho N, Schuh S, Kindermann N, et al. Optical coherence tomography for margin definition of basal cell carcinoma before micrographic surgery-​ recommendations regarding the marking and scanning technique. Skin Res Technol 2018;24:145–​51. Di Monta G, Caracò C, Simeone E, et  al. Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-​cases retrospective analysis. J Transl Med 2017;15:82.

Dinnes J, Deeks JJ, Chuchu N, et  al. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev 2018;12:CD013191. Ducroux E, Martin C, Bouwes Bavinck JN, et  al. Risk of aggressive skin cancers after kidney retransplantation in patients with previous posttransplant cutaneous squamous cell carcinomas: a retrospective study of 53 cases. Transplantation 2017;101:e133–​41. Farasat S, Yu SS, Neel VA, et al. A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumour (T) characteristics. J Am Acad Dermatol 2011;64:1051–​9. Farley CR, Perez MC, Soelling SJ, et  al. Merkel cell carcinoma outcomes:  does AJCC8 underestimate survival? Ann Surg Oncol 2020 Feb 26. doi:  10.1245/​s10434-​019-​08187-​w. [Epub ahead of print] Garbutcheon-​Singh KB, Curchin DJ, McCormack CJ, et al. Trends in the incidence of Merkel cell carcinoma in Victoria, Australia, between 1986 and 2016. Australas J Dermatol 2020;61:e34–​8. Garcia C, Crowson AN. Acantholytic squamous cell carcinoma: is it really a more-​aggressive tumour? Dermatol Surg 2011;37:353–​6. Gargiulo M, Papa A, Moio M, et  al. Electrochemotherapy for non-​ melanoma head and neck cancers: clinical outcomes in 25 patients. Ann Surg 2012;255:1158–​64. Griffin JR, Wriston CC, Peters MS, et  al. Decreased expression of intercellular adhesion molecules in acantholytic squamous cell carcinoma compared with invasive well-​differentiated squamous cell carcinoma of the skin. Am J Clin Pathol 2013;139:442–​7. Haug K, Breuninger H, Metzler G, et  al. Prognostic impact of perineural invasion in cutaneous squamous cell carcinoma: results of a prospective study of 1,399 tumors. J Invest Dermatol 2020 Mar 10. pii:  S0022-​202X(20)30254-​2. doi:  10.1016/​j.jid.2020.01.035. [Epub ahead of print] Hult J, Dahlstrand U, Merdasa A, et al. Unique spectral signature of human cutaneous squamous cell carcinoma by photoacoustic imaging. J Biophotonics 2020;13:e201960212. Hussain AA, Themstrup L, Jemec GB. Optical coherence tomography in the diagnosis of basal cell carcinoma. Arch Dermatol Res 2015;307:1–​10. Hussain AA, Themstrup L, Nürnberg BM, et al. Adjunct use of optical coherence tomography increases the detection of recurrent basal cell carcinoma over clinical and dermoscopic examination alone. Photodiagnosis Photodyn Ther 2016;14:178–​84. Iftimia N, Yelamos O, Chen CJ, et  al. Handheld optical coherence tomography-​reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins. J Biomed Opt 2017;22:76006. Jemec GBE, Miech D, Kemeny L. Non-​ Surgical Treatment of Keratinocyte Skin Cancer. Heidelberg: Springer, 2010. Kadouch DJ, Elshot YS, Zupan-​Kajcovski B, et al. One-​stop-​shop with confocal microscopy imaging vs. standard care for surgical treatment of basal cell carcinoma: an open-​label, nononferiority, randomized controlled multicentre trial. Br J Dermatol 2017;177:735–​41. Kang S, Goldfarb MT, Weiss JS, et al. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. J Am Acad Dermatol 2003;49:83–​90. Kim C, Cheng J, Colegio OR. Cutaneous squamous cell carcinomas in solid organ transplant recipients: emerging strategies for surveillance, staging, and treatment. Semin Oncol 2016;43:390–​4. Lallas A, Tzellos T, Kyrgidis A, et al. Accuracy of dermoscopic criteria for discriminating superficial from other subtypes of basal cell carcinoma. J Am Acad Dermatol 2014;70:303–​11.

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SECTION 1  General principles and techniques

LeBlanc K, Hughes M, Sheehan DJ. The role of sirolimus in the prevention of cutaneous squamous cell carcinoma in organ transplant recipients. Dermatol Surg 2011;7:744–​9. Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012;366:1010–​19. Lecluse LL, Spuls PI. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-​cell carcinoma:  a single blind, non-​inferiority, randomised controlled trial: a critical appraisal. Br J Dermatol 2015;172:8–​10. Leonardi G, Vahter M, Clemens F, et al. Inorganic arsenic and basal cell carcinoma in areas of Hungary, Romania, and Slovakia: a case-​ control study. Environ Health Perspect 2012;120:721–​6. Lewis KG, Weinstock MA. Nonmelanoma skin cancer mortality (1988–​2000):  the Rhode Island follow-​back study. Arch Dermatol 2004;140:837–​42. Lindelöf B, Sigurgeirsson B, Gäbel H, et al. Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol 2000;143:513–​19. Manfredini M, Longo C, Ferrari B, et  al. Dermoscopic and reflectance confocal microscopy features of cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2017;31:1828e33. Mandaliya H, Nordman I. Metastatic eccrine porocarcinoma: a rare case of successful treatment. Case Rep Oncol 2016;9:454–​6. Matthiesen C, Thompson S, Ahmad S, et al. A comparison of the sixth and seventh editions of the AJCC TNM systems for T classification and predicting the outcomes of advanced (T2–​T4) non-​melanoma skin cancers treated with radiotherapy. J Radiat Oncol 2013;2:79–​85. McLoone NM, Tolland J, Walsh M, et al. Follow-​up of basal cell carcinomas: an audit of current practice. J Eur Acad Dermatol Venereol 2006;20:698–​70. Mendenhall WM, Amdur RJ, Hinerman RW, et al. Radiotherapy for cutaneous squamous and basal cell carcinomas of the head and neck. Laryngoscope 2009;119:1994–​9. Motley RJ, Preston PW, Lawrence CM. Multi-​professional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma 2009 -​update of the original guideline which appeared in Br J Dermatol 2002;146:18–​25. https://​www.bad.org.uk/​ shared/​get-​file.ashx?id=59&itemtype=document Munyao TM, Othieno-​Abinya NA. Cutaneous basal cell carcinoma in Kenya. East Afr Med J 1999;76:97–​100. Nori S, Rius-​Díaz F, Cuevas J, et  al. Sensitivity and specificity of reflectance-​ mode confocal microscopy for in vivo diagnosis of basal cell carcinoma:  a multicenter study. J Am Acad Dermatol 2004;51:923–​30. Ogawa T, Kiuru M, Konia TH, et al. Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not ’high risk’:  Diagnosis, management, and clinical outcomes in a series of 115 cases. J Am Acad Dermatol 2017;76:327–​33. Pan ZY, Lin JR, Cheng TT, et al. In vivo reflectance confocal microscopy of basal cell carcinoma: feasibility of preoperative mapping of cancer margins. Dermatol Surg 2012;38:1945–​50. Peng L, Wang Y, Hong Y, et  al. Incidence and relative risk of cutaneous squamous cell carcinoma with single-​agent BRAF inhibitor and dual BRAF/​MEK inhibitors in cancer patients: a meta-​analysis. Oncotarget 2017;8:83280–​91. Pirard D, Vereecken P, Mélot C, Heenen M. Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses:  a meta-​analysis of the recent studies. Arch Dermatol Res 2005; 297:185–​9.

Rebegea LF, Firescu D, Dumitru M, et al. Skin spiradenocarcinoma –​ case presentation. Rom J Morphol Embryol 2016;57:327–​30. Reichgelta BA, Visserb O. Epidemiology and survival of Merkel cell carcinoma in the Netherlands. A  population-​based study of 808 cases in 1993–​2007. Eur J Cancer 2011;47:579–​85 Rizvi SMH, Aagnes B, Holdaas H, et al. Long-​term change in the risk of skin cancer after organ transplantation: a population-​based nationwide cohort study. JAMA Dermatol 2017;153:1270–​7. Romano RA, Teixeira Rosa RG, Salvio AG, et  al. Multispectral autofluorescence lifetime dermoscope for skin lesion assessment. Photodiagnosis Photodyn Ther 2020:101704. Rosentdahl C, Tschandl P, Cameron A, et al. Diagnostic accuracy of dermatoscopy for melanocytic and nonmelanocytic pigmented lesions. J Am Acad Dermatol, 2011;64:1068–​73. Schröder U, Dries V, Klussmann JP, et  al. Successful adjuvant tamoxifen therapy for estrogen receptor-​positive metastasizing sweat gland adenocarcinoma:  need for a clinical trial? Ann Otol Rhinol Laryngol 2004;113:242–​4. Stratigos AJ, Garbe C, Dessinioti C, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: part 2. Treatment. Eur J Cancer 2020 Feb 26. pii: S0959-​8049(20)30019-​8. doi: 10.1016/​j.ejca.2020.01.008. [Epub ahead of print] Tan ES, Ee M, Shen L, et al. Basal cell carcinoma in Singapore: a prospective study on epidemiology and clinicopathological characteristics with a secondary comparative analysis between Singaporean Chinese and Caucasian patients. Australas J Dermatol 2015;56:175–​9. Taylor G, Mollick DK, Heilman ER. Merkel cell carcinoma. In: Rigel DS, Friedman RJ, Dzubow LM, et al. (eds.) Cancer of the Skin, pp. 323–​8. Philadelphia, PA: Elsevier, 2005. Telfer NR, Colver GB, Morton CA. Guidelines for the management of basal cell carcinoma. Br J Dermatol 2008;159:35–​48. Thompson AK, Kelley BF, Prokop LJ, et al. Risk factors for cutaneous squamous cell carcinoma outcomes: a systematic review and meta-​ analysis. JAMA Dermatol 2016;152:419–​28. Tyers AG. Orbital exenteration for invasive skin tumours. Eye (Lond) 2006;20:1165–​70. Wahrlich C, Alawi SA, Batz S, et al. Assessment of a scoring system for basal cell carcinoma with multi-​beam optical coherence tomography. J Eur Acad Dermatol Venereol 2015;29:1562–​9. Walker P, Hill D. Surgical treatment of basal cell carcinomas using standard postoperative histological assessment. Australas J Dermatol 2006;47:1–​12. Waltari M, Sihto H, Kukko H, et  al. Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-​alpha and survival in Merkel cell carcinoma. Int J Canc 2011;129:619–​28. Weinstein MC, Brodell RT, Bordeaux J, et al. The art and science of surgical margins for the dermatopathologist. Am J Dermatopathol 2012;34:737–​45. Wolberink EA, Pasch MC, Zeiler M, et  al. High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases. J Eur Acad Dermatol Venereol 2013;27:985–​9. Yaroslavsky AN, Feng X, Yu SH, et  al. Dual-​wavelength optical polarization imaging for detecting skin cancer margins. J Invest Dermatol 2020 Apr 6. pii:  S0022-​202X(20)31348-​8. doi:  10.1016/​ j.jid.2020.03.947. [Epub ahead of print] Zaar O, Gillstedt M, Lindelöf B, et  al. Merkel cell carcinoma incidence is increasing in Sweden. J Eur Acad Dermatol Venereol 2016;30:1708–​13.

1.12

Pigmented lesions and melanoma including premalignant conditions Michael Henderson, John Spillane, David Gyorki, and Christopher McCormack

Introduction Throughout the world, each year, approximately 250,000 people develop melanoma and 40,000 die from the disease. Melanoma is characteristically a disease of fair-​skinned people exposed to high ambient levels of ultraviolet (UV) radiation. The incidence has doubled over the last 20  years with an annual increase of 4–​6% although there are marked differences between and within populations, geographical location, age, and gender. Probably as a consequence of public health education programmes, the incidence in Australia appears to have plateaued and may actually be falling. The reduction in incidence has largely occurred in patients less than 65 years but as seen elsewhere around the world, the incidence of melanoma in persons over the age of 65 years has increased significantly. Nevertheless, melanoma in younger people (1.0–​2.0

No

T2a

1B

92

>1.0–​2.0

Present

T2b

2A

88

>2.0–​4.0

No

T3a

2A

88

>2.0–​4.0

Present

T3b

2B

81

>4.0

No

T4a

2B

83

>4.0

Present

T4b

2C

75

(b)  Stage groupings and 10-​year survivals for stage 3 cutaneous melanoma Stage 3

T, N status

10-​year melanoma-​specific survival (%)

3a

T1a/​b, T2a and N1a/​b

88

3b

T1a/​b and N1b/​c or N2b T2b/​T3a and N1a–​N2b

77

3c

T1a–​T3a and N2c or N3a/​b/​c T3b/​T4a and  N2–​N3 T4b and N1c–​N2c

60

3d

T4b and N3a/​b/​c

24

N status: N1, 1 node involved; N2, 2–​3 nodes involved; N3 >3 nodes involved; N4a, lymph nodes clinically occult; N4b clinically apparent lymph nodes. N1c, in-​transit or satellite lesions present, no lymph nodes, N2c, in-​transit or satellite lesions present and 1 lymph node involved; N3c, in-​transit or satellite lesions present and >1 lymph nodes involved. Data from: Gershenwald JE, Scolyer RA, Hess et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:472–92.

benign pigmented naevi which may cause confusion macroscopically. Computer-​aided diagnosis based on machine learning algorithms has demonstrated similar sensitivity and specificity to expert clinicians and while an attractive approach has yet to be shown to reduce mortality (Dick et al., 2019).

Biopsy The options for biopsy of a suspicious lesion include either a complete excision with a minimal margin or a partial biopsy (e.g. punch, incisional or shave biopsy). As a general rule, when a diagnosis of melanoma is suspected, an excisional biopsy is the test of choice, as partial biopsy runs the risk of a sampling error and misdiagnosis along with underestimation of thickness and other important prognostic characteristics (Tran et  al., 2008). Exceptions to this rule include larger lesions where excisional biopsy could cause significant functional or cosmetic consequences. Histopathology reports of partial biopsies need to be carefully correlated with the clinical findings. Consideration should be given to re-​biopsy if there are concerns about the adequacy of a partial biopsy.

Histopathology report A comprehensive synoptic report includes the thickness, type of melanoma, mitotic rate, and comments on the presence of satellites, lymphatic and/​or vascular invasion, lymphotropism, desmoplasia, regression, and measured margins of excision. Tumour ulceration is a histological diagnosis and refers to loss of the upper epidermis overlying the melanoma. Tumour thickness as described by the American pathologist Alexander Breslow in 1969 is now accepted as the most reliable method of evaluating cutaneous melanoma. Levels of invasion first described in 1967 by Wallace Clark, also an American pathologist, have significant inter-​and intra-​observer variation and have been shown repeatedly to be less effective in staging primary melanomas than tumour thickness. Unless a complete pathology report is available, the surgeon is not in an optimal position to plan appropriate management. Melanoma pathology can be difficult and if there are any concerns a further expert review should be considered, particularly if the report is incomplete or is not consistent with the clinical scenario (van Dijk et al., 2008). This is particularly important for borderline lesions, highly dysplastic naevi, and those with spitzoid features in the younger age group where misdiagnosis may lead to inappropriate management.

1.12  Pigmented lesions and melanoma including premalignant conditions

Naevoid melanomas and desmoplastic melanomas can be particularly difficult to diagnose particularly on inadequate specimens. Four main types of invasive melanoma are recognized as well as pre-​invasive melanoma in situ: 1. Superficial spreading melanoma is the commonest histological type and usually presents with the classic ‘ABCD’ appearance. Most are thin (50% of cases) and therefore should be supplemented by attempts to kill remaining active cells by the use of phenol, freeze-​thawing with liquid nitrogen, or insertion of methylmethacrylate cement, which acts by generating heat and also supports the bone. Some use grafting with bone chips. Recurrence is dealt with by further intralesional surgery. However, in the upper limb where the distal radius is most often affected, an alternative treatment is available:  the use of a proximal fibular graft (vascularized or non-​vascularized) after en bloc resection of the tumour (Kumta et al., 1998). Recently, the molecular biology of this tumour has been established with the multinucleate giant cells of the lesion recruited by overexpression of a specific ligand (RANKL) by the neoplastic tumour cells. There is a role for adjuvant treatment for complex lesions with denosumab, an inhibitor of the RANKL ligand (van der Heijden et al., 2014) Giant cell tumours in the tubular bones of the hand are rare, but have been described in cases series from India and China. They appear to have a high propensity for metastasis to the lungs. Amputation is therefore more appropriate than curettage.

Aneurysmal bone cyst The aneurysmal bone cyst is probably not a true tumour but may represent a reactive process to some other underlying abnormality in the bone from which it arises. It presents with pain and swelling developing over several weeks. The ‘soap bubble’ appearance on radiographs is characteristic and the presence of multiple fluid levels on MRI is confirmatory. Most lesions can be treated by curettage and packing with bone chips or methylmethacrylate cement. However, recurrence may occur. The behaviour of an aneurysmal bone cyst may be classed as intermediate for this reason and because a rapidly expansile lesion can destroy bone and be difficult to treat by simple methods. Excision of the lesion and reconstruction with a vascularized bone graft may then need to be considered.

Bizarre parosteal osteochondromatous proliferation (Nora’s lesion) This uncommon lesion, first described by Nora in 1983, may be rapidly growing and can be mistaken for a malignant growth because of its behaviour and appearance; however, the bone from which the lesion originates is normal in appearance and the surrounding soft tissues are unaffected, as can be shown by MRI. Its most characteristic feature is a tendency to rapid recurrence, in 50% or more of cases, after excision. Recurrence can be dealt with by repeated surgery. No cases have been reported to undergo malignant transformation (Gruber et al., 2008).

Malignant behaviour As can be seen in Table 4.25.1, the most common site for malignant bone tumours in the upper limb is the proximal humerus, but they can occur elsewhere. The general principles of the management of malignant bone tumours in the upper limb are to establish a diagnosis and carry out en bloc resection of the tumour with a margin of normal tissue, followed by reconstruction. Amputation may be the alternative when reconstruction is not feasible. A balance between adequate resection and the maintenance of upper limb function is often difficult to achieve, particularly in elderly patients. The use of adjuvant chemotherapy and radiotherapy and their timing in relation to surgical treatment requires careful planning by the multidisciplinary team. MRI is very helpful in the assessment of malignant tumours as it shows changes within the tumour and the surrounding soft tissues.

Chondrosarcoma This is the most common malignant tumour in the upper limb, where it may complicate the condition of multiple enchondromatosis in the proximal part of the limb. The patient presents with pain and swelling. Radiologically, there is cortical destruction with radiating spicules of bone and sometimes punctate calcification. The histology of chondrosarcomas is graded from relatively well differentiated (grade I) to highly undifferentiated (grade III) but the histology may vary within the tumour as with all sarcomas. A core biopsy grading is therefore likely to be upgraded after the full specimen is available. Management follows the general principles for dealing with malignant bone tumours although radiotherapy and chemotherapy are not usually effective. Chondrosarcomas in the upper limb tend not to metastasize but are very prone to recurrence.

Osteogenic sarcoma (osteosarcoma) The tumour is characterized by the production of malignant osteoid tissue. Pain is the presenting feature. The radiograph shows a destructive lesion often with an aggressive periosteal reaction producing Codman’s triangle (a triangular area of bone that forms subperiosteally at the margin of the lesion where the primary bone lesion expands and raises the periosteum off the cortex) or a sunburst effect (a periosteal bone reaction where rapid growth of the lesion stretches the Sharpey’s fibres of the periosteum which ossify and produce the characteristic spiculated bone perpendicular to the cortex). Metastasis to the lung can occur. After careful staging and establishing the extent of the tumour within the bone, the treatment

4.25  Bone lesions in the upper limb and hand

is by a course of chemotherapy followed by resection and reconstruction when possible. The tumour is very rare in the hand and affects a much older age group. Treatment is by ray resection rather than hand amputation.

Ewing’s tumour This tumour may present with bone pain associated with fever and sometimes anaemia. The white blood count and erythrocyte sedimentation rate may be raised. The characteristic radiographic appearance is of a laminated ossifying periosteal reaction giving an ‘onion-​skin’ effect. Histologically, the tumour is of a small round-​cell type. Many patients have metastases at the time of presentation. The main treatment is chemotherapy, with local control achieved with surgery and/​or radiotherapy.

Metastatic tumours The humerus is a common site for metastatic tumours from the lung, breast, kidney, and elsewhere. Renal tumours may present with a solitary pathological fracture in the humerus. If the bone is at imminent risk of fracture (>50% of the cortex affected) or has fractured, treatment is by intramedullary fixation, with or without bone cement, and postoperative radiotherapy. Smaller lesions can be treated by radiotherapy alone. Very extensive lesions can be treated by resection and prosthetic replacement (Frassica and Frassica, 2003). Metastatic disease in the hand is rare (an estimated 0.1% of skeletal metastases). It usually affects the terminal phalanges and the lung is a common primary site, although many other primaries have been reported (Kerin, 1987). Bony destruction is seen on the radiograph. The main worry about these infrequent tumours is that they may be mistaken for some other condition such as infection or gout, because the surrounding soft tissue may be red and swollen. Treatment is by radiotherapy although amputation may be required for fungating lesions.

Other bony swellings Subungual exostosis In comparison to their occurrence in the toes, these are quite uncommon in the hand digits, and probably represent a reaction to an injury to the terminal phalanx. As with other subungual lesions they present with a deformity of the nail although they may project beyond the nail at the tip of the finger (Nowillo and Simpson, 2010). Radiography will show a spike of bone, although various angles of view may be required before it is well shown. The spike can be removed after elevating the nail bed with the nail plate for access if necessary.

Turret exostosis This lesion occurs as a reaction to minor trauma usually to the dorsum of the hand. A  slowly growing bony lump develops beneath the extensor apparatus. It may be painful if knocked. If troublesome it can be excised. Although it is probably part of the same spectrum of reactive disorders that includes bizarre parosteal osteochondromatous proliferation, it does not have the same tendency to recurrence (Stahl et al., 2000).

Epidermoid cyst This lesion presents as a progressive, drumstick-​like swelling of the terminal phalanx with enlargement and increased curvature of the nail (Schajowicz et al., 1970). The radiographic appearance is of a large clear cyst in the bone, often with loss of some of the cortex but without periosteal reaction. It is the result of implantation of keratin-​ producing cells (e.g. from the germinal matrix of the nail fold) into the bone, and thus may follow a crushing injury of the fingertip in childhood, although the injury may be more recent. Careful removal of the wall of the cyst and its contents is usually followed by remodelling of the bone.

Carpal boss The carpal boss is an abnormal bony prominence of the margins of the second or third carpometacarpal joints. The cause of this condition is unknown but it has been proposed that the lesion arises consequent to repetitive trauma or stress in a joint with partial or fibrous coalition (Alemohammad et al., 2009). The patient with a symptomatic carpal boss presents with irritation of the extensor tendons where they pass over the boss on the dorsum of the hand, and may often be in the habit of flicking them over the prominence. The lesion is bony hard but there may be an associated small ganglion in the region and some inflammation around the tendons. A lateral radiograph taken with the hand carefully positioned so that the boss is in profile will confirm the diagnosis. Treatment is problematic (Park et al., 2008). Often a clear explanation is all that is required. Although some have reported excellent results from surgical excision (Fusi et al., 1995), this is not always the case. The swelling and discomfort that follow removal of the lips of bone may be more troublesome than the presenting condition and recurrence is common (Clarke et al., 1999). Attempts have been made to prevent this by a radical removal of bone in a ‘V’ fashion into the joint, but this may cause problems of instability. Fusion of the joints to prevent this is probably too radical an approach (Loréa et al., 2008).

Brown tumour of hyperparathyroidism These are seen as multiple osteolytic lesions in the hand. They rarely present to the surgeon but are mentioned here because when they do, the possibility of this diagnosis may be overlooked and inappropriate investigations or treatments are used. In this situation, laboratory blood tests are useful in diagnosis: the level of calcium is raised and usually so is the level of parathyroid hormone.

REFERENCES Alemohammad AM, Nakamura K, El-​Sheneway M, et al. Incidence of carpal boss and osseous coalition: an anatomic study. J Hand Surg Am 2009;34:1–​6. Campanacci M, Baldini N, Boriani S, et al. Giant-​cell tumour of bone. J Bone Joint Surg Am 1987;69:106–​14. Chen W, DiFrancesco LM. Chondroblastoma: an update. Arch Pathol Lab Med 2017;141:867–​71. Clarke AM, Wheen DJ, Visvanathan S, et al. The symptomatic carpal boss. Is simple excision enough? J Hand Surg Br 1999;24:591–​5. Frassica FJ, Frassica DA. Metastatic bone disease of the humerus. J Am Acad Orthop Surg 2003;11:282–​8. Fusi S, Watson HK, Cuono CB. The carpal boss. A 20-​year review of operative management. J Hand Surg Br 1995;20:405–​8.

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SECTION 4  Upper limb

Gruber G, Giessauf C, Leithner A, et  al. Bizarre parosteal osteochondromatous proliferation (Nora lesion): a report of 3 cases and a review of the literature. Can J Surg 2008;51:486–​9. Hasselgren G, Forssblad P, Törnvall A. Bone grafting unnecessary in the treatment of enchondromas in the hand. J Hand Surg Am 1991;16:139–​42. Kerin R. The hand in metastatic disease. J Hand Surg Am 1987;12:77–​83. Kumta SM, Leung PC, Yip K, et  al. Vascularized bone grafts in the treatment of juxta-​articular giant-​cell tumors of the bone. J Reconstr Microsurg 1998;14:185–​90. Le HBQ, Lee ST, Munk PL. Image-​guided musculoskeletal biopsies. Semin Intervent Radiol 2010;27:191–​8. Loréa P, Schmitz S, Aschilian M, et al. The preliminary results of treatment of symptomatic carpal boss by wedge joint resection, radial bone grafting and arthrodesis with a shape memory staple. J Hand Surg Eur 2008;33:174–​8. Nowillo KS, Simpson RL. Subungual exostosis of the finger with nail plate induction. Hand (N Y) 2010;5:203–​5. Park MJ, Namdari S, Weiss AP. The carpal boss: review of diagnosis and treatment. J Hand Surg Am 2008;33:446–​9. Rosenthal DI, Springfield DS, Gebhardt MC, et al. Osteoid osteoma: percutaneous radio-​frequency ablation. Radiology 1995;197:451–​4.

Qasem SA, DeYoung BR. Cartilage-​forming tumours. Semin Diag Pathol 2014;31:10–​20. Schajowicz F, Aiello CL, Slullitel I. Cystic and pseudocystic lesions of the terminal phalanx with special reference to epidermoid cysts. Clinical Orthop Relat Res 1970;68:84–​92. Simon M, Pogoda P, Hovelborn F, et al. Incidence, histopathologic analysis and distribution of tumours of the hand. BMC Musculoskelet Disord 2014;15:182. Sobti A, Agrawal P, Agarwala S, et al. Giant cell tumour of bone—​an overview. Arch Bone Jt Surg 2016;4:2–​9. Stahl S, Schapira D, Nahir AM. Turret exostosis of the phalanges presenting as limited motion of the finger. Eur J Plast Surg 2000; 23:82–​4. Stieber JR, Dormans JP. Manifestations of hereditary multiple exostoses. J Am Acad Orthop Surg 2005;13:110–​20. van der Heijden L, Dijkstra PD, van de Sande MA, et al. The clinical approach toward giant cell tumor of bone. Oncologist 2014;19: 550–​61. Verdegaal SH, Bovée JV, Pasuriya TC, et al. Incidence, predictive factors, and prognosis of chondrosarcomas in patient with Ollier disease or Mafucci syndrome: an international multicentre study of 161 patients. Oncologist 2011;16:1771–​9.

4.26

Systemic disorders reflected in the hand Stewart Watson

Introduction Our hands reveal much about us: age, ethnicity, possibly our occupation, and the care we take over ourselves. Rings and bracelets signal our taste, wealth, and marital status, and wrist bangles are worn as an outward display of the causes we espouse. Movement of the hand is important to cosmesis. The hand that does not move and gesticulate normally is very noticeable. A hand that moves normally even though its physical structure is different will still be perceived as more normal than one which is stiff or does not move appropriately—​a phenomenon known as dynamic cosmesis. For doctors, the hands reveal a wealth of information regarding systemic disease processes as well as the features of specific disorders of the hand. There can be important observations to be made in respect of the overall size of the hand, its shape, abnormal movements, colour, and pigmentation. This is in addition to the features of primary hand disorders where abnormalities of joint, tendon, and nerve function may be apparent. Many signs are subtle and before the mid-​twentieth century they might have been the initial clinical observations leading to the diagnosis of systemic disease, for instance, splinter haemorrhages in the nail or pulps (Osler’s nodes) or palm (Janeway lesions) may be due to subacute bacterial endocarditis. Clubbing of the fingertips can be caused variously by cardiac, liver, or pulmonary disease, skin dermatitis, or heavy metal poisoning. Today, with modern diagnostic tools, the initial diagnosis of most conditions will be made by other means and clinical signs in the hand have become less important diagnostically. Nonetheless, clinical signs in the hand are still valuable. They can indicate the activity of a systemic disease. The pain and swelling of the finger joints or tendons can warn of a flair up in an arthritic condition, prioritizing medical treatment before consideration of surgery. Vasculitic lesions can be caused by cryoglobulin disorders which are caused by a wide variety of systemic conditions such as hepatitis C or connective tissue disorders. Acromegaly can present as overgrowth of the hands; it is caused by excess growth hormone from an adenoma in the pituitary. Carpal tunnel syndrome can occur secondary to a variety of disorders including the amyloid deposition of chronic diseases such as renal failure, or the flexor synovitis of rheumatoid arthritis.

Erythema of the palm occurs physiologically in pregnancy but can indicate cirrhosis of the liver. Addison’s disease can increase palmar pigmentation. Combinations of signs in the hand can resolve diagnostic difficulties. A skin rash with nail pitting will more likely be psoriasis than dermatitis, as the latter would not involve the nail. Serial transverse ridges or marks indicate serial insults in the germination of the nail from illness. The distribution and symmetry of polyarthritis can help to differentiate the causes of inflammatory conditions.

Assessment The clinician should always take a focused medical history (Lister, 2001) from the patient that should include an occupational history, all pastimes (including keeping tropical fish and other pets), travel, medical and family history, medication including herbal and over-​ the-​counter remedies, and ultraviolet light exposure. The patient needs to be questioned directly as to the duration and periodicity of symptoms, and whether they have observed changes in shape, size, or colour of the lesion or hands as a whole. The history should also include whether the problem involves one hand or both, and whether there are symptoms of involuntary movement, weakness, or sensory change. From a general perspective, it is important to obtain a history of whether the patient has had a concurrent illness, a sore throat, or viral illness. The patient’s urine should be tested for diabetes, haematuria, and proteinuria where indicated. Hand surgeons examine their patients across a hand table but many systemic conditions can affect the hand so the clinician must be prepared to stand to examine the shoulder, thoracic outlet, and spine and use the examination couch for a thorough examination of the torso and legs.

Skin Textbooks (White and Cox, 2006; Griffiths et al. 2016; Bolognia et al., 2017), and websites (http://​www.dermnet.org.nz) are essential resources, but beware. Skin conditions not normally presenting in the upper limb may present there, and of course uncommon conditions

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SECTION 4  Upper limb

do present themselves to the hand surgeon, and experience has shown there should be only a low threshold to seek multispecialty consultations (Fig. 4.26.1). The skin on the dorsum of the hand is thin and is constantly exposed to ultraviolet radiation. With sun exposure, the dermis becomes thinner and less elastic, becoming wrinkled and seemingly translucent. Other stigmata of sun exposure include lentigines and actinic damage (solar elastosis). Advancing age brings thinning of the subcutaneous fat, atrophy of the intrinsic muscles, and the veins appear more prominent. The nails are important for supporting the pulp in tactile and fine manipulative function and they are also an important indicator of health. Pallor of the nail bed can indicate anaemia and cyanosis can indicate cardiorespiratory disease. Nail signs are also particularly valuable in evaluating dermatological disease. The palmar skin is glabrous, meaning that it contains no hair follicles, and is uniquely thick. Manual work will produce thicker skin and callosities possibly with dirt engraving in skin or nails, with some occupations causing localized subcutaneous thickening. The palmar aponeurotic system tethers the palmar skin to the skeleton with both vertical septa and transverse and longitudinal fibres that stop the skin shearing on the underlying tissues thus adapting it for gripping. The glabrous skin of the finger tips is modified further in the form of unique finger prints of the pulps. In the palm, there are normally two palmar creases. Bilateral single creases will almost always indicate a chromosomal anomaly, commonly trisomy 21, whereas a unilateral single transverse palmer crease most probably does not indicate an abnormality. An experienced clinician will recognize patterns of rashes and lesions. Constitutional conditions will tend to be symmetrical whereas infections, vascular lesions, injury, tumours, and contact dermatitis will not be. Rashes are evaluated for colour, surface, distribution, and other anomalies, which might indicate the diagnosis. Eczema and psoriasis

Fig. 4.26.1  Erythema multiform minors triggered by a systemic infection. This illustration is included to emphasise the importance of multi specialty collaboration. Skin lesions are very likely to have an underlying cause and secure diagnoses requires dermatology expertise. Courtesy of James Heilman, MD

can seem similar to the inexperienced, but eczema may have vesicles that can weep, and psoriasis is accompanied by nail changes (see ‘Joints’). Their treatment is very different. Many other conditions have a rash as part of their presentation. Skin lesions such as papules, pustules, plaques, nodules, ulcers, vesicles, blisters, and vasculitic lesions can all be manifestations of systemic disease. Itching (pruritus) is a common symptom. Eczema, lichen planus, and scabies are typically itchy, but itching without an observable skin rash requires thorough investigation as it can herald a systemic problem, including malignancy. Blistering disorders in the palm or dorsum of the hand have many aetiologies and the hand surgeon needs help in their evaluation. Bacterial infections, viral infections in general, and the herpes viruses in particular, present with typical signs. The viral infections produce multiple vesicles and it is important to recognize these, as the treatment is by antiviral agents rather than surgical incision and drainage. Other blistering disorders include rare conditions such as xeroderma pigmentosum (marked by photosensitivity), porphyria cutanea tarda which produces blistering on the dorsum of the fingers, and drug eruptions. Epidermolysis bullosa presents early in life. It is important to recognize and distinguish from the blistering of a burn so the parents are not accused of negligence. Eczema can present with small blisters on the palm called pompholyx or vesicular eczema. Pemphigoid has larger blisters and occurs in the older age group with the oral mucosa rarely involved. Pemphigus has more superficial blisters, a younger age group and with oral involvement. The autoimmune condition of lichen planus gives lesions on the palm and wrist and nail changes. Other important systemic conditions can present with signs in the hand. Sarcoidosis can produce nodules on the dorsum of the fingers and also nail changes. Systemic lupus erythematosus (male-​ to-​female ratio of 1:9) is a rare systemic disease affecting the pericardium, pleura, and kidneys, with a photosensitive butterfly rash on the face but also occurring on the hands. Scleroderma presents to hand surgeons. As it progresses, the skin becomes tight and hard, with vasculitic lesions and atrophic finger tips. Related disorders manifest in the hand include Raynaud’s disease, calcinosis, and CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia). Cutaneous signs of HIV/​AIDS include Kaposi’s sarcomas (purple cutaneous tumours which can be confused with pyogenic granuloma), and other tumours so biopsy for histology is necessary. Chronic nail changes and infections occur with immunosuppression. The skin rash associated with dermatomyositis is typically purplish with longitudinal streaks along the dorsum of the fingers (Gottron’s sign) with papules over the proximal interphalangeal joints. Up to 25% of these patients have an underlying malignancy. Purpura is due to extravasation of blood from cutaneous vessels, reflecting local vascular injury or emboli. It can be due to cutaneous small vessel vasculitis or secondary to a wide range of conditions such as collagen disorders or connective tissue diseases such as lupus erythematosus, scleroderma, dermatomyositis, Henoch–​Schönlein purpura, infection (e.g. meningococcal purpura fulminans), granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), or polyarteritis nodosa. A biopsy might be necessary to distinguish these. Two other skin conditions very rare in the upper limb but life-​ threatening deserve a special mention. Pyoderma gangrenosum can

4.26  Systemic disorders reflected in the hand

occur in isolation but is commonly associated with bowel or other systemic disease or after surgery. There is a rapidly developing tender inflammatory skin condition with ulceration. Necrotizing fasciitis is a rapidly progressing infective necrosis of the skin and subcutaneous tissue following injury caused typically by a combination of bacteria (see Chapter 1.3 and Chapter 4.4). The two conditions can be confused but failure to make the right diagnosis can be fatal for the patient as the two conditions have very different treatments.

Joints Arthritis and other medical conditions produce joint swelling and deformity and again multispecialty input is required (Wolfe et al., 2016). A detailed consideration of osteoarthritis and inflammatory arthritis conditions is made in Chapter 4.14. Rheumatoid arthritis (Firestein et al., 2016; Wolfe et al., 2016) is a seropositive (rheumatoid factor positive) systemic disease characterized by synovial proliferation leading to polyarthropathy and tendon synovial thickening. The wrist, metacarpophalangeal and interphalangeal joints are commonly involved, usually symmetrically. Since the introduction of anti-​tumour necrosis factor-​alpha drugs in the treatment of rheumatoid arthritis and possibly other factors as well, the progression of hand deformities in patients under treatment has slowed and the referral of patients for hand surgery much less common. Psoriatic arthritis is seronegative (rheumatoid factor negative) (Mease and Helliwell, 2008; Wolfe et al., 2016). The majority of patients have the rash before the arthritis although this may be just a small patch. A high percentage of patients have pitting of their nails and distal or proximal interphalangeal joint involvement. This distal interphalangeal joint and nail involvement differentiates psoriatic arthritis from typical rheumatoid arthritis. Psoriatic arthritis tends to be less symmetrical. Some cases can resemble rheumatoid arthritis. Psoriatic arthritis has a low incidence of tenosynovitis and subcutaneous nodules. Septic arthritis, acute or chronic, has to be considered with monoarticular arthropathy. Gout, a very painful arthropathy, can also present with single joint involvement, but may also be a polyarthropathy. Subcutaneous nodules (tophi) and tenosynovial thickening may also be seen. Systemic lupus erythematosus can present with hand changes similar to rheumatoid arthritis with symmetrical joint swelling, tenderness, and tenosynovitis but with joint ligament laxity and preserved joints on radiographs.

Tenosynovitis Tenosynovitis is a widely used term encompassing synovial proliferation from non-​infective causes (multispecialty help will certainly be needed to diagnose and treat) and infective causes of proliferation but the term is also used in cases of stenosing tenosynovitis where the synovium is thickened or the tendon itself is thickened (Wolfe et al., 2016). In the hand, the commonest cause of inflammation of the synovium—​ proliferative tenosynovitis—​ is rheumatoid arthritis. It can involve either the flexor or extensor tendons, or both. The

resulting synovial swelling can be bulky and lobulated but is generally not painful. It is seen on the dorsum of the wrist and hand and the flexor surface of wrist and along the course of the flexor tendons. The proliferation can cause carpal tunnel syndrome. Proliferative tenosynovitis can infiltrate the tendons leading to tendon rupture. Other systemic inflammatory disorders can cause tenosynovial thickening. In amyloid, there is the deposition of low-​molecular-​ weight serum protein beta-​microglobulin in bones and soft tissue. In gout, urate crystalline material is deposited within joints and synovium producing acute inflammation, erythema, and pain. With calcific tenosynovitis, calcium salts are deposited (visible on radiographs) producing acute inflammatory swelling and pain in the affected finger or wrist. It can resemble an acute infection. Pseudogout and sarcoidosis involving the flexor tendons can also cause diagnostic difficulties. Xanthomas (lipid deposits) can occur in the extensor tendons over the metacarpophalangeal joints with or without abnormal blood lipids. Infective causes of synovial proliferation include acute septic tenosynovitis and chronic infective tenosynovitis from tuberculosis, atypical mycobacterium, gonococcal infections, and fungal infections. These chronic infections can be very difficult to diagnose and history can be very important, see ‘Assessment’. The common tendon entrapments (or stenosing tenosynovitis) are trigger finger, where the finger flexors obstruct at the A1 pulley, and de Quervain’s tenosynovitis, which affects the first extensor tendon compartment. The tendon can impinge upon osteophytes or internal fixation. All these are localized conditions.

Cold hands, vascular disorders, and ulceration Many people complain of ‘cold hands’ but do not prove to have a specific regional or systemic condition. Clinical assessment has to look for an underlying diagnosis. Features such as the sequence of colour change in response to cold or temperature change, whether the reaction is unilateral or bilateral, and how much of the length of the fingers are involved can all be diagnostic. Occupational exposure to trauma or vibration is a common cause of vasospastic conditions or arterial thrombosis. Factors such as tobacco use and other drug intake or a family history of blood dyscrasias or haemoglobinopathies may cause or exacerbate vasospastic or vaso-​occlusive diseases. Atherosclerosis in the upper limb is much less common than in the lower limb but the patient must be questioned for symptoms of ischaemia and claudication. Clinical examination requires a careful examination for vascular signs, including purpura and petechial haemorrhage, and vasculitic lesions in skin or nail beds can be inflamed, tender, and palpable (White and Cox, 2006). If these are confined to one limb, there may be a focal vascular lesion on that side. Systematic examination of the pulses from the thoracic outlet distally is required including cubital, wrist, and digital pulses together with Allen’s testing to establish the patency of the palmar arches. A cardiac examination is also essential as vascular lesions may be caused by embolism from the heart or major vessels. In acrocyanosis, the fingers become dusky blue with exposure to the cold. It can be accompanied by chilblains (tender erythematous thickenings on the dorsum of the fingers) (White and Cox, 2006).

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SECTION 4  Upper limb

While for most it is idiopathic, it can be part of a systemic collagen disorder and needs multidisciplinary investigation. Raynaud’s phenomenon is a sequence of colour changes in one or more digits, the colour changes are pathognomonic—​often marked pallor followed by cyanosis then hyperaemia on warming. It is classed as a vasospastic disorder and the common idiopathic form is usually referred to as Raynaud’s disease (Fig. 4.26.2). There is a sharp cut-​off of the discolouration around proximal interphalangeal joint level. Single or several fingers can be involved in any one attack but both hands must be involved at some time but not necessarily together. Raynaud’s disease is commoner in women than men; it occurs under the age of 40 years and usually resolves by that age or by the menopause. However, 5–​10% will go on to develop permanent Raynaud’s disease, with more males than females affected. Thus any sufferer needs thorough clinical evaluation, investigations, and regular reviews. Raynaud’s disease can be precipitated by cold and possibly by emotional upset. If there are changes to the nail, nail folds, or pulp there may well be a systemic cause. Raynaud’s phenomenon (White and Cox, 2006; Wolfe et  al., 2016) can be part of the manifestation of a systemic disease. It is seen in collagen disease such as scleroderma, CREST syndrome, in 25% of patients with systemic lupus erythematosus or Sjögren’s syndrome, and 95% of patients with systemic sclerosis (Fig. 4.26.3). It can also

accompany rheumatoid and other inflammatory arthritides. It can be an occupational disease due to vibration exposure and be caused by haematological conditions such as polycythemia and abnormal cold precipitating globulins. Pulp atrophy and persistent digital ulcers can develop as the conditions progress.

Neurological disorders Neurological deficiencies need very thorough motor, sensory, and reflex examination peripherally, regionally at the spinal and central level, along with cranial nerves, leg, and full body examination. It is important to try to identify upper and lower motor neuron pathology. The history must include questioning on sphincter control and erectile function. The urine must be tested. Neuropathies can be mononeuropathies, affecting one or multiple individual nerves, or be generalized peripheral ‘glove-​and-​stocking’ neuropathies. Single neuropathies of the median, ulnar, and radial nerves present commonly and are due to localized compression in the upper limb but beware of exceptions caused by systemic disease. Carpal tunnel syndrome can be produced with amyloid and rheumatoid arthritis and other causes of synovial proliferation. Of the other mononeuropathies perhaps the best known is leprosy (Fig. 4.26.4). Leprosy is a Mycobacterium leprae infection of the nerves and skin. Sensory loss can precede the motor loss. The diagnosis is clinical and is based on the presence of hypopigmented macular skin lesions that are anaesthetic. These patches can appear on any part of the body surface and will be later associated with peripheral neuropathy in either the lepromatous or tuberculous versions of the disease. Poliomyelitis, a viral infection of the motor neurons, can present with partial or complete lower motor neuron flaccid paralysis and preserved sensation. The commonest cause of a generalized peripheral neuropathy is diabetes but vitamin B12 deficiency can also cause a similar deficit. These ‘glove-​and-​stocking’ neuropathies are a mixture of motor and sensory loss spreading proximally as they progress. The degenerative condition of syringomyelia will present bilaterally with loss of sensation in the hands but with the preservation of the dorsal column and medial lemniscus of the spinal cord, leaving pressure, vibration, touch, and proprioception intact in the upper extremities. There is extensive weakness. Charcot–​Marie–​Tooth neuropathy is a genetic condition presenting with both a motor and a sensory neuropathy bilaterally, more commonly presenting in the lower limb than the upper limb. If nerve deficiencies cannot be explained by a peripheral nerve pathology then the brachial plexus, thoracic outlet, and thoracic roots and central nervous system must be fully evaluated by clinical examination and by imaging.

Tumours

Fig. 4.26.2  Raynauld’s phenomenon. An underlying systemic cause must be excluded. This case unusually involves all five digits. Courtesy of MSM98/Wikimedia

Some soft tissue swellings have already been discussed in the ‘Tenosynovitis’ section. The commonest tumours in the hand are common ganglion, giant cell tumours, and other soft tissue tumours (e.g. lipomas), that all occur incidentally. Swellings and tumours of all the tissues of the hand are assessed with history, examination, appropriate special tests including imaging (ultrasound scanning

4.26  Systemic disorders reflected in the hand

(a)

(b)

(c)

(d)

Fig. 4.26.3 Scleroderma. Scleroderma with its subcutaneous calcium deposits can be an underlying cause of late onset Raynauld’s Reproduced from Remuzzi G, Lynch B, Burns A. The patient with scleroderma: systemic sclerosis. In: Oxford Textbook of Clinical Nephrology 4e, eds. Turner, N., Lameire, N., Goldsmith, D., Winearls, C., Himmelfarb, J., and Remuzzi, G., Oxford, UK: Oxford University Press; 2015:1395-1402 with permission from Oxford University Press.

staging, and discussion at the multidisciplinary team meeting should precede biopsy (Wafa and Tillman, 2015). Skin tumours can be primary or secondary tumours and can be associated with immunosuppression from medical therapy or from infection such as HIV/​AIDS (see ‘Skin’). Tumours associated with systemic conditions presenting to hand surgeons include multiple neurofibroma of type I  neurofibromatosis. The condition may also present with café-​au-​lait spots. The hereditary condition of Gorlin’s syndrome, presenting with multiple basal cell carcinomas, can be diagnosed by erythematous pits in the palm.

Congenital hand and upper limb anomalies Fig. 4.26.4  Bilateral Claw. Wasting of the median and ulnar innervated intrinsic muscles in both hands caused by leprosy infection of the nerves. Photo courtesy of Vivien Lees.

being very useful initially), and biopsy. Then proceed to discussion at a multidisciplinary team meeting if appropriate. The exceptions to proceeding to early biopsy is where a sarcoma is suspected and also with bone tumours. In these cases, preliminary clinical diagnosis,

These are considered in Chapter 4.21 of this textbook and in detail by Gupta and colleagues (2000). Anomalies may be confined to the hand or upper limb but many anomalies are part of wider syndromes. For instance, a radial club hand can be an isolated condition but more commonly it is associated with vertebral, anal, and tracheo-​oesophageal abnormalities as VATER syndrome, often expanded to include cardiac and renal abnormalities as VACTERL syndrome (D’Arcangelo et  al., 2000). Radial ray anomalies can also be associated with congenital heart disease in isolation (Holt–​Oram syndrome).

573

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SECTION 4  Upper limb

Many genetic causes of congenital hand anomalies have known chromosomic anomalies or known DNA anomalies but there are some conditions which are presumed to have DNA anomalies that have yet to be identified (Hersh, 2000). Congenital hand anomalies can be caused by drugs and medication taken during pregnancy including fetal alcohol syndrome, valproate anticonvulsant therapy, and, historically, thalidomide.

Conclusion Much can be gleaned about the patient by careful examination of the hands and the surgeon is obliged to systematically assess the hands and upper limbs in arriving at a diagnosis. The involvement of the hands in systemic conditions will often direct the surgeon to involve other specialists in care of the patient.

REFERENCES Bolognia JL, Schaffer JV, Cerroni L. Dermatology, 4th ed. Philadelphia, PA: Elsevier, 2017.

Griffiths C, Barker J, Bleiker T, et  al. (eds). Rook’s Textbook of Dermatology, 9th ed. Chichester: Wiley-​Blackwell, 2016. Gupta A, Scheker LR. Radial club hand. In:  Gupta A, Kay SPJ, Scheker LR (eds) The Growing Hand, 1st ed, pp. 147–​ 70. London: Mosby, 2000. Firestein GS, Budd RC, Gabriel SE, et al. Kelley and Firestein’s Textbook of Rheumatology, 10th ed. Philadelphia, PA: Elsevier. 2016. Gupta A, Kay SPJ, Scheker LR (eds). The Growing Hand, 1st ed. London: Mosby, 2000. Hersh J. Genetics and hand malformations. In:  Gupta A, Kay SPJ, Scheker LR (eds) The Growing Hand, 1st ed, pp. 5–​ 20. London: Mosby, 2000. Mease PS, Helliwell PS. Atlas of Psoriatic Arthritis. London: Springer, 2008. Smith P (ed). Lister’s The Hand:  Diagnosis and Indications, 4th ed. Edinburgh: Churchill Livingstone, 2001. Wafa HYM, Tillman RM. Tumours of the hand. In: Trail I, Flemming ANM (eds) Disorders of the Hand, pp. 49–​68. London:  Springer,  2015. White GM, Cox NH. Diseases of the Skin: A Colour Atlas and Text, 2nd ed. St Louis, MO: Mosby, 2006. Wolfe SW,  Pederson WC,  Hotchkiss RN,  et al. (eds) Green’s Operative Hand Surgery, 7th ed. Philadelphia, PA: Elsevier, 2016.

SECTION 5

Lower limb Section editor: Umraz Khan

5.1 Classification of lower limb trauma  577 Umraz Khan 5.2 Principles of acute management of lower limb trauma  583 Michael Kelly

5.9 Lower limb trauma outcome measures: limb salvage and amputation  635 David Wallace 5.10 Lower limb osteomyelitis  643 Umraz Khan

5.3 The devascularized limb  585 Kaz M.A. Rahman and Shehan Hettiaratchy

5.11 Management of congenital limb deficiency  651 Fergal Monsell

5.4 Management of soft tissue loss without microsurgery  593 Thomas C. Wright

5.12 Orthopaedic management of congenital pseudarthrosis of the tibia  655 Fergal Monsell

5.5 Microvascular cover in the lower limb: indications and timing, flap types, and technique  601 Zoran M. Arnež

5.13 How the foot and ankle works (mechanics of the foot)  661 Ian Winson

5.6 Management of bone loss  611 Mark Jackson 5.7 Lower limb replantation  617 Moazzam N. Tarar and Ata Ul Haq 5.8 Amputations in the lower limb  625 Umraz Khan and Alan Gordon

5.14 The skeletal consequences of meningococcal septicaemia  665 Fergal Monsell

5.1

Classification of lower limb trauma Umraz Khan

Introduction to classification of lower limb There are numerous methods that have been used to classify injured limbs. The popular systems rely upon two basic attributes that can be applied to the injury. Scoring systems such as the extremity injury scoring systems assign a numerical value to objective aspects of the injured patient in general as well as the injured limb. These methods of classification focused on grading the extent of injury to important limb structures such as the vessels and nerves. One of the values of these scoring systems is as an aide in helping the treating surgeons in deciding on whether an amputation is indicated and thus avoiding futile attempts at limb salvage. There are also classification systems with more appeal as they aim to document the injured limb more comprehensively. Energy transfer (low, medium, high, or extreme), the tissue damage from the deforming forces, as well as demographics of the patient are carefully documented in these classification systems. Finally, the physiological response of the patient to the injury is given a numerical value. A final numeral value is then available for documentation.

Extremity injury scoring systems Extremity injury scoring systems have found favour with trauma teams faced with a severely injured limb. A threshold score may assist in the decision to amputate or to attempt salvage of a severely traumatized limb, but these scoring systems generally have limited sensitivity and any decisions based on a particular score must take individual circumstances into account.

Mangled Extremity Severity Score The Mangled Extremity Severity Score (MESS) (Johansen et  al., 1990) was derived from data from 25 trauma patients presenting to a level 1 trauma centre. Data included the skeletal and soft tissue damage, limb ischaemia, shock, and the age of each patient. It was developed to identify those patients who would benefit from a primary amputation after trauma. In retrospective analysis of all severely injured limbs, two groups emerged: those that were ultimately salvaged and those that required amputation. The mean scores for these two groups were found to be significantly different. A score of 7 or greater was suggested as predictive for amputation. There are limitations to the scoring system as factors such as concomitant other trauma, the state of the sensation of the sole of the foot, and the age of the patient were not included. The MESS has been shown to be specific but it does lack sensitivity.

Overall, it may have a role in helping the surgeon make the decision of whether to amputate a severely traumatized lower limb.

Nerve injury, Ischaemia, Soft tissue injury, Skeletal injury, Shock, and Age score In an attempt to address the shortcomings of the MESS, McNamara and colleagues (1994) proposed to separate the soft tissue score from the skeletal score and include nerve injury. It was found that when this schema is applied to a severely injured limb, the Nerve injury, Ischaemia, Soft tissue injury, Skeletal injury, Shock, and Age (NISSSA) score was not only more sensitive than the MESS but also more specific.

Limb Salvage Index The Limb Salvage Index (LSI) was applied to injured limbs with arterial compromise (Russell et al., 1991). Warm ischaemia time together with scores attributed to injured skin, nerve, muscle, bone, artery, and deep veins were added to give a total score. All limbs with LSI scores of 6 or greater and Gustilo IIIC fractures (see ‘Gustilo and Anderson classification’) were amputated. All of these scoring systems have shortcomings and are unable to accurately predict limb salvagability in all cases (Bosse et al., 2001), the return of limb function(Ly et al., 2008), or patient satisfaction (O’Toole et al., 2008).

Grading systems Gustilo and Anderson classification During an audit of infection of open long bone fractures, a team from Minnesota, United States, reflected on a scheme to grade the wound. The fractures were classified according to Table 5.1.1 Table 5.1.1  The Gustilo and Anderson classification of compound fractures of the long bones Type I

A clean wound 1 cm without extensive flaps, avulsions, or soft tissue damage

Type III

Either an open segmental #, an open # with extensive soft tissue damage, or a traumatic amputation

#, fracture. Reproduced with permission from RB Gustilo, JT Anderson et al., Prevention of infection in the treatment of one thousand and twenty-​five open fractures of long bones: retrospective and prospective analyses, Journal of Bone & Joint Surgery, Volume 58, Issue 4, pp.453–​458, Copyright © 1976 Wolters Kluwer Health, Inc.

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SECTION 5  Lower limb

Table 5.1.2  The subclassification of the Gustilo type III fracture subsequently proposed by Gustilo and colleagues (1984) Type IIIa

Adequate soft tissue coverage of # or high-​energy trauma irrespective of wound size

Type IIIb

Extensive soft-​tissue loss with periosteal stripping and bone exposure

Type IIIc

Open fracture associated with arterial injury requiring repair

#, fracture. Reproduced with permission from Gustilo RB, Mendoza RM, Williams DN, Problems in the management of type III (severe) open fractures: a new classification of type III open fractures, Journal of Trauma-​Injury Infection & Critical Care, Volume 28, Issue 8, pp.742–​746, Copyright © 1984 Wolters Kluwer Health, Inc.

(Gustilo and Anderson, 1976). The high-​energy injuries (type III) with severe soft tissue loss had the highest infection rates. Type III injuries were found to be protean and so a further subclassification was proposed by Gustilo and Mendoza (Gustilo et  al., 1984)  (Table 5.1.2). This subclassification was ratified by analysis of this group of patients with an amputation rate in the type IIIa group of 0%, compared to 16% for type IIIb fractures and 42% in the type IIIc fractures. Deep infection was also related to grade with a 4% incidence in the type IIIa fractures compared to 52% and 42% in type IIIb and type IIIc fractures, respectively. This grading system is simple and has found widespread application but is prone to poor interobserver reliability, especially with inexperienced surgeons. It has emerged that injured limbs are more appropriately categorized by this system if assessed after wound excision. A drawback of the Gustilo classification is the relative lack of sophistication in the description of the skeletal injury. Chummun and colleagues (2013) evaluated the impact of loss of an axial vessel on post reconstruction recovery. That study concluded that loss of an axial named vessel leads to a delay in fracture union as well as an ultimate lesser functional recovery. Chummun and colleagues (2013) thus suggested a further refinement of the Gustilo system by introducing the concept of the grade IIIB+ fracture (a single vessel (a)

(b)

Fig. 5.1.1  Byrd classification of compound leg fractures.

limb). It seems that preoperative angiography may help with both surgical planning and prognosis.

Byrd classification The vascularity of the fracture and the surrounding soft tissues form the basis of this classification. In type I  injuries, both the endosteal and periosteal circulation to the bone fragments is maintained and the surrounding soft tissues are relatively healthy. In type II injuries, the endosteal circulation is interrupted but the periosteal circulation is maintained through the surrounding soft tissues. In type III injuries, there are devascularized bone fragments and the wound requires flap coverage, while the type IV injuries require free flap coverage (Byrd et al., 1985) (Fig. 5.1.1). This classification lacks sophistication and has not found widespread application.

Comprehensive systems AO classification The AO Foundation has devised a reliable comprehensive classification that incorporates elements of both the scoring and (c)

(d)

5.1  Classification of lower limb trauma

(a)

Humerus 1

Radius/Ulna 2

Femur 3

Tibia/Fibula 4

(b) A

A

2 diaphyseal

B

B

3 distal (4 malleolar)

C

C

Segments 1 proximal

(c)

Type

Group

Subgroup Scale of severity

A1

A

A2 A3 B1

B Bone Segment

B2 B3 C1

C

C2 C3

(d)

(e) IC1

101

IC2

102

5 cm IC3

103

IC4

104

IC5

105

Fig. 5.1.2  AO comprehensive classification system. (a) Bone involved and segment of bone. (b) Severity of fracture pattern of diaphyseal or metaphyseal fracture. (c) Subclassification of fracture pattern progressing with comminution. (d) Classification of closed (integument closed—​IC) and (e) open (integument open—​IO) soft tissue injuries.

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SECTION 5  Lower limb

Table 5.1.3  Waikakul classification of soft tissue degloving injury Type I

Severely damaged skin and subcutaneous tissue

Type II

Moderately damaged skin and subcutaneous tissue and subcutaneous veins thrombosed

Type III

Moderately damaged skin and subcutaneous tissue but subcutaneous veins intact

Reprinted from Injury, Vol 28, issue 4, Saranatra Waikakul, Revascularization of degloving injuries of the limbs, pp. 271–​274, Copyright (1997), with permission from Elsevier.

grading systems. The skin, muscle or tendon, neurovascular structures, and the skeleton are graded separately. The reliability of fracture grading improves with the surgeon’s experience (Martin et al., 1997). The AO score appears to allow more accurate prognosis of outcome when compared with the Gustilo grading (Arnez et al., 1999) but its complexity makes the system difficult to commit to memory, and so limits its role in clinical practice (Fig. 5.1.2).

Ganga Hospital score This classification system (Rajasekaran et  al., 2006, 2007)  developed in Ganga Hospital, Coimbatore, India, aims to use the best aspects of the scoring systems and the grading systems based on the experience of a dedicated trauma and reconstruction team of orthopaedic, plastic surgeons, and anaesthetists. The system allocates scores for injuries to skin and fascia, bone and joints, musculotendinous units, and nerves and if there is compartment syndrome. A numerical value is also added for comorbidities such as diabetes and cardiorespiratory disease, if the time to debridement exceeds 12 hours, if there is contamination with sewage, or if the injury was sustained in a farmyard. The Ganga Hospital score also considers if the injured limb is in a patient who has suffered trauma to the chest or abdomen. A cutaneous score of 3 or more was predictive of complex soft tissue reconstruction and a score of 17 or more was predictive of amputation. It is not clear as to how some of the scoring parameters were derived (e.g. time to

(a)

Fig. 5.1.3  Degloving injury of the lower limb.

debridement of >12 hours), and shortcomings of the system have been highlighted (Kurup, 2007).

Degloving injuries Degloving injuries are a distinct and unpredictable group with the risk of extensive skin and soft tissue necrosis. Contemporary analyses have led some to suggest that the state of the subcutaneous veins holds the key to the fate of the degloved skin (Fig. 5.1.3). Waikakul (1997) reported that when the subcutaneous veins were thrombosed, the skin rarely survives, and on this basis he proposed a system to classify degloved skin (Table 5.1.3). Arnez and colleagues (2010) proposed a similarly logical pattern of degloving which was a progressive increase in energy transfer (Fig. 5.1.4) and, using primary healing as an outcome measure, the authors were able to validate this schema (Fig. 5.1.5).

Conclusion An ideal classification system for lower limb trauma does not currently exist. The Gustilo system is simple and, despite the limitations, is used widely though it should only be applied after wound debridement or excision, and ideally assessed by experienced surgeons. For the purposes of audit and database input the more

(b)

5.1  Classification of lower limb trauma

(a)

(b)

(c)

(d)

Fig. 5.1.4  Arnez classification of degloving injuries. (a) Pattern 1. These injuries are due to abrasive forces, which abrade the skin over bony landmarks such as the malleoli/​condyles. (b) Pattern 2. The defining feature of pattern 2 injuries is the non-​circumferential and single plane degloving. (c) Pattern 3. This pattern is defined by a circumferential degloving in a single plane. The crux of these injuries is that the skin which has suffered a circumferential degloving rarely survives. (d) Pattern 4. This pattern represents the most severe injuries and is defined by circumferential, multiplanar degloving. Reproduced with permission from Arnez ZM, Khan U, Tyler MP., Classification of soft-​tissue degloving in limb trauma, Journal of Plastic, Reconstructive & Aesthetic Surgery, Volume 63, Issue 11, pp.1865–​1869, Copyright © 2010 Elsevier.

Numbers 20

(Primary healing rates given as a percentage) 88% 93%

15

39%

10

63%

5

Pattern 1

Pattern 2

Pattern 3

Pattern 4

Healing rate: Primary Secondry

Fig. 5.1.5  Rate of wound healing (primary and secondary healing) according to the stages of degloving injury as classified by Arnez and colleagues (2010). Reproduced with permission from Arnez ZM, Khan U, Tyler MP., Classification of soft-​ tissue degloving in limb trauma, Journal of Plastic, Reconstructive & Aesthetic Surgery, Volume 63, Issue 11, pp.1865–​1869, Copyright © 2010 Elsevier.

comprehensive AO system should be considered, despite its greater complexity.

REFERENCES Arnez ZM, Tyler MP, Khan U. Describing severe limb trauma. Br J Plast Surg 1999;52:280–​5. Arnez ZM, Khan U, Tyler MP. Classification of soft-​tissue degloving in limb trauma. J Plast Reconstr Aesthet Surg 2010;63:1865–​9. Bosse MJ, Mackenzie EJ, Kellam JF, et al. A prospective evaluation of the clinical utility of the lower extremity injury-​severity scores. J Bone Joint Surg Am 2001;83:3–​14. Brumbach RJ, Jones AL. Interobserver agreement in the classification of open fractures of the tibia. The results of a survey of two hundred and forty-​five orthopaedic surgeons. J Bone Joint Surg Am 1994;76:1162–​6. Byrd HS, Spicer TW, Cierney G 3rd. Management of open tibial fractures. Plast Reconstr Surg 1985;76:719–​30. Chummun S, Wigglesworth TA, Young K, et  al. Does vascular injury affect the outcome of open tibial fractures? Plast Reconstr Surg 2013;131:303–​9.

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SECTION 5  Lower limb

Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-​five open fractures of long bones: retrospective and prospective analysis. J Bone Joint Surg Am 1976;58:453–​8. Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. J Trauma 1984;24:742–​6. Helfet DL, Howey T, Sanders R, et al. Limb salvage versus amputation. Preliminary results of the Mangled Extremity Severity Score. Clin Orthop Relat Res 1990;256;80–​6. Johansen K, Daines M, Howey T, et  al. Objective criteria accurately predict amputation following lower extremity trauma. J Trauma 1990;30:568–​72. Kurup HV. A score for predicting salvage and outcome in Gustilo type-​IIIA and type-​IIIB open tibial fractures. J Bone Joint Surg Br 2007;89:562. Ly TV, Travison TG, Castillo RC, et al. Ability of lower-​extremity injury severity scores to predict functional outcome after limb salvage. J Bone Joint Surg Am 2008;90:1738–​43. Martin JS, Marsh JL, Bonar SK, et  al. Assessment of the AO/​ ASIF fracture classification for the distal tibia. J Orthop Trauma 1997;11:477–​83.

McNamara MG, Heckman JD, Corely FG. Severe open fractures of the lower extremity:  a retrospective evaluation of the mangled extremity severity score (MESS). J Orthop Trauma 1994; 8:81–​7. Melvin JS, Dombroski DG, Torbert JT, et  al. Open tibial shaft fractures:  1. Evaluation and initial wound management. J Am Acad Orthop Surg 2010;18:10–​19. O’Toole RV, Castillo RC, Pollak AN, et al. Determinants of patient satisfaction after severe lower-​extremity injuries. J Bone Joint Surg Am 2008;90:1206–​11. Rajasekaran S, Naresh Babu J, Dheenadhayalan J, et  al. A score for predicting salvage and outcome in Gustilo type-​ IIIA and type-​ IIIB open tibial fractures. J Bone Joint Surg Br 2006;88: 1351–​60. Rajasekaran S. Early versus delayed closure of open fractures. Injury 2007;38:890–​95. Russell WL, Sailors DM, Whittle TB, et al. Limb salvage versus traumatic amputation. A  decision based on a seven-​part predictive index. Ann Surg 1991;213:473–​80. Waikakul S. Revascularisation of degloving injuries of the limbs. Injury 1997;28:271–​4.

5.2

Principles of acute management of lower limb trauma Michael Kelly

Introduction to acute management of lower limb trauma Surgical techniques have developed to allow treatment not simply to preserve life or limb but to re-​establish function. Godina’s (1986) landmark work on early microsurgical management of the soft tissues paved the way to this goal. Nanchahal and co-​workers (Naique et  al., 2006; Glass et  al, 2009a, 2009b; Nayagam et  al., 2011)  have demonstrated the benefits of a combined approach to these injuries and have coined the term ‘orthoplastics’. This concept may remain aspirational in many units where service structures separate the plastic and orthopaedic expertise, but it has been adopted by the British Association of Plastic, Reconstructive and Aesthetic Surgeons and the British Orthopaedic Association in the United Kingdom in guidelines for the standard of care for these injuries (Nanchahal et al., 2009). These guidelines cover the whole treatment pathway from immediate care to the audit of outcomes. The key recommendation is that complex open fractures of the lower limb, defined by the nature of the fracture and soft tissue injury, should be promptly managed in a specialist centre with combined expertise in order to optimize outcomes. Khan and colleagues (2011) described the advantages of this approach which include reducing the number of surgeries for these patients. Much discussion about the management of high-​energy open fractures of the lower limb comes from the Lower Extremity Assessment Project (LEAP) group (MacKenzie and Bosse, 2006). Even in these large level 1 North American centres plastic surgical input can be difficult to achieve, leading to additional surgical debridements that may adversely affect outcome. Orthoplastic centres are likely to be centralized in a major trauma or level 1 unit, often requiring a lot of travel for patients during follow-​up.

Initial surgical assessment Every unit adapts the standards and guidelines to the resources available including the local expertise. Most acute receiving hospitals

have an orthopaedic department but may lack appropriate plastic surgery facilities, constraining the initial care. An early principle of treatment was that open fractures needed to be taken to the operating theatre within 6 hours. Increasingly, this concept has been challenged, particularly for the injury without gross contamination, and the accepted standard of practice now is that they are dealt with on the next planned list where appropriate expertise is available within 12 hours of injury. There is no good evidence that operating before 6 hours influences outcome but there is robust evidence that operating out of hours is associated with worse outcomes. The initial surgical management aims to decontaminate, sterilize, and fully evaluate the zone of injury. This includes the soft tissue and the bony components of the injury. This involves excision of the traumatic wound with extension of the wound along the nearest fasciotomy incisions. It is important to appreciate the cavitatory effect of the energy transfer of the trauma through the limb, and therefore the need for wound extensions. It is very common for debris or contaminated material to be sequestered remote to the open wound at the extent of this traumatic cavity. Adequate wound extension allows for the bone ends to be delivered, thoroughly assessed, and cleaned without creating further stripping. The current standard is that bone fragments that are free floating or completely stripped and devascularized should be discarded. If there are soft tissue attachments then the fragments should be thoroughly cleaned and assessed. This will require curettage and rongeurs. The debridement should also include the medullary canal containing contaminated haematoma. The soft tissues are also fully assessed. This should include documentation of any degloving of the tissues, either subcutaneous or multiplanar involving detachment of muscle insertions. The full extent of a degloving injury can be difficult to appreciate at the initial surgery. Obviously, devitalized tissue needs to be removed and the higher the energy of the injury, the more likely that further operative assessment will be required to monitor the viability of the remaining tissues prior to definitive reconstruction. Once the injury has been fully debrided and assessed, the bone will need to be stabilized and the wound covered. Very occasionally

584

SECTION 5  Lower limb

this can be undertaken primarily where the soft tissue envelope can be closed without tension, particularly if there has been an acute shortening. Most will require some sort of flap coverage. Godina (1986) highlighted the need to undertake this as soon as is feasible. Although the Leeds group in the United Kingdom have shown that it can be safe and efficient to do the final reconstruction acutely (Gopal et al., 2000), in most circumstances temporizing measures will be undertaken prior to the definitive reconstruction. The most important step is to agree in advance what these measures should be with the unit that will undertake the definitive procedure. In England, most of these cases are undertaken as a centralized service in a major trauma centre within a major trauma network. Each region will have its own particular standards based on local geography and service provision. In some, the definitive orthopaedic and plastic surgical reconstructions are performed at different times in different units. In others, the reconstructions are done at different times in the same units and in a few they are undertaken at the same time in the same unit. There is some evidence that the latter can substantially lower infection rates (Mathews et al., 2015) but the resources to achieve this may not be available. Stabilization of the fractured long bone will most commonly be achieved acutely using a uniplanar external fixator. The pins should be sited outside of the zone of injury, away from neurovascular structures, and not impede the anticipated definitive fixation. In some centres, particularly where the definitive stabilization can be undertaken within 24–​48 hours, a splint or a traction pin and bed-​mounted traction is an acceptable alternative method of stabilization. Increasingly, negative pressure dressings are used to cover the wound. This is based in part on military reports from conflict zones. This dressing is useful but is not a substitute for definitive soft tissue cover by appropriate plastic surgical intervention. There has been an assumption that these dressings offer an advantage in the prevention of bacterial ingress in civilian hospitals but in units where the definitive surgery is likely to be undertaken within 72 hours, their cost-​effectiveness has been questioned (Petrou et al., 2019).

Fix and flap principle The relative timings of the orthopaedic and plastic surgical interventions are controversial. Each can be complex and lengthy in its own right, particularly if there are complex periarticular fractures or free flaps are involved. In many units throughout the world, including major trauma centres, a staged approach is used, with the plastic surgeons providing free flap cover within 7 days of the orthopaedic reconstruction. This approach, popularized by Godina, is the accepted standard of care. The advantages of this approach are that each surgery can be undertaken in a specialized theatre used to undertaking that particular type of procedure. It also means that the cases can

be scheduled on available lists within each speciality. Unfortunately, overall, the infection rate remains around 16% with this approach (Weber et al., 2014). The simultaneous orthoplastic approach has been championed by several authors (Gopal et al., 2000; Naique et al., 2006; Khan et al., 2011; Nayagam et al., 2011). This approach means that the orthopaedic and plastic surgical reconstructions are undertaken in the same surgery, with the advantage that the bone can be thoroughly cleaned and debrided immediately prior to definitive soft tissue cover. The implants and the fracture thrombus or callus are therefore never exposed to dressings and thereby colonized. This approach does require careful planning of cases both from technical and logistical points of view but has led to infection rates being lowered from 17% to 4%, a very significant achievement.

REFERENCES Glass GE, Pearse MF, Nanchahal J. Improving lower limb salvage following fractures with vascular injury:  a systematic review and new management algorithm. J Plast Reconstr Aesthet Surg 2009a;62:571–​9. Glass GE, Pearse M, Nanchahal J. The ortho-​plastic management of Gustilo grade IIIB fractures of the tibia in children: a systematic review of the literature. Injury 2009b;40:876–​9. Godina M. Early microsurgical reconstruction of complex trauma of the extremities. Plast Reconstr Surg 1986;78:285–​92. Gopal S, Majumder S, Batchelor AG, et  al. Fix and flap:  the radical orthopaedic and plastic treatment of severe open fractures of the tibia. J Bone Joint Surg Br 2000;82:959–​66. Khan U, Kelly MB, Pleat J, et al. Orthoplastics: an integral evolution within comprehensive trauma care. Injury 2011;42:969–​71. Mathews JA, Ward J, Chapman TW, et al. Single-​stage orthoplastic reconstruction of Gustilo-​Anderson Grade III open tibial fractures greatly reduces infection rates. Injury 2015;46:2263–​6. Naique SB, Pearse M, Nanchahal J. Management of severe open tibial fractures: the need for combined orthopaedic and plastic surgical treatment in specialist centres. J Bone Joint Surg Br 2006;88:351–​7. Nanchahal J, Nayagam S, Khan U, et al. Standards for the Management of Open Fractures of the Lower Limb. BAPRAS/​BOA. London: Royal Society of Medicine Press Ltd, 2009. Nayagam S, Graham K, Pearse M, et  al. Reconstructive surgery in limbs:  the case for the orthoplastic approach. Ann Plast Surg 2011;66:6–​8. Petrou S, Parker B, Masters J, et  al. Cost-​effectiveness of negative-​ pressure wound therapy in adults with severe open fractures of the lower limb: evidence from the WOLLF randomized controlled trial. Bone Joint J 2019;101-​B:1392–​401. Weber D, Dulai SK, Bergman J, et al. Time to initial operative treatment following open fracture does not impact development of deep infection: a prospective cohort study of 736 subjects. J Orthop Trauma 2014;28:613–​19.

5.3

The devascularized limb Kaz M.A. Rahman and Shehan Hettiaratchy

Introduction to devascularized limb The devascularized limb is a surgical emergency as without prompt diagnosis and treatment, salvage of a functional limb will not be achieved. The aim of this chapter is to review current practice and describe the correct management of this condition. As muscle necrosis occurs after 6 hours of ischaemia, the guiding principle of treatment is, where possible, to restore blood flow within 4–​6 hours in major vascular injuries of the extremities. There have been two major advances in the last 5 years to improve the care of these injuries in the United Kingdom. The first was the development of major trauma centres so that critically injured patients could be triaged to centres specializing in such injuries. The second was the publication by the joint British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) and British Orthopaedic Association (BOA) of Standards for the Management of Open Fractures of the Lower Limb (Nanchahal et al., 2009) with a chapter dedicated to managing the devascularized limb. This publication is the standard of care in the United Kingdom for all lower limb injuries. The surgical technique of revascularizing the injured lower limb will be described in this chapter. In addition, fasciotomies may be employed, either pre-​emptively or following the recognition of compartment syndrome. Of greater difficulty to the clinician is deciding when salvaging the mangled limb is futile. Reconstruction of a mangled limb is a lengthy process and where outcomes are likely to be poor, a primary amputation may be in the patient’s best interest.

would be used for a prolonged period of time, as a patient would be transferred from the scene of the injury to hospital and then to theatre. Best practice would still be early revascularization with the tourniquet remaining on until in theatre. The recent experience with blast injuries has also refined our concept of Advanced Trauma and Life Support (ATLS) and some now consider an additional C at the start for ‘catastrophic haemorrhage’ giving rise to ABC (Hodgetts et al., 2006). Analysis of the Vietnam War data saw 50% of military deaths were attributable to exsanguination from extremity injuries. In the early twenty-​first century, the Israeli military were able to demonstrate the safe use of tourniquets with no deaths in 91 cases. This led to deployment initially in the military and now in civilian prehospital care. The ATLS algorithm is still followed in the emergency department, remembering the importance of haemorrhage control and fluid resuscitation. The assessment of the limb should include the degree of limb deformity, the wound itself including the degree of contamination, the sensation, and the vascularity of the limb. The temperature and colour of the distal limb should be recorded as well as palpation of the distal pulses. A simple technique is to use a pulse oximeter probe on a distal toe. An arterial waveform demonstrated by the probe will confirm the presence of arterial inflow (Fig. 5.3.1).

The initial management in the emergency department Initial care starts in the prehospital care setting. Fluid resuscitation is initiated while tourniquets are now used to control haemorrhage prior to transfer. Until recently, tourniquets were shunned due to the complications in their use in the First World War. The recent military experience in Afghanistan and Iraq has highlighted safety in the use of tourniquets to prevent haemorrhage from the main limb vessels in a blast injury (Doucet et al., 2011). Most would advocate use of tourniquet is safe for up to 2 hours without nerve and muscle ischaemia, although there has been documented safe use for up to 6 hours (Pasquier et al., 2011). In a Western trauma network, it is unlikely that a tourniquet

Fig. 5.3.1  Pale foot seen in the emergency department following an open tibial fracture. Note that the skin of the foot is not uniformly pale due to some venous pooling and bruising.

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SECTION 5  Lower limb

The difficulty in palpating a peripheral pulse can be overcome with a handheld Doppler. This assessment may be difficult in a cold, shocked patient who is peripherally shut down and so should be regularly repeated. Reassessment should also follow any manipulation or splinting of the limb both before and after the procedure. When a vascular injury is suspected, ankle–​brachial pressure index (ABPI) measurements can be useful. A  value less than 0.9 raises suspicion of a vascular injury in the presence of a normal measurement in the contralateral limb in a patient without peripheral vascular disease. Schwartz and colleagues (1993) demonstrated that in the absence of a pulse deficit, an abnormal ABPI is a good screening tool for the need for angiography. One should consider both the hard and soft signs of vascular injury. Hard signs include haemorrhage or pulsatile bleeding, expanding haematoma, a cold extremity, absent distal pulses, or the presence of bruits or thrills. Soft signs include unexplained hypotension, non-​expanding haematomas, decreased pulse or ABPI, weak distal pulses, or a wound in proximity to major vessels. The hard signs are diagnostic of a major arterial injury and require immediate surgical intervention. The soft signs require further assessment and investigation (Table 5.3.1). In 2009, BAPRAS in conjunction with the BOA produced a joint document on the standards of care for open tibial fractures. While the overall steps are described elsewhere, key steps pertaining to a devascularized limb with an open fracture are: • The early administration of intravenous co-​ amoxiclav or cefuroxime, which is continued until debridement. • Regular neurovascular assessment of the limb. • Documentation of the wound with photography. • Only gross contamination of the wound is removed before the wound is covered with sterile saline soaked gauze and an impermeable film dressing in the emergency department. • Early surgical intervention if there is vascular impairment, ideally within 2–​3 hours, and no later than 6 hours of warm ischaemia. • A combined plan with both plastic and orthopaedic surgeons. A plan incorporating prompt management is important. While the aim is to revascularize the limb within 6 hours to prevent irreversible muscle and nerve damage, animal studies such as Labbe’s canine gracilis studies demonstrate myocyte death at 3, 4, and 5 hours of 2%, 30%, and 90% respectively (Labbe et al., 1987), and therefore the emphasis on managing the devascularized limb with urgent recognition and rapid revascularization through prompt surgical intervention.

Table 5.3.1  Hard and soft signs of vascular injury. The presence of hard signs warrants immediate surgical exploration. The presence of solely soft signs indicates a degree of diagnostic uncertainty for which further investigations are warranted Hard signs

Soft signs

Haemorrhage/​pulsatile bleeding

Unexplained hypotension

Expanding haematoma

Non-​expanding haematoma

Presence of bruits/​thrills

Decreased pulse/​ABPI

Cold extremity

Weak distal pulse

Absent distal pulses

Wound in proximity to major vessels

(a)

(b)

Fig. 5.3.2  (a) CT angiography and (b) three-​dimensional reconstruction demonstrating a popliteal artery injury.

Preoperative angiography is unnecessary to establish a diagnosis in the devascularized limb when obvious hard signs are present (Foster et  al., 2006), although in ballistic injuries, which can be complex with fragmentation of the missile resulting in multiple secondary missiles and multiple levels of injury, angiography may establish the level(s) of arterial injury. The value of this additional information needs to weighed against the extra time required before surgery, with a mean delay from 3.8 to 7.6 hours in one meta-​ analysis (Glass et al., 2009). An alternative to preoperative angiography is on-​table angiography. While this does not delay the patient reaching theatre, there is still a significant delay to revascularizing the injured limb as the study is time-​consuming. Multi-​row detector computed tomography (CT) imaging is becoming commonplace, replacing plain radiographs. A trauma CT will now incorporate both head and abdominal imaging when necessary. If a patient is to undergo a trauma CT, there is little difficulty or delay in adding CT angiography of the injured limb which has similar sensitivity and specificity of traditional invasive angiography (Callcut and Mell, 2013) (Fig. 5.3.2).

When to attempt limb salvage? The key decision to be made with a mangled or devascularized limb is whether the patient is better served by reconstruction with a prolonged period of rehabilitation or by a primary amputation. Indications for a primary amputation following extremity trauma may include (Jain et al., 2013): • An almost completely severed limb with significant distal trauma. • Extensive crush injuries. • An ischaemic limb with greater than 6 hours of warm ischaemia time. • Segmental bone loss (more than one-​third of the length of the tibia). • Muscle loss in more than two compartments (particularly the posterior compartment). • Severe foot injuries. Several scoring systems have been developed in an attempt to predict the need for limb amputation.

5.3  The devascularized limb

Johansen and colleagues (1990) developed the Mangled Extremity Severity Score (MESS). This system attributes scores for age, limb ischaemia (doubled if over 6 hours), skeletal and soft tissue injury, and the degree of shock. A score greater than 7 correlated with the need to amputate in both civilian and military settings. However, a score of less than 7 was not a strong negative predictor of amputation (Robertson, 1991). The Lower Extremity Assessment Project (LEAP) study reviewed MESS along with four other lower extremity trauma scoring systems (Bosse et al., 2001). These were the Limb Salvage Index (LSI), the Predictive Salvage Index (PSI), the Nerve injury, Ischaemia, Soft tissue injury, Skeletal injury, Shock, and Age of patient (NISSSA) score, and the Hannover Fracture Scale-​97 (HFS-​97). This was the first study to prospectively evaluate these scores. With each scoring system, a low score was highly specific in predicting limb salvage but there was low sensitivity in predicting limbs requiring amputation across all five systems. This may be explained by the refinements in technique in skeletal fixation, vascular repair, and soft tissue reconstruction allowing for more severely injured limbs being salvaged than previously possible. Of greater importance with any limb injury is the functional outcome following reconstruction. Again, there appears to be little predictive correlation in the short or long term between extremity injury scores and the functional outcome following limb salvage. Consideration must be given to the delayed amputation. The decision to amputate is neither easy nor lightly taken. A delayed amputation is a failure of limb salvage and arguably a failure in early decision-​making or to provide prompt surgery. It has also been shown that performing an amputation after 5 days is associated with a significantly higher deep infection rate (Jain et al., 2013). The decision to attempt limb salvage or to amputate should focus on which is more likely to deliver a long-​term functional limb. This will depend on injury factors and patient factors. Because of this, each decision has to be individualized and must be left to the patient to make after appropriate counselling (Fig. 5.3.3).

Nerve injury in the lower limb Major nerve injury may occur in conjunction with vascular injury. An insensate foot is often cited as an indication for primary amputation but the LEAP study data indicated that plantar sensation returns in 55% of patients at 2 years suggesting Sunderland grade 1 and 2 injuries of the tibial nerve are common (Bosse et al., 2005). Matters are a lot less clear when the nerve has been divided. Transection of the tibial nerve causes loss of protective plantar sensation, paralysis of the foot musculature, and consequent deformity of the foot. This can lead to neuropathic ulceration and destruction of the foot with amputation of the foot often required. Avoiding this sequence is the basis of primary amputation in patients with proximal tibial nerve transection. There are now data that potentially contradict this approach. The Ganga Hospital (Coimbatore, India) has reported that lower limb trauma patients with posterior tibial nerve injuries that were repaired had similar outcomes to patients without nerve injury (Momoh et  al., 2015). Infrapopliteal replantation for traumatic amputation can also be functionally successful when direct nerve coaptation is performed (Cavadas et al., 2009).

C-ABC Assessment of limb

Hard or Soft Signs

Soft

CT angiography

Hard

No Amputate

Surgery to salvage limb

Yes

Shunt to bypass injury

Yes

Vascular injury?

No

Monitor

Debride and bony stabilization

Vascular repair ‘+/–’ interposition vein graft

Fig. 5.3.3  Flowchart of decision-​making when treating a trauma patient with a devascularized limb.

The aim is to achieve protective sensation in the foot and some ankle function which allows ambulation. The outcomes of nerve reconstruction in the lower extremity are affected by the timing of repair, the length of nerve graft, and the level of injury. In common peroneal nerve repairs, there is clear benefit in performing an early nerve reconstruction. Outcomes are also superior with shorter segments of nerve grafting (George and Boyce, 2014). Proximal injuries have worse outcomes than distal injuries (Roganovic and Pavlicevic, 2006). Individual patient factors need to be considered rather than decision-​making based simply on nerve injury. In well-​financed healthcare systems, it may be easier to find a good-​fitting prosthesis. In poorer nations, limb salvage may be a more sensible option. The type of injury must also be considered, as clearly high-​energy blast injuries will fare worse compared to incised nerve transections. In summary, functional limb salvage even if the tibial nerve requires repair is possible. The evidence at present is small and larger studies with longer periods of follow-​up are needed to answer this question.

Approaches to limb salvage The quickest means of restoring distal circulation is with a temporary shunt. This can be done using the specific vascular shunts

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SECTION 5  Lower limb

used for carotid surgery such as the Pruitt-​Inahara® (Le Maitre, Burlington, MA, USA) shunt. This has a balloon at either end to maintain position within the lumens of the shunted vessel. Other commonly used shunts include Bard®Javid™ (Tempe, AZ, USA) and Argyle™ (Medtronic, Dublin, Ireland) shunts. If no dedicated shunt kits are available, the silastic tubing from a blood giving sets can be used and maintained in position with ligatures. The purpose of shunting is to buy time. Distal circulation is re-​ established in a prompt and relatively simple manner. The surgeon can then debride, reassess the extent of injury, and continue with the bony, soft tissue, and vascular reconstruction. Following the re-​establishment of perfusion, there will be a flushing of toxic metabolites through the venous system that may cause haemodynamic instability with acidosis and hypotension. This is transient but may be significant and it is important to make the anaesthetist aware when this can be expected. When both arterial and venous injuries are present, it is the authors’ practice to place the venous shunt first unless the warm ischaemia time exceeds 3–​4 hours, in which case the arterial shunt is placed first and the part is allowed to bleed out for a period to flush out toxic metabolites. A standard technique of shunting has been described (Glass et al., 2009). The vessels are dissected to allow proximal and distal exposure of the vessels clear of the zone of injury. In a transected vessel, any clots are removed and flushed out with heparinized saline. An embolectomy catheter may be employed to remove any further clots. The shunt is then inserted and secured within the lumen. If the vessels are in continuity, longitudinal arteriotomies are made proximal and distal to the site of injury. These incisions are made just large enough to permit the shunts to be placed within the lumens. After shunting, the surgeon can use the standard orthoplastic approach to bony and soft tissue debridement and stabilization. Reverse saphenous grafts remain the best option for definitive reconstruction of injured vessels. Alternatives include the cephalic and basilic veins although they lack both the calibre and length available with the long saphenous vein. This is autologous tissue with an endothelial lining. All attempts should be made to use autologous vein grafts as synthetic alternatives, such as polytetrafluoroethylene (PTFE) grafts, have a very high failure rate in the trauma setting. The plastic surgeon should note that it is preferable to use non-​ microsurgical sutures such a 5/​0 polypropylene suture instead of 9/​ 0 nylon for the vascular anastomosis as the vessels are much larger and the repair will have to withstand much higher intraluminal pressures (Fig. 5.3.4). When there is a need for immediate soft tissue and vascular reconstruction, flow-​through flaps may be necessary such as an anterolateral thigh flap using the descending branch of the lateral circumflex femoral artery as the conduit to re-​establish distal flow. By doing so, it is also possible to avoid exposure of both the great vessels and the vascular repair. The routine use of antiplatelet agents is not indicated in the trauma setting. Thromboprophylaxis against deep vein thrombosis should be started with low-​molecular-​weight heparin and continued until the patient is mobilizing.

(a)

(b)

(c)

Fig. 5.3.4  This series of images show an arterial injury of the brachial artery. (a) The wound is explored, and a shunt is initially used to revascularize the distal extremity. (b) The limb can then be debrided and stabilized with a monolateral external fixator device. (c) A vein graft is then used to bridge the injured arterial segment including the proximal and distal vessel that was traumatized by the shunt.

5.3  The devascularized limb

Fasciotomies Compartment syndrome will occur when the perfusion pressure falls below the tissue pressure within a closed anatomical space. The outcome can be limb-​or life-​threatening. In the limb, the muscle compartments are enclosed within an unyielding osteofascial envelope. With vascular limb injuries, compartment syndrome may arise from a space-​occupying lesion such as a haematoma, from the tissue oedema following tissue hypoxia, acidosis, and reperfusion injury following revascularization. Once the compartment pressure rises above capillary perfusion pressure, there is a failure to oxygenate the enclosed tissues leading to further tissue ischaemia. This leads to release of inflammatory and hypoxic mediators leading to more soft tissue swelling. Compartment syndrome lasting over 6 hours will lead to muscle necrosis. When muscle necrosis has already occurred, revascularization and rhabdomyolysis can result in renal failure. While fasciotomy is clearly indicated in known compartment syndrome, when the diagnosis is uncertain, the threshold for fasciotomy is low since the consequence of a neglected compartment syndrome is so significant. There are risks associated with fasciotomy including neurovascular injury and muscle herniation with or without skin grafting can be painful and unsightly. Prophylactic fasciotomy should be undertaken following revascularization of the limb with an ischaemic time over 4 hours, or if there is associated extensive soft tissue injuries such as crushing. If some perfusion was maintained (as recognized by back bleeding from the transected distal vessel), fasciotomies may be avoided.

A  review of shunting following vascular extremity trauma has shown that fewer fasciotomies are performed when the limb is shunted initially, implying that prolonged ischaemia is a major risk factor for developing a compartment syndrome (Glass et al., 2009). In the United States, a review of the National Trauma Data Bank has shown that early fasciotomies are associated with a lower infection rate, a lower amputation rate, and a shorter hospital stay compared to those who had fasciotomies over 8 hours after a vascular repair (Farber et al., 2012). If prophylactic fasciotomies are not performed, regular assessment of the limb is important. The diagnosis of compartment syndrome is suspected when pain is out of keeping with the injury, pain is exacerbated on passive stretch of the compartment muscles, or a firm, tender, and swollen muscle compartment is encountered. The loss of distal sensation or pulses is a late sign. Compartment pressure monitoring is a useful adjunct particularly in patients with altered consciousness, with a difference of more than 30 mmHg between the diastolic blood pressure and compartment pressure being the threshold for surgery in the presence of corresponding clinical features. The technique for fasciotomy release in the lower limb (Pearse et al., 2002) has been standardized by the BAPRAS/​BOA guidelines. The technique involves initially marking the medial and lateral subcutaneous borders of the tibia. Parallel lines are then designed longitudinally on the limb, 2 cm laterally to the tibia and 1.5 cm medially. Fasciotomy incisions are placed here to avoid the medial and lateral skin perforators needed for local fasciocutaneous flaps (Fig. 5.3.5).

Fig. 5.3.5  The technique for performing fasciotomies of the leg. Reproduced with permission from Jagdeep Nanchahal et al., Standard for the Management of Open Fractures of the Lower Limb, the British Association of Plastic and Aesthetic Surgeons (BAPRAS) & the British Orthopaedic Association (BOA) Copyright © 2009.

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The two skin incisions need to be long enough to release the entire muscle groups adequately. The anterolateral incision gives access to the anterior muscle group then a lateral subfascial dissection to the anterior crural septum is performed. This septum is divided to release the peroneal compartment. The medial incision will access the superficial posterior compartment containing gastrocnemius and soleus. A deeper dissection and release of the insertion of the soleus onto the tibia allows access to the fascial lining over the deep posterior compartment, which is divided to decompress these muscles. The key principles are making long incisions, inspecting all four muscle groups, and debriding dead muscle. The wounds can be dressed with a negative pressure dressing. If there is doubt about tissue viability, further inspection at 48 hours is required. A delayed inspection allows for oedema to settle and may allow for delayed primary closure of at least one of the fasciotomy incisions. Any wounds that cannot be closed can then be skin grafted. A primary skin graft can only be performed safely when there is no doubt about tissue viability. While this technique for the leg compartments is the standard in the United Kingdom, releases for the foot compartments are far more complicated. Two dorsal incisions over the second and fourth metatarsals allow access to the intrinsic muscles of the foot. These incisions can then be deepened to access the plantar muscles or a separate incision may be required for the medial side of the foot to access the deep plantar muscles of the foot. There is debate about whether fasciotomy in the foot is necessary. Without decompression, the foot muscles may undergo necrosis and fibrosis, but the ensuing deformity can then be addressed with contracture release and this may avoid the scars associated with fasciotomy, which are commonly painful. The management of the delayed presentation of a compartment syndrome is important to consider. There is now evidence to suggest that a compartment syndrome of the leg presenting over 24 hours should not be released, as the injury is now irreversible. The literature shows that release at this time point correlates to a very high rate of amputation due to infection and the need to remove all the dead, exposed muscle. If the compartments are left closed, the muscles can be left to fibrose with preservation of any viable myocytes. These may recover functionally over the course of a few years to allow reasonable limb function. In these cases, the patient needs to be carefully monitored to look for evidence of metabolic acidosis and rhabdomyolysis that may occur. High urine output (75–​100 mL/​ hour) should be maintained and renal function monitored.

Outcomes following vascular repair A vascular repair is only worthwhile if successful limb salvage leads to a good functional outcome. Prompt revascularization should result in less muscle and nerve necrosis, but the outcome also depends on the level and the mechanism of injury. Unsurprisingly, sharp vascular transections carry the best prognosis, while higher-​energy injuries such as severe blunt trauma and missile injuries produce worse outcomes (Hafez et al., 2001). The Gustilo and Anderson grade IIIC injuries are rare and so the published series are generally small in number. These injuries are associated with a high rate of amputation, often delayed following an unsuccessful salvage, and recovery is often characterized by

depression and chronic pain. Distal tibial fractures have a higher non-​union rate in a devascularized limb (Soni et al., 2012). When comparing the long-​term outcomes of salvage and amputation cases, a large meta-​analysis (Busse et al., 2007) showed remarkable concordance between the functional outcomes, even at 7 years. Both groups had low function scores, which reflect the extensive nature of their injuries. Approximately half of all patients in either group returned to work at 2 years. A similar proportion of patients in each group suffered from disability and the functional status of these patients deteriorated with time. The key difference between the groups was that the overall period of operative treatment and the initial length of rehabilitation was longer in the salvage group. This important fact should be considered early in the decision-​making process.

Conclusion The prompt evaluation and management of the devascularized limb is essential to maintain all reconstructive options. The rapid re-​ establishment of circulation must be the first priority. Any attempts at limb salvage must be focused on delivering a long-​term functional limb. This decision is bespoke for each patient. It is one of the hardest choices in limb reconstruction but getting it right is essential if the best outcomes are to be achieved.

REFERENCES Bosse MJ, MacKenzie EJ, Kellam JF, et  al. A prospective evaluation of the clinical utility of the lower-​extremity injury-​severity scores. J Bone Joint Surg Am 2001;83:3–​14. Bosse MJ, McCarthy ML, Jones AL, et al. The insensate foot following severe lower extremity trauma: an indication for amputation? J Bone Joint Surg Am 2005;87:2601–​8. Busse JW, Jacobs CL, Swiontkowski MF, et al. Complex limb salvage or early amputation for severe lower-​limb injury: a meta-​analysis of observational studies. J Orthop Trauma 2007;21:70–​6. Callcut RA, Mell MW. Modern advances in vascular trauma. Surg Clin North Am 93:941–​61,  ix. Cavadas PC, Landín L, Ibáñez J, et al. Infrapopliteal lower extremity replantation. Plast Reconstr Surg 2009;124:532–​9. Doucet JJ, Galarneau MR, Potenza BM, et al. Combat versus civilian open tibia fractures: the effect of blast mechanism on limb salvage. J Trauma 2011;70:1241–​7. Farber A, Tan TW, Hamburg NM, et al. Early fasciotomy in patients with extremity vascular injury is associated with decreased risk of adverse limb outcomes: a review of the National Trauma Data Bank. Injury 2012;43:1486–​91. Foster BR, Anderson SW, Soto JA. CT angiography of extremity trauma. Tech Vasc Interv Radiol 2006;9:156–​66. George SC, Boyce DE. An evidence-​based structured review to assess the results of common peroneal nerve repair. Plast Reconstr Surg 2014;134:302–​11. Glass G, Pearse M, Nanchahal J. Improving lower limb salvage following fractures with vascular injury: a systematic review and new management algorithm. J Plast Reconstr Aesthet Surg 2009;62:571–​9. Hafez HM, Woolgar J, Robbs JV. Lower extremity arterial injury: results of 550 cases and review of risk factors associated with limb loss. J Vasc Surg 2001;33:1212–​19.

5.3  The devascularized limb

Hodgetts TJ, Mahoney PF, Russell MQ, et  al. ABC to ABC:  redefining the military trauma paradigm. Emerg Med J 2006;23:745–​6. Jain A, Glass GE, Ahmadi H, et  al. Delayed amputation following trauma increases residual lower limb infection. J Plast Reconstr Aesthet Surg 2013;66:531–​7. Johansen K, Daines M, Howey T, et  al. Objective criteria accurately predict amputation following lower extremity trauma. J Trauma 1990;30:568–​72. Labbe R, Lindsay T, Walker PM. The extent and distribution of skeletal muscle necrosis after graded periods of complete ischemia. J Vasc Surg 1987;6:152–​7. Momoh AO, Kumaran S, Lyons D, et al. An argument for salvage in severe lower extremity trauma with posterior tibial nerve injury: the Ganga Hospital experience. Plast Reconstr Surg 2015;136:1337–​52. Nanchahal J, Nayagam D, Khan U, et al. Standards for the Management of Open Fractures of the Lower Limb. London:  Royal Society of Medicine Press Ltd, 2009. http://​www.bapras.org.uk/​docs/​

default-​source/​commissioning-​and-​policy/​standards-​for-​lower-​ limb.pdf?sfvrsn=0 Pasquier P, Malgras B, Martinaud C, et al. Limb salvage in open tibia fractures: are prehospital time and tourniquet significant? J Trauma 2011;71:1093. Pearse MF, Harry L, Nanchahal J. Acute compartment syndrome of the leg. BMJ (Clin Res Ed) 2002;325:557–​8. Robertson PA. Prediction of amputation after severe lower limb trauma. J Bone Joint Surg Br 1991;73:816–​18. Roganovic Z, Pavlicevic G. Difference in recovery potential of peripheral nerves after graft repairs. Neurosurgery 2006;59:621–​33. Schwartz MR, Weaver FA, Bauer M, et al. Refining the indications for arteriography in penetrating extremity trauma: a prospective analysis. J Vasc Surg 1993;17:116–​22. Soni A, Tzafetta K, Knight S, et  al. Gustilo IIIC fractures in the lower limb:  our 15-​year experience. J Bone Joint Surg Br 2012;94: 698–​703.

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5.4

Management of soft tissue loss without microsurgery Thomas C. Wright

Pretibial injuries Pretibial lacerations are a common referral to plastic surgery units, and are associated with high levels of morbidity and even mortality (Glass and Jain, 2014). Patients suffering this type of injury are commonly elderly and female. Multiple comorbidities are associated with these injuries, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, dementia, diabetes, cancer, and renal failure, which put patients at risk of further complications (Lo et al., 2012). It has become increasingly recognized that these injuries should be managed according to an evidence-​based pathway to achieve the best outcomes. Once referred to a plastics unit, there should be a timely assessment of the wound, and the patient, by an experienced plastic surgeon. The decision to debride and graft or manage with dressings should not be taken lightly. Although grafting may speed wound healing when compared with dressings (60 days vs 123 days on average), there may be a significant delay in donor site healing in this group (50 days on average) (Cahill et al., 2015). The patient should be counselled appropriately and their preference should be respected. If grafting is thought to be necessary, a full preoperative assessment should be made, including comorbidities, anaesthetic review, mobility, and discharge planning. These vulnerable patients should, ideally, be listed for surgery on a planned operating list to avoid cancellations and excessive periods of starvation. Where possible, local and regional anaesthesia techniques should be considered. It is advisable to avoid splints after grafting, and mobilize early. By adhering to these principles, it should be possible to minimize the morbidity and even mortality of these significant, but sometimes underestimated injuries.

Decision-​making in lower limb reconstruction Reconstruction begins with clinical assessment of the patient. The mechanism of injury, comorbidities, and functional requirements must be considered. The neurovascular status of the limb is assessed clinically, with Doppler and with computed tomography

(CT) angiography if required (Chummun et al., 2013). The wound must be adequately debrided (repeatedly if necessary) and the full zone of injury and extent of degloving appreciated. Only then can the decision to reconstruct with local, regional, or distant options be made. Increasingly, microsurgical techniques are preferred, but facilities for these procedures and their aftercare may not always be available, the patient may not be deemed fit for a long surgical procedure, or non-​microsurgical techniques may be deemed adequate for the defect. These decisions must be made after discussion between the surgical and anaesthetic team and the patient. It is not unusual for patients suffering polytrauma to have a decreased level of consciousness that precludes competent consent to surgery. In these situations the surgeon should, where possible, discuss the case with consultant colleagues in plastic surgery, orthopaedics, intensive care, and any other surgical specialties involved in the care of the patient. The family of the patient should, ideally, also be involved in these discussions. A decision to perform limb salvage (or not) must be made in a timely fashion, so as not to compromise the outcome of the reconstruction, assuming the patient is well enough to undergo surgery, and that there is a reasonable chance they will survive their other injuries. Pedicled or local flaps may be harvested from the abdomen, groin, thigh, leg, or foot.

Abdominal flaps There are a variety of flaps from the abdominal region that may be used to cover defects of the groin, hip, and thigh. These include a rectus abdominis muscle flap, vertical or transverse rectus abdominus myocutaneous flaps, or deep inferior epigastric perforator flap. The size, contour, and location of the defect may lend itself to one design over another, but all are based on the deep inferior epigastric artery with the origin of this vessel acting as the pivot point (usually on the ipsilateral side). The inclusion of muscle may help with control of dead space in deep cavities, whereas the design of the skin island can be tailored to the defect and its location. Despite the potential variations in skin flap position and orientations available,

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SECTION 5  Lower limb

including upper transverse, these flaps will only reach to the thigh due to the position of the pivot point (Irons, 1983; Deo et al., 2001; De la Plaza et al., 1984; Straeley and Parry, 1957; Senchenkov et al., 2003; Cedidi et al., 2005).

Groin flap This pedicled axial pattern skin flap is based on the superficial circumflex iliac artery. The flap may be raised with a skin pedicle or islanded, and is designed with its axis centred 2 cm below and parallel to the inguinal ligament. In reconstruction of the upper limb it is performed in stages but in defects of the thigh it may be used as a one-​stage reconstruction. It is a good source of well-​vascularized skin although the thickness of this tissue will vary according to the patient’s body habitus. The donor defect may usually be closed directly unless a particularly wide flap is required. It is, however, limited by the position of the pivot point at the femoral vessel and the fact that the portion of the flap lateral to the anterior superior iliac spine should be regarded as a random pattern flap and limited in dimension because of this (I.A. McGregor and Jackson, 1972; Ohtsuka et al., 1985).

Tensor fascia lata flap This flap is a very reliable option for cover of defects of the groin, proximal thigh, and trochanteric region. The tensor fascia lata muscle originates from the anterior iliac crest and inserts onto the iliotibial tract and fascia lata. Its vascular supply (type I) is from the transverse branch of the lateral circumflex femoral vessels. It is generally used as a myocutaneous flap with the overlying skin paddle extending over the iliotibial tract down the proximal two-​thirds of the lateral thigh (10 cm proximal to the knee joint), or more distally if a delay procedure is performed. The skin paddle may be islanded if preferred and either transposed or advanced in a V-​to-​Y fashion. The tensor fascia lata flap also provides an excellent source of vascularized fascia, and the donor site can usually be closed directly if less than 9 cm wide. It has even been reported for coverage of the heel, although this requires the knee to be kept in full flexion until division of the flap (J.C. McGregor and Buchan, 1980; Shubailat et al., 1980; Jósvay et al., 2006).

Anterolateral thigh flap The anterolateral thigh flap has become a workhorse perforator free flap with numerous applications (Song et al., 1984). It has also been widely used as a pedicled flap (Ng et al., 2008). The flap is generally raised as a fasciocutaneous island (although skin-​only and fascia-​ only varieties are reported) from the anterolateral aspect of the thigh, based on a perforator from the descending branch of the lateral femoral circumflex artery and venae comitantes. When pedicled proximally, the anterolateral thigh flap can be used to cover defects of the thigh, groin, and pelvis. Excess fascia lata may be included if required, or a portion of vastus lateralis muscle may be harvested, for control of dead space. The anterolateral thigh flap has also been

described as a retrograde or reverse flow flap to cover defects of the knee and proximal tibia, or in a cross-​leg design for contralateral leg defects (Zhou et al., 2005; Demirseren et al., 2011). These designs rely on the distal anastomoses of the descending branch of the lateral femoral circumflex artery with the lateral superior geniculate artery or the profunda femoris itself. The flap should be planned in reverse with a skin paddle of up to 8 cm width (to allow direct closure) and the distal pivot point expected to lie 10 cm proximal to the superolateral aspect of the patella. The flap perforator should be marked with a Doppler in a standard fashion and the descending branch of the lateral femoral circumflex vessel dissected just proximal to the perforator and distally towards the knee. Perfusion in the flap should be assessed by clamping the proximal vessel before ligation and then the flap may be transferred to the defect. This flap is prone to venous congestion, so skin flaps over the pedicle must not be closed under tension, and a split-​skin graft over the pedicle may be necessary to reduce the risk of this.

Vastus lateralis flap Alternatively, the vastus lateralis muscle itself may be used with a similar approach (Bovet et al., 1982). The vastus lateralis is released from the extensor mechanism of the knee and is separated from the vastus intermedius and its attachment to the linea aspera of the femur. The muscle is then raised from distal to proximal, preserving the vascular pedicles from the lateral femoral circumflex artery and its descending branch. This allows coverage of defects over the trochanter and femoral vessels with minimal donor morbidity.

Rectus femoris flap The rectus femoris is an alternative choice of muscle or myocutaneous flap from the thigh to cover defects of the groin, perineum, and ischium (Bhagwat et al., 1978). It originates from the anterior superior iliac spine and acetabulum to insert onto the patella and act as an important thigh flexor and leg extensor. It is therefore not the most expendable of the quadriceps group. It has a type II vascular supply with the dominant pedicle from the descending branch of the lateral femoral circumflex artery (between 7 and 10 cm inferior to the pubic symphysis) and minor pedicles from the ascending branch and superficial femoral artery. If harvested with a skin paddle, this should be over the middle third of the muscle to ensure inclusion of perforators. The remaining vastus medialis and lateralis tendinous fascia may be sutured together to reduce donor morbidity and preserve knee extensor function. Quadriceps weakness has been demonstrated by objective testing, but this appears to be well tolerated and does not affect daily activities (Daigeler et  al., 2005; Flurry et al., 2011).

Gracilis flap The gracilis muscle and myocutaneous pedicled flaps have been used to cover pelvic (including ischium) and groin defects (McCraw and Furlow, 1975; Wingate and Friedland, 1978). The muscle originates

5.4  Management of soft tissue loss without microsurgery

from the pubic ramus, inserts onto the medial tibia, is innervated by a branch of the obturator nerve, and is a weak adductor and flexor of the thigh. It has a mean width of 6 cm and length of 38 cm. The vascular supply is from one dominant proximal vessel and up to three minor distal pedicles. The proximal (9 cm distal to the inferior pubic ramus) and dominant is a branch from the medial circumflex femoral artery and the distal pedicles from a branch of the superficial femoral artery (or popliteal). When designing a proximally based flap on the dominant proximal pedicle, it is worth noting that the overlying skin paddle is unreliable unless centred over the proximal third, so is generally not useful in this scenario (Giordano et al., 1990). The reverse or distally based gracilis flap has also been described for coverage of defects of the proximal knee and patella. When planning a gracilis muscle flap based on the secondary pedicles it is important to know that the most proximal secondary pedicle is located approximately 21 cm distal to the proximal muscle origin (Tiengo, 2010) or 17 cm from the joint line of the knee (Cavadas et al., 2004). This distance may vary and will serve as the pivot point of the flap. CT angiography may help define the location and calibre of secondary pedicles to aid planning (Cavadas et al., 2004). Preoperative CT scanning and ligation of the major pedicle as a delay procedure is not, however, thought to be essential (Mitsala et al., 2014). The donor morbidity of gracilis flaps is low and the dissection is relatively simple. The muscle flap will, however, require a split-​skin graft and may be more difficult to re-​raise than a fasciocutaneous option if revision surgery is needed.

Biceps femoris flap The biceps femoris flap (long head) is a reliable option for coverage of ischial defects. It can be transposed or reflected as a muscle flap or advanced as a myocutaneous flap (often in a V-​to-​Y or hatchet design) by dividing its origin and insertion but leaving a proximal vascular pedicle arising from the profunda femoris. The loss of muscle function is well tolerated, although this flap is commonly used in paraplegic patients (James and Moir, 1980; Tobin et al., 1981).

Local flaps These flaps by definition use tissue from directly adjacent to the defect. Their use has evolved greatly since it was observed that local skin flaps were unreliable in the leg. Pontén (1981) noted that including the fascia increased the reliability and dimensions of transposition flaps. He also noted the importance of preserving perforators and including superficial veins in these proximally based flaps. Fasciocutaneous flaps are planned in reverse in a standard fashion, according to the defect. Coverage of upper-​and middle-​thirds of leg defects can be achieved, but the donor site requires skin grafting and large flaps create significant dog-​ears. The donor sites are therefore often considered unsightly. When distally based flaps in the leg were described, coverage of distal-​third and ankle defects became possible. These include reverse sural flaps (described in ‘Sural flaps’) but also distally based fasciocutaneous flaps based on perforators from the posterior tibial or anterior tibial artery (Amarante et al., 1986; Wee 1986; Hong et al., 1989). When planning these types of

flaps, knowledge of local perforator anatomy is essential. Handheld Doppler may be of assistance in identifying the main vessel and its perforators. High-​energy and degloving injuries will compromise the vascularity and preclude the use of these flaps. Adipofascial turnover flaps have also been described for distal defects (Lai et al., 1992). The concept of these flaps is to raise a paddle of subcutaneous fat and deep fascia based on distal perforators. The flap is then reflected back on itself to reach the defect. Although this leaves a less conspicuous donor defect, the flaps themselves must be carefully planned, as much of the flap length is lost when reflected over the pivot point (the distal perforator). It is difficult to monitor the vascularity of the skin-​grafted flap and the tissue transferred is less robust than that of fasciocutaneous flaps. Propeller flaps are a further development of distally based local fasciocutaneous perforator flaps. These flaps evolved from the knowledge that these distally based flaps could be islanded and thus rotate around a single perforator to cover the distal leg. Once the defect is defined, handheld Doppler is used to identify a promising perforator close to the defect. The flap is then designed by measuring the distance from the perforator to the distal edge of the defect. The proximal part of the flap is outlined along the axis of the perforator’s main vessel measuring the original distance plus 1 cm. This defines the proximal limit of the flap, allowing the width to be designed according to the width of the defect plus 0.5 cm. This then forms the two unequal blades of a propeller that may be raised and rotated up to 180° to cover the defect. The smaller blade may help allow closure of the donor but often a skin graft is required (Fig. 5.4.1). The flap design should not transgress the border of the tibia nor the Achilles tendon so that the donor is easily skin grafted if required. These flaps have the advantage of a more acceptable donor site than

(a)

(b)

(c)

(d)

a

b + c

Fig. 5.4.1  (A) The propeller flap concept can be thought of as a propeller with two blades of unequal length with the perforator forming the pivot point; when the blades are switched, the long arm comfortably fills in the defect. (B) Marking of the flap. The distance between the perforator and the proximal tip of the flap (a) is equal to length of the defect (c) plus the distance between the proximal edge of the defect and the perforator (b) with 1 cm added to allow for the tissue retraction and to facilitate tension free closure when the flap is rotated. The width of the flap is equal to the width of the defect with 0.5 cm added. (C) After the flap and the perforator are completely dissected, the flap is rotated to cover the defect. (D) The short arm of the propeller flap is used to aid closure of the secondary defect either completely or with a skin graft. Reprinted from Clinics in Plastic Surgery, Volume 37, issue 4, Tiew Chong Teo, The Propeller Flap Concept, pp. 615–​626, Copyright (2010), with permission from Elsevier.

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SECTION 5  Lower limb

other fasciocutaneous flaps with no dog-​ear and can be relatively quick to raise. Care must be taken in assessing the local tissues to exclude degloving around the perforator. Microsurgery skills are required to skeletonize the perforating artery and its venae comitantes, ideally from its source vessel to the point where it passes through the deep fascia, to ensure there is no kinking or compression of the venous pedicle on rotation (Murakami et al., 2005; Pignatti et al., 2008; Teo, 2010). The keystone flap is another technique used to cover lower limb defects. The original technique describes the use of a keystone-​ shaped, islanded, fasciocutaneous flap adjacent to the defect, that is mobilized by a combination of lateral advancement, V-​to-​Y advancement, and local skin recruitment, while preserving the underlying perforators, superficial veins, and lymphatics. Their use has been adopted more commonly in skin oncology reconstruction than in trauma. The reliability of perforators at the level of the injury is of more concern in trauma, especially in the presence of degloving, and so this flap has not been taken up widely in traumatic wounds (Behan, 2003; Chaput et al., 2014).

Gastrocnemius flap This muscle is ideally suited for coverage of the upper third of the tibia and knee (Ger, 1971; Pers and Medgyesi, 1973). It has a medial and lateral head with vascular supply from the medial and lateral sural vessels respectively branching from the popliteal artery. Both heads (along with soleus) act as plantar flexors of the foot. Dissection of this muscle flap is relatively easy either by extending the wound obliquely towards the posterior midline inferiorly down to the Achilles or by making a separate posterior incision. The medial, lateral, or both muscle heads may be used as long as the soleus is left intact for plantar flexion. The choice will depend on the site of the defect and pre-​existing wounds. The medial head is usually preferred as the muscle belly extends more distally and the risk of damage to the peroneal nerve is avoided. The muscle is dissected along the median raphe and divided at the junction with the Achilles distally. The planes superficial and deep to the muscle are relatively avascular which allows for quick dissection. The muscle is then transposed to the defect, releasing tight skin bridges if present. Releasing the proximal muscle origin in the popliteal fossa may increase the arc of rotation and scoring the fascial layer on the deep surface of the muscle allows the muscle to cover a larger surface area. The gastrocnemius muscle flap is extremely reliable and has become a workhorse for proximal-​third and knee reconstruction, but it struggles to cover defects over the patella and more proximally. The flap may also be raised in a myocutaneous fashion with the skin paddle based on a perforator of the sural vessel. A modification of this is to design the skin paddle as a propeller flap to allow coverage more proximally over the patella (Innocenti et al., 2014).

Tibialis anterior flap This muscle lies in the anterior compartment just lateral to the tibial crest. It is an important dorsiflexor of the foot and has a segmental vascular supply from the anterior tibial artery. It is possible to cover small defects of the upper and middle third of the tibia by

performing a sagittal split along the length of the muscle from proximal to the defect, to distal to the defect. This manoeuvre requires the surgeon to preserve some muscle over the central tendon, and then the anterior portion of the muscle can be stretched over the defect, while preserving the function of the remaining muscle. The muscle flap is then skin grafted. This reconstructive option is often already exposed by the injury, or may require minimal wound extension. This allows assessment of its condition and suitability. The use of this flap is often precluded by the zone of trauma and is limited by the small size of defects it may cover (Hallock, 2002).

Soleus flap Variations of the soleus muscle flap have been widely used for many decades, in particular for coverage of middle-​third tibial defects (Ger, 1971; Pers and Medgyesi, 1973). The muscle lies within the superficial posterior compartment, deep to gastrocnemius and inserts onto the Achilles to aid plantar-​flexion of the foot. Soleus is bipennate and its vascular supply is from branches of the popliteal artery proximally, posterior tibial artery medially, and peroneal artery laterally. This anatomy allows the muscle to be divided distally while preserving the Achilles and gastrocnemius, while dissecting out the muscle from distal to proximal in a relatively avascular plane both deep and superficially. Depending on the shape and position of the defect, it is more common to raise the medial half of the muscle as a hemisoleus (although lateral is also described) (Tobin, 1985). The muscle may already be exposed in the traumatic wound or that of a fasciotomy incision. This allows inspection to assess the viability of the muscle and the condition of the proximal vessels prior to a decision on reconstruction. The muscle flap then requires skin graft cover. An advantage of this flap is that of its simple dissection and low donor morbidity. It must not be chosen if the viability of the muscle has been compromised by the energy of the injury. A proximally based soleus flap will also fail to cover defects of the distal third of the tibia. However, a distally based or reverse hemisoleus flap has been described, whereby the medial hemisoleus is transected at the junction of the proximal and middle third of the muscle (Tobin, 1985). It is said that this will allow coverage of the medial malleolus via supply from distal perforators of the posterior tibial artery. Other reconstructive options may be preferable in this situation.

Sural flap This distally based neurocutaneous flap was described in 1983 (Donski and Fogdestam, 1983). A fasciocutaneous paddle or island overlying the calf is designed based on reverse flow through vessels running subcutaneously along the course of the sural nerve that anastomose distally, just proximal to the ankle, with the peroneal artery. Sural flaps have been described for coverage of the distal third of the leg, ankle, heel, and foot. A flap of up to 14 cm in diameter may be raised, or up to 6 cm if the donor site is to be closed directly. The axis of the flap is marked from the point halfway between the lateral malleolus and the Achilles tendon, to a midline point between the two heads of gastrocnemius. The flap is planned in reverse with the distal anastomosis (and pivot point) 5 cm proximal to the lateral malleolus.

5.4  Management of soft tissue loss without microsurgery

The sural flap has gained much popularity as a local option for cover of distal defects as it can provide good-​quality thin skin cover, albeit insensate. However, it should be used with caution in patients with venous insufficiency, the elderly, or patients with injuries where the distal anastomosis may be compromised such as significant degloving, or suspicion of peroneal artery injury. The donor site may be unsightly if grafted or may affect the design of below knee amputation stump flaps if limb salvage is not achieved (Masquelet et  al., 1992; Hasegawa et  al., 1994; Parrett et  al., 2009; de Blacam et al., 2014).

Peroneus brevis flap This muscle flap may be proximally designed to cover small defects of the lower third of the tibia or, importantly, it has been found to be reliable as a distally based flap to cover small defects around the ankle, especially the lateral malleolus and Achilles region. The peroneus brevis lies deep to the peroneus longus in the lateral compartment of the leg. It originates from the mid-​shaft of the lateral fibula, passing posterior to the lateral malleolus to insert on the fifth metatarsal. To raise this flap, the skin and fascia are incised just posterior to the subcutaneous border of the fibula up to the midpoint of the leg, and the muscle is dissected from the adjacent peroneus longus and superficial peroneal nerve (anteriorly). The dissection proceeds from proximal to distal up to 6 cm from the lateral malleolus, preserving the distal perforator from the peroneal vessel as it enters the muscle. It is then rotated into the defect and covered with a split-​skin graft. Proponents of this flap have found it to be easy to raise, reliable in patients with vascular risk factors, and also when there has been previous fracture or fixation of the distal fibula. The donor site is closed directly with negligible morbidity (Eren et al., 2001; Lorenzetti et al., 2010; Kneser et al., 2011; Bajantri et al., 2013).

Fibula flap The fibula flap is most commonly used as a free tissue transfer. It has, however, also been described for bony reconstruction of the ipsilateral tibia. This involves raising a length of the proximal fibula along with a cuff of muscle and the peroneal vessels. The vessels are divided proximally but preserved distally to allow the bone to rotate into the defect. It has even been possible to harvest a skin paddle to aid flap monitoring and reconstruct the soft tissue defect. A preoperative angiogram is essential to ensure an intact peroneal artery and adequate distal perfusion from anterior or posterior tibial vessels (Chen et al., 1986; Minami et al., 1990; Rajacic and Dashti, 1996; Vyas et al., 2011).

Cross-​leg flap The cross-​leg flap is an extremely robust and versatile option for coverage of the foot and leg. It has been used for many decades and was a popular choice for coverage of traumatic defects in the Second World War. Its use has largely been superseded by free flap surgery. The use of the cross-​leg flap, however, continues in some

units when free flaps are contraindicated, either due to lack of resources, or patient comorbidities, and when other local options are not available. There are many variations in surgical technique described. The classical description is akin to a cross-​finger flap, raised subfascially from the posterior aspect of the contralateral limb in a random pattern with a 1:2 width-​to-​length ratio. This can be harvested from the distal edge of the popliteal fossa, up to the proximal edge of the Achilles tendon. The flap is raised and reflected to cover the defect. The donor site and raw surface of the carrier skin bridge is then grafted and both legs are immobilized adequately to avoid any compression, kinking, or tension on the pedicle. Flap division is performed at around 2 weeks postoperatively, although the safe timing of this may be guided by ligation of the pedicle (Stark, 1952). Cross-​leg flaps may also be raised based on specific vessels or perforators such as saphenous, posterior tibial, sural, or peroneal, and retrograde or distally based flaps are often preferred as they may allow more comfortable positioning of the limbs for coverage of distal defects (Yildirim et al., 2001; Georgescu et al., 2007; Basile et al., 2008; Lu et al., 2013). The choice will depend on the site of the defect and availability of donor tissues. The optimum design will provide reliable robust cover while achieving the best comfort in positioning for the patient by allowing a much longer carrier portion of the flap. The obvious drawback of cross-​leg flaps is that that both legs must be immobilized for around 2 weeks. This may be achieved with splints or external fixators, but it is important to try to mobilize joints as best as possible during this period, avoid pressure ulcers, and provide thromboembolic prophylaxis.

Extensor digitorum brevis flap The extensor digitorum brevis muscle may be used to cover defects of the foot and ankle. It takes origin on the calcaneum, lies deep to the extensor digitorum longus tendons, and inserts as four slips onto the long extensor tendon mechanism of the toes to aid dorsiflexion. The main vascular pedicle is the lateral tarsal artery, which branches from the dorsalis pedis before the latter continues as the first dorsal metatarsal artery. The muscle also receives a branch from the peroneal artery. There are also important anastomoses with the medial plantar artery via the medial tarsal artery proximally and the first dorsal metatarsal artery distally. The muscle has dimensions of up to 5 × 6 cm. The dissection requires an incision over the dorsum of the foot from the muscle origin to the first web preserving cutaneous nerves. The dorsalis pedis and lateral tarsal vessels are identified and the long extensors retracted to allow the muscle to be divided from its origin and insertions. The extensor digitorum brevis flap may be designed on the dorsalis pedis pedicle to allow coverage of small defects of the lateral or medial malleolus. If designed distally on the first dorsal metatarsal artery, it may cover the dorsum of the forefoot, or if pedicled medially on the medial tarsal vessels, it may be reflected to cover defects of the medial foot. The muscle flap is then skin grafted. With experience, this flap is easy to raise and has minimal donor site morbidity. It may only be used for small defects and it is vital to request angiography if there is any doubt as to the circulation to the flap or remainder of the foot, so that neither is compromised (Barfred and Reumert, 1973; Bakhach et al., 1998; Torres et al., 2014).

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Dorsalis pedis flap The dorsalis pedis flap is used to cover defects of the foot and ankle including the lateral and medial malleoli. It is a fasciocutaneous flap based on perforators of the dorsalis pedis and first dorsal metatarsal vessels. The flap design should be planned in reverse and the skin island over the axis of the dorsalis pedis artery as defined by handheld Doppler. The skin island extends from just distal to the extensor retinaculum, to the middle of the metatarsals, and from just medial to the extensor hallucis longus to just lateral to extensor digitorum longus tendons. Care must be taken to retract the extensor hallucis longus tendon medially to allow division of the most medial tendon of extensor digitorum brevis to be divided. The first head of the extensor digitorum brevis may be included with the skin to improve vascularity and the lateral tarsal artery may then be ligated. The remaining skin island is raised in the plane just superficial to the paratenon of the long extensors to include superficial veins and branches of the superficial peroneal nerve. The flap must then be released from its deep tarsal bony connections and the artery divided distally to allow the flap to be mobilized into the defect. The extensor retinaculum may be divided and the pedicle traced back to the anterior tibial vessels to allow a greater arc of rotation. The donor site is covered with a split-​skin graft. Although the dorsalis pedis flap has been used successfully for many decades, it requires a relatively difficult dissection and there may be significant donor site morbidity including delayed healing, poor cosmesis, and ongoing pain. An intact posterior tibial artery and plantar arch are also important prerequisites (McCraw and Furlow, 1975; Samson et al., 1998).

Medial plantar flap The medial plantar flap has been described to cover defects of the foot and ankle region. It offers the opportunity to transfer specialized glabrous skin and subcutaneous tissue from the instep. The skin paddle of the flap is raised from the non-​weight-​bearing region of the medial plantar arch and has a vascular supply from the medial plantar artery which arises as the posterior tibial branches into the dominant lateral plantar artery and smaller medial plantar artery. Branches of the medial plantar nerve provide sensation to this region. To elevate the medial plantar flap, the defect must be assessed and a skin island designed on the glabrous skin of the instep measuring up to 12 × 8 cm. The posterior tibial artery must be located and an incision made posterior to the medial malleolus extending to the proximal edge of the flap. The posterior tibial artery and its bifurcation is then located and dissected with the venae comitantes; this will require opening the tarsal tunnel and dividing the abductor hallucis muscle which lies superficial to the pedicle. The skin island is then conventionally raised from distal to proximal to include the skin and plantar fascia with, of course, the neurovascular pedicle in the plane just superficial to the flexor hallucis brevis, which covers the flexor hallucis longus tendon. To do this, the distal end of the medial plantar vessel is ligated and the plantar digital nerves are preserved. An intraneural dissection is required to provide mobility to a sensate flap, and to create even further mobility; it may be necessary to ligate the lateral plantar vessel so that the flap may pivot on the posterior tibial vessels at the medial malleolus. Although the venous drainage

usually relies on the venae comitantes, if they are injured, it is possible to include a superficial vein instead. The medial plantar flap will allow coverage of the weight-​bearing plantar region, the calcaneum, ankle, and Achilles (Harrison and Morgan, 1981; Baker et al., 1990; Yang et al., 2011; Wright et al., 2013). In the absence of other injuries, the medial plantar artery also has considerable distal anastomoses (with the plantar arch and first dorsal metatarsal perforating artery), which allow a reverse-​flow flap to be raised. The flap is designed in the same region but the proximal ends of the medial plantar vessels are ligated so that the flap may be pivoted around the distal end of the vessels for coverage of the forefoot. The distally based flap is insensate and cutaneous nerves need not be included but some deep sensation may be reported (Masquelet et al., 1988). The medial plantar flap has proved to be a reliable method of transferring specialized skin, especially to the weight-​bearing sole. The skin is hardwearing, glabrous, and heavily keratinized with fibrous septa between the fibrofatty tissues connecting to the plantar aponeurosis. Importantly, it is sensate unless raised in a retrograde fashion.

Fillet flaps This type of flap was born out of the ‘spare part’ concept, whereby composite tissue may be harvested from the intact extremities of otherwise amputated or unsalvageable limbs. This principle is used to preserve the length of amputations with sensate tissue (where possible), without additional donor site morbidity. Preservation of limb length is of paramount importance to reduce the energy cost of ambulation. Fillet flaps may be taken from the digits, the sole (on the posterior tibial neurovascular pedicle), the dorsum of the foot (anterior tibial pedicle), or both. It may even be necessary to use a fillet of leg or thigh flap, depending on the availability of tissue and the nature of the defect. The viability of the tissue must be carefully assessed, which may require serial debridement, and care must be taken when transferring the flap as it may be necessary to coil the long pedicle into a loose subcutaneous pocket within the stump (Küntscher et al., 2001; Ghali et al., 2005).

Conclusion There are many flaps described for cover of soft tissue defects in the lower limb, and this chapter describes the more commonly used options that do not require free tissue transfer techniques. Decision-​ making can be complex and requires a thorough assessment of the patient, the defect, and a sound working knowledge of the available reconstructive options.

REFERENCES Amarante J, Costa H, Reis J, et al. A new distally based fasciocutaneous flap of the leg. Br J Plast Surg 1986;39:338–​40. Bajantri B, Bharathi R, Ramkumar S, et al. Experience with peroneus brevis muscle flaps for reconstruction of distal leg and ankle defects. Indian J Plast Surg 2013;46:48–​54.

5.4  Management of soft tissue loss without microsurgery

Baker GL, Newton ED, Franklin JD. Fasciocutaneous island flap based on the medial plantar artery: clinical applications for leg, ankle, and forefoot. Plast Reconstr Surg 1990;85:47–​58. Bakhach J, Demiri E, Chahidi N, et  al. Extensor digitorum brevis muscle flap: new refinements. Plast Reconstr Surg 1998;102:103–​10. Barfred T, Reumert T. Myoplasty for covering exposed bone or joint on the lower leg. Acta Orthop Scand 1973;44:532–​8. Basile A, Stopponi M, Loreti A, et al. Heel coverage using a distally based sural artery fasciocutaneous cross-​leg flap: report of a small series. J Foot Ankle Surg 2008;47:112–​17. Behan FC. The keystone design perforator island flap in reconstructive surgery. ANZ J Surg 2003;73:112–​20. Bhagwat BM, Pearl RM, Laub DR. Uses of the rectus femoris myocutaneous flap. Plast Reconstr Surg 1978;62:699–​701. Bovet JL, Nassif TM, Guimberteau JC, et  al. The vastus lateralis musculocutaneous flap in the repair of trochanteric pressure sores: technique and indications. Plast Reconstr Surg 1982;69:830–​4. Cahill KC, Gilleard O, Weir A, et al. The epidemiology and mortality of pretibial lacerations. J Plast Reconstr Aesthet Surg 2015;68:724–​8. Cavadas PC, Sanz-​Giménez-​Rico JR, Landín L, et al. Segmental gracilis free flap based on secondary pedicles:  anatomical study and clinical series. Plast Reconstr Surg 2004;114:684–​91. Cedidi CC, Felmerer G, Berger A. Management of defects in the groin, thigh, and pelvic region with modified contralateral TRAM/​VRAM flaps. Eur J Med Res 2005;10:515–​20. Chaput B, Herlin C, Espié A, et al. The keystone flap alternative in posttraumatic lower-​extremity reconstruction. J Plast Reconstr Aesthet Surg 2014;67:130–​2. Chen ZW, Chen LE, Zhang GJ, et al. Treatment of tibial defect with vascularized osteocutaneous pedicled transfer of fibula. J Reconstr Microsurg 1986;2:199–​203,  205. Chummun S, Wigglesworth TA, Young K, et  al. Does vascular injury affect the outcome of open tibial fractures? Plast Reconstr Surg 2013;131:303–​9. Daigeler A, Dodic T, Awiszus F, et  al. Donor-​ site morbidity of the pedicled rectus femoris muscle flap. Plast Reconstr Surg 2005;115:786–​92. de Blacam C, Colakoglu S, Ogunleye AA, et al. Risk factors associated with complications in lower-​extremity reconstruction with the distally based sural flap: a systematic review and pooled analysis. J Plast Reconstr Aesthet Surg 2014;67:607–​16. De la Plaza R, Arroyo JM, Vasconez LO, et al. Upper transverse rectus abdominis flap: the flag flap. Ann Plast Surg1984;12:410–​18. Demirseren ME, Efendioglu K, Demiralp CO, et al. Clinical experience with a reverse-​flow anterolateral thigh perforator flap for the reconstruction of soft-​tissue defects of the knee and proximal lower leg. J Plast Reconstr Aesthet Surg 2011;64:1613–​20. Deo SV, Nootan KS, Niranjan B, et  al. Vertical rectus abdominis myocutaneous flap cover for lower abdomen, chest wall, groin and thigh defects following resection of malignant tumours. Indian J Cancer 2001;38:33–​7. Donski PK, Fogdestam I. Distally based fasciocutaneous flap from the sural region. A preliminary report. Scand J Plast Reconstr Surg 1983;17:191–​6. Eren S, Ghofrani A, Reifenrath M. The distally pedicled peroneus brevis muscle flap: a new flap for the lower leg. Plast Reconstr Surg 2001;107:1443–​8. Flurry MD, Michelotti BF, Moyer KE. Pedicled rectus femoris flap for coverage of complex open pelvic fractures. J Plast Reconstr Aesthet Surg 2011;64:1490–​4. Georgescu AV, Irina C, Ileana M. Cross-​leg tibial posterior perforator flap. Microsurgery 2007;27:379–​83.

Ger R. The technique of muscle transposition in the operative treatment of traumatic and ulcerative lesions of the leg. J Trauma 1971;11:502–​10. Ghali S, Harris PA, Khan U, et al. Leg length preservation with pedicled fillet of foot flaps after traumatic amputations. Plast Reconstr Surg 2005;115:498–​505. Giordano PA, Abbes M, Pequignot JP. Gracilis blood supply: anatomical and clinical re-​evaluation. Br J Plast Surg 1990;43:266–​72. Glass GE, Jain A. Pretibial lacerations: experience from a lower limb trauma centre and systematic review. J Plast Reconstr Aesthet Surg 2014;67:1694–​702. Hallock GG. Sagittal split tibialis anterior muscle flap. Ann Plast Surg 2002;49:39–​43. Harrison DH, Morgan BDG. The instep island flap to resurface plantar defects. Br J Plast Surg 1981;34:315–​18. Hasegawa M, Torii S, Katoh H, et al. The distally based superficial sural artery flap. Plast Reconstr Surg 1994;93:1012–​20. Hong G, Steffens K, Wang FB. Reconstruction of the lower leg and foot with the reverse pedicled posterior tibial fasciocutaneous flap. Br J Plast Surg 1989;42:512–​16. Innocenti M, Cardin-​Langlois E, Menichini G, et al. Gastrocnaemius-​ propeller extended miocutanous flap:  a new chimaeric flap for soft tissue reconstruction of the knee. J Plast Reconstr Aesthet Surg 2014;67:244–​51. Irons GB. Rectus abdominis muscle flaps for closure of osteomyelitis hip defects. Ann Plast Surg1983;11:469–​73. James JH, Moir IH. The biceps femoris musculocutaneous flap in the repair of pressure sores around the hip. Plast Reconstr Surg 1980;66:736–​9. Jósvay J, Sashegyi M, Kelemen P, et  al. Modified tensor fascia lata musculofasciocutaneous flap for the coverage of trochanteric pressure sores. J Plast Reconstr Aesthet Surg 2006;59:137–​41. Kneser U, Brockmann S, Leffler M, et  al. Comparison between distally based peroneus brevis and sural flaps for reconstruction of foot, ankle and distal lower leg: an analysis of donor-​site morbidity and clinical outcome. J Plast Reconstr Aesthet Surg 2011;64:656–​62. Küntscher MV, Erdmann D, Homann HH, et al. The concept of fillet flaps: classification, indications, and analysis of their clinical value. Plast Reconstr Surg 2001;108:885–​96. Lai CS, Lin SD, Chou CK. Clinical application of the adipofascial turnover flap in the leg and ankle. Ann Plast Surg 1992;29:70–​5. Lo S, Hallam MJ, Smith S, et al. The tertiary management of pretibial lacerations. J Plast Reconstr Aesthet Surg 2012;65:1143–​50. Lorenzetti F, Lazzeri D, Bonini L, et  al. Distally based peroneus brevis muscle flap in reconstructive surgery of the lower leg: postoperative ankle function and stability evaluation. Br J Plast Surg 2010;63:1523–​33. Lu L, Liu A, Zhu L, et al. Cross-​leg flaps: our preferred alternative to free flaps in the treatment of complex traumatic lower extremity wounds. J Am Coll Surg 2013;217:461–​71. Masquelet AC, Penteado CV, Romana MC, et  al. The distal anastomoses of the medial plantar artery: surgical aspects (2.10.1987). Surg Radiol Anat SRA 1988;10:247–​9. Masquelet AC, Romana MC, Wolf G. Skin island flaps supplied by the vascular axis of the sensitive superficial nerves:  anatomic study and clinical experience in the leg. Plast Reconstr Surg 1992; 89:1115–​21. McCraw JB, Furlow LT. The dorsalis pedis arterialized flap. A clinical study. Plast Reconstr Surg. A clinical study 1975;55:177–​85. McGregor IA, Jackson IT. The groin flap. Br J Plast Surg 1972;25:3–​16. McGregor JC, Buchan AC. Our clinical experience with the tensor fasciae latae myocutaneous flap. Br J Plast Surg 1980;33:270–​6.

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Minami A, Itoga H, Suzuki K. Reverse-​flow vascularized fibular graft: a new method. Microsurgery 1990;11:278–​81. Mitsala G, Varey AH, O’Neill JK, et al. The distally pedicled gracilis flap for salvage of complex knee wounds. Injury 2014;45:1776–​81. Murakami M, Hyakusoku H, Ogawa R. The multilobed propeller flap method. Plast Reconstr Surg 2005;116:599–​604. Ng RWM, Chan JY, Mok V, et al. Clinical use of a pedicled anterolateral thigh flap. J Plast Reconstr Aesthet Surg 2008;61:158–​64. Ohtsuka H, Nakaoka H, Saeki N, et  al. Island groin flap. Ann Plast Surg1985;15:143–​50. Parrett BM, Pribaz JJ, Matros E, et al. Risk analysis for the reverse sural fasciocutaneous flap in distal leg reconstruction. Plast Reconstr Surg 2009;123:1499–​504. Pers M, Medgyesi S. Pedicle muscle flaps and their applications in the surgery of repair. Br J Plast Surg 1973;26:313–​21. Pignatti M, Pasqualini M, Governa M, et al. Propeller flaps for leg reconstruction. J Plast Reconstr Aesthet Surg 2008;61:777–​83. Pontén B. The fasciocutaneous flap: its use in soft tissue defects of the lower leg. Br J Plast Surg 1981;34:215–​20. Rajacic N, Dashti H. Reconstruction of the lateral malleolus using a reverse-​flow vascularized fibular head: a case report. Microsurgery 1996;17:158–​61. Samson MC, Morris SF, Tweed AE. Dorsalis pedis flap donor site: acceptable or not? Plast Reconstr Surg 1998;102:1549–​54. Senchenkov A, Thomford NR, Barone FE. Reconstruction of an extensive thigh defect with the paraumbilical TRAM flap. Ann Plast Surg2003;51:91–​6. Shubailat GF, Ajluni NJ, Kirresh BS. Reconstruction of heel with ipsilateral tensor fascia lata myocutaneous flap. Ann Plast Surg1980;4:323–​5. Song YG, Chen GZ, Song YL. The free thigh flap: a new free flap concept based on the septocutaneous artery. Br J Plast Surg 1984;37:149–​59. Stark RB. The cross-​ leg flap procedure. Plast Reconstr Surg 1952;9:173–​204.

Straehley CJ, Parry WL. The utilization of the rectus muscle as a pedicle flap in closure of pelvic defects. Surgery 1957;41:990–​92. Teo TC. The propeller flap concept. Clin Plast Surg 2010;37:615–​26. Tiengo C, Macchi V, Vigato E, et  al. Reversed gracilis pedicle flap for coverage of a total knee prosthesis. J Bone Joint Surg Am 2010;92:1640–​6. Tobin GR. Hemisoleus and reversed hemisoleus flaps. Plast Reconstr Surg 1985;76:87–​96. Tobin GR, Sanders BP, Man D, et al. The biceps femoris myocutaneous advancement flap:  a useful modification for ischial pressure ulcer reconstruction. Ann Plast Surg1981;6:396–​401. Torres LR, Paganelli PM, Dos Santos RP, et  al. Extensor digitorum brevis flap on the treatment of lower limb injuries. Acta Ortop Bras 2014;22:86–​9. Vyas RM, Ready JE, Guo L. Use of a retrograde pedicled double-​ barreled osteocutaneous fibula flap for reconstruction of distal tibia and soft-​tissue defects. Plast Reconstr Surg 2011;127:173e-​5e. Wee JT. Reconstruction of the lower leg and foot with the reverse-​ pedicled anterior tibial flap:  preliminary report of a new fasciocutaneous flap. Br J Plast Surg 1986;39:327–​37. Wingate GB, Friedland JA. Repair of ischial pressure ulcers with gracilis myocutaneous island flaps. Plast Reconstr Surg 1978; 62:245–​8. Wright TC, Mossaad BM, Chummun S, et  al. Proximally pedicled medial plantar flap based on superficial venous system alone for venous drainage. J Plast Reconstr Aesthet Surg 2013;66:e201–​4. Yang D, Yang JF, Morris SF, et al. Medial plantar artery perforator flap for soft-​tissue reconstruction of the heel. Ann Plast Surg2011;67:294–​8. Yildirim S, Akan M, Giderodğlu K, et al. Use of distally based saphenous neurofasciocutaneous and musculofasciocutaneous cross-​leg flaps in limb salvage. Ann Plast Surg2001;47:568–​74. Zhou G, Zhang QX, Chen GY. The earlier clinic experience of the reverse-​flow anterolateral thigh island flap. Br J Plast Surg 2005;58:160–​4.

5.5

Microvascular cover in the lower limb Indications and timing, flap types, and technique Zoran M. Arnež

Introduction Since the introduction of microvascular free tissue transfer in the lower extremity, the outcomes from treatment of trauma and its consequences, oncological surgery, chronic wounds (diabetic foot), and complex non-​traumatic defects have improved considerably (Godina, 1986; Arnež, 1991; Heller and Levin, 2001; Pu et al., 2004; Mardini et al., 2005; Reddy and Stevenson, 2008). Free flap reconstruction has become a widely accepted method for providing a safe, reliable wound closure and for composite tissue reconstruction (Gustilo and Anderson, 1976; Godina, 1986; Lister and Scheker, 1988; Chen et al., 1992; Ninkovic et al., 1999; Nakatsuka et al., 2003). Providing soft tissue cover remains the key to a successful reconstruction of injuries to the lower extremities, and microvascular free tissue transfer is an integral part of the treatment algorithm. Complex high-​energy injuries of the lower extremity are best managed in combined orthopaedic and plastic surgery specialist centres with reliable high-​level microsurgical services (Chummun et al., 2013). Free flaps are still, however, considered a complex and complicated reconstructive method in institutions where microvascular surgery is not being practised routinely. A decreasing trend in the use of free flaps for coverage of open lower leg fractures has been observed in the last 20 years in some centres as new wound care technologies, such as negative pressure wound therapy (NPWT), dermal substitutes, and the use of local pedicle flaps, have been popularized for the treatment of lower extremity open wounds (DeFranzo et al., 2001; Herscovici et al., 2003; Molnar et al., 2004; Parrett et al., 2006). The use of these techniques has not increased the amputation rate nor had a negative impact on long-​term results compared to free tissue transfer (Parrett et al., 2006). Such a shift away from free tissue transfer has become possible because of better understanding of the anatomy, improved bone fixation systems, and earlier involvement of plastic surgeons in treatment of lower extremity trauma and disease (Heller and Levin, 2001;

Lin and Lin, 2013). Long-​term studies are necessary to identify the appropriate indications for each reconstructive option as a less time-​consuming, less labour intensive, and cheaper approach may provide healing but not guarantee the same-​quality durable soft tissue cover, with the ultimate consequence of more surgery, time, and resources.

Advantages of free tissue transfer Free flaps provide the desired quantity and quality of tissues, tailored to the requirements of each particular defect, taken from numerous potential donor sites all over the body. They can cover large soft tissue defects (the latissimus dorsi muscle flap can cover the whole circumference of the lower leg), obliterate large and/​or irregular cavities after trauma or tumour excision, provide vascularized bone for support (using either a single or ‘double-​barrel’ fibula), vascularized nerve (anterolateral thigh (ALT) or radial forearm flap), or blood flow together with skin cover (‘flow-​ through’ ALT or radial forearm flaps). In chimeric fasciocutaneous flaps (such as the ALT flap), different components of the flap, perfused by different perforators from the same feeding vessel, can be moved in the three-​dimensional space separately, thus increasing the flap versatility and efficiency (Chan et al., 2012; Wong et al., 2012). Flap design is more versatile with free flaps than pedicle flaps as the surgeon is not obliged to rely on the local tissues that have often been compromised by trauma or disease. The free flap is tailored exactly to the dimensions (size, shape, volume, and components) of the defect. No flap length is wasted to reach the desired recipient defect by transposition, rotation, or advancement, and free flaps do not have a limited arc of rotation. Any of a number of free flaps with a vascular pedicle long enough to escape the ‘zone of injury’ (caused by trauma or radiotherapy) can be selected. Free tissue transfer can be performed without further affecting the blood supply of the damaged lower limb. Often the blood supply is better after free flap

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SECTION 5  Lower limb

transfer as the axial vessels can be restored with a ‘flow-​through’ flap. Since their donor site is usually remote, they leave no secondary defect or scar on the exposed and traumatized lower leg. Contrary to the staged techniques of reconstruction, free flap transfer offers less surgeries and a shorter recovery time to full weight-​bearing due to the possibility of single-​stage salvage and reconstruction of composite defects (Yazar et al., 2004).

Free flaps have virtually no size limits and can easily cover the entire sole or dorsum of the foot. If a thin and innervated flap is needed for coverage of the dorsum, fasciocutaneous free flaps are preferred. When instead padding and amortization over fractured calcaneus or metatarsals are required, muscle free flaps covered by skin grafts may be the best solution (Hidalgo and Shaw, 1986; May and Rohrich, 1986).

‘Spare parts’ surgery

Disadvantages of free tissue transfer Free tissue transfer is a microsurgical technique that requires expensive equipment (an operating microscope), trained nurses for postoperative monitoring of free flap vitality, special instruments and sutures, a long period of training, long operating theatre time, and complex organization. Errors at critical steps of this complex procedure can result in partial or total free flap failure. The microvascular anastomosis is the critical event in free tissue transfer. The failure rate is related to surgical experience and should be less than 5%, although the failure rate of free flap transfer for the lower extremity is higher compared to other regions of the body (Lin and Lin, 2013). Not all patients are suitable for free flap transfer. Detailed preoperative evaluation should identify patients with important comorbidities that require preoperative treatment and medical optimization, or even present with contraindications for general anaesthesia. In critically ill patients, a distally based, local pedicle fasciocutaneous flap may represent a better reconstructive option (Quaba, 2006).

Indications for free flap transfer in the lower extremity Lower limb reconstruction Free flaps are indicated for coverage of soft tissue or composite defects with exposed critical structures when adequate local pedicle flaps cannot be raised outside the zone of injury and especially when sensory reinnervation is important (Saint-​Cyr et al., 2012). Current high-​ energy trauma creates extensive zones of injury with crush, avulsion, or multiplanar degloving (Arnež et  al., 2010). Such large and deep, and often heavily contaminated, complex wounds should not be skin grafted because of the poor blood supply of the recipient bed. Avulsion and degloving disrupt fascio/​ septocutaneous perforators, so the use of local fasciocutaneous flaps is not safe. Regional muscle and musculocutaneous flaps that are not involved in the zone of injury may not reach the distal third of the lower leg and their use may create important functional and cosmetic deficits (Lin and Lin, 2013).

Foot and sole reconstruction Reconstruction of foot defects is demanding since the use of local pedicle flaps is often impossible, or their small size and limited arc of rotation prevent the coverage of all regions of the sole or dorsum of the foot. The cross-​leg flap is not very reliable, requires many surgical procedures, prolonged immobilization, and hospitalization, and has significant and unsightly donor scars.

Soft tissues and bone taken as a free flap from a non-​salvageable extremity at amputation, may convert an above-​knee to a functionally better below-​knee amputation in cases when soft tissues or bone are insufficient otherwise to provide an adequate amputation stump. Specially structured tissues from the sole of the foot and the heel pad are the best cover for an inadequate below-​knee amputation stump. Surgical use of redundant or discarded parts leaves no additional donor site defect or scar (Chiang et al., 1995).

Reconstruction of bone gaps When the bone defect is longer than 6 cm or the recipient bed is fibrotic from previous attempts at bone reconstruction, the vascularized bone transfer (fibula, iliac crest, scapula, rib) can be the best option for treatment since it promotes bone healing, better resists infection, and better tolerates mechanical loading (Yazar et al., 2004). The time to full mechanical loading can be further enhanced by adding a vascularized pedicle fibula transfer from the same leg (‘fibula pro tibia’) or by a ‘double-​barrel’ design of the free fibula (Banic and Hertel, 1993).

Reconstruction after tumour excision Limiting local recurrence after removal of soft tissue or/​and bone tumours of the lower extremity is improved by wide excision of the lesion and achieving tumour-​free surgical margins. This extensive surgery results in complex defects of such size and volume that they can be only reconstructed by free tissue transfer. When the disease control is achieved, reconstruction by free flaps transfer can ensure the patient has an acceptable quality of life (Cordeiro et al., 1994; Schwarz et al., 2012).

Reconstruction after chronic osteomyelitis Chronic bone infection is often characterized by multiple fistulae producing exudate with multiple resistant bacteria, surrounded by inflamed and fibrotic soft tissues and possible focal lesions, non-​ union of associated fractures, or bone defects that preclude reconstruction by local flaps. Osteomyelitis is treated in stages. During the first stage, radical excision of all fibrotic tissue and involved bony lesions is performed and soft tissue cover is established by well-​ vascularized tissues (either muscle or fasciocutaneous free flap) which is followed by the appropriate antibiotic therapy. Bone reconstruction, when necessary, is performed at a second stage. Muscle/​ musculocutaneous free flaps, because of muscle pliability, obliterate irregular cavities better but fasciocutaneous flaps are equally efficient in treating bone infection in shallow defects (Kawakatsu et al., 2010; Khan et al., 2012).

Reconstruction for aesthetic improvement Any (soft tissue) deformity in the lower extremity, in particular in the lower leg in females, may be functionally, psychologically,

5.5  Microvascular cover in the lower limb: indications and timing, flap types, and technique

and socially disturbing. Larger volume replacements after loss of skin and muscle bulk can be repaired only by free (muscle/​ musculocutaneous) flaps harvested from distant areas.

Contraindications for free flaps The patient who is not fit for surgery because of severe comorbidities does not qualify for free tissue transfer. Wound healing complications may be expected in patients with systemic diseases (e.g. diabetes) or certain treatments or therapies (e.g. corticosteroids, immuno-​suppressants) as well as in smokers (Reus et  al., 1992; Chang et al., 1996, 2000; Genden et al., 2004). In patients with severe atherosclerotic disease or in trauma patients with suspected arterial injury, preoperative computed tomography (CT) scanning or CT angiography is required for appropriate planning (Lutz et al., 2000; Chow et al., 2005; Duymaz et al., 2009).

Timing of reconstruction Traumatic wounds and wounds after excision of tumours are best covered definitively as soon as possible. Such treatment results in the lowest free flap failure and lowest rate of deep infection (Breindenbach, 1989; Arnež, 1991; Chick et al., 1991; Najean et al., 1994; Ninkovic et al., 1996). Before closure, a definitive wound debridement or clear margin tumour excision, fracture stabilization, and good limb blood supply should be established. Advantages of early or immediate wound closure are primary healing, coverage of exposed essential tissues (blood vessels (an absolute indication), nerves, joints, bones without periosteum, tendons denuded of paratenon, or prosthetic material (relative indications)), the prevention of nosocomial infections, fewer operations or dressing changes, earlier mobilization, and shorter hospitalization (Arnež, 1991; Carsenti et al., 1999; Saint-​Cyr et al., 2012). Early treatment of patients with complex lower extremity wounds leads to shorter time to weight-​bearing, fracture union, and lower infection rate (Hertel et al., 1999; Medina et al., 2011). The main contraindications to immediate reconstruction are patients who are not fit for surgery, or patients in whom an amputation and prosthesis would be a better solution, for instance, avoiding long periods of medicalization and slow return to employment. Acute complex lower extremity injuries are best treated by a combined team of orthopaedic and plastic surgeons, who apply principles such as the British Association of Plastic, Reconstructive and Aesthetic Surgeons/​ British Orthopaedic Association guidelines (Nanchahal et al., 2009) as soon as possible (within the first 24 hours after injury) by debridement, vascular repair (when necessary), and (provisional) fracture fixation (by an external fixator). Internal fracture fixation is limited only to cases when soft tissue coverage can be performed at the same time (Nanchahal et al., 2009). Early wound coverage is important, since 92% of open fractures are infected by nosocomial bacteria (Carsenti-​Etesse et al., 1999). Soft tissue cover of acute wounds can be performed safely at any time within 1 week after injury, preferentially during the first 72 hours. At that time, the provisional external fixation can be changed to internal (plates or intramedullary nails) or, in case of a segmental bone defect, for a

frame permitting bone transport. When the circumstances allow (a plastic surgeon available, a stable patient fit for surgery, radical debridement feasible, wound macroscopically clean after debridement, and fractures appropriately fixed), the soft tissue defect can be covered at the time of the first surgical procedure in the first 24 hours after injury by emergency (immediate) free tissue transfer (Lister, 1988; Arnež, 1991; Gopal et al., 2000). There is little evidence of the 5-​day rule, which states that one can expect a decreased rate of infection and an increased rate of bone union in open tibial fractures if covered by muscle tissue within 5  days of injury (Caudle and Stern, 1987). The interval between the injury and definitive soft tissue cover can be prolonged safely provided the fractures are provisionally fixed by external fixation and the wound kept clean, (often achieved with NPWT) following primary debridement. When so, a short time to fracture union and low incidence of bone infection (osteomyelitis) can be expected (Francel et al., 1992). Definitive soft tissue reconstruction should be performed within the first 7  days after injury.

Early free flap coverage Early free flap coverage of the acute wound is a procedure performed in two stages. During the first stage (in the first 24 hours after injury), wound debridement, provisional fracture fixation by external fixation, and vascular repair are done. The wound is then sealed by NPWT. Two to 6 days later, during the second stage, a second-​look debridement can be performed, the external fixator is changed for internal fixation or a bone transport frame, and the wound is closed by the appropriate free flap. When soft tissue closure is delayed beyond 1 week (delayed free flap coverage), the wound enters the subacute period where it becomes blocked in the inflammatory phase of healing. Since inflamed wounds are more difficult to debride (unless a pseudotumour-​like debridement converts the wound from untidy to tidy), soft tissues become oedematous and recipient blood vessels fragile, it is best to postpone surgical procedures until inflammation subsides. Godina’s complication rate of free tissue transfers during the subacute period was 16 times higher and the infection rate 11 times higher compared to those in the acute period (Godina, 1986). These results in view of developments in recent decades in antibiotic therapy and wound treatment (particularly NPWT) are in the author’s opinion mainly of historic value. Subacute wounds (between 1 week and 1  month post injury) are best treated first by assisted healing (optimal dressing change, antibiotic therapy, selective removal of clearly necrotic tissue, and NPWT) aimed at elimination of infection and stimulation of tissue regeneration, followed by delayed reconstruction using techniques from the reconstructive ladder as necessary. This author has found that such an approach reduces the need for (large) flap reconstruction, carried out when the wound is bacteriologically clean. In patients with chronic wounds (e.g. osteomyelitis), it is very important to diagnose and treat all comorbidities preoperatively since deep infection depends largely on the complexity of trauma (defined by the Gustilo and Anderson classification (Table 5.5.1)) (Gustilo and Anderson 1976) and the number of compromising comorbidities (Bowen et al., 2005). Muscle flaps are generally preferred for coverage of chronic wounds because of their plasticity and ability to obliterate bony cavities, though fasciocutaneous flaps can be used successfully in this scenario. Hong and colleagues successfully

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SECTION 5  Lower limb

Table 5.5.1  Gustilo and Anderson classification of open fractures Gustilo grade

Definition

I

An open fracture with a wound less than 1 cm long and clean

II

An open fracture with a laceration more than 1 cm long with extensive soft tissue damage, flaps, or avulsions

III

Either an open segmental fracture, an open fracture with extensive soft tissue damage, or a traumatic amputation. Special categories in type III were gunshot injuries, any open fracture caused by a farm injury, and any open fracture with accompanying vascular injury requiring repair

IIIA

Adequate soft tissue coverage of a fractured bone despite extensive soft tissue lacerations or flaps, or high-​energy trauma irrespective of the size of the wound

IIIB

Extensive soft tissue injury with periosteal stripping and bony exposure. This is usually associated with massive contamination

IIIC

Open fracture associated with arterial injury requiring repair

Reproduced with permission from RB Gustilo, JT Anderson et al., Prevention of infection in the treatment of one thousand and twenty-​five open fractures of long bones: retrospective and prospective analyses, Journal of Bone & Joint Surgery, Volume 58, Issue 4, pp.453–​458, Copyright © 1976 Wolters Kluwer Health, Inc.

treated infection in 28 patients with chronic osteomyelitis of the lower extremity with extensive surgical debridement, and coverage by the free ALT perforator (fasciocutaneous) flap (Nakatsuka et al., 2003; Hong et al., 2005; Medina et al., 2011).

Late free tissue transfer Late free tissue transfer may be performed several months after surgery when the acute wounds are healed in order to resolve residual complications (diabetic foot, osteomyelitis, etc.) or restore function or form resulting from previous disease or trauma.

Selection of the appropriate free flap Since many different free flap donor sites are available, choosing the right free flap for the right patient is based on evaluation of the defect location, size (surface and volume), presence, and complexity of an associated fracture and the function and cosmetic appearance of the donor and recipient sites. The condition of the tissues surrounding the defect (avulsion, crush, degloving), the structures needing reconstruction, the available recipient vessels, and the degree of contamination or infection of tissues should also be taken into consideration (Saint-​Cyr et al., 2012). (Free) flaps are necessary to close complex lower extremity wounds with extensive soft tissue loss thus preventing the desiccation of the wound tissues (and further loss) as well as infection. The surgeon can choose between muscle/​ musculocutaneous, fascio/​septocutaneous, or perforator free flaps. Free flaps with large skin islands (not in muscle flaps), long vascular pedicles, and medium/​large diameter vessels are used if they allow simultaneous access for two surgical teams, flap harvesting in the supine or lateral decubitus position, and direct donor closure. Biological characteristics of the tissues in a flap can significantly influence fracture healing. Flap tissues feature as a local source of stem or osteo-​progenitor cells, growth factors, and vascular supply (Chan

et al., 2012). Soft tissue flaps in lower limb trauma serve to bring a vascular supply to the fractured bone end deprived of endosteal or periosteal circulation (Richards and Schemitsch, 1989). Initial studies reported that muscle contributed greater vascularity to a defect than fasciocutaneous tissue (Trueta and Buhr, 1963). More recent work with a canine model showed the vascular density at all times is greater with fasciocutaneous flaps than muscle flaps and fasciocutaneous flaps experience greater blood flow and oxygen tension (Gosain et  al., 1990). Despite this, fracture repair is believed to be more rapid with muscle coverage because even though vascularity is essential for bone repair and wound healing, once an adequate blood supply has been reached, cellular factors become the limiting factor (Harry et al., 2008, 2009). In closed fractures, the main sources of osteo-​progenitor cells are the bone marrow and periosteum (Hutmacher and Sittinger, 2003). In high-​energy open fractures, the main osteo-​progenitor cells originate from local soft tissues or the circulation (Schindeler et al., 2009). Muscle demonstrates a significant osteogenic effect (Zacks and Sheff, 1982). Muscle-​derived stem cells can be recruited from muscle and stimulated by proinflammatory cytokines (tumour necrosis factor-​alpha) released at the site of injury (Glass et al., 2011). Intact muscle releases trophic factor myokines, key regulators of muscle and bone mass, and bone anabolics (insulin-​ like growth factor-​1, interleukin-​6, brain-​derived neurotrophic factor, and fibroblast growth factor-​2) that induce bone repair (Vogt et  al., 2005; Cairns et  al., 2010; Pedersen, 2011). Severely injured muscle releases catabolic myokines (myostatin) that inhibit bone repair (McPheron et  al., 1997; Hamrick et  al., 2010; Hamrick, 2011). Also, muscles have a greater ability to reduce the bacterial count and stimulate collagen deposition and wound repair at the muscle interface (Calderonet al., 1986; Gosain et al., 1990). Muscle flaps are ideal for the reconstruction of large volume and deep irregular defects where the filling of a dead-​space is necessary or large superficial circumferential defects. The author’s preferred muscle flaps for coverage of small volume defects are chimeric free ALT with a portion of vastus lateralis muscle, gracilis, and serratus anterior muscles, whereas large volume and very large superficial circumferential defects are best covered by the latissimus dorsi/​ serratus anterior muscles based on subscapular vascular axis (Fig. 5.5.1 and Fig. 5.5.2). Muscle flaps are the best cover for open (complex) diaphyseal fractures. When placed in direct apposition to the bone, they aid healing (Chan et al., 2012). Fasciocutaneous free flaps offer several advantages:  availability, versatility, replacing ‘like with like’, facilitating secondary reconstructive procedures, and no sacrifice of muscle function (Hallock, 1991, 1993, 2000; Khan and Pickford, 2000). Fasciocutaneous free flaps can be adjusted in size to cover large defects and still close the donor site directly (Izadi et  al., 2012) (Fig. 5.5.3). There are limits though and they are not able to provide circumferential cover of the lower extremity. Harvesting fasciocutaneous flaps as perforator flaps reduces donor morbidity. Fasciocutaneous flaps provide the same rates of fracture union as muscle flaps (Yazar et al., 2006). Also, they have been found useful in chronic osteomyelitis, in particular over the distal third of the lower leg and ankle (Hong et al., 2005). Fasciocutaneous flaps may be superior to muscle flaps for coverage of rapidly uniting metaphyseal

5.5  Microvascular cover in the lower limb: indications and timing, flap types, and technique

(a)

(b)

(c)

(d)

(e)

(f)

Fig. 5.5.1  (a) Arnež and Tyler pattern 1 degloving injury (abrasion), open fracture of external malleolus of tibia with division of tibialis anterior tendon. (b) After primary debridement and open reduction internal fixation with two screws, external fixation, and tibialis anterior tendon repair. (c) Coverage by emergency latissimus dorsi free flap with monitoring island of skin anastomosed end-​to-​side to posterior tibial vessels. (d) Early result at 14 days after injury when the monitoring island has been removed. (e, f) End result at 1 year after surgery (anterior and posterior views) showing atrophy of muscle. Patient is wearing normal shoes and has no limits in ambulation.

fractures around the ankle since the use of skin grafts is avoided (Chan et al., 2012). When used as chimeric free flaps (ALT plus segment of vastus lateralis muscle), the biological benefits of muscle apposition to the bone and obliteration of dead space are retained (Wong et al., 2012). Fasciocutaneous flaps are indicated for the coverage of superficial wounds, where return of sensitivity is important, as well as for coverage of tendons for better gliding. Since elevation of the flap is

usually straightforward, they are used when further reconstructions under the flap are planned in future. The author’s preferred free fasciocutaneous flaps for coverage of small/​moderately large defects are ALT, groin, and lateral arm flaps, whereas large defects are covered preferentially by the ALT flap and the thoracodorsal artery perforator flap. The radial forearm flap is used on occasion for simultaneous revascularization and very thin, innervated soft tissue cover. Scapular and parascapular flaps are

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SECTION 5  Lower limb

(a)

(b)

(c)

(d)

(f)

(e)

Fig. 5.5.2  (a) High-​energy injury caused by explosion of chlorine dust in a swimming pool. This is a Gustilo IIIB open fracture with circumferential soft tissue injury and extensive contamination. (b) Postoperative view after initial debridement, fracture fixation with external fixator, and direct wound closure performed by orthopaedic surgeons. Note the ischaemic skin flaps. (c) After second operation at 72 hours after injury, consisting of radial soft tissue debridement. Note the extensive circumferential soft tissue defect and the quantity of ischaemic skin and soft tissue excised. (d) The defect is resurfaced with a latissimus muscle flap wrapped around the leg with the flap pedicle anastomosed end-​to-​end to the anterior tibial vessels. The muscle was covered with dermal substitute at the end of the operation. (e) The result at 1 month after injury and 10 days after the third operation of split-​thickness skin grafting over the dermal substitute. Note the complete take of the graft. (f) The result at 3 months after the injury.

5.5  Microvascular cover in the lower limb: indications and timing, flap types, and technique

(a)

(b)

Fig. 5.5.3  (a) Gustilo IIIB open fracture after debridement and fracture fixation (internal and external fixation). Note the approach to the posterior tibial vessels for anastomosis distal to the injury. (b) Immediate coverage by scapular fasciocutaneous free flap.

useful alternatives for coverage of large and superficial defects when bone stabilization can be performed in the lateral decubitus position without the need of patient repositioning (Khan and Pickford, 2000).

Selection of recipient vessels The recipient vessels are searched for outside the zone of injury where they should be free of any signs of trauma. When one of the two main lower leg arteries is divided by trauma, the divided vessel can be used for anastomosis with the flap vessels provided the diameter ratio between the donor and the recipient vessels does not substantially exceed 1:1.5. End-​to-​side arterial anastomosis is imperative when no artery is divided. In motor vehicle collisions, trauma to the lower leg usually arrives from anteriorly, therefore the anterior tibial vessels, lying within the zone of injury, are usually damaged. Since the posterior tibial vessels, lying deep, behind the tibia are better protected, we prefer to perform the anastomosis in the end-​to-​side fashion to the posterior tibial artery using the posterior midline approach. By exposing the trifurcation of the popliteal artery, the posterior tibial artery is followed distally to the site of the anastomosis (Godina et al., 1991). Many surgeons prefer to perform end-​to-​end arterial anastomosis to the anterior tibial vessels proximal to the zone of injury, when skin cover over is not traumatized, since the access is easier and more superficial. Some surgeons anastomose their flaps distal to the zone of injury if they are able to find a pulsatile flow from the distal stump of the dorsalis pedis or the tibialis anterior artery relying on the reverse arterial flow (Cormack and Lamberty, 1994; Lin et al., 1996; Park et al., 1999).

Technique (management of soft tissue injuries on the lower extremities by free tissue transfer)

are ruled out adhering to the principles of Advanced Trauma Life Support® (ATLS®). Associated comorbidities are ruled out or taken into consideration. Information about the site and the mechanism of injury is also obtained. This is followed by the physical examination of the lower, extremity checking vascularity of the limb, sensibility of the foot, and looking for signs of compartment syndrome. A  thorough evaluation of the wound follows, establishing its dimensions and depths, whether it is simple or complex, tidy or untidy, acute or chronic, and inflamed or non-​inflamed. Surrounding tissues (the zone of injury) are inspected for crush and avulsion. Associated degloving is classified using the Arnež and Tyler classification (Arnez et al. 2010) (Table 5.5.2). Open fractures are classified by the Gustilo–​Anderson classification (Table 5.5.1) (Gustilo and Anderson, 1976) The surgeon and the anaesthetist decide whether the patient is fit for surgery and whether any preoperative examinations (besides X-​rays) or treatment (blood volume replacement) is necessary first. Angio-​CT scanning is indicated in avascular limbs caused by blunt trauma, where the zone of injury is large and the level of vascular injury is difficult to establish. The operative treatment is then planned. Based on whether a definitive wound debridement is feasible or not, they decide on one-​step (emergency) definitive reconstruction or take a two-​step approach of early wound coverage within 72 hours. The two consultants decide also about the positioning of the patient on the operating table. This depends largely on the selected method of bone fixation and the free flap donor site. It is either the supine or lateral decubitus position. The orthoplastic two-​team approach allows wound debridement and fracture fixation to be done by the orthopaedic team while the plastic surgery team is raising the free flap, performing the microvascular anastomosis, and closing the

Table 5.5.2 Arnež and Tyler classification for degloving injuries Pattern 1: limited degloving with abrasion/​avulsion Pattern 2: non-​circumferential degloving Pattern 3: circumferential single-​plane degloving

The decision-​making process in lower extremity reconstruction starts with initial patient assessment in the emergency room performed together by experienced (consultant) trauma/​orthopaedic and plastic surgeons. Initially, life-​endangering concomitant injuries

Pattern 4: circumferential multiplane degloving Reprinted from Journal of Plastic, Reconstructive & Aesthetic Surgery, Vol 63, issue 11, Z.M. Arnež, U. Khan, M.P.H. Tyler, pp1865–​1869, Copyright (2010), with permission from Elsevier.

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SECTION 5  Lower limb

donor defect. This is practised widely since it shortens the operating time dramatically. When possible, fixator pins should be placed away from clusters of perforators from the three lower leg vessels. The patient is then taken to the operating room and the operation starts with the debridement. This is the most important part of the operation since incomplete debridement will inevitably lead to complications (wound infection and secondary healing). Therefore, it should be performed by the most senior surgeons, who decide on the type of debridement (definitive or sequential). Prerequisites for soft tissue reconstruction are perfusion of the limb and stable skeleton. When dealing with the avascular limb (10 denote severe disability Changes of 2 or 3 indicate meaningful difference

Jurkovich et al., 1995 Bosse et al., 2002 MacKenzie and Bosse, 2006 LEAP study

Short Form health survey (SF-​36)

Generic health-​related quality Eight health attributes: physical of life measure function, limitations in activities because of physical health problems, limitation in activities because of emotional problems, bodily pain, general health perceptions, vitality, social function, and mental health

Each section scored separately 0–​100 Lower scores indicate a poorer function

Dagum et al., 1999 Pezzin et al., 2000

Nottingham Health Profile (NHP)

Two-​part generic health status measure of physical, emotional and social health problems

Part I measures subjective health status in six categories (mobility, energy level, pain, sleep, emotional reaction, and social isolation) Part II limitations due to health problems in paid employment ( job), housework, family life, social life, sexual function, recreation, and enjoyment of holidays

Part I: 0 points represents no limitations and 100 points represents maximum disability Part II: seven yes-​or-​no statements

Georgiadis et al., 1993 Hoogendoorn and van der Werken, 2001

Short Musculoskeletal Functional Assessment (SMFA)

General health status

Dysfunction index: 34 items for Scored  0–​100 the assessment of patient function. Higher scores indicate poorer Bother index (BI): 12 items for the function assessment of how much patients are bothered by functional problems

Western Ontario and McMaster University Osteoarthritis Index (WOMAC)

Disease-​specific health status measure

24-​item  scale Three dimensions: pain (5 items), stiffness (2 items), physical function (17 items)

Best to worst scale Dagum et al., 1999 Lower subscale scores represent Dattani et al., 2013 less pain, less stiffness, or better physical function

Enneking score

Limb assessment

Assessing pain, function, emotional acceptance, walking supported, gait, skin quality and donor site

0 to 5 visual analogue scale (VAS) Range 0 to 40 High score indicating a better return of function. Expressed as a proportion of the expected normal function

Naique et al., 2006 Khan et al., 2007

Hamlyn Mobility Score (HMS)

Objective performance test and generic health

6-​minute walk, Timed Up and Down Stairs (TUDS) and the Timed up and Go (TUG). These tests demonstrate balance, load, strength, and flexibility. Subjective evaluation of pain, satisfaction, walking support

Subjective by 0–​5 VAS

Kwasnicki et al., 2014

EQ-​5D (EuroQol)

Measure of health-​related quality of life

Assess patients’ perceived problems based on five dimensions: anxiety and depression, pain and discomfort, usual activity, self-​care, and mobility

Each is scored as 1, 2, or 3 1 represents no problems, 2 some problems, and 3 severe problems

Gopal et al., 2004 Giannoudis et al., 2009

Swiontkowski et al., 1999 Castillo et al., 2012 Dattani et al., 2013

5.9  Lower limb trauma outcome measures: limb salvage and amputation

project, 545 patients showed no difference in the general health outcome measure, the Sickness Impact Profile (SIP) score (Bergner et al., 1981) between salvage and amputation, with SIP levels indicative of severe disability for around half of all patients (Bosse et al., 2002; MacKenzie et  al., 2005). The impact of injury is prolonged with predictors of poor outcome including female sex, non-​white race, lower education level, living in a poor household, smoking, low self-​efficacy, poor self-​reported health status before the injury, and involvement with the legal system in an effort to obtain disability payment (MacKenzie et  al., 2005). Over time, function deteriorates in both salvage and amputee groups (MacKenzie et al., 2005), and the same has been seen over the long term in military amputees (Gailey et al., 2010). A careful utility analysis of the value of reconstruction or amputation showed that while physicians rated both options equally, patients rated the utility of reconstruction more highly than amputation despite the extra hospitalization, additional interventions, and personal resource cost required (MacKenzie et al., 2007; Chung et al., 2009). Amputation is not without ongoing problems: 6.5% of amputees are unhealed, 15% have revisions, and 30% have been hospitalized at 2 years post injury (Harris et al., 2009). Walking speed appears to be universally better in the limb salvage group in the LEAP studies (Ellington et al., 2013) and numerous other comparative cohorts (Georgiadis et al., 1993; Hertel et al., 1996; Hoogendoorn and van der Werken, 2001). In a subgroup analysis of the LEAP study, patients with proximal tibial injuries achieved a walking speed of 4 feet per second in 33% of amputees and 61% of salvage patients. A different subgroup analysis of the mangled foot and ankle group that required a free flap for limb salvage have worse SIP scores than those with amputation, although when looking at all salvage patients, the SIP scores are better than those for amputation (Ellington et al., 2013). In military patients, a review demonstrated amputees had a threefold increased rate of involvement in sports compared with patients with limb salvage (Doukas et al., 2013). Longer periods of inpatient physical therapy for rehabilitation result in better outcomes for all patients (Pezzin et  al., 2000). An intensive ‘Return-​to-​Run’ physical therapy regime combined with an energy-​storing splint (Intrepid Dynamic Exoskeletal Orthosis (IDEO)) has been introduced for military personnel. This regimen has shown an extraordinary increase in return to active duty of 17 of 91 military personnel with limb salvage and a fourfold increase in return to duty with the intensive regimen (Blair et al., 2014). In a series of 50 military patients, 41 reversed their preference for late amputation to salvage with use of the device and these physical benefits are sustained at 2 years (Bedigrew et al., 2014). In the United Kingdom, military personnel remain as inpatients at a specialist rehabilitation unit outside London, achieving significant increases in the physical part of SF-​36 scores (Dharm-​Datta et al., 2011). Further, they report excellent return to work rates of at least 78% (both within service and in private employment), compared to the best recoveries elsewhere despite the significantly worse Injury Severity Scores (ISSs) and multiple limb injuries of the very seriously injured (ISS averages 9 for civilians and 26 for military personnel) (Staruch et al., 2013). The authors conclude much of this is to do with the multidisciplinary nature of the support given, which addresses the need for physical therapy, mental health support, self-​management, and vocational and other support. Interestingly, these are the unmet needs identified by the LEAP study (Castillo et al., 2005b). This suggests

the possible benefits from addressing the non-​surgical factors that are often thought to be unmodifiable (Bosse et al., 2002). Such care might avoid the downward spiral into depression, anxiety, and pain (MacKenzie and Bosse, 2006). The LEAP study group found self-​efficacy (the patient’s confidence in being able to resume life activities), pain, anxiety, and depression are all elevated in survivors of lower limb trauma (Bosse et al., 2002) and correlate very well with outcome. The patients in the lowest quartile of depression scores have the lowest SIP scores (9) and quickest return to work (292 days); while those in the highest depression scores have the highest SIP scores (16) and the longest time to return to work (492 days). These factors are not related to the injury, and the likelihood of post-​traumatic stress disorder correlates with the perceived threat to life and the intent of the injury, that is, assault (Holbrook et al., 2001). In the civilian setting, peer support networks hold early promise with a significant improvement in depression ratings (Castillo et al., 2013). Specific self-​management training has led to decreased depression and improved self-​efficacy and pain control (Wegener et al., 2009). Global support strategies such as the patient/​family-​centred care approach has helped with anxiety and pain control, leading to significantly improved satisfaction of both patients and staff (DiGioia and Greenhouse, 2012). In the LEAP study, the main determinants of patient satisfaction are pain, depression, and function (O’Toole et  al., 2008). Therefore, the previously mentioned supportive strategies to help with self-​ management will assist with the pain and depression.

Impact of employment and return to duty In a 2008 review of over 1300 patients, the average return to work was reported as 64% for patients with reconstructed limbs and 73% for amputees, at around 14 and 13 months respectively (Saddawi-​ Konefka et al., 2008). The LEAP study does show a difference (but it is not significant) in return-​to-​work rates for reconstruction (0.62) and amputation (0.47) at 7 years (MacKenzie et al., 2006). Although these rates are similar, a review of amputees reported an 82% incidence of job loss due to the amputation (Sinha and Van Den Heuvel, 2011)  and several large military series demonstrate an almost total shift from frontline to clerical and administrative roles (Gunawardena et al., 2006; Dharm-​Datta et al., 2011). A comparative series of 39 patients found 19% of reconstruction and 56% of amputee patients required retraining prior to return to work (Hertel et al., 1996). These studies show that return to work is both quantitative and qualitative as an outcome measure, and careful consideration of injury and patient factors are required in communicating with a patient when asked ‘When will I return to work?’. The LEAP study found the numerous factors significantly associated with a greater likelihood of return to employment were younger age, higher education, non-​smoker, high self-​efficacy, employed with high job demand, and not involved in litigation. Self-​ efficacy is the ability to perform specific tasks and activities. An aggressive approach to limb salvage encouraging early mobilization allowed Francel (1994) to improve the return-​to-​work rate from 28% to 68% at 2 years.

Education level and social capital Education is relatively more protective for ultimate outcome than employment status pre-​injury, and the university education is more protective still (odds ratio of 3.1) (MacKenzie et  al., 2006). Low

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educational levels appear to be associated with poorer outcomes in a variety of different scenarios. In vascular dysfunction amputees, there is a greater likelihood of successful rehabilitation to walking with higher education (55% vs 27%) and a lower likelihood of death (5-​year mortality of 62.6% vs 84.3%, P = 0.001) (Corey et al., 2012). Education is postulated as both a buffer and an engagement facilitator (Bosse et al., 2002; MacKenzie et al., 2004). The LEAP studies have drilled into the data further, demonstrating a greater likelihood of unmet need for physical therapy, vocational support, mental health support, and other supports in the lower educational group (Castillo et al., 2005b; Archer et al., 2010). Patients with low education level, low social capital, and lower self-​efficacy are over-​represented in the open tibial fracture group (MacKenzie et al., 2000). Improving the patients’ perceptions of these challenges is one of the greatest tasks for those caring for these patients. Self-​management training techniques show improvement in self-​efficacy (Wegener et  al., 2009), especially as these patients place a greater value on reconstruction rather than amputation for quality of life (Chung et al., 2011). In the longer term this gives a specific injury group that should occur less frequently and have better functional recovery if there was greater investment in education and social equality for the population (Power and Matthews, 1997; Banks et al., 2006).

Bony union In isolated midshaft fractures, time to union has become the standard outcome measure though this is a more complex parameter than one may initially think. The issue is complex due to the difference between radiographic and clinical union, the nature of the high-​ energy transfer, internal and external fixation techniques, stimulating procedures to prevent non-​union, and treating non-​union. A review of fracture healing has shown fracture stiffness per degree of angular movement in the sagittal plane is a more reliable marker for bony union than radiography or clinical assessment (Wade and Richardson, 2001). The authors defined non-​union as ‘the cessation of both periosteal and endosteal healing responses without bridging’ and delayed union as ‘the cessation of periosteal response before the fracture has been successfully bridged’.

Smoking The LEAP study demonstrated a significant increase in the time to union, complications, and likelihood of osteomyelitis in current and previous smokers compared to non-​smokers (Castillo et al., 2005a). The previous smokers are a heterogeneous group with numerous studies demonstrating variable success in stopping. Therefore the odds ratio for osteomyelitis is 3.7 for current smokers and 2.8 for previous smokers, which may represent a dose-​dependent effect or a sequela from smoking (Castillo et al., 2005a). In addition to the increased morbidity, an increase in mortality has been shown for patients with amputation resulting from vascular dysfunction (Corey et al., 2012). Smoking cessation strategies should therefore be supported and signposted for potential gain for the patient (Thomsen et al., 2014).

Infection Huh and colleagues (2011) demonstrated that patients with late amputation are more likely to have had their limb salvage complicated by infection. Johnson and colleagues (2007) found that four of five late amputations were due to infection. A military series of

115 patients demonstrated any infection, including osteomyelitis, significantly reduced return-​to-​duty rates (Napierala et al., 2014).

Time to initial surgery (debridement/​wound excision) The 6-​hour rule for the first operative procedure to debride and assess the open tibial wound has been debated for years (Nanchalal, 2009). One review collated numerous small studies and was unable to discern a difference in infection rates with earlier intervention (Crowley et al., 2007). Numerous studies with larger numbers (89 patients (Enninghorst et al., 2011), 736 patients (Weber et al., 2014), and 383 patients (Charalambous et al., 2005)) have failed to demonstrate a difference. The LEAP (307 patients in analysis) did not detect a significant increase in infection, noting an average time to debridement from injury of 11.2 hours for those without infection and 13.5 hours with major infection (Pollak et al., 2010). A qualitative analysis of 415 patients demonstrated a significantly worse infection rate if the first operation took place after 8 hours, and noted an increasing risk as that time progressed (Malhotra et al., 2014). The national figures for the United States (7526 patients) demonstrate an odds ratio of 3.81 for amputation if the first operation is delayed for more than 24 hours, even after controlling for biases (Sears et al., 2012). We are probably thinking of a linear relationship with time when in reality there may well be non-​linear interaction between degree of contamination, severity of injury, vascular dysfunction, and capability of the treating provider. Further, we need to acknowledge that time is a continuous variable, yet we ascribe a discrete quantity to this of early and late. This can be explained by what Richard Dawkins has called the ‘tyranny of the discontinuous mind’, as the human mind tries to categorize in order to compare and understand (Dawkins, 2011). Hull and colleagues (2014) looked at 459 patients and assessed time as an hourly variable to give an increasing likelihood of infection, albeit an odds ratio of only 1.033 per hour delay for infection which was significant. Moving the concept of time to theatre from a fixed number to every hour matters provides useful planning information for healthcare organizations around a waiting patient. This has to be balanced against the acknowledged risk of complication associated with operating in the middle of the night (Gray, 2003). Given the data available, the national standards in the United Kingdom strike a sensible optimum by recommending the next routine trauma list within 24 hours, ensuring senior orthopaedic and plastic surgeons are present (Nanchalal, 2009), unless there are indications for immediate surgery (vascular compromise; multiple injuries; severe contamination such as marine, farmyard, and sewage).

Time to definite soft tissue cover There is a steady accumulation of evidence of the preference for early wound coverage. The LEAP group study showed the significant difference between the patients who developed infection and those who did not was the delay between injury and admission to the trauma centre in the infection group but there was no difference between the groups in the time to wound debridement or time to soft tissue closure (Pollak et al., 2010). In contrast, Jain and colleagues (2013) in a series of 42 patients showed delay in soft tissue closure not only influenced the outcome of flap surgery, but also that delayed amputation past 5 days leads to a significant increase in infection (odds ratio 4.5). A further study of 72 patients showed 3.6% suffered major complications when cover was achieved in less than 15 days, 29%

5.9  Lower limb trauma outcome measures: limb salvage and amputation

when cover was provided between 15 and 30 days, and 38% after 30 days (Francel et al., 1992). Liu and co-​workers’ (2012) study of 103 patients showed a significant decrease in rate of wound infection from 57% for those closed after 7 days to 4% for those closed in less than 7 days. A further study of only 38 patients demonstrated a similar significant decrease from 57% to 12% between closure after and before 7 days (Bhattacharyya et al., 2008). Shorter time frames continue to show benefit for early closure with a series of 29 patients showing a significant difference in rates of bony union and infection, between the day of admission and later (average 4.4 days) (Hertel et al., 1999). A temporal correlation was shown with a 3% infection rate for soft tissue closure by 24 hours, 10% from 24 to 72 hours, and 30% for closure after 72 hours in a series of 84 patients (Gopal et al., 2000). The national standards in the United Kingdom recommend soft tissue closure by 7 days (Nanchalal, 2009), which allows sufficient time to organize definitive care. This is supported by D’Alleyrand and colleagues (2014) who with a logistic regression model that separated the first 7 days after injury from subsequent days found no increased risk for days 1 through 7. The odds of complications, and of infection in particular, significantly increased by 11% and 16%, respectively, for each day beyond day 7.

Soft tissue injury Soft tissue injury is given great weight in the decision-​making process by clinicians, relatively greater than bony injury and vascular status put together (Swiontkowski et al., 2002). As the Gustilo score increases, a series of 89 patients showed a significantly longer time to union (Enninghorst et al., 2011). Another study of 415 patients was able to show a significant correlation across the grades (Malhotra et al., 2014) and a series of 130 patients showed a significant decrease in the quality of life outcomes (Giannoudis et al., 2009). In the LEAP studies, there is an odds ratio of 3.1 for poorer functional outcome on the SIP with increased soft tissue injury (MacKenzie et al., 2005). In the proximal tibial injuries this held true, with severity correlating well with outcome (Starman et al., 2010). Mangled foot and ankle injuries may support this further, as ankle reconstructions around the ankle that require free flap reconstruction have poor functional outcomes (Ellington et  al., 2013). This could be that complex microsurgical reconstructions reverse any benefit of salvage or that the need for complex reconstruction being a marker for severity of injury has not been appreciated by the Gustilo score. This is an area with minimal soft tissue, evidenced by the complexity of injuries in surgical series around this area (Naique et al., 2006; Khan et al., 2007; Ellington et al., 2013). A LEAP subgroup analysis found that the 107 patients undergoing free flap surgery were significantly more likely to have more compartments of the leg injured than those treated by a rotational flap—​87 patients (Pollak et al., 2000). Neither the ISS nor the Gustilo score record the need for fasciotomy. Patients undergoing fasciotomy in the absence of fractures had pain and activity outcomes similar to amputees (Giannoudis et al., 2009). Fasciotomy could be used as a proxy or independent marker of soft tissue severity, as these patients have been found to have poorer functional outcomes (Giannoudis et al., 2009; Starman et al., 2010) and are more likely to have a later amputation (Fochtmann et al., 2014) especially if the fasciotomy requires revision (Farber et al., 2012).

Absent plantar sensation was considered to be a relative indication for amputation at the start of the LEAP study (Swiontkowski et al., 2002). One of the most important findings of the observational study was that at 2-​year follow-​up of patients undergoing limb salvage, normal plantar sensation was present in an equal proportion (55%) of patients that had an initially insensate sole of foot and those that had some sensation in the foot. Nearly all gained some sensory improvement, with only one patient having completely absent sensation (Bosse et al., 2005). Therefore, absent plantar sensation can no longer be considered a strong indicator for amputation.

Late amputation Late amputation is more likely with increasing severity of soft tissue injury (thereby requiring flap reconstruction) and by the presence of infection (Huh et al., 2011). Late amputations have demonstrated a significantly worse physical and psychological outcome compared to either primary amputation or successful salvage (Melcer et  al., 2013). Understandably, the rate of late amputees wishing they had opted for a primary amputation is high. In one series, six of eight late amputees wished they had opted for an early amputation (Dahl et  al., 1995), compared to the rate at which patients are pleased with successful limb salvage or primary amputation of 83–​100% (Hoogendoorn and van der Werken, 2001; Gopal et al., 2004). One can see the consequence of the late amputation being a terribly demotivated patient who may move from survivor to victim status and the ensuing potential downward spiral. Therefore, persevering to avoid a late amputation would be considered reasonable for a fully informed patient. The published definitions of when an amputation is considered late are rather broad from more than 24 hours, to after initial hospitalization (LEAP) to more than 1 year (Busse et al., 2007). On average, 7% of limb salvage patients proceed to late amputation on systematic review (Saddawi-​Konefka et al., 2008), through a broad range from 0% (Gopal et al., 2004; Naique et al., 2006; Khan et al., 2007) to 40% (Fairhurst, 1994). Injury severity and vascular compromise appear to be the main indications initially, then sepsis control inside the first year, then non-​union thereafter (Huh et al., 2011). The rate of late amputation has significantly decreased over time, when analysed by year of publication (Saddawi-​Konefka et al., 2008). High rates of late amputation have been shown for microsurgical flap failure, particularly for open tibial fractures at 3 of 6 (Hallock, 2001), 10 of 14 (Khouri and Shaw, 1989), and 8 of 23 cases (authors noted an eightfold increase risk of late amputation) (Culliford et al., 2007). However, late amputation has been avoided in other small series, by a variety of plastic surgery techniques (Naique et al., 2006; Culliford et al., 2007).

Level of amputation The LEAP study rates the functional outcome for through-​knee amputation as poor, with an odds ratio of 11.5 for poor functional SIP score (MacKenzie et al., 2005). In addition, the walking speed of 4 feet per second is achieved by only 21% of through-​knee amputees, while 43% of above-​knee amputees and 62% of below-​knee amputees achieve this speed (MacKenzie et al., 2004). Energy consumption of walking increases as the level of amputation moves proximally, with a 9% increase in oxygen consumption for a unilateral below-​knee amputee, a 49% increase for a unilateral above-​ knee amputee, and 280% higher for bilateral above-​knee amputees

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SECTION 5  Lower limb

(Huang et al., 1979). A review of the world literature confirms the LEAP study conclusions of aiming to maximize length (Penn-​ Barwell, 2011) apart from the finding that patients with a through-​ knee amputation have a better physical quality of life than those with an above-​knee amputation. Therefore, reviews propose supporting a strategy of maintaining maximum length and performing through-​ knee amputations in preference to above-​knee amputations (Tintle et al., 2010; Penn-​Barwell, 2011). The majority of the through-​knee amputees are from military conflicts, which may compromise the applicability of the review’s findings for the civilian population.

Surgical organization The United Kingdom national standards have combined orthoplastic care at their core. In the United Kingdom, a survey of orthopaedic surgeons revealed a rate of plastic surgery contact similar to that reported in the LEAP study. In the United Kingdom, 29% of consultants would consider contacting the plastic surgeon preoperatively (Toms et al., 2003). In the LEAP study, plastic surgeons were directly involved in 14% of cases and indirectly in 12% (Swiontkowski et al., 2002). In recognized joint orthoplastic centres, rates of 95% limb salvage have been reported (Gopal et al., 2000; Naique et al., 2006), while the LEAP study in trauma centres has a 64% limb salvage rate. A multicentre study demonstrated similar length of stay in orthoplastic centres in the United Kingdom and Pakistan of 25 and 24  days respectively, while a specialist orthopaedic centre in Italy had a length of stay of 72 days (Boriani, 2013).

Costs The LEAP group looked at costs at 2  years and concluded that healthcare costs are greater for amputation than for reconstruction (MacKenzie et  al., 2007). When lifetime costs are postulated then the difference becomes profound, dependent upon how many years of life the patient has (Chung et al., 2009). This leads to a projected lifetime cost excess of US$300,000 for amputation compared to reconstruction and the costs may be even greater as costs such as adaption for home and work, an adapted vehicle, and indirect work costs. There is no consideration of personal effect of loss of body image. The social cost of potentially earlier death and social support for a wheelchair amputee has not been calculated. In addition, the complexity of prosthesis is increasing and the prosthetic demand increasing (Branemark et  al., 2014). A  study of military veterans showed that recent veterans use 3.1 prosthetic devices per annum, while Vietnam veterans use 1.2 devices per annum (Gailey et al., 2010). Therefore, there is a considerable probability there will be substantial increases in the lifetime excess cost for amputation to the individual, healthcare provider, and society.

Conclusion Functional outcomes appear equivalent for limb salvage and amputation. Walking speeds are slower for patients with an amputation than limb salvage. The cost to the individual and providers is greater with amputation. If amputation is unavoidable, limb length should be maximized and a through-​knee amputation should be considered. The main determinants of outcome are non-​surgical and a broad multidisciplinary team should provide management in a defined pathway to optimize individual outcomes.

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5.9  Lower limb trauma outcome measures: limb salvage and amputation

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SECTION 5  Lower limb

Johnson EN, Burns TC, Hayda RA, et al. Infectious complications of open type III tibial fractures among combat casualties. Clin Infect Dis 2007;45:409–​15. Jurkovich G, Mock C, Mackenzie E, et al. The Sickness Impact Profile as a tool to evaluate functional outcome in trauma patients. J Trauma Inj Infect Crit Care 1995;39:625–​31. Khan U, Smitham P, Pearse M, et al. Management of severe open ankle injuries. Plast Reconstr Surg 2007;119:578–​89. Khouri RK, Shaw WW. Reconstruction of the lower extremity with microvascular free flaps: a 10-​year experience with 304 consecutive cases. J Trauma Inj Infect Crit Care 1989;29:1086–​94. Kwasnicki RM, Shehan Hettiaratchy D, Jarchi D, et  al. Assessing functional mobility after lower limb reconstruction. Ann Surg 2015;261:800–​6. Liu DSH, Sofiadellis F, Ashton M, et al. Early soft tissue coverage and negative pressure wound therapy optimises patient outcomes in lower limb trauma. Injury 2012;43:772–​8. Ly TV, Travison TG, Castillo RC, et al. Ability of lower-​extremity injury severity scores to predict functional outcome after limb salvage. J Bone Joint Surg Am 2008;90:1738–​43. MacKenzie EJ, Bosse MJ. Factors influencing outcome following limb-​ threatening lower limb trauma:  lessons learned from the Lower Extremity Assessment Project (LEAP). J Am Acad Orthop Surg 2006;14:S205–​10. MacKenzie EJ, Bosse MJ, Castillo RC, et al. Functional outcomes following trauma-​related lower-​extremity amputation. J Bone Joint Surg 2004;86:1636–​45. MacKenzie EJ, Bosse MJ, Kellam JF, et  al. Characterization of patients with high-​energy lower extremity trauma. J Orthop Trauma 2000;14:455–​66. MacKenzie EJ, Bosse MJ, Kellam JF, et al. Early predictors of long-​term work disability after major limb trauma. J Trauma Acute Care Surg 2006;61:688–​94. MacKenzie EJ, Bosse MJ, Pollak AN, et al. Long-​term persistence of disability following severe lower-​limb trauma:  results of a seven-​ year follow-​up. J Bone Joint Surg 2005;87:1801–​9. MacKenzie EJ, Jones AS, Bosse MJ, et al. Health-​care costs associated with amputation or reconstruction of a limb-​threatening injury. J Bone Joint Surg 2007;89:1685–​92. Malhotra AK, Goldberg S, Graham J, et  al. Open extremity fractures:  impact of delay in operative debridement and irrigation. J Trauma Acute Care Surg 2014;76:1201–​7. McNamara MG, Heckman JD, Corley FG. Severe open fractures of the lower extremity:  a retrospective evaluation of the Mangled Extremity Severity Score (MESS). J Orthop Trauma 1994;8:81–​7. Melcer T, Sechriest VF, Walker J, et  al. A comparison of health outcomes for combat amputee and limb salvage patients injured in Iraq and Afghanistan wars. J Trauma Inj Infect Crit Care 2013;75(Suppl. 2):S247–​54. Naique SB, Pearse M, Nanchahal J. Management of severe open tibial fractures the need for combined orthopaedic and plastic surgical treatment in specialist centres. J Bone Joint Surg Br 2006;88:351–​57. Nanchalal JN, Khan U, Moran C, et  al. (eds). Standards for the Management of Open Fractures of the Lower Limb. London: Royal Society of Medicine; 2009. Napierala MA, Rivera JC, Burns TC, et al. Infection reduces return-​to-​ duty rates for soldiers with Type III open tibia fractures. J Trauma Acute Care Surg 2014;77(Suppl. 2):S194–​7. O’Toole RV, Castillo RC, Pollak AN, et al. Determinants of patient satisfaction after severe lower-​extremity injuries. J Bone Joint Surg Am 2008;90:1206–​11. Penn-​Barwell JG. Outcomes in lower limb amputation following trauma: a systematic review and meta-​analysis. Injury 2011;42:1474–​9.

Pezzin LE, Dillingham TR, MacKenzie EJ. Rehabilitation and the long-​ term outcomes of persons with trauma-​related amputations. Arch Phys Med Rehabil 2000;81:292–​300. Pollak AN, Jones AL, Castillo RC, et al. The relationship between time to surgical debridement and incidence of infection after open high-​ energy lower extremity trauma. J Bone Joint Surg 2010;92:7–​15. Pollak AN, McCarthy ML, Burgess AR, et al. Short-​term wound complications after application of flaps for coverage of traumatic soft-​ tissue defects about the tibia. J Bone Joint Surg 2000;82:1681–​91. Power C, Matthews S. Origins of health inequalities in a national population sample. Lancet 1997;350:1584–​9. Puno RM, Grossfeld SL, Henry SL, et al. Functional outcome of patients with salvageable limbs with grades III-​B and III-​C open fractures of the tibia. Microsurgery 1996;17:167–​73. Russell WL, Sailors DM, Whittle TB, et al. Limb salvage versus traumatic amputation. A  decision based on a seven-​part predictive index. Ann Surg 1991;213:473–​80. Saddawi-​Konefka D, Kim HM, Chung KC. A systematic review of outcomes and complications of reconstruction and amputation for type IIIB and IIIC fractures of the tibia. Plast Reconstr Surg 2008;122:1796–​805. Sears ED, Davis MM, Chung KC. Relationship between timing of emergency procedures and limb amputation in patients with open tibia fracture:  United States, 2003–​2009. Plast Reconstr Surg 2012;130:369–​78. Sinha R, Van Den Heuvel WJ. A systematic literature review of quality of life in lower limb amputees. Disabil Rehabil 2011; 33:883–​99. Song JW, Chung KC. Observational studies: cohort and case-​control studies. Plast Reconstr Surg 2010;126:2234–​42. Starman JS, Castillo RC, Bosse MJ, et al. Proximal tibial metaphyseal fractures with severe soft tissue injury: clinical and functional results at 2 years. Clin Orthop Relat Res 2010;468:1669–​75. Staruch RMT, Yim JP, G, Hodson J, et al. Traumatic lower limb amputation from resuscitation to reconstruction—​comparing the military and civilian experience at QEHB. Combined Services Plastic Surgery Society meeting, RAF Middle Wallop, 2013. Swiontkowski MF, Engelberg R, Martin DP, et al. Short musculoskeletal function assessment questionnaire: validity, reliability, and responsiveness. J Bone Joint Surg 1999;81:1245–​60. Swiontkowski MF, MacKenzie EJ, Bosse MJ, et al. Factors influencing the decision to amputate or reconstruct after high-​energy lower extremity trauma. J Trauma Inj Infect Crit Care 2002;52:641–​9. Thomsen T, Villebro N, Møller AM. Interventions for preoperative smoking cessation. Cochrane Database Syst Rev 2014;3: CD002294. Tintle SM, Forsberg JA, Keeling JJ, et  al. Lower extremity combat-​ related amputations. J Surg Orthop Adv 2010;19:35–​43. Toms AD, Green AL, Giles S, et al. The current management of tibial fractures:  are clinical guidelines effective? Ann R Coll Surg Engl 2003;85:413–​16. Tscherne H, Oestern HJ. [A new classification of soft-​tissue damage in open and closed fractures (author’s transl)]. Unfallheilkunde 1982;85:111–​15. Wade R, Richardson J. Outcome in fracture healing: a review. Injury 2001;32:109–​14. Weber D, Dulai SK, Bergman J, et al. Time to initial operative treatment following open fracture does not impact development of deep infection: a prospective cohort study of 736 subjects. J Orthop Trauma 2014;28:613–​19. Wegener ST, MacKenzie EJ, Ephraim P, et  al. Self-​management improves outcomes in persons with limb loss. Arch Phys Med Rehabil 2009;90:373–​80.

5.10

Lower limb osteomyelitis Umraz Khan

Introduction Deep bone infection is not an uncommon condition and is one that damages the normal structure of bone and joint with concomitant potential for substantial long-​term morbidity. Osteomyelitis is a chronic inflammatory often destructive process involving bone. Often there is suppuration of bone and bone marrow. The purulence is always accompanied by vascular stasis with small vessel thrombosis and oedema. The condition is frequently progressive, leading in time to bone destruction due to a number of interacting pathological processes. Bacterial invasion of the delicate Haversian canal systems within normal bone directly destroys bone through release of bacterial enzymes. Bacterial invasion also leads to bone ischaemia and consequent necrosis. Infection also provokes inflammation which leads to bone necrosis and new bone formation. Pyogenic osteomyelitis is frequently seen in the developing world due mainly to poor management of both haematogenous and traumatic causes. In the developed world, the incidence is less and mainly due to wounding with a contribution from poor vascularity. The management of osteomyelitis remains a considerable challenge despite recent advances. Improved understanding of the microbiological basis and the pathophysiology of the condition has failed to reduce either the incidence or the morbidity with which this condition is associated, particularly where it persists to become a chronic condition. In the United Kingdom, there are now regional services dedicated to the care of patients suffering with bone infection. The multidisciplinary teams (MDTs) are ideally composed of: • Microbiologists. • Orthopaedic surgeons. • Plastic surgeons. • Diabetic or vascular teams. • Occupational and rehabilitation teams. The core decisions made by this team revolve around the ‘grade’ of the condition and the ‘state’ of the individual. Both grade and state are investigated thoroughly to ensure that what can be exhaustive and expensive treatment is given appropriately. Bone infections differ in duration, aetiology, pathogenesis, and the extent of bone involvement. The bone infection team must assess all of these aspects of the infected bone. Managing diabetes and peripheral vascular

disease appropriately is central to prevention in susceptible individuals, while orthopaedic and plastic surgeons undertake ablative and reconstructive surgery for these lesions. The pathogenesis is similar for all types of bone infection. Initially there is a host response to the invading bacteria. Inflammation is followed by suppuration. Pus tracks within the canalicular systems of bone (Haversian and Volkmann canals) making its way to the surface of the bone to produce a subperiosteal swelling. The eventual suppuration leads to stripping of the periosteum and the formation of an abscess. These pathophysiological processes combine to produce or induce bone ischaemia and finally to bone necrosis. The formation of a focus of necrotic bone is referred to as a sequestrum and is pathognomonic of osteomyelitis. The inner cambium layer of viable periosteum attempts to regenerate new bone. This ‘reactive’ new bone is called the involucrum. The presence of both sequestra and involucra are almost diagnostic of osteomyelitis. With persistent infection, cloacae (sinuses between new bone and the skin) form allowing discharge of purulence. The latter leads to a relief of pain. Bone biopsy of osteomyelitis is characterized by the presence of a necrotic bone (sequestrum) surrounded by an involucrum with cloacae. These classical histological findings may not always be present. Sclerosis of the bone alone without the combination of sequestrum, involucrum, and cloacae can also be pathognomonic of osteomyelitis. The hallmarks of chronic inflammation, dead bone (sequestrum), new immature bone (involucrum), sinuses (cloacae), and bacteria may be seen histologically. Clinically, the overlying skin is often hard and unyielding because the deep fascia is stuck to the affected bone and because the subcutaneous fat may have necrosed. The latter means that in osteomyelitis of the tibia (a subcutaneous bone), the entire length of the pretibial skin may be involved. There may be a discharging sinus evident, and on radiographs the changes of sclerosis with or without a focus of a sequestra and the periosteal reaction with an involucrum may be seen. In osteomyelitis, bacteria can adhere to both the extracellular matrix of bone and/​or to surgical implants. The most common bacterial species, the staphylococci, possess adhesive proteins and glycoproteins, which mediate binding to fibronectin (an important connective tissue protein) via receptors. Osteolysis, the loss of the normal trabeculations of normal healthy cancellous bone and thinning of

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the bone cortex, occurs by the processes of inflammation. It is due to the cytokine production by immune cells which are recruited by the interaction of bacteria with white blood cells and macrophages. Bacteria elude antibiotics and host defences by lowering their metabolic rates, formation of a glycocalyx barrier, and by surviving intracellularly (Zimmerli et  al., 2004). The latter may explain why in clinical practice osteomyelitis is described as ‘waxing and waning’. Antibiotic suppression and metabolically inactive bacteria lead to a quiescent state. If the area of infected bone is then injured (low energy and often innocuous), the bacterial load is increased due to a purge from the intracellular sanctuaries leading to a ‘flare-​up’. There is evidence that the presence of orthopaedic implants may induce a reduction in local polymorphonuclear cell recruitment. A  negative surface charge on the metallic implant affects any devitalized bone and is thought to promote bacterial adherence. As this process progresses, fibrous tissue forms at the interface of bone and metallic implant. Thick fibrous tissue prevents blood perfusion which lowers oxygen tension. The knock-​on effect is that any antibiotics being administered in the presence of metallic hardware can result in a reduced bioavailability of the antibiotics to the area where it is required.

Classification There are various systems available for classifying osteomyelitis. In the lower limb, these rely on one or more of the following: • Aetiology. • Extent of bone involvement and destruction. • The health of the limb. • The health of the patient (the host). The aetiology often determines the condition. Haematogenous osteomyelitis is most frequently seen in the metaphyses of the long bones of the lower limb in the growing skeleton of the child. It can present with acute sepsis and focal symptoms and be complicated by ischaemic necrosis of growth plates with long-​term effects on limb growth and deformity. Osteomyelitis other than haematogenous in origin may be due to surgical site infection. This can happen around an implant following, for example, arthroplasty or fracture fixation, especially in open tibial fractures. Classifying osteomyelitis based on haematogenous or non-​haematogenous aetiology has the appeal of simplicity, but does not describe the extent of the bone infection or the attributes of the patient. Of the classification systems that consider the attributes of the patient, the Cierny–​Mader and the Waldvogel schemes are the two most frequently used in the Anglophone literature.

Cierny–​Mader classification The extent of long bone involvement of osteomyelitis can be classified into four predictable and progressive stages (Cierny et  al., 2003) (Fig. 5.10.1): • Stage 1—​confined to the medulla of the bone. • Stage 2—​only the cortex is involved. The aetiology is often from a direct inoculation but can result from an infection of the overlying skin/​soft tissue.

Fig. 5.10.1  Cierny classification of osteomyelitis (Cierny et al., 2003). Stage 1: medullary—​infection confined to the medullary cavity. Stage 2: superficial—​contiguous type of infection, confined to surface of cortical bone. Stage 3: localized—​full-​thickness cortical sequestration localized to one segment of bone and the bone remains stable. Stage 4: diffuse—​the entire thickness of the bone is involved with loss of stability of the limb. Reproduced with permission from George Cierny, Jon Mader, and Johan Penninck, The Classic: A Clinical Staging System for Adult Osteomyelitis, Current Orthopaedic Practice, Volume 414, pp.7–​24, Copyright © 2003 Wolters Kluwer Health, Inc.

• Stage 3—​is a combination of both stages 1 and 2 but is localized to one segment of bone. In stage 3 the osteomyelitis does not involve the entire diameter. The bone remains stable. • Stage 4—​is a progression of stage 3 with involvement of the entire diameter which produces an inherent instability of the bone and also of the limb. The Cierny–​Mader system also characterizes the patient into a type of ‘host’: • Type A—​a patient without any compromising factors. • Type B—​a patient affected by one or more compromising factors. • Type C—​ a patient so severely compromised that the treatment necessary for eradication of osteomyelitis would have unacceptable risks. One shortfall of this classification is that there are aspects of osteomyelitis which are not taken into account. The system does not, for example, consider chronicity of the condition, nor if there are surgical implants present and does not consider the age of the patient. Adverse host factors are either local (chronic oedema, vascular disease, extensive scarring, previous radiation, soft tissue defect) or systemic (malnutrition, immunodeficiency, organ failure, diabetes, advanced age, malignancy, obesity, smoking, medications including glucocorticoids).

Waldvogel classification With the Waldvogel system, osteomyelitis is described according to three attributes: the duration of the infection (acute or chronic); the source of infection such as haematogenous seeding or if the source of the infection originates from a contiguous wound (when it originates from an infection in a nearby tissue); lastly the vascular status of the limb has to be ascertained (peripheral vascular disease versus normal peripheral circulation). A  limitation of the

5.10  Lower limb osteomyelitis

Waldvogel classification system is that it does not consider infection after trauma or surgery, two of the most important causes of osteomyelitis. Due to its emphasis on aetiology, the Waldvogel classification system (unlike the Cierny–​Mader system) cannot be used as a management guide. The system is used specifically for osteomyelitis in the diabetic foot as it is comparatively simple to document (Waldvogel et al., 1970).

Diagnosis The diagnosis of osteomyelitis is relatively straightforward in adults but in children with haematogenous osteomyelitis the picture may be acute and not immediately obvious. The MDT must grade and stage the disease and take account of the general health of the patient. Plain radiographs may help identify the focus as well as indicate whether sequestra or involucra are present. Blood tests are non-​specific but may indicate inflammation with an elevated white cell count as well as acute-​phase proteins. The full blood count may reveal anaemia (of chronic inflammation) in chronic osteomyelitis. A bone biopsy may be required in cases that are not obvious as histology can provide definitive evidence of osteomyelitis.

Imaging Together with plain radiographs, the baseline imaging includes both computed tomography scans and magnetic resonance imaging with contrast. These investigations have replaced radionucleotide scans as the first-​line investigation. Each has merit for defining differing aspects of the disease. In difficult cases, either a bone biopsy or a positron emission tomography (PET) scan can be helpful. PET scans appear to be the most sensitive and most specific for osteomyelitis (Termaat et al., 2005). Once the infected bones or joints have been assessed, it is prudent to assess the arterial anatomy in the lower limb and the soft tissue surrounding the infected bone. This can be accurately done by the combination of magnetic resonance imaging and magnetic resonance angiography, allowing a safe management plan to be formulated.

Management The MDT management starts with establishing the aetiology and staging the osteomyelitis. Surgery may be required acutely for washout of a septic joint or collection, or for obtaining bone specimens for diagnosis. Where there is an infected prosthesis or necrotic bone, surgery is usually required together with prolonged antibiotic therapy. Establishing the extent of bone necrosis can be difficult and is aided by appropriate imaging and intraoperative fluorescein staining of vital bone has also been used (Dahners and Bos, 2002). Reconstruction of tissue defects following excision of necrotic infected bone may require either replacement of a prosthesis or reconstruction with either soft tissue to obliterate dead space and maintain the vascularity of the remaining bone (Fig. 5.10.2) or with bone to restore structural integrity. The overlying skin is often scarred and inadequate and resurfacing may be required. For

some post-​excision defects, free flap transfer may be required (Fig. 5.10.3). Where limb salvage is not feasible, an amputation or the alternative of suppression of the osteomyelitis alone may need to be considered. The various sites of osteomyelitis in the lower limb will be discussed in turn.

Hip joint The hip joint infection in children is mostly secondary to haematogenous seeding while in adults surgical site infection (trauma or arthroplasty) predominates. The treatment is different for the two groups. In children once diagnosed, urgent decompression (either by open or arthroscopic techniques) and antibiotics for at least 2 weeks, depending on response, is appropriate (Peltola et al., 2009). This treatment pathway is comparatively predictable. In adults, the two most likely scenarios are an infected arthroplasty (prosthetic joint infection) or osteomyelitis following trauma. The extent of infection and bone destruction and the identity of the microorganism must be ascertained. If the patient is deemed too frail or high risk for joint salvage then explantation of the hip prosthesis together with any membrane/​biofilm and abnormal bone/​soft tissues is indicated, followed by a defined period of antibiotics targeted to the particular bacteria isolated. Six separate deep tissue biopsies are taken with six separate surgical instruments to avoid cross contamination. If three or more specimens grow the same bacteria then that should be the organism targeted. Patients are then rehabilitated as for a Girdlestone’s procedure. For patients suitable for joint salvage, a decision between two-​ stage or single-​stage joint replacement is made. This decision is based on the state of the prosthesis and the extent of bone and soft tissue destruction. A two-​stage joint salvage is indicated where there is substantial destruction of the native tissue. The first stage is aimed at eradicating the infection by a combination of implant removal and tissue excision as well as the delivery of high-​dose, prolonged local antibiotics. The former requires expertise to ensure that affected tissue is accurately excised and the latter is achieved in part by the use of antibiotic-​loaded cement spacers. The patient is also treated with antibiotics and followed up in a specialist clinic. The duration of antibiotic therapy is determined by the response judged from blood markers of inflammation and infection. When serial blood markers are normal and the joint is clinically quiescent, the second stage is undertaken. This may require bespoke prosthetic joints with the inherent careful preoperative planning they demand. In cases where the hip joint is deemed unsalvageable and a Girdlestone’s procedure is inappropriate due to the extent of osteomyelitis in the femur, a hip disarticulation is indicated.

Knee joint In cases of prosthetic joint infection of the knee, similar principles are applied as used in the hip with implant and infected tissue excision and a decision made as to the suitability of salvage of the joint. It has been proposed that in cases when there is early infection but no instability of the prosthesis or bone osteolysis, the prosthesis can be retained. In such cases, the polyethylene tibial plateau can be exchanged together with removal of any infected periprosthetic membrane, but leaving the implanted stemmed components in situ and the patients given targeted antibiotics. This has been termed the DAIR procedure (Debridement, Antibiotics, Implant Retention).

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(a)

(b)

(c)

(d)

(e)

(f)

Fig. 5.10.2  Clinical images illustrating the surgical strategy when the bone infection is localized. Panels (a)–​(d) show the extent of skin resection, which for purposes of sterilization is to include all scarred areas and areas of induration. The bone resection is undertaken piecemeal. Panel (c) shows wire localization of the cloacae and (d) shows the gentle nature by which the abnormal bone is removed. Minimal use of power tools avoids disseminating any bacterial load. Panel (e) shows the end result of this orthoplastic surgery of a large composite defect which is sterile. The next phase of the surgery relies on a safe strategy to fill in any bony defects and then secure a well-​vascularized resurfacing procedure. In this case, a distally based medial fasciocutaneous flap is designed and harvested such that part is de-​epithelialized and inset into the bony ‘dead-​space’ (f–​h). The final panels (i, j) show the result at 6 months.

5.10  Lower limb osteomyelitis

(g)

(h)

(i)

( j)

Fig. 5.10.2 Continued

The majority of patients who are suitable for DAIR have a very early infection and thus have not developed osteomyelitis of the femur or tibia. When there are open sinuses with soft tissue infection and bone destruction then two-​stage revision arthroplasty akin to that for the hip joint prosthetic joint infection may be preferred to DAIR. Knee arthrodesis may be offered in those patients unsuitable for staged reconstruction, otherwise above-​knee amputation must be contemplated.

Osteomyelitis of femur or tibia Without a prosthetic hip or knee, isolated osteomyelitis of the femur is unusual in adults. The extent is staged as usual and a decision made as to how much of the diaphysis is involved, as this will dictate the techniques necessary for limb salvage. If segmental loss is anticipated then a plan must be made preoperatively for bone reconstruction. Invariably there is extensive soft tissue excision and thus vascularized cover is required. Free tissue transfer may demand a preoperative angiogram as well as a venous duplex and may be technically difficult since perivascular fibrosis often requires vein grafts. In addition, the soft tissues may be swollen and unyielding. Some believe muscle flaps offer superior qualities for treating osteomyelitis but this has not been substantiated by large clinical studies (Yazar et al., 2006).

Diabetic foot disease The prevalence of diabetes is rising, and so is diabetic foot disease. The complex mechanics of the foot and gradual attrition of these attributes will lead to loss of function, which is summative (see Chapter 5.13). The majority of diabetic complications in the feet are preventable. The contributory factors include: • Peripheral neuropathy. • Peripheral microvascular disease. • Dry skin. Diabetic neuropathy may lead to Charcot joint disease (Fig. 5.10.4) which then subjects the atrophic skin to impingement and necrosis. Peripheral vascular disease and dryness leave the skin vulnerable to infection from even minor trauma which rapidly extends into the deeper layers of the foot including the skeleton.

Antibiotics The antibiotic therapy used is dictated by the bacterial isolates, but the route of administration and the period necessary for effective treatment is less clear. Most chronic osteomyelitis is caused by Staphylococcus aureus. These species are often sensitive to the beta-​ lactams. Although bone penetration is poor (5–​20% of serum levels)

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(a)

(b)

(c)

(d)

Fig. 5.10.3  Clinical images of a case of a pathological tibial fracture through infected bone. Panel (a) shows some wound excision after initial presentation but further wound excision was undertaken (b). The X-​rays shown in panels (b) and (c) are prior to bone resection. These plain X-​rays show the extent of the underlying osteomyelitis. Panels (e) and (f) illustrate the extensive soft tissue and bone resection that is necessary to control the deep infection Panels (g, h, i) show the further efforts used to sterilize the bone infection. Antibiotic impregnated into bone cement is inserted into the bony defect according to the technique described by Masquelet and colleagues. The soft tissue defect is reconstructed with a fasciocutaneous flap (in this case a free anterolateral thigh flap). The bone is then stabilized by way of a circular frame. It must be noted that this was stage one of a two-​stage procedure with stage two planned as a free vascularized fibula transfer.

5.10  Lower limb osteomyelitis

(e)

(f)

(g)

(h)

Fig. 5.10.3  Continued

(i)

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antibiotics are combined with surgical excision of the necrotic bone, including the biofilm and all infected tissue. Prolonged antibiotic therapy needs to be simple and well tolerated. It has been shown that trimethoprim with sulphamethoxazole is effective in Gram-​positive osteomyelitis. There appears to be an additive effect when monotherapy of ciprofloxacin is combined with rifampicin, especially in cases with extensive membrane or biofilm formation. Prolonged outpatient parenteral antibiotic therapy requires organization (Tice et al., 2003) but is often feasible and should be available particularly in regions with a specialist bone infection service.

REFERENCES

Fig. 5.10.4  Radiograph of a Charcot foot with neuropathic destruction of the talonavicular joint and midtarsal joints.

it exceeds the minimum inhibitory concentration for a therapeutic effect. To reach these levels it is often best to administer these antibiotics intravenously. Four to six weeks of targeted therapy is often used. A systematic review (Lazzarini et al., 2005) reported that most clinical studies employed 6 weeks of targeted antibiotic therapy as there was no evidence of improved outcomes when the treatment period is prolonged. Patients and their individual circumstances should be discussed with the infectious diseases team and therapy duration planned accordingly. The ‘cure’ rates are low when treatment is by antibiotics only, as there is poor penetration of antibiotics into necrotic bone, in addition to which bacteria can secrete a glycocalyx biofilm within which they remain dormant and protected. Some bacteria can survive for a long time within macrophages and other host cells. The success of treatment unsurprisingly therefore increases significantly when

Cierny G III, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res 2003;414:7–​24. Dahners LE, Bos GD Fluorescent tetracycline labeling as an aid to debridement of necrotic bone in the treatment of chronic osteomyelitis. J Orthop Trauma 2002;16:345–​6. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis 2005;9:127–​38. Peltola H, Pääkkönen M, Kallio P, et al. Prospective, randomized trial of 10  days versus 30  days of antimicrobial treatment, including a short-​term course of parenteral therapy, for childhood septic arthritis. Clin Infect Dis 2009;48:1201–​10. Termaat MF, Raijmakers PG, Scholten HJ, et al. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-​analysis. J Bone Joint Surg Am 2005;87:2464–​71. Tice AD, Hoaglund PA, Shoultz DA. Outcomes of osteomyelitis among patients treated with outpatient parenteral antimicrobial therapy. Am J Med 2003;114:723–​8. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis—​a review of clinical features, therapeutic considerations and unusual aspects. 3: osteomyelitis associated with vascular insufficiency. N Engl J Med 1970;282:316–​22. Yazar S, Lin CH, Lin YT, et  al. Outcome comparison between free muscle and free fasciocutaneous flaps for reconstruction of distal third and ankle traumatic open tibial fractures. Plast Reconstr Surg 2006;117:2468–​75. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-​joint infections. N Engl J Med 2004;351:1645–​54.

5.11

Management of congenital limb deficiency Fergal Monsell

Introduction Human limb bud development begins 24 days after conception with the appearance of the upper limb bud, and the lower limb bud appearing 4  days later. Limb bud development proceeds in a highly organized and predictable three-​dimensional pattern. The position of the embryonic limb is under control of HOX gene expression (Burke et al., 1995) and temporospatial control of limb bud development is mediated by the interaction of local gene expression and concentration gradients of cytokines driving highly organized development of the limb bud in the axial, dorsoventral, and pre-​and post-​axial planes. The limb bud is formed from of a core derived from the lateral plate mesoderm and an outer epithelial layer, which is ectodermal in origin (Searls and Janners, 1971). Mesodermal differentiation is responsible for the formation of connective tissues, and primary ossification centres develop in all long bones by the end of the first trimester. The limb musculature is derived from migration of adjacent mesodermal somites while the peripheral nerves originate from the neural crest.

causes are unknown, and no simple mechanism explains the broad spectrum of abnormality. The only known genetic predisposition for conditions affecting the femur is the rare femoral hypoplasia–​unusual facies syndrome. Thalidomide directly inhibits angiogenesis induced by bFGF or VEGF in vivo (D’Amato et al., 1994) and the patterns of limb deficiency observed after the thalidomide disaster are similar to those that occur spontaneously. It is thought that inhibition of angiogenesis is the mechanism responsible for teratogenicity (Therapontas et al., 2009) contributing to the femoral abnormalities seen in this overall group of conditions. Congenital longitudinal deficiency of the femur covers a broad spectrum, from minor hypoplasia to virtual absence of the femur, and is associated with abnormalities of the hip joint, which cause the limbs to be held in position of flexion, abduction, and external rotation (Fig. 5.11.1). There is often either abnormality or absence of the

Prenatal diagnosis Ultrasonography has been used since it was introduced in the late 1950s to assess the progress of the fetus and has become a routine component of antenatal care. Chitty and co-​workers (1994) produced standardized charts outlining the increase in dimensions of the radius, ulna, humerus, tibia, fibula, femur, and foot between 12 and 42 weeks of gestation. This information allows accurate monitoring of fetal limb development and facilitates antenatal recognition of skeletal malformation syndromes and isolated limb abnormalities.

Clinical features Femoral deficiency The incidence of major congenital abnormalities of the femur ranges from 1:50,000 to 1:200,000 live births (Oppenheim et al., 1998). The

Fig. 5.11.1  Characteristic clinical appearances of flexion, abduction, and external rotation of the left hip.

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SECTION 5  Lower limb

on the stability of the relationship between the deficient femur and pelvis. Sanpera and Sparkes (1994) confirmed that this classification was the most reliable for predicting outcome and Goddard and colleagues (1995) established that the X-​ray taken at 12–​15 months of age when the child was starting to stand and walk was easier to interpret and more reliable than that taken shortly after birth. The classification system described by Gillespie (1998) accounts for the extent of longitudinal deficiency, the morphology of the proximal femur, and the stability of the hip (Fig. 5.11.3). It is a straightforward system that defines those limbs in which surgical equalization is a realistic option and those that are more suitable for prosthetic reconstruction. A comprehensive, age independent classification system based on the degree of development and morphology of the femur is now in common use (Paley, 1998). This was designed to plan surgical reconstruction, with each sub-type having a separate surgical strategy. Fig. 5.11.2  Characteristic femoral geometry (varus retroversion and pseudarthrosis).

Fibula

articulation with a subtrochanteric pseudoarthrosis (Fig. 5.11.2). The distal femur may show a lateral femoral hypoplasia with valgus malalignment of the limb. The anterior cruciate ligament is often absent or rudimentary giving a complex instability pattern.

The fibular reduction abnormalities are generally described in terms of the morphology of the fibula. The Achterman and Kalamchi classification describes either complete absence (type 1) or proximal or distal deficiency (type 2A or 2B respectively) (Achterman and Kalamchi, 1979). Because it does not consider the condition of the foot and ankle, nor the concentric reduction in length, it is of little practical value in determining the optimum management and potential outcome.

Fibular deficiency

Tibia

Fibular hemimelia or longitudinal deficiency of the lateral structures is the most common lower limb long bone deficiency syndrome (Coventry and Johnson, 1952; Achterman and Kalamchi, 1979) and is accompanied by an associated (apex anterolateral) bowing deformity of the tibia. There is often associated dimpling of the skin at the apex of the tibial deformity. Foot and ankle abnormalities are common and range from complete absence of the lateral three rays to hypoplasia of the fifth toe. There is often an associated failure of segmentation of the tarsal bones and ankle abnormalities. The characteristic abnormalities of the femur described previously may also be seen.

The Jones radiological classification (Jones et al., 1978) of tibial longitudinal deficiencies is largely based on the site and pattern of tibial abnormality. There are five groups which describe either complete absence or a relative shortening of the tibia in association with diastasis of the fibula. This classification does not consider the condition of the foot and

Group A

Tibial deficiency Congenital deficiency of the tibia is a rare congenital malformation (approximately one per million live births). This is a pre-​axial deficiency with the tibia either absent or deficient in some degree. The foot and ankle can also be affected with a broad range of abnormalities from a duplication of the foot to a rudimentary foot with absence of any functional structure. This condition can be inherited and this is more likely the case if the deformity is bilateral (Clark, 1975).

Group B

Group C

Classification Femur Aitken (1969) suggested the term proximal femoral focal deficiency, which has become well established, but concentrates on the more severe end of the spectrum. The classifications of Hamanishi (1980) and Pappas (1983) cover the whole range of femoral deficiency. As there is characteristically delay in ossification of the femur in this condition, radiological groupings can change with age and radiological classification only becomes clearly established on serial X-​rays over time. Fixsen and Lloyd-​Roberts (1974) classified femoral deficiency based

Fig. 5.11.3  Gillespie’s clinical classification. Reprinted with permission from Herring J, Birch JG, (eds): The Child with a Limb Deficiency. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1998.

5.11  Management of congenital limb deficiency

ankle, the stability of the knee, or the proportion of shortening and is not of any practical use in terms of management planning or outcome.

Management options Advances over the last 20 years have broadened the indications for surgical reconstruction of this patient group, particularly the introduction of distraction lengthening in limb reconstruction, and it is possible to increase the length of the affected limb by up to 20–​25 cm in some cases. The goal must be to provide a patient with optimum function. While it is technically possible to increase the length of a limb, this is not always associated with improvement in function. Surgical reconstruction in these conditions usually requires multiple procedures throughout childhood and because of the associated joint abnormalities and instability, overall function is often poor when this approach is used for severe cases. The worst-​case scenario is for a child and family to embark on a decade or more of surgical reconstruction, to fail to achieve the primary goal of adequately increasing length of the limb, and to cause deterioration in function due to secondary abnormalities and complications affecting the joints, having fruitlessly ‘medicalized’ the child. It is thus important that the strategy for reconstruction, whether by lengthening or prosthesis, is determined in early childhood. The standard in the more significant abnormalities should be management with a prosthesis and surgery remains directed at optimizing this. The goal should be to enable the patient to walk with a normal or near-​normal pattern, and engage in normal employment, education, recreational, and social activities. Surgical lengthening is indicated in less severe deficiencies and when performed in early childhood is generally undertaken using an external fixator. The essential components of the external fixator are stable attachment to the proximal and distal segments and the ability to control the direction of lengthening in three dimensions. The different construction options are generally grouped as monolateral uniplanar, or circular fixators. The author’s preference is to use a circular fixator which allows control in three axes and reduces the risk of subsequent deformity. Aston and colleagues (2009) observed an incidence of 50% of subsequent fracture in lengthened femurs without intramedullary stabilization in congenital short femurs and irrespective of device, it is generally now agreed that attempted surgical lengthening of the femur should be accompanied by intramedullary stabilization. Knee instability following lengthening is due to the structural abnormality of the distal femur together with deficient cruciate ligaments aggravated by increasing tension in the hamstrings with lengthening, leading to posterior subluxation of the tibia at the knee joint. Extension of the fixator across the knee (Fig. 5.11.4) to the tibia will reduce the risk of subsequent dislocation but is complicated by protracted knee stiffness that often requires later surgical release of the quadriceps group. Prior to surgery, clinical assessment of the current and predicted leg length discrepancy, the range and stability of joints, and of any fixed joint deformity are essential for the preoperative planning. It is often necessary to perform surgical stabilization of the adjacent joints as a precursor to surgical lengthening. The lengthening proceeds at 1 mm per day in four increments, allowing satisfactory bone formation and being tolerated by the soft tissue structures, particularly the nerves and biarticular muscles. In general, lengthening is conducted in increments of 5 cm as this is generally agreed to be the limit that the soft tissues can tolerate.

Fig. 5.11.4  Anteroposterior radiograph during femoral lengthening. Note that the fixator crosses the knee to prevent subluxation.

Using a tactical series of reconstructive procedures, it is possible to achieve up to 20–​25  cm of lengthening. Growth plate ablation (epiphysiodesis) in the normal limb, inhibiting longitudinal growth on this side, can produce a further equalization of 5 cm at the expense of adult height. In practical terms, for a limb length discrepancy of 20 cm, this will require three lengthening procedures and epiphysiodesis and it is the author’s view that this is the limit of what can be sensibly achieved with the currently available techniques. Each lengthening process lasts for between 6 and 9 months and is monitored radiographically to assess the quality of new bone formation. Following each lengthening procedure, a protracted period of physiotherapy and rehabilitation is required to maximize the range of joint movements. Surgical reconstruction for congenital femoral abnormality is usually commenced in early childhood. This uses a combination of joint reconstruction and bony lengthening techniques. Any significant anatomical deficiency of the hip is addressed before the age of 3 years. The characteristic abnormality involves three-​dimensional correction of the proximal femur with augmentation of the acetabulum using conventional techniques. This is often associated with soft tissue releases and soft tissue reconstruction, particularly re-​ attachment of the hip abductors, to provide a more favourable moment arm. It is also possible to combine surgical lengthening with a three-​dimensional correction of distal femoral valgus and rotation. Contemporary techniques have expanded to involve the use of im-plantable, intramedullary lengthening devices. Recent improvements in design have led to a rapid increase in use and this approach is likely to replace external fixator correction, particularly for more modest femoral lengthening in older children. The concern with these devices is that while the bone will lengthen in a relatively predictable manner, the

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soft tissue complications remain the limiting factor and injudicious use of an intramedullary lengthening device may lead to joint subluxation. Surgical reconstruction of fibular dysplasia is conducted along similar lines using an external fixator to distract the tibia/fibula. It is often necessary to extend this fixator across the ankle and into the foot to protect the alignment of the ankle or to correct any associated deformity. The abnormalities associated with tibial dysplasia are generally unsuitable for surgical reconstruction and the majority of patients are managed with a prosthesis. The nature of congenital limb deformity, with the associated field defect that involves all tissue types, creates substantial difficulties when surgical lengthening is undertaken and these techniques are associated with an extremely high, but not necessarily prohibitive, complication rate. The knowledge that complication rates can approach 100% should not lead to a feeling of inevitability or complacency. Pin site infection is a common consequence of prolonged external fixation. Careful pin and wire insertion, wound care, and postoperative pin site care reduces but does not abolish this complication. Pain and erythema usually reflect infection. The use of broad-​spectrum antibiotics in appropriate doses for body weight is often effective. If resolution does not occur rapidly, parenteral antibiotics according to microbiological culture are needed. It is occasionally necessary to remove the infected fixation, and very rarely to abandon the procedure. Pain is often associated with infection, although neurogenic pain associated with the lengthening process may limit the rate of lengthening, as may mechanical symptoms related to instability due to improper fixator construction or loosening. The quality of the new (regenerate) bone depends on a number of mechanical and biological factors. An excessive rate of distraction may lead to deficient regenerate bone while premature consolidation is associated with slow distraction. Bone formation is monitored with frequent radiographs, and in some centres ultrasonography and computed tomography scanning are used. The optimum time for fixator removal is difficult to predict in some cases. Premature removal is complicated by regenerate failure, with deformity or fracture. The joint laxity that is commonly encountered in congenital femoral deficiency predisposes to joint subluxation and dislocation. This is an extremely grave occurrence and often leads to the procedure being abandoned. Careful preoperative assessment, surgical reconstruction of the joints before lengthening, and aggressive physical therapy during lengthening is important to prevent this complication.

Conclusion Congenital abnormalities of the lower limb are relatively uncommon group of conditions, but introduce significant challenges to the children’s orthopaedic surgeon. The fibular longitudinal reduction abnormalities are more common followed by femoral deficiency and the tibial reduction syndromes are rare. While it is technically possible to increase the length of an involved limb by up to 25%, this approach has to be balanced against the likely level of long-​term function. These procedures are subject to frequent complications often leading to a deteriorating level of function. The alternative approach is to manage this with a prosthesis confining a surgical treatment to modification of the limb to enhance

prosthetic use. This is an ongoing debate among clinicians involved in the care of these children and an individualized approach is necessary. The worst-​case management is to embark upon a difficult and protracted surgical sequence that leads to poor long-​term function and suboptimal prosthetic use.

REFERENCES Achterman C, Kalamchi A. Congenital deficiency of the fibula. J Bone Joint Surg Br 1979;61:133–​7. Aitken GT. Proximal femoral focal deficiency—​definition, classification, and management. In:  Aitken GT (ed) Proximal Femoral Focal Deficiency:  A Congenital Anomaly, pp. 1–​62. Washington, DC: National Academy of Sciences, 1969. Aston WJ, Calder PR, Baker D, et al. Lengthening of the congenital short femur using the Ilizarov technique: a single-​surgeon series. J Bone Joint Surg Br 2009;91:962–​7. Burke AC, Nelson CE, Morgan BA, et al. Hox genes and the evolution of vertebrate axial morphology. Development 1995;121:333–​46. Chitty LS, Altman DG, Henderson A, et  al. Charts of fetal size:  4. Femur length. Br J Obstet Gynaecol 1994;101:132–​5. Clark MW. Autosomal dominant inheritance of the tibial meromelia. J Bone Joint Surg Am 1975;57:262–​4. Coventry MB, Johnson EW. Congenital absence of the fibula. J Bone Joint Surg Am 1952;34:941. D’Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 1994;91:4082–​5. Fixsen JA, Lloyd-​Roberts GC. The natural history and early treatment of proximal femoral dysplasia. J Bone Joint Surg Br 1974;56:86–​95. Gillespie R. Classification of congenital abnormalities of the femur. In:  Herring J, Birch JG (eds) Classification of Congenital Abnormalities of the Femur, pp. 63–​72. Rosemont, IL:  American Academy of Orthopaedic Surgeons; 1998. Goddard NJ, Hashemi-​Nejad A, Fixsen JA. Natural history and treatment of instability of the hip in proximal femoral focal deficiency. J Pediatr Orthop B 1995;4:145–​9. Hamanishi C. Congenital short femur. Clinical, genetic and epidemiological comparison of the naturally occurring condition with that caused by thalidomide J Bone Joint Surg Br 1980;62:307–​20. Jones D, Barnes J, Lloyd-​Roberts GC. Congenital aplasia and dysplasia of the tibia with intact fibula. Classification and management. J Bone Joint Surg Br 1978;60:31–​9. Oppenheim W, Setoguchi Y, Fowler E. Overview and comparison of Syme’s amputation and knee fusion with the van Nes rotationplasty procedure in proximal femoral focal deficiency. In: Herring J, Birch JG (eds) The Child with a Limb Deficiency, pp. 61–​63. Rosemont, IL: American Academy of Orthopaedic Surgeons; 1998. Paley D. Lengthening reconstruction surgery for congenital femoral deficiency. In: Herring JA, Birch JG (eds). The child with a limb deficiency, pp. 113–32. Rosemount, IL: AAOS; 1998. Pappas AM. Congenital abnormalities of the femur and related lower extremity malformations:  classification and treatment. J Pediatr Orthop 1983;3:45–​60. Sanpera I Jr, Sparks LT. Proximal femoral focal deficiency:  does a radiologic classification exist? J Pediatr Orthop 1994;14:34–​8. Searls RL, Janners MY. The initiation of limb bud outgrowth in the embryonic chick. Dev Biol 1971;24:198–​213. Therapontos C, Erskine L, Gardner ER, et  al. Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proc Natl Acad Sci U S A 2009;106:8573–​8.

5.12

Orthopaedic management of congenital pseudarthrosis of the tibia Fergal Monsell

Introduction Congenital pseudarthrosis of the tibia (CPT) is an uncommon condition that is responsible for significant functional morbidity. There is no unified approach to management and surgical reconstruction is challenging. Approximately 55% of patients will have neurofibromatosis type 1 (NF1) (Hefti et al., 2000), but only 3–​5% of patients with florid neurofibromatosis will have evidence of CPT (Friedman and Birch, 1997). NF1 is an autosomal dominant disorder affecting approximately 1:4500 live births in the United Kingdom (Evans et al., 2010) and is caused by mutations in the NF1 gene. This gene encodes neurofibromin (Viskochil et al., 1990, 1993), a 240 kDa peptide that stimulates the intrinsic hydrolysis of Ras-​bound guanosine triphosphate (GTP) (Martin et  al., 1990). Mutations of Ras superfamily genes are seen in association with 20–​30% of all human tumours (Bos, 1989). The diagnosis of NF1 is initially based on clinical features including axillary freckling, cutaneous and plexiform neurofibromas, and café-​au-​lait spots with well-​demarcated edges, compared to the irregular margins seen in conditions including McCune–​Albright syndrome. Ocular signs include hamartomas of the iris (Lisch nodules) which are identified with a slit lamp, and optic nerve gliomas that are properly assessed with axial computed tomography or magnetic resonance imaging (MRI) scanning. The diagnosis in families with a recognized pedigree is relatively straightforward but a significant proportion present de novo with new mutations (Evans et al., 2010). The initial consultation is ideally conducted in conjunction with a clinical geneticist and the diagnosis secured with genomic analysis confirming the NF1 gene mutation. NF1 is associated with generalized abnormalities of bone metabolism including decreased bone mineral content and bone mineral density (Dulai et  al., 2007; Stevenson et  al., 2007). Other skeletal manifestations include scoliosis, which is either a characteristic adolescent pattern but with higher frequency than the general population, or a dysplastic, aggressive curvature, which is often due to neurofibromas of the spinal nerves as they exit the intervertebral foramen.

Sphenoidal wing hypoplasia, mosaic gigantism, leg length inequality, and pseudoarthrosis of clavicle and ulna are also occasional features of this condition and approximately 30% of patients with NF1 have one or more skeletal abnormalities (Crawford and Schorry, 1999). CPT is usually, but not invariably, present at birth as an anterolateral deformity of the leg. It is typically unilateral (Friedman and Birch, 1997) and there are a series of radiological subtypes classified according to cystic, dysplastic, or sclerotic changes (Boyd, 1982). Fracture typically follows a trivial injury and Stevenson and colleagues (1999) reported an average age at first fracture of 4.6 years (range 0–​28  years). The resultant pseudarthrosis is composed of cellular fibrocartilage, described as a ‘fibrous hamartoma’ (Ippolito et al., 2000; Sakamoto et al., 2007; Cho et al., 2008; Leskela et al., 2009; Heerva et  al., 2010). Cho and co-​workers (2008) reported that these cells maintained mesenchymal lineage phenotypes and were strongly osteoclastogenic. Heervä and colleagues (2010) demonstrated that multinuclear osteoclasts resided within the fibrotic pseudarthrosis tissue but 50% were not attached to bone. Selective staining is negative for S100, a Schwann cell marker (Stevenson et al., 2006; Sakamoto et al., 2007).

Orthopaedic management CPT is a difficult clinical problem and the therapeutic aim is to optimize long-​term function. There is often emphasis on achieving bone healing maintaining the integrity of the tibia, irrespective of the functional quality of the limb. Typically this involves surgical intervention on numerous occasions. Limb alignment and length, ankle function, and the risk of refracture are often omitted in descriptions of surgical techniques where bone healing is the reported outcome measure. Stevenson and colleagues (1999) reported that an average of three surgical procedures were necessary in this condition with some patients having as many as ten. The timing of optimum management is controversial but the consensus view in the orthopaedic community is that treatment should begin when the child begins to walk, a milestone often delayed in

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SECTION 5  Lower limb

these children. There is some evidence that aggressive management of the tibial abnormality with vascularized fibular flap transfer produces early union (Erni et al., 2010) but the general approach, and the author’s view, is that it is prudent to brace the limb in the dysplastic stage as outcomes tend to be worse when the fractures occur in younger patients (Murray and Lovell, 1982). Provided the splints are well made, there are few disadvantages associated with this pragmatic approach. There is often a considerable apex anterolateral deformity of the tibia (Fig. 5.12.1), but the author’s view is that this in itself does not mandate the immediate osteotomy and stabilization. There is a high risk of non-​union following osteotomy and the alternative approach is to delay surgery until there is an obvious functional deterioration. Provided mobility is improving, there is no urgency to proceed to osteotomy and this can be performed at any point during childhood after discussion about a relatively high risk of non-​union and other complications. For patients with an established non-​union, management can initially be with an orthosis to stabilize the affected segment and a shoe lift to accommodate the evolving leg length discrepancy. (a)

(b)

Fig. 5.12.1  A 6-​year-​old girl with NF1. Anterolateral bowing, thickening of cortex, and narrowing of medullary canal. (a) Anteroposterior radiograph. (b) Lateral radiograph.

When surgical correction is indicated, the principles include mechanical realignment of the leg, preservation of good ankle and foot function, and establishing union of the tibia where the tibia is likely to be adequate. It is of no benefit to the patient to re-​establish tenuous bone continuity if this results in a functionally inferior limb. Surgical management of an established pseudoarthrosis has evolved over the last few decades (Coleman et al., 1995; Grill et al., 2000) and usually involves stabilization with an intramedullary device. This approach was initially described in the 1950s (Charnley, 1956) and subsequently modified to include iliac crest bone grafting (Umber et al., 1982). Johnston (2002) described a series of 23 consecutive patients with CPT reviewed between 4 and 14 years after surgical intervention. Unequivocal union of the tibia was achieved in 48%, but usually required more than one surgical procedure. Dobbs and colleagues (2004) reported results at a mean time of 9 years in 21 patients with an eventual healing rate of 86%. The mean time to union was 16 months and this also required multiple procedures but the rate of refracture at the site of the initial pseudarthrosis was 57%. A number of more recent modifications have been made to this technique and include extraperiosteal excision of the pseudarthrosis site and intramedullary rod stabilization augmented with autogenous iliac crest bone graft (Johnston, 2002; Dobbs et al., 2004). The author uses a sliding intramedullary device (Fassier–​Duval rod) as it provides robust stabilization and elongates, allowing for longitudinal growth. Long-​standing deformity is associated with secondary changes in the growth plate of the distal tibia. This can lead to valgus deformity of the ankle, which is confounded by the fibular non-​union that often accompanies the CPT (Fig. 5.12.2). It is possible to correct the ankle alignment using hemiepiphyseal stapling and the combination of rodding and stapling can result in a good functional outcome (Fig. 5.12.3).

Fig. 5.12.2  An 8-​year-​old boy with NF1. Chronic pseudarthrosis.

5.12  Orthopaedic management of congenital pseudarthrosis of the tibia

(a)

(b)

(c)

Fig. 5.12.3  A 9-​year-​old boy with CPT. (a) Managed with intramedullary rod. (b) Subsequent lengthening and hemiepiphyseal stapling aged 11 years. (c) Result at 16 years of age.

Patients with good evidence of bone healing, in whom the mechanical axis of the tibia is restored, require surveillance to ensure that the longitudinal growth proceeds in a satisfactory manner. There is often an associated leg length discrepancy and this can be managed along conventional lines, usually with a contralateral epiphysiodesis. It is possible to lengthen the affected tibia using standard distraction osteogenesis techniques but there are occasional cases in which bone formation is very poor. In cases that have been stabilized with an intramedullary device but have a persistent non-​union, the decision to attempt surgically to eradicate the pseudoarthrosis needs to be made very carefully. The aim is to perform an extraperiosteal excision of all diseased tissues and the author’s standard age for excision of pseudoarthrosis and reconstruction with bone transport is between 8 years and puberty based solely on the ease of surgery in the older patient. The extent of the pseudoarthrosis can be evaluated preoperatively with an MRI scan, but the standard approach is to excise the affected tibia and periosteum until there is an established intramedullary canal and visibly normal periosteal tissue. This often results in a significant bone defect, reconstituted with bone transport using an external fixator or using the contralateral fibula as a vascularized flap. Bone transport with an external fixator is commonly complicated by pin site infection, particularly if there is a long transporting segment. The ankle is often affected either because of lack of the fibular buttress or secondary growth disturbance, and addressing this should form part of the correction. Routinely crossing the ankle joint to recruit the os calcis is illogical and condemns the patient to poor ankle function and therefore an abnormal pattern of walking. There is also a high risk of fracture at the docking sites, which also precludes early return to normal function. Grill and colleagues (2000) reported an eventual healing in 75% of patients following surgery using the Ilizarov technique but this involved multiple procedures and was associated with a protracted time to final healing. Vascularized free fibula transfer is a recognized technique in the management of CPT (Fig. 5.12.4). Most reports, however, are of small groups of patients using a variety of techniques to augment the vascularized bone flap. The literature has generally reported on small

series of patients followed up for less than 10 years and which are unable to comment on the outcome in the skeletally mature patient. Weiland and colleagues (1990) reported the result of free vascularized fibula transfer in 19 patients with CPT at a mean age of 5.1 years, followed for 6.3 years. Healing of the graft occurred in 18 patients, with a relatively modest leg length discrepancy but ten patients had residual or progressive valgus malalignment suggestive of recurrence of deformity. The authors did not present any functional data but noted that there was minimum morbidity at the fibula donor site. Kanaya and co-​workers (1996) reported the use of vascularized fibular and rib flaps in the treatment of CPT with mean follow-​up of 8 years. They observed that although nine of the ten transferred fibulae united within

Fig. 5.12.4  Free fibular transfer.

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4 months, there was a mean residual shortening of 3.8 cm and 20° and 24° of flexion and valgus deformity respectively. Korompilas and colleagues (2009) reported the results of free vascularized fibula transfer in eight patients with union of both ends of the flap in seven of eight patients within 4  months. Treatment in this group was augmented with internal fixation in five patients and external fixation in the other three. Complications included non-​union requiring multiple procedures in one patient and a stress fracture in a second patient. The authors made the point that long-​term follow-​up is necessary to properly evaluate the surgical results. Finally, Dormans and co-​workers (1990) reported union in 11 of 12 patients with CPT managed with free vascularized fibula transfer at a mean age at surgery of 6.5 years and an average follow-​up of 3.4 years. One patient required multiple operations and the authors recommended that all angulation should be corrected at the first sign of delayed union and that regrafting and intramedullary fixation should be used. The potential risk of surgical reconstruction by either bone transport or free fibula transfer is non-​union after intercalary excision with the patient undergoing a protracted period of what can be difficult treatment with no long-​term functional benefit. It is unfortunately impossible to predict the quality of union on the preoperative radiographs and MRI scans but the requirements of the technique are that all visibly affected bone is excised and that a mechanical axis of the bone is accurately re-​established. If there is residual deformity, the risk of fracture remains high and it is not possible for the patient to return to a full repertoire of physical activities. The alternative approach to pseudarthrosis excision and reconstruction is a below-​knee amputation and prosthetic rehabilitation. This option needs to be discussed very carefully with the family of an affected child. There has been considerable interest in pharmacological manipulation of the pseudarthrosis site using bisphosphonates and bone morphogenetic proteins (BMPs). There is a large body of experimental and clinical work directed to this issue and clinical algorithms which can be used in this circumstance are evolving. BMPs have been used in the management of patients with open tibial fractures (Govender et al., 2002) and tibial fractures with cortical defects (Jones et al., 2006) but the literature considering the use in CPT is scant. Richards and colleagues (2010) reported five of seven patients (71%) with radiographic union at a mean time of 6.4 months following stabilization with an intramedullary rod, augmented with autogenous iliac crest and rhBMP-​2 saturated absorbable collagen sponge. Schindeler and colleagues (2011) induced fractures of the distal tibia in Nf1+/​− heterozygous and wild type mice treated with surgical pinning and placement of BMP-​2 at the fracture site with or without biweekly intraperitoneal injection of zolendronic acid. The NF1 mice showed a lesser response to BMP-​2 alone compared to the wild type group however, when bisphosphonate (zolendronate) was added to BMP, the NF1 group healing rate improved significantly, with 75% showing partial or total bridging of the fracture site.

Conclusion CPT is an uncommon condition which is challenging to treat. A  number of surgical approaches have been developed but none consistently produce union of the tibial deformity.

Expectant management is appropriate until mid-​childhood when function tends to deteriorate. At this point, the surgical options include intramedullary stabilization using a variety of devices. Excision and bone transport can produce satisfactory rates of union although surgery is difficult and protracted with complications including malalignment and leg length discrepancy. Vascularized fibula transfer can also produce union in a high number of cases but is often complicated by a refracture or subsequent deformity. An alternative approach is below-​knee amputation which although extreme, in the presence of good prosthetic provision, is the only predictable method of producing normal function for this difficult condition.

REFERENCES Bos JL. Ras oncogenes in human cancer:  a review. Cancer Res 1989;49:4682–​9. Boyd HB. Pathology and natural history of congenital pseudarthrosis of the tibia. Clin Orthop Relat Res 1982;166:5–​13. Charnley J. Congenital pseudarthrosis of the tibia treated by intramedullary nail. J Bone Joint Surg Am 1956;38:283–​90. Cho TJ, Seo JB, Lee HR, et  al. Biologic characteristics of fibrous hamartoma from congenital pseudarthrosis of the tibia associated with neurofibromatosis type 1. J Bone Joint Surg Am 2008; 90:2735–​44. Coleman S, Coleman D, Biddulph G. Congenital pseudarthrosis of the tibia: current concepts of treatment. Adv Oper Orthop 1995;3:121–​45. Crawford AH, Schorry EK. Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 1999;7:217–​30. Dobbs MB, Rich MM, Gordon JE, et al. Use of an intramedullary rod for treatment of congenital pseudarthrosis of the tibia. A long-​term follow-​up study. J Bone Joint Surg Am 2004;86:1186–​97. Dormans JP, Krajbich JI, Zuker, R, et al. Congenital pseudarthrosis of the tibia:  treatment with free vascularized fibular grafts. J Pediatr Orthop 1990;10:623–​8. Dulai S, Briody J, Schindeler A, et al. Decreased bone mineral density in neurofibromatosis type 1: results from a pediatric cohort. J Pediatr Orthop 2007;27:472–​5. Erni D, De Kerviler S, Hertel, R, et al. Vascularised fibula grafts for early tibia reconstruction in infants with congenital pseudarthrosis. J Plast Reconstr Aesthet Surg 2010;63:1699–​704. Evans DG, Howard E, Giblin C, et al. Birth incidence and prevalence of tumor-​prone syndromes:  estimates from a UK family genetic register service. Am J Med Genet A 2010;152A:327–​32. Friedman JM, Birch PH. Type 1 neurofibromatosis:  a descriptive analysis of the disorder in 1,728 patients. Am J Med Genet 1997;70:138–​43. Govender S, Csimma C, Genant HK, et al. Recombinant human bone morphogenetic protein-​2 for treatment of open tibial fractures:  a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 2002;84-​A:2123–​34. Grill F, Bollini G, Dungl P, et al. Treatment approaches for congenital pseudarthrosis of tibia:  results of the EPOS multicenter study. European Paediatric Orthopaedic Society (EPOS). J Pediatr Orthop B 2000;9:75–​89. Heerva E, Alanne MH, Peltonen S, et al. Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity, aberrant morphology, and resistance to serum deprivation. Bone 2010;47:583–​90.

5.12  Orthopaedic management of congenital pseudarthrosis of the tibia

Hefti F, Bollini G, Dungl P, et  al. Congenital pseudarthrosis of the tibia:  history, etiology, classification, and epidemiologic data. J Pediatr Orthop B 2000;9:11–​15. Ippolito E, Corsi A, Grill F, et  al. Pathology of bone lesions associated with congenital pseudarthrosis of the leg. J Pediatr Orthop B 2000;9:3–​10. Johnston CE 2nd. Congenital pseudarthrosis of the tibia:  results of technical variations in the Charnley-​Williams procedure. J Bone Joint Surg Am 2002;84:1799–​810. Jones AL, Bucholz RW, Bosse MJ, et al. Recombinant human BMP-​2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial. J Bone Joint Surg Am 2006;88:1431–​41. Kanaya F, Tsai TM, Harkess J. Vascularized bone grafts for congenital pseudarthrosis of the tibia. Microsurgery 1996;17:459–​69. Korompilias AV, Lykissas MG, Soucacos PN, et  al. Vascularized free fibular bone graft in the management of congenital tibial pseudarthrosis. Microsurgery 2009;29:346–​52. Leskela HV, Kuorilehto T, Risteli J, et  al. Congenital pseudarthrosis of neurofibromatosis type 1:  impaired osteoblast differentiation and function and altered NF1 gene expression. Bone 2009;44: 243–​50. Martin GA, Viskochil D, Bollag G, et al. The GAP-​related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 1990;63:843–​9. Murray HH, Lovell WW. Congenital pseudarthrosis of the tibia. A  long-​term follow-​up study. Clin Orthop Relat Res 1982; 166:14–​20.

Richards BS, Oetgen ME, Johnston CE. The use of rhBMP-​2 for the treatment of congenital pseudarthrosis of the tibia: a case series. J Bone Joint Surg Am 2010;92:177–​85. Sakamoto A, Yoshida T, Yamamoto H, et al. Congenital pseudarthrosis of the tibia: analysis of the histology and the NF1 gene. J Orthop Sci 2007;12:361–​5. Schindeler A, Birke O, Yu NY, et al. Distal tibial fracture repair in a neurofibromatosis type 1-​deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate. J Bone Joint Surg Br 2011;93:1134–​9. Stevenson DA, Birch PH, Friedman JM, et al. Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1. Am J Med Genet 1999;84:413–​19. Stevenson DA, Moyer-​Mileur LJ, Murray M, et al. Bone mineral density in children and adolescents with neurofibromatosis type 1. J Pediatr 2007;150:83–​8. Stevenson DA, Zhou H, Ashrafi S, et al. inactivation of NF1 in tibial pseudarthrosis. Am J Hum Genet 2006;79:143–​8. Umber JS, Moss SW, Coleman SS. Surgical treatment of congenital pseudarthrosis of the tibia. Clin Orthop Relat Res 1982;166:28–​33. Viskochil D, Buchberg AM, Xu G, et al. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 1990;62:187–​92. Viskochil D, White R, Cawthon R. The neurofibromatosis type 1 gene. Annu Rev Neurosci 1993;16:183–​205. Weiland AJ, Weiss AP, Moore JR, et al. Vascularized fibular grafts in the treatment of congenital pseudarthrosis of the tibia. J Bone Joint Surg Am 1990;72:654–​62.

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5.13

How the foot and ankle works (mechanics of the foot) Ian Winson

Introduction The foot is a complex structure that has evolved from the hind limbs of an arboreal ape-​like ancestor to an efficient propulsion mechanism for the upright human. The foot’s ability to combine efficient shock absorption, standing (body support), propulsion, and accommodating surface irregularities has been a major contributor to the evolutionary success of Homo sapiens. The foot must not only absorb shock or impact, but support the weight of the body and accommodate the irregularities of the surfaces upon which we stand or walk while providing propulsion. This is achieved by being a torque converter of rotational movement of the limb as a whole, by being an energy store, and by being able to accommodate different surfaces and different levels of function. Essentially it has spare capacity when undertaking normal gait in normal people. It is intrinsically stable in all positions when in contact with the floor so that a great deal of mechanical behaviour of the foot through the stance phase of gait is passive in nature. To produce a stable and a propulsive foot, it is critical that once the forefoot is in contact with the floor, it does not move from that contact position until the very late stage of toe-​off. In order to achieve this, there are specific characteristics, both in shape and position of the ligaments, bones, and joints, and of muscle activity. When observing the standing foot that is flat to the floor, the heel is in valgus and there is no possibility of the foot moving out or flattening further. When a normal individual stands on their toes, their heel is in varus and the longitudinal arch is more pronounced. There is some requirement of muscle activity to maintain this posture, but the foot is equally stable in both positions. It is common for clinicians to mistake the characteristics of the pathological foot as a predictor of behaviour of the normal foot. Equally, the behaviour of the normal foot is somehow extrapolated to represent the appearances seen in the pathological foot.

Kinematics of the foot and ankle When examining foot movement, especially when all joints are taken into account, there are six degrees of freedom of motion with

rotation in three planes (axial, coronal, and sagittal) and translation in the same three planes. The limit of motion is defined by the shape of the joints and more particularly the ligamentous restraints. All described motions and direction of movement of course depend on the starting point. Effectively for the foot, that is best defined as the position the joints assume on weight-​bearing (neutral standing). This is the position at which the foot is stable, with the body’s weight loaded axially through the apex of the longitudinal arch and with no muscles active. To achieve this, both feet need to be on the ground with the load evenly distributed through each foot.

The ankle joint The ankle is essentially an obliquely placed hinge. The talus forms the inferior part of the ankle joint and has a shorter medial border than lateral border. As a consequence, as the talus rotates around the axis defined by the two malleoli, the movement laterally is greater than the degree of movement medially. Hence, when going from plantarflexion to dorsiflexion, the talus goes from a position of relative internal rotation to relative external rotation (Lundberg et al., 1989a). To an extent this is facilitated by rotation through the inferior tibiofibular joint (Lundberg et  al., 1989b, 1989c). This axis is oblique in both the horizontal and vertical planes. As no tendon is attached to the talus, its range of movement is solely defined by its ligamentous restraints. Proportionally, the lateral ligaments are clearly mechanically weaker than the medial ligaments (Attarian et al., 1985) but the lateral ligaments have an important role as the obliquity of the rotation of the talus means that as the ankle becomes more plantigrade and even dorsiflexed, the ligamentous restraints on the lateral side become orientated to resist anterior displacement (Stormont et  al., 1985; Renstrom et  al., 1988; Burks and Morgan, 1994). Bony anatomy prevents inversion (Renstrom et al., 1988). Approximately 50% of foot dorsiflexion and plantarflexion occurs through the ankle (Arndt et al., 2004). The talus can be seen to be effectively conical with a smaller medial facet to the lateral facet. One might imagine that the axis of rotation of the ankle would be reproducible in in vivo studies. A study using Roentgen stereophotogrammetry markers showed that the dorsiflexion axis (from plantigrade to maximum dorsiflexion) is very reproducible with the locus of the axis at the midpoint of the talus (Lundberg,

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1989). In contrast, the axis of rotation into plantarflexion varies from a predictable axis between the malleoli, to an axis that is at least 30° offset to that. This is almost certainly related to the relative underlying foot shape. With this oblique axis, measured in a horizontal plane, the ankle both supinates and pronates, and rotates internally and externally with variation in these axes between individuals (Lundberg, 1989). These movements are passive rather than active. They are based on the ligamentous restraints, rather than being initiated by specific muscle groups as the muscles attach anteriorly to the midtarsal joints and beneath the subtalar joint.

Subtalar joint The kinematic characteristics of the subtalar (talocalcaneal) joint are intimately linked to the talonavicular joint (TNJ) and the calcaneocuboid joint (CCJ). It is through the change in orientation of the axis of the subtalar joint in relationship to the ankle joint that the torque converted characteristics of the ankle and foot in relationship to the overall axis of alignment of the lower limb is best defined (Fig. 5.13.1). The axis of rotation of the ankle could be broadly described as being around a transverse plane. The axis of rotation of the subtalar joint is oblique to the horizontal plane and the sagittal plane (Inman, 1976). In a normal foot, it effectively runs from the posterior process of the calcaneum, to exit more medially on the foot through the midpoint of the head of the talus. Its exact position is quite variable, depending on the underlying foot morphology. The range of movement is approximately 40° around that axis and the arc of that movement is again dependent on the underlying foot type. It is often pointed out that there is an element of translation down the length of the foot, in keeping with the characteristics of an Eulerian screw. This is an elongated screw thread; the effect

being to produce fairly rapid translation down the axis of rotation as it runs from the position of eversion to inversion, pronation to supination. This translation is extremely limited as the total arc of movement is only 40°. The subtalar joint movement is limited by its ligamentous restraints and the ligaments are influenced heavily by the action of the Achilles tendon, which acts on the calcaneum.

Talonavicular and calcaneocuboid joints The TNJ and the CCJ are mechanically linked and ultimately represent the greatest available range of movements in the normal foot around the longitudinal axis (pronation and supination). They also allow abduction and adduction (motion around the vertical axis) and contribute to motion around the transverse axis (dorsiflexion and plantarflexion). Both joints are capable of six degrees of freedom with the TNJ being a ball-​and-​socket joint and the CCJ a saddle joint. They have some bony characteristics that help with stability but it is their ligamentous restraints which limit the range of motion and define the behaviour of the two joints in relationship to each other. The bone anatomy of the TNJ shows a marginally incongruent fit. This means that as the load goes through the joint, the talus is forced more into the navicular. This increases the contact area between these bones and therefore makes the joint marginally stiffer. At the same time, the cuboid has an extra facet of bone whose function is to impact on the calcaneum once the limit of motion is achieved to prevent it moving any further. These factors are relatively minor in comparison to the effect of the ligamentous restraints. The motions of the two joints do seem to be intimately linked so that as the foot moves from two extremes of position, the TNJ range of movement is nearly twice that of the range of movement of the CCJ. If one regards the proximal bone as being the reference point, then the effect of the greater range of movement of the TNJ is to change the position of the cuboid and the navicular. This is the same effect as is seen in the subtalar joint where the calcaneum and the talus change their positions where rotation into inversion places the calcaneum under the talus. Here it is best described as the two extreme positions. When the foot is flat to the floor as in neutral standing, the two bones are essentially in the same plane horizontally, that is, next to each other. In contrast, at the other end of the excursion of movement when standing on the toes (with the heel in varus and the longitudinal arch raised), the cuboid rotates until it is lying inferior to the navicular. This influences all of the joint orientations ahead of the two midtarsal joints.

Midtarsal joints and Lisfranc (tarsometatarsal) joints

Fig. 5.13.1  The complex inter-​relationship between the axes of rotation of the various component joints of the hindfoot and the restraints created by the ligaments allows rotational movements down the length of the limb to be converted through 90°. This leads to changes in alignment between the hind-​and the forefoot which makes the foot both stable and propulsive.

The range of movement and functional implications of the midtarsal and tarsometatarsal joints (TMTJs) have not been accurately studied. The general shape of the navicular cuneiform joint would suggest it is functioning as a very restricted form of ball-​and-​socket joint. The range of movement of the TMTJs varies across from the first to the fifth metatarsal. The first TMTJ has an arc of movement no more than 15° and the majority of that is around a longitudinal axis (Wanivenhaus and Pretterklieber, 1989). The central two metatarsals don’t move significantly in any plane but the fourth and fifth have the most movement with a range of movement of about 20°, the majority being in the dorsiflexion–​plantar flexion plane (Ouzounian and Shereff, 1989).

5.13  How the foot and ankle works (mechanics of the foot)

The net effect of this differential movement is to produce rotation around a central longitudinal axis of the central two metatarsals. This means that as the longitudinal axis of the foot rises and falls, the first metatarsal will change its presentation to the ground so that load will always be through the sesamoids onto the metatarsal head. On the lateral border, the fourth and fifth movement will cause the metatarsal heads to rise and fall which will create apparent pronation and supination around an axis defined by the two central stable metatarsals.

The metatarsals and toes The importance of the metatarsophalangeal joints (MTPJs) to the function of the foot cannot be overemphasized. The axis of movement of the great toe is in the transverse plane. The lesser MTPJ’s axis is basically transverse but has an element of obliquity from proximal–​lateral to distal–​medial. They essentially work in the dorsiflexion and plantar flexion planes with some abduction and adduction. This explains why they look like small ball-​and-​socket joints. Because the plantar fascia is attached to the base of the toes, the position of the MTPJs can potentially influence the position and stability of the whole foot (see ‘Mechanical structure of the foot’). Combined with the toes, the metatarsal fat pad does not move from where they first make contact with floor. Under normal gait conditions, the interphalangeal joints function in a fully dorsiflexed (i.e. straight) position.

Mechanical structure of the foot The mechanical structure of the foot is often thought of in relatively simplistic terms as a simple Roman arch along the longitudinal axis of the foot. Though one can conceive that this concept has possible validity in a static position, it is clearly far too simplistic to explain the function of the foot in dynamic terms. The foot is essentially an extension of the lower limb, rotated through 90° to the longitudinal axis of the leg. The change in rotation commences at the level of the ankle. It is obvious from the distribution of the ligaments and tendons that between the ankle, hindfoot, and midfoot, the change in rotation is clearly dependent on the shape of joints. The shapes of the bones and the joints have a degree of intrinsic stability but it is the ligamentous structures that define the stability of the foot. Furthermore, the ligaments produce linked movements such that from the point of contact of the heel on the ground, through the various stages of the stance and swing phase, the stability of the foot is maintained, despite significant changes in the rotational alignment of both the limb and the foot. The foot has no muscle attachments on the distal side of the ankle joint and only the tendo-​Achilles on the distal side of the subtalar joint. The role of the ligaments is therefore critical not only to the stability of the joints but also to the movement of the foot and it is they that most transmit the rotation motion of the limb to the foot. The foot’s stability would be best described as a tie bar system and the same mechanism causes the foot to produce linked movement. The plantar fascia is the important structure for stability. The plantar fascia takes its proximal origin from the calcaneum passing forwards to attach mainly to the base of the toes, spreading from the base of the first to the fifth toe, mimicking the contact area of the foot in standing neutral. It ensures that once the toes are in contact

with the floor, under normal circumstances they stay in that position. It is often described in functional terms as being the cause of the windlass mechanism—​as the toes dorsiflex, the unsupported heel will swing into varus thus increasing the height of the longitudinal arch. It is often forgotten that the reverse windlass mechanism is important in maintaining the toes in a stable position once a flat foot is achieved. Because it is furthest from the axis of rotation of the midfoot joints, the plantar fascia through its attachments will have the biggest influence on weight-​bearing stability and the position of the foot as a whole. The plantar ligaments are also very strong as they link various joint segments together and they prevent the apex of the arch flattening any further once the foot achieves its flattest position. This mechanism begins at the ankle as the medial deltoid ligament. The deltoid ligament is linked intimately with the ligaments of the medial subtalar joint and ultimately the spring ligament. This combination prevents excessive eversion and abduction and thus defines the limit of ‘flatness’ of the foot by keeping the midtarsal joints over the triangle of support provided by the plantar fascia. Offsets to this ‘normal’ mechanical situation can produce a considerable increase in forces tilting the foot either into a more everted or inverted position. The medial ligament is considerably stronger than the lateral ligaments. Indeed, if you test the strength of the lateral ligaments they are not strong enough to resist forces that could go through them in relatively normal circumstances and muscle action is necessary to maintain stability under circumstances where the foot and ankle is functioning at more than a normal paced gait. The ligaments have an important role in proprioception and consequent dynamic stability with muscle action supporting joint stability.

Muscle function, tendon position, and the axis of rotation As it is normal practice to define motion against the proximal bone, it is easy to forget that the fixed point around which motion has to occur is whatever the contact point the foot has at any point in time. It is conventional to describe gait in swing and stance phases. In the normal foot, it is the stance phase that most defines the elegance of the mechanism that has evolved. The floor contact can be broken down into first contact (most commonly heel strike), flat foot (when all of the plantar aspect is in contact), mid stance (a point at which load is evenly distributed between the hindfoot and forefoot), heel-​ off, and toe-​off. The muscle functions vary to some extent depending on the point of contact of the foot during stance. What is clear is that the convention of agonists and antagonists has little validity in the behaviour of muscle action. It is the relationship of the muscle attachment to the position of the joint axes that determines their exact action at any one time. As previously stated, the position and initial movement of any of the joints through their potential range of movement is determined by the input motion created by the rest of the limb and the contact area of the foot. Accordingly, although the TA is the major plantar flexor of the foot, it can act either side of the subtalar axis depending on whether the heel is in contact with the ground. It can increase the eversion or inversion power that is enhanced by virtue of its attachment to the very posterior part of the calcaneum increasing its lever arm. Similarly, the tibialis anterior lies on the subtalar axis making it an efficient dorsiflexor. If the foot is prepositioned in inversion or

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eversion it will contribute to movement in that direction. Tibialis posterior and peroneus longus act as a sling support to foot when the heel is off the ground. Tibialis posterior inverts the subtalar joint and also increases the longitudinal arch (plantar flexing the midfoot joints). What is not so well recognized is that peroneus longus tendon effectively has the same effect because of its sling around the cuboid and its attachment to the medial cuneiform and the base of the first metatarsal. If the forefoot is on the ground, the effect of peroneus longus is to decrease the distance between the lateral and medial borders of the foot. It does this by pushing the cuboid under the navicular with the inevitable increase in the longitudinal arch height. The peroneus brevis is the major abductor of the foot and primarily acts at a point where the strong medial and plantar ligaments of the midfoot are at their maximum excursion. The long flexors and extensors do not significantly contribute to movement or stability in normal gait. In combination with the intrinsic muscles, their main function is to help hold the toes straight and stable against the floor. This maximizes the plantar fascia’s windlass and reverse windlass mechanisms.

Conclusion The foot is a highly complex structure which is essentially stable in all positions under normal circumstances. Its functions are primarily those of support, propulsion, and adaption with shock absorption being achieved in a manner that allows the foot to store and release energy. It achieves these functions by acting as a torque converter, changing rotational forces down the limb to stabilizing and propulsive forces. The support structure of the foot and ankle is robust and particularly involves those ligamentous structures on the plantar and medial aspect of the foot, especially the plantar fascia. Muscle and tendon function needs to be balanced for best function

to be achieved. Clinicians need to recognize that in any pathological situation the ability of the foot to maintain its function is compromised by shape, stability, and muscle function.

REFERENCES Arndt A, Westblad P, Winson I, et al. Ankle and subtalar kinematics measured with intracortical pins during the stance phase of walking. Foot Ankle Int 2004;25:357–​64. Attarian DE, McCrackin HJ, Devito DP, et al. Biomechanical characteristics of human ankle ligaments. Foot Ankle 1985;6:54–​8. Burks RT, Morgan J. Anatomy of the lateral ankle ligaments. Am J Sports Med 1994;22:72–​7. Inman VT. The Joints of the Ankle. Baltimore, MD:  Williams & Wilkins; 1976. Lundberg A. Kinematics of the ankle and foot. In vivo roentgen stereophotogrammetry. Acta Orthop Scand Suppl 1989;233:1–​24. Lundberg A, Goldie I, Kalin B, et  al. Kinematics of the ankle/​foot complex:  plantarflexion and dorsiflexion. Foot Ankle 1989a;9: 194–​200. Lundberg A, Svensson OK, Bylund C, et  al. Kinematics of the ankle/​foot complex  –​Part  3:  influence of leg rotation. Foot Ankle 1989b;9:304–​9. Lundberg A, Svensson OK, Nemeth G, et al. The axis of rotation of the ankle joint. J Bone Joint Surg Br 1989c;71:94–​9. Ouzounian TJ, Shereff MJ. In vitro determination of midfoot motion. Foot Ankle 1989;10:140–​6. Renstrom P, Wertz M, Incavo S, et al. Strain in the lateral ligaments of the ankle. Foot Ankle 1988;9:59–​63. Stormont DM, Morrey BF, An KN, et al. Stability of the loaded ankle. Relation between articular restraint and primary and secondary static restraints. Am J Sports Med 1985;13:295–​300. Wanivenhaus A, Pretterklieber M. First tarsometatarsal joint: anatomical biomechanical study. Foot Ankle 1989;9:153–​7.

5.14

The skeletal consequences of meningococcal septicaemia Fergal Monsell

Introduction Neisseria meningitidis is a Gram-​negative diplococcus, which is uniquely pathogenic to humans. It exists as a commensal in the nasopharynx and causes a spectrum of disease including meningitis, septicaemia, or a combination of these. The rate of infection has varied considerably over the last decade and the introduction of active vaccination against type C strain in 1999 led to a significant reduction in cases due to this serotype. Almost all cases of meningococcal disease in England and Wales at the present time are caused by serotype B (National Institute for Health and Care Excellence, 2010).

Management of meningococcal septicaemia Sophisticated algorithms for management for the acute phase of this disease have been produced, initially by Pollard and colleagues (1999) and more recently by the National Institute for Health and Care Excellence (2010). The overall mortality from meningococcal septicaemia has improved significantly in the last three decades and an increasing number of survivors with long-​term skeletal consequences are being seen. Edwards and colleagues (2016) reported on a consecutive cohort of 138 patients admitted to a regional paediatric intensive care unit with a primary diagnosis of meningococcal septicaemia. There was a gradual decline in the annual admission rate over the study period. The mortality rate was 5.8% (8/​138) and 7.7% (10/​130) of the patients alive at discharge required an amputation or sustained a growth plate injury leading to angular and axial limb deformity. All those with orthopaedic complications had noticeable skin involvement, compared to only a single case in patients without skin involvement. The priorities of acute management are to optimize the metabolic profile of the patient, manage the systemic consequences including renal failure, preserve potentially viable tissue, and prevent secondary soft tissue infection. This management is complicated

by the coagulopathy associated with meningococcal sepsis and the increased capillary permeability that is the consequence of the endotoxic response, compounded by aggressive intravenous fluid therapy in addition to the effect of inotropic agents used to manage the cardiogenic shock often seen in this condition. Compartment syndrome is another potential early complication and is possibly the only area in which immediate surgery can benefit the patient. Sacks and colleagues (2009) described an aggressive approach to selected patients and recommended decisions based on a clinical assessment, which included evaluation of limb posture and turgor, passive movements, colour changes, and capillary refill. They reported the outcome of nine patients from a group of 122, two patients died due to fulminating septicaemia and 15 limbs were salvaged in the survivors, with good reported long-​term function. Davies and co-​workers (2000) reported the outcome of 14 children with meningococcal septicaemia with associated severe limb ischaemia. Surgery was required in 13 patients, eight of whom had early fasciotomies. Based on this experience, the authors proposed a protocol for early management, which included early referral to a vascular surgeon for Doppler and duplex studies and suggested that this should occur in all limbs with peripheral ischaemia. They recommended fasciotomy in the presence of peripheral ischaemia and raised compartment pressures if the purpuric rash had been present for no more than 24 hours. Bache and Torode (2006) identified four patients that underwent fasciotomy for compartment syndrome from a series of 143 patients with meningococcal septicaemia. They considered that fasciotomy, in the presence of peripheral ischaemia and absent pulses, was of dubious merit and may lead to a higher level of amputation. Compartment pressure measurement is difficult to interpret in this situation and the decision to intervene is based on clinical judgement. Fasciotomy is relatively straightforward from a technical perspective and involves incision of skin, subcutaneous fat, and fascia and can be conducted using one or two longitudinal incisions below the knee. If the patient is in extremis, this can be conducted at the bedside in the paediatric intensive care unit although ideally should be performed in the sterile environment of an operating theatre.

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SECTION 5  Lower limb

Following muscle release, there is often bulging of muscle, which is covered with a non-​absorbent dressing with a lightly applied non-​ occlusive bandage. Fasciotomy can lead to considerable difficulties with bleeding in the presence of a coagulopathy and this complicates an already precarious haemodynamic balance. Subsequent closure of fasciotomy wounds can be problematic, due to the poor condition of adjacent skin in severely affected individuals. Placement of scars may also cause future difficulties, particularly if amputation is eventually required and this leads to difficulties with prosthetic application and use. Ischaemia is due to a combination of small vessel thrombosis, vasculitis, generalized coagulopathy, and cardiogenic shock as well as to the use of potent peripheral vasoconstrictors during resuscitation. The degree of skin involvement is variable, ranging from isolated superficial islands to global involvement of one or more limbs. The management strategy should be individualized but in general, there is no imperative to perform early debridement of even frankly necrotic areas of skin. The optimum management is identical to the treatment of peripheral gangrene, allowing affected areas of skin to demarcate and spontaneously separate. Early skin grafting is inappropriate, particularly if there are large areas involved. This is due to limited donor skin and the lack of any convincing evidence of long-​term benefit. The only reason to be more aggressive is in the presence of secondary infection, which is relatively uncommon. The necrotic tissue will eventually separate and although the underlying area often appears macerated, generalized infection is uncommon and systemic involvement is unusual. If there are unepithelialized areas following spontaneous demarcation, skin grafting can be considered, often several weeks after the onset of the septicaemic illness. The eventual area of skin loss is often considerably less than would be expected after assessment in the early stages of the disease. Adopting an expectant approach also allows an improvement in metabolic and nutritional parameters and increases the likelihood of successful grafting. Peripheral gangrene is common and affects the digits, genitalia, and nose and extends proximally to a variable and unpredictable extent. The necrotic tissue has no vascular continuity with the unaffected limb and the risk of a significant reperfusion injury or metabolic upset due to necrotic tissue is therefore small. Secondary infection is rarely a clinical problem and in the absence of these two scenarios, there is no surgery that will contribute to an improved outcome. There is often improvement in the condition of the limb with time, and the eventual amount of tissue loss is less than would have been predicted by the early appearances. Preservation of the major joints will result in enhanced options for prosthetic management even if more distal structures are lost and every effort should be made to maintain viable tissue and avoid early amputation. When there is clear demarcation between necrotic, mummified tissue and viable tissue, elective amputation can be performed and this may be several weeks after the onset of the disease. It is common for the joints in an involved limb to become contracted and it is important that splints are applied at an early stage to prevent this. This is particularly relevant for the wrists, fingers, ankles, and toes and should commence immediately after the onset of ischaemia. This can be conducted in association with physiotherapy to maintain passive range of movement of all joints. This is often

difficult, due to the surrounding ischaemic and necrotic areas but, with diligent care, is possible and is an extremely important part of the management at this point. As the patient’s general condition improves, the emphasis of treatment is maintenance and optimization of long-​term function and involves an extension of the algorithms outlined previously. There is further demarcation of necrotic skin and while small areas can be removed for reasons of convenience, generalized debridement is not recommended. In the weeks following the onset of illness, these areas will separate and uncover healthy epithelialized dry areas providing adequate covering or areas that require skin grafting. The septicaemic illness usually occurs in the neonatal and infant period meaning that there are more than 10 years of longitudinal growth remaining. It is very likely that revision surgery will be necessary due to the relative overgrowth of the bony components compared to the soft tissues during the period of remaining growth. The family should be informed at an early stage that it is occasionally necessary to perform repeated surgical revision procedures before skeletal maturity. Edwards and co-​workers (2016) reported that 9/​130 (6.9%) of patients who survived the initial disease, required amputation and Nectoux and colleagues (2010a) reported that 13/​19 patients with purpura fulminans (the necrotic cutaneous rash typical of intravascular thrombosis) due to meningococcal septicaemia required an amputation with a mean delay of 4 weeks from the onset of disease. The authors concluded that surgery during the acute phase of purpura fulminans did not improve the orthopaedic outcome in children. Buysse and co-​workers (2009) reviewed 120 of 179 consecutive patients with meningococcal septicaemia and reported that 8% required amputation of the extremities ranging from one toe to both legs and one arm. The site of amputation is important and should be decided after liaison with the prosthetics service. Amputation in this condition is technically difficult because the adjacent soft tissues are often scarred and the surrounding muscle is ischaemic, leading to suboptimal soft tissue coverage and poor end-​bearing tissue. The surgical principles are to provide bony stability, good soft tissue coverage, good skin coverage, and a functional adjacent joint. In a below-​knee amputation, it is useful to perform a surgical synostosis of the tibia and fibula as this provides better support and better long-​term prosthetic use. Canavese and colleagues (2010) retrospectively reviewed 48 patients and described the early (within 6 months) and late sequelae. Bone overgrowth occurred in 23 patients with an amputation. Soft tissue and bone infections at the distal portion of an amputation occurred in 17% at the mean of 7 years after the initial sepsis. Nectoux and co-​workers (2010b) reported a total of six revisions because of soft tissue coverage or to improve prosthetic wear in seven patients who had below knee amputations. A combined approach involving orthopaedic and plastic surgeons is necessary to revise the limb remnant and so optimize prosthetic use. This involves excision of prominent bone and provision of optimum soft tissue coverage and release of joint contractures. If there is a paucity of local tissue, then local or free flaps are occasionally necessary. Although the skin is insensate, it provides superior cover in circumstances in which prosthetic use would otherwise be impossible. It is common for an amputated limb to have associated ischaemic injury to remaining growth plates. This results in a gradual

5.14  The skeletal consequences of meningococcal septicaemia

deterioration of the length and alignment of the residual limb and results in considerable difficulties with prosthetic use. In this circumstance, the surgical options are limited due to the condition of the soft tissues but it is possible to use a fine wire external fixator to realign and if necessary lengthen the residual limb to improve the prosthetic attachment. Recent developments in prosthetic technology include attachment of a titanium socket to the bone/​soft tissue remnant, providing a superior interface for prosthetic attachment. This has been used in adult patients following trauma and tumours and while not currently available for children, remains a potential option for adolescents and young adults. The pathological process that leads to amputations and growth plate damage is likely to be multifactorial. Trueta and Amato (1960) reported changes in the growth plate as a result of experimentally induced ischaemia. It is likely that there is a direct injury to the physis as a result of endotoxin-​induced microvascular damage leading to ischaemia. An indirect mechanism may also be associated with full-​ thickness involvement of the skin and underlying tissue resulting in an interruption to the angiosomal blood supply. Damage to either true anastomotic connections or reduced calibre choke vessels linking adjacent vascular territories may represent a pathological mechanism. In comparison to the posterior and lateral compartments of the lower leg, where at least two source vessels exist, the anterior and medial aspects may be at increased risk. This is due to the sparseness of choke vessels across the boundaries of the anterior compartment, and the particularly susceptible periosteum and cutaneous vessels that connect the medial subcutaneous area with the anterior and posterior tibial arteries. Grogan and colleagues (1989) investigated the physeal changes in nine children who had survived the acute stage of meningococcal septicaemia and identified small vessel thrombi, osteonecrosis, and subperiosteal new bone formation compatible with a combination of acute osteomyelitis and ischaemia. In specimens obtained during revision procedures, the growth plates demonstrated variable permanent ischaemic damage with bone bridges connecting the epiphysis and metaphysis at various stages of formation. Nogi (1989) reported multiple growth plate involvement in three children who had survived meningococcal disease but with partial amputation of all four extremities. Growth plate damage was due to ‘dry gangrene’ with no evidence of an infective cause. The conclusion was that premature physeal closure was due to ischaemia and led to significant leg length discrepancy. Watson and Ashworth (1983) suggested that some of the angular deformity is due to growth tethering due to dense scarring. Monsell and colleagues (2011) postulated that certain areas are particularly susceptible to ischaemic damage and described a series of 11 patients in whom there was a distal tibial growth arrest with sparing of the fibula leading to a rapidly evolving ankle contracture. The incidence of growth plate injury following meningococcal septicaemia is unknown. National Institute for Health and Care Excellence (2010) guidelines suggest that the rate of growth disturbance is approximately 3%, based on the available published literature. This may be an underestimate as the consequences of growth plate injury may initially be subtle and not clinically obvious nor functionally important for several years. Bache and Torode (2006) reported 16/​143 patients with a total of 41 growth arrests, 23 of which occurred beneath an area of cutaneous scarring, diagnosed

2–​9 years after the index admission. Edwards and co-​workers (2016) identified eight patients with documented growth plate abnormalities, representing an overall incidence of 6.2% in a contemporaneous Northern European population. Nectoux and colleagues (2010b) reported the outcome of 14/​19 patients who developed at least one orthopaedic consequence after a mean of 2 years. The most common presentation was lower limb growth plate arrest in eight patients involving 18 growth plates, leading to limb length discrepancy in five patients and significant knee or ankle malalignment in 12 patients. Belthur and co-​workers (2005) reported the outcome of 23/​24 patients that required realignment surgery following meningococcal septicaemia with 15 requiring surgery for angular deformity around the knee. Due to the multicentre origin of patients, it was not possible to determine the total population of patients and therefore the actual incidence of growth arrest for this patient population. Park and Bradish (2011) reported the skeletal maturity review of ten patients treated for growth plate arrest involving 27 sites, most commonly the proximal and distal tibia. The most common presentation was limb length discrepancy and angular deformity at the knee and ankle. All patients with this deformity around the knee had an angular correction with or without lengthening using a circular fixator. Buysse and co-​workers (2009) reported that 6% of survivors had lower limb length discrepancy, usually in combination with angular deformity. They noted that patients with orthopaedic sequelae had significantly higher severity of illness scores determined by the paediatric risk of mortality score, vasopressor score, and disseminated intravascular coagulation score. The author’s management algorithm is to keep all patients who are admitted with meningococcal septicaemia under close surveillance with clinical assessment and radiological confirmation of growth arrest as evidenced by limb leg discrepancy or evolving angular deformity. The upper limb is also at risk and clinical assessment of humeral length and forearm rotation, in addition to radiological assessment of any visible abnormality, is also necessary. The consequences of growth plate injury are leg length discrepancy, angular deformity, and distorted body proportion, and the management options are predicated by the ultimate goal, which is to provide equal leg lengths, functional joints, and mechanical axis alignment at the time of skeletal maturity. This often involves a combination of epiphysiodesis (growth plate ablation), acute osteotomy, and limb lengthening/​realignment using an external fixator. As growth disturbance occurs in the very early period of growth, it is often necessary to perform surgery on a number of occasions.

Conclusion Advances in disease recognition and early aggressive resuscitation have led to an increased survival from meningococcal septicaemia, which has improved over the last two decades from 70% to 95%. Musculoskeletal consequences include amputation, skin loss, and growth plate injury and are commonly seen in survivors. It is likely that the long-​term burden of disease will increase in this patient group with important management decisions, which need to be considered in the early phases. A strategic approach to the management of the limbs in these patients is required for an optimum

667

668

SECTION 5  Lower limb

outcome and this begins with consideration for fasciotomy in the first 24 hours. It is recognized that early ablative surgery does not improve the long-​term outcome for these patients and the initial management is expectant with delayed amputation and skin grafting. The management of complex deformity that evolves in the longer term is suitable for surgical reconstruction and involves external fixator realignment and lengthening, which may be necessary on several occasions.

REFERENCES Bache CE, Torode IP. Orthopaedic sequelae of meningococcal septicemia. J Pediatr Orthop 2006;26:135–​9. Belthur MV, Bradish CF, Gibbons PJ. Late orthopaedic sequelae following meningococcal septicaemia. A multicentre study. J Bone Joint Surg Br 2005;87:236–​40. Buysse CM, Oranje AP, Zuidema E, et al. Long-​term skin scarring and orthopaedic sequelae in survivors of meningococcal septic shock. Arch Dis Child 2009;94:381–​6. Canavese F, Krajbich JI, LaFleur BJ. Orthopaedic sequelae of childhood meningococcemia: management considerations and outcome. J Bone Joint Surg Am 2010;92:2196–​203. Davies MS, Nadel S, Habibi P, et al. The orthopaedic management of peripheral ischaemia in meningococcal septicaemia in children. J Bone Joint Surg Br 2000;82:383–​6. Edwards TA, Bowen L, Bintcliffe F, et al. The orthopaedic consequences of childhood meningococcal septicaemia. J Meningitis 2016;1:109. Grogan DP, Love SM, Ogden JA, et al. Chondro-​osseous growth abnormalities after meningococcemia. A  clinical and histopathological study. J Bone Joint Surg Am 1989;71:920–​8.

Monsell FP, McBride AR, Barnes JR, et al. Angular deformity of the ankle with sparing of the distal fibula following meningococcal septicaemia: a case series involving 14 ankles in ten children. J Bone Joint Surg Br 2011;93:1131–​3. National Institute for Health and Care Excellence. Meningitis (bacterial) and meningococcal septicaemia in under 16s:  recognition, diagnosis and management. Clinical guideline [CG102]. 2010. (Last updated 2015.) http://​guidance.nice.org.uk/​CG102 Nectoux E, Mezel A, Raux S, et al. Meningococcal purpura fulminans in children:  I. Initial orthopedic management. J Child Orthop 2010a;4:401–​7. Nectoux E, Mezel A, Raux S, et al. Meningococcal purpura fulminans in children: II. Late orthopedic sequelae managemnt. J Child Orthop 2010b;4:409–​16. Nogi J. Physeal arrest in purpura fulminans. A report of three cases. J Bone Joint Surg Am 1989;71:929–​31. Park DH, Bradish CF. The management of the orthopaedic sequelae of meningococcal septicaemia: patients treated to skeletal maturity. J Bone Joint Surg Br 2011;93:984–​9. Pollard AJ, Britto J, Nadel S, et al. Emergency management of meningococcal disease. Arch Dis Child 1999;80:290–​6. Sacks LW, Wolf P, Murphy A, et al. Very early fasciotomies in meningococcal septicaemia purpura fulminans and compartment syndrome. Presented at ‘Meningitis and Septicaemia in Children and Adults’. Royal Society of Medicine, London, 11–​12 November 2009. Trueta J, Amato VP. The vascular contribution to osteogenesis. III. Changes in the growth cartilage caused by experimentally induced ischaemia. J Bone Joint Surg Br 1960;42:571–​87. Watson CH, Ashworth MA. Growth disturbance and meningococcal septicemia. Report of two cases. J Bone Joint Surg Am 1983;65:1181–​3.

SECTION 6

Craniofacial and cleft Section editors: Hiroshi Nishikawa, Felicity V. Mehendale, and David C.G. Sainsbury

6.1 Classification of craniofacial anomalies  671 Jagajeevan Jagadeesan and Hiroshi Nishikawa 6.2 Embryology of craniofacial skeleton  685 Mark S. Lloyd 6.3 Genetics of craniofacial anomalies  691 Andrew O.M. Wilkie 6.4 Assessment of patients with craniosynostosis  697 Nicholas White 6.5 Non-​syndromic craniosynostosis  705 Christian Duncan and Hiroshi Nishikawa 6.6 Syndromic craniosynostosis  713 Stephen Dover and Martin Evans 6.7 Hypertelorism and orbital dystopia  721 Aina V.H. Greig and David J. Dunaway

6.8 Orofacial clefts: embryology, epidemiology, and genetics  729 David R. FitzPatrick 6.9 Classification, evaluation, and management of the neonate with a cleft  737 David C.G. Sainsbury 6.10 Primary management of cleft lip and palate  745 Jason Neil-​Dwyer 6.11 Outcome assessment in cleft lip and palate surgery  761 Marc C. Swan, Conrad J. Harrison, and Tim E.E. Goodacre 6.12 Secondary surgery in cleft lip and palate  767 Peter D. Hodgkinson 6.13 Velopharyngeal dysfunction  777 David C.G. Sainsbury, Caroline C. Williams, and Felicity V. Mehendale

6.1

Classification of craniofacial anomalies Jagajeevan Jagadeesan and Hiroshi Nishikawa

Introduction Craniofacial anomalies are a rare group of congenital disorders that affect the cranium and the face. Due to the rarity and diverse nature of presentation, classifying them has always posed a challenge. An ideal classification system is meant to be simple, effective, and reproducible. This chapter provides a brief history of the different classification schemes and explains a simple, modified, and descriptive classification system. A brief description of the more common craniofacial conditions and their clinical features is presented. The management of individual conditions is discussed in their respective chapters.

History The earliest documented classification system by Sommering in 1791 was based on morphogenesis (Fig. 6.1.1). This was followed by several morphogenetic (Taullard, 1961; DeMyer, 1967; Pfeifer, 1967, 1974, Sedano et  al., 1970, Mazzola, 1976)  and anatomical

classifications (Greer Walker, 1961; Duhamel, 1966; Karfík, 1966; Tessier, 1976; van der Meulen et al., 1983). The Whittaker and van der Meulen classification systems are commonly mentioned in the literature—​a consensus has never been achieved (van der Meulen et al., 1983). Whitaker and colleagues (1981) classified malformations into five different types based on their aetiology, anatomical site, and treatment principles (Box 6.1.1). Van der Meulen and colleagues (1983), however, classified anomalies according to the stage of embryogenesis, anatomical site, and time of development affected (Fig. 6.1.2). Based on chronology of when the malformation arises, this classification system starts with anencephaly, the most severe form of craniofacial malformation, moving to milder forms. To make classification more precise, van der Meulen and colleagues (1983) introduced the pathomorphogenetic system, which classifies anomalies into cerebrocranial, cerebrofacial, and craniofacial malformations. These categories are further divided based on the topographical sites of the anomaly. This resulted in a descriptive and extensive classification system (Box 6.1.2). In order to simplify these schemes, the classifications of Whitaker and van der Meulen have been combined. A version of this new classification system, including the common conditions and their genetic inheritance, is outlined in Table 6.1.1.

Box 6.1.1  Whittaker classification system (1981) I Clefts: • Centric. • Acentri. II Synostoses: • Symmetric. • Asymmetric. III Atrophy—​hypoplasia. IV Neoplasia—​hyperplasia. V Unclassified.

Fig. 6.1.1  Morphogenetic classification by Sommering (1791).

Reproduced with permission from Whitaker LA, Pashayan H, Reichman J., A proposed new classification of craniofacial anomalies, The Cleft Palate Journal, Volume 18, Issue 3, pp.161–​76, Copyright © 1981 SAGE Journals.

672

SECTION 6  Craniofacial and cleft

Common craniofacial conditions Craniosynostosis

Fig. 6.1.2  Chronological basis of van der Meulen’s classification system. Reproduced with permission from J. van der Meulen, R. Mazzola, C. Vermey-​Keers, et al., A Morphogenetic Classification of Craniofacial Malformations, Plastic and Reconstructive Surgery, Volume 71, Issue 4, pp.560–​572, Copyright © 1983 Wolters Kluwer Health, Inc.

Craniosynostosis was first described by Otto (1830). Premature fusion of a cranial suture results in an abnormal head shape which is dependent upon which suture is involved. Raised intracranial pressure (ICP) is observed in up to 33% of cases and variable degrees of cognitive impairment can occur (Thompson et al. 1995a; Tuite et al., 1996). Raised ICP is more commonly associated with syndromic (53%) than non-​syndromic craniosynostosis (24%) and multisuture (57%) than single-​suture synostosis (13%) (Thompson et al., 1995b). Skull growth is restricted perpendicular to the affected suture and so is compensated by growth parallel to that suture—​a phenomenon first described by Virchow in 1885 (Fig. 6.1.3). The prevalence of craniosynostosis of any type is 1:2500. Craniosynostosis can be described according to:

Box 6.1.2  Van der Meulen pathomorphogenetic classification system I Cerebrocranial dysplasias

Anencephaly Microcephaly Others II Cerebrofacial dysplasias

Rhinencephalic dysplasias Oculo-​orbital dysplasias III Craniofacial dysplasias







(a) With clefting: Latero-​nasomaxillary  cleft Medio-​nasomaxillary Intermaxillary clefting Maxillo-​mandibular  cleft (b) With dysostosis (craniofacial helix): Sphenoidal Spheno-​frontaI Frontal Fronto frontal Fronto-​nasoethmoidal Internasal Nasal Premaxillo-​maxillary and intermaxillo-​palatine Naso-​maxillary and maxillary Maxillo-​zygomatic Zygomatic Zygo-​auromandibular Temporo-​aural Temporo–​auromandibular Mandibular Intermandibular (c) With synostosis: Craniosynostosis: Parieto-​occipital Interparietal





Cranio-​faciosynostosis: Interfrontal Spheno-​frontoparietal Pronto-​parietal Fronto-​interparietal Faciosynostosis: Fronto-​malar Vomero-​premaxillary (Binder) Perimaxillary (post.) (clefting) Perimaxillary (ant.) (pseudo Crouzon) Perimaxillary (total) (Crouzon) (d) Wash dysostosis and synostosis: Crouzon Acro-​cephalosyndactyly (Apert) Triphyllocephaly (cloverleaf skull) (e) With dyschondrosis: Achondroplasia

IV Craniofacial dysplasias with other origin







(a) Osseous: Osteopetrosis Cranio tubular dysplasia Fibrous dysplasia (b) Cutaneous: Ectodermal dysplasia (c) Neurocutaneous: Neurofibromatosis (d) Neuromuscular: Robin syndrome Mobius syndrome (e) Muscular: Glossoschizis (f) Vascular: Haemangioma Haemolymphangioma Lymphangioma

Reproduced with permission from J. van der Meulen, R. Mazzola, C. Vermey-​Keers, et al., A Morphogenetic Classification of Craniofacial Malformations, Plastic and Reconstructive Surgery, Volume 71, Issue 4, pp.560–​572, Copyright © 1983 Wolters Kluwer Health, Inc.

6.1  Classification of craniofacial anomalies

Table 6.1.1  New classification system, combining the work of Whitaker and van der Meulen Type

Hereditary

Craniosynostosis

Sporadic

Craniodysostosis

Rare syndromes

Undiagnosed

• Apert’s • Crouzon’s • Pfeiffer’s • Carpenter’s

• Muenke’s • Saethre–​Chotzen

• Unicoronal • Bicoronal • Multisuture

Craniofacial clefts

Sagittal Metopic Lambdoid

Cleft lip/​palate Craniofacial clefts

Encephaloceles

• Midline facial • Lateral facial • Oblique Hypoplasia

Craniofacial microsomia Treacher Collins syndrome

Parry–​Romberg (hemifacial atrophy)

Hyperplasia

Neurofibromatosis

Fibrous dysplasia Osteopetrosis Vascular anomalies

Miscellaneous

Dermoids

Source data from Whitaker, L.A., Pashayan, H., Reichman, J. A proposed new classification of craniofacial anomalies. Cleft Palate J, 1981;18(3):161–​7 and Van der Meulen, J.C., Mazzola, R., Vermey-​Keers, C., Strieker, M., Raphael, B. A morphogenetic classification of craniofacial malformations. Plast Reconstr Surg 1983;71:560–​72.

(a)

(b) Bones Frontal 4

1

• The resultant head shape. • Aetiology (primary or secondary). • The number of sutures involved (single suture, multisuture, or pansynostosis). • Non-​syndromic or syndromic. The descriptive classification system of the different types of craniosynostosis is displayed in Table 6.1.2. A brief description of the common craniosynostoses is provided in the following sections.

Parietal

Sagittal craniosynostosis

Temporal Occipital 3 2

Fig. 6.1.3  Diagrams demonstrating the direction of bone growth across the cranial sutures based on Virchow’s theory.

Sagittal craniosynostosis accounts for approximately 50% of all craniosynostoses, is mostly sporadic (6% are familial), affects mostly males, and occurs in approximately 1:5000 births (Lajeunie et al., 1996). The classical clinical findings (Fig. 6.1.4) are scaphocephaly (boat-​shaped skull) with or without ridging of the sagittal suture, frontal bossing, bitemporal hollowing, and an occipital bullet. Raised ICP is uncommon, occurring in 10% of cases (Thompson

Table 6.1.2  Classification of craniosynostosis

Single suture

Multiple sutures

Non-​syndromic isolated synostosis, may be familial

Type

Shape

Synostosis

Scaphocephaly

Boat-​shaped

Sagittal

Trigonocephaly

Triangular

Metopic

Plagiocephaly

Twisted

Unicoronal

Posterior plagiocephaly

Twisted

Lambdoid

Brachycephaly

Short

Bicoronal

Oxycephaly/​turricephaly/​acrocephaly

Pointed

Bicoronal + sagittal

Kleeblattshädel/​cloverleaf

Tower-​like

Multiple suture

Complex synostosis

Peak head

Multiple suture Single or multiple sutures

673

674

SECTION 6  Craniofacial and cleft

Fig. 6.1.4  Photographs and three-​dimensional computed tomography scans of a patient with sagittal craniosynostosis.

et al., 1995a). The main aim of treatment is to alleviate the possibility of raised ICP and improve head shape.

the orbital and base of skull asymmetry, resulting in nasal deviation, orbital dystopia, and malpositioned ears (Aviv et al., 2002).

Metopic craniosynostosis

Lambdoid craniosynostosis

Metopic craniosynostosis is now the second most common type of single-​suture craniosynostosis due to a recent increase (420%) in incidence, now accounting for 27% of cases (van der Meulen et al., 2009). It is more common in males and is familial in 2% of the cases. The classic presentation is a triangular-​ shaped skull (trigonocephaly) with ridging of the metopic suture, hypotelorism, and bilateral supraorbital recession (Fig. 6.1.5). The presentation can be variable. Mild forms may present with just palpable or visible ridging of the metopic suture. These cases may not require any surgical intervention but, along with the operated patients, require monitoring of their speech and language as well as neuropsychological development. Metopic craniosynostotic patients are noted to have the highest incidence of developmental and speech delay compared to other single-​suture craniosynostosis patients (Sidoti et al., 1996; Bottero et al., 1998; Warschausky et al., 2005; van der Meulen, 2012).

This is the least common type of single-​suture craniosynostosis, accounting for 1–​4% of cases (around 1:40,000 to 1:200,000 live births) (Mulliken et al., 1999). This has to be differentiated from deformational positional plagiocephaly (Fig. 6.1.8). The clinical features of lambdoid craniosynostosis are ipsilateral occipitoparietal flattening and contralateral frontal bossing resulting in a trapezium-​shaped skull. The ipsilateral ear position is shifted posteriorly and inferiorly. There may be ipsilateral mastoid bossing (Fig. 6.1.9). The other feature to note in differentiating positional plagiocephaly from lambdoid craniosynostosis is the difference in the skull base axis. The axis of the base of skull in positional plagiocephaly is perpendicular to the sagittal axis of the skull (Fig. 6.1.10a). With lambdoid craniosynostosis (Fig. 6.1.10b), the skull base is tilted and the vertical and sagittal axes are not at right angles. This is further demonstrated in Fig. 6.1.11.

Unicoronal craniosynostosis

Syndromic craniosynostoses present with either multisuture craniosynostosis, pansynostosis, or, more rarely, single-​ suture unicoronal craniosynostosis. The synostosis often coexists with well-​defined patterns of facial, skeletal, and other clinical anomalies. The clinical presentation varies based on the genetic factors, cellular events, and the impact of local forces influencing normal growth and development. These can be classified based on their morphological features, aetiology, or genetic factors. Due to the number of sutures

This accounts for around 13% of all single-​suture craniosynostosis (Hansen and Mulliken, 1994) and is now the third most common type of craniosynostosis. The classic features of unicoronal synostosis (Fig. 6.1.6) are ipsilateral flattening of frontal and parietal bones, contralateral frontal bossing, and harlequin orbital asymmetry due to failure of descent and constriction of the sphenoid wing (Fig. 6.1.7). Patients can also develop varying degrees of facial deformity due to

Syndromic craniosynostosis

6.1  Classification of craniofacial anomalies

Fig. 6.1.5  Photographs and three-​dimensional computed tomography scans demonstrating metopic craniosynostosis. Trigonocephaly, hypotelorism, and bilateral supraorbital recession.

Fig. 6.1.6  Photographs and three-​dimensional computed tomography scans demonstrating left unicoronal craniosynostosis.

675

676

SECTION 6  Craniofacial and cleft

Fig. 6.1.7  X-​ray and coronal section of three-​dimensional computed tomography scan of patients with unicoronal craniosynostosis demonstrating harlequin sign.

involved in syndromic craniosynostosis, there is a significant risk of raised ICP (Tamburrini et al., 2005). This is compounded by the frequent coexistence of other causes of raised ICP in this complex group of patients, such as hydrocephalus, intracranial venous congestion, and upper airway obstruction (Gonsalez et  al., 1997; Taylor et  al., 2001). The priorities of treatment of these patients is divided into crisis management, emergency management, and elective management based on the urgency of intervention required. The common craniofacial syndromes and their key diagnostic features are described as follows. Their detailed management is discussed in subsequent chapters in this book.

ipsilateral frontal bossing

ipsilateral ear displaced anteriorly

contralateral occipital bossing

ipsilateral occipitoparietal flattening

Crouzon syndrome This is the most frequent syndromic craniosynostosis, occurring in around 1:25,000 live births. It arises due to mutation of the fibroblast growth factor receptor type 2 gene (FGFR2) and is transmitted in an autosomal dominant inheritance pattern. Presentation varies, based on expression of the genes. The classical clinical finding is brachycephaly, secondary to bicoronal craniosynostosis, although other sutures may be affected. The constriction of the skull base results in midface hypoplasia, leading to dental crowding, a constricted maxilla, Class III malocclusion, and shallow orbits resulting in proptosis. Learning difficulties are rare, in 3% of cases.

contralateral frontal bossing

contralateral parietal bossing

ipsilateral ear displaced posteriorly, inferiorly, or not at all

ipsilateral occipitoparietal flattening

Fig. 6.1.8  Demonstration of the vertex view of findings in positional plagiocephaly (left) compared to lambdoid craniosynostosis (right).

6.1  Classification of craniofacial anomalies

Fig. 6.1.9  Photo and three-​dimensional computed tomography scans demonstrating a patient with lambdoid craniosynostosis.

Fig. 6.1.12 shows a computed tomography scan of pansynostosis in Crouzon syndrome showing multiple calvarial erosions (extreme copper-​beating) due to raised ICP. Apert syndrome Eugene Apert, a French neurologist, first described this syndrome in 1906, which occurs in 1:100,000 live births and also results from a mutation in the FGFR2 gene (Wilkie et al., 1995). The syndrome shows autosomal dominant inheritance with complete penetrance, but can occur sporadically, when it is associated with increased parental age (Tunte and Lenz, 1967). The classical clinical feature is turribrachycephaly (Fig. 6.1.13) secondary to bicoronal

Fig. 6.1.10  Figures demonstrating the tilt in skull base due to lambdoid craniosynostosis compared to positional plagiocephaly.

craniosynostosis with a large anterior fontanelle extending through the metopic and sagittal sutures. Raised ICP is found in 45% of cases (Renier et al., 2000). The ocular findings include down-​slanting palpebral fissures and severe proptosis secondary to shallow orbits. Syndactyly of the digits of the hands and feet is a constant finding. Hand syndactyly is classified into three types (Fig. 6.1.14). Type 1—​syndactyly of middle, index, and ring fingers sparing thumb and little finger (spade hand); type II—​syndactyly of all fingers sparing the thumb (‘mitten’ hand); and type III—​syndactyly of all fingers and thumb (‘rosebud’ hand; Upton, 1991). Patients with Apert syndrome have varying degrees of mental development.

Fig. 6.1.11  Diagram demonstrating the tilt in the skull base due to lambdoid craniosynostosis.

677

678

SECTION 6  Craniofacial and cleft

• Similarities: both Apert and Crouzon syndromes are transmitted by autosomal dominant inheritance by mutations that occur in the FGFR2 gene. • Differences: see Table 6.1.3 for the differences between Apert and Crouzon syndromes. Pfeiffer syndrome

Fig. 6.1.12  Computed tomography scan of pansynostosis in Crouzon syndrome showing multiple calvarial erosions (extreme copper-​beating), due to raised intracranial pressure.

This is a rare type of syndromic craniosynostosis described by Rudolph Pfeiffer in 1964. It presents in around 1:100,000 live births and is due to a mutation of FGFR2 in 95% of cases and FGFR1 in 5% (usually less severe forms) (Muenke et al., 1994). The classic clinical presentation includes turribrachycephaly (tall and flat skull shape) (Fig. 6.1.15) secondary to bicoronal craniosynostosis, short broad thumbs and big toes, and partial syndactyly involving fingers and toes. The other features present in varying degrees include proptosis secondary to shallow orbits, down-​slanting palpebral fissures, orbital hypertelorism, and midface hypoplasia resulting in Class III malocclusion. The other, less common, features include airway problems secondary to midface hypoplasia and tracheal anomalies, intellectual disability, low-​set ears, and auditory canal stenosis. The lambdoid and sagittal sutures are less commonly involved. Cohen (1993) classified Pfeiffer syndrome into three types based on the severity of the clinical features (Table 6.1.4). Saethre–​Chotzen syndrome

Similarities and differences between Apert and Crouzon syndromes Apert and Crouzon syndromes are the most common syndromic craniosynostosis. Therefore, it is important to be able to differentiate between the two, both phenotypically and genotypically.

First described by Haakan Saethre in 1931 and Chotzen in 1932, this syndrome presents in 1:25,000 to 1:50,000 live births. It arises as a result of a mutation in the TWIST1 gene located on chromosome 7p21.1 and is transmitted by autosomal dominant inheritance (Wood et  al., 2009). Clinical presentation is variable and

Fig. 6.1.13  Photographs and three-​dimensional computed tomography scans demonstrating a clinical features of a patient with Apert syndrome.

6.1  Classification of craniofacial anomalies

Fig. 6.1.14  Complex syndactyly a classical clinical feature of a patient with Apert syndrome.

includes craniosynostosis (sutures involved are, in decreasing order of frequency, bicoronal, unicoronal, and multisuture), low-​ set hairline, eyelid ptosis, broad and indented nasal bridge, facial asymmetry, external anomalies (prominent crus helices extending

through the conchal bowl), variable presentation of syndactyly, clinodactyly, and broad toes (Fig. 6.1.16). In contrast to Pfeiffer syndrome, patients do not display proptosis or midface hypoplasia (Foo et al., 2009).

Table 6.1.3  Differences between Crouzon and Apert syndromes Morphology

Crouzon syndrome

Apert syndrome

Inheritance

Mostly autosomal dominant, up to 50% sporadic

Mostly sporadic, some autosomal dominant

Presentation

Most features are cranial and facial

Characteristic involvement of cranium, face, and limbs (acrocephalosyndactyly)

Cranium

• Turribrachycephaly due to bicoronal synostosis but progressive and premature fusion of other sutures • Chiari malformation more common (72%)

• Turribrachycephaly—​commonly due to bicoronal synostosis. • Chiari malformation less common (2%)

Intellectual disability

Rare

Frequent

Eyes

Proptosis and hypertelorism

Down-​slanting palpebral fissures Severe proptosis due to shallow orbits

Nose

Flattened nasal bridge, Parrot beak appearance of tip, deviated nasal septum

Depressed nasal bridge

Face

• Midface hypoplasia with relative mandibular prognathism • Shortened upper lip with bulging lower lips • Sleep apnoea—​peripheral and central (due to hindbrain herniation)

• Midface hypoplasia with relative mandibular prognathism • Lips have a trapezoid configuration • Sleep apnoea—​usually peripheral

Dentition

Class III malocclusion, dental crowding, anterior open bite, and mandibular overjet

Class III malocclusion, dental crowding, cleft of soft palate, anterior open bite, anterior and posterior crossbite

Extra-​craniofacial features

Usually not present

• Varying degrees of syndactyly of fingers and toes. • Varying degrees of spontaneous and progressive spinal fusions • Cutaneous manifestations—​hyperhidrosis, acne.

679

680

SECTION 6  Craniofacial and cleft

Fig. 6.1.15  Photographs and three-​dimensional computed tomography scans demonstrating clinical features of a patient with Pfeiffer syndrome.

Muenke syndrome This is the most common type of syndromic craniosynostosis, occurring in 1:30,000 live births. Muenke and colleagues (1997) first described the pro250Arg mutation in the FGFR3 gene located on chromosome 6. The classic clinical features include craniosynostosis (mostly bicoronal but can involve other combinations), hearing loss, developmental delay, high-​arched/​cleft lip with or without palate, carpal and tarsal bone fusion, broad fingers and toes with thimble-​ shaped middle phalanges, and triangular-​shaped epiphysis (Fig. 6.1.17) (Agochukwu et al., 2012a, 2012b). Carpenter syndrome This is the rarest form (one per million live births) of syndromic craniosynostosis which was first described by Carpenter in 1901 and Table 6.1.4  Cohen’s classification of Pfeiffer syndrome Type

Morphological features

Type 1

‘Classic’ Pfeiffer syndrome Phenotype: mild manifestations including brachycephaly, midface hypoplasia, and finger and toe abnormalities Other features: normal neurological and intellectual development Outcome: good

Type 2

Phenotype: trilobated skull deformity (cloverleaf skull), extreme proptosis, finger and toe abnormalities Other features: elbow ankyloses or synostosis, developmental delay and neurological complications, visual disturbances Outcome: risk of early death due to neurological and respiratory issues

Type 3

Phenotype: severe form similar to type 2, without cloverleaf skull Outcome: risk of early death due to neurological and respiratory issues

Reproduced with permission from M. Michael Cohen, Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis, American Journal of Medical Genetics Part A, Volume 45, Issue 3, pp.300–​307, Copyright © 1993 John Wiley and Sons.

later by Tamtamy in 1966. The syndrome displays an autosomal recessive inheritance and results from mutation of the RAB23 gene on chromosome 6 and the MAG8 gene located on chromosome 19q13.2 (Jenkins et al., 2007; Twigg et al., 2012). The clinical features are variable and include multisuture craniosynostosis (any sutures apart from coronal involved), asymmetric head shape, flat facies, orbital anomalies, midface hypoplasia, high-​arched palate, ear anomalies, deafness, polysyndactyly, obesity, endocrine disorders, cardiac anomalies, and learning difficulties (Chen, 2012).

Orofacial clefts and encephaloceles Orofacial clefts are a rare and complex group of anomalies of the cranium and face arising due to deficiency or excess of tissues which result in cleavage of anatomical planes along embryologically predictable lines. They are postulated to arise as a result of failure of fusion of the facial processes during embryogenesis or due to lack of mesodermal penetration into the ectoderm. Excluding cleft lip and palate, these rare forms occur in around 1 to 4 per 100,000 live

Fig. 6.1.16  A child with Saethre–​Chotzen syndrome.

6.1  Classification of craniofacial anomalies

Fig. 6.1.17  Photographs and three-​dimensional computed tomography scans demonstrating clinical features of a patient with Muenke syndrome.

births and have a variable presentation. They can be either unilateral or bilateral and are frequently asymmetric. Hence, classifying these anomalies has been a challenge. Tessier’s anatomical classification (1976) and van der Meulen’s (1983) embryological classification are the most commonly used (Eppley et al., 2005). Tessier’s classification (Fig. 6.1.18) is based on the clefts involving soft tissue and skeleton centred on the orbit. Cranial clefts are clefts around the upper lid and cranium and facial clefts are clefts around the lower lid and face. Frequently, facial and cranial clefts combine. Each cleft type is allocated a number from 0 to 14 and arranged in clockwise or anticlockwise fashion based on their presentation. The total always adds up to 14 apart from the midline mandibular cleft, which is numbered 30. For descriptive purposes they can be classified as midline cleft ‘0/​14’; oronasal: 0–​3; oro-​ocular: 4–​6 (Treacher Collins syndrome); lateral facial:  7–​ 9 (hemifacial microsomia); orbito-​cranial: 10–​14; and median mandibular: 30. The exact aetiology of craniofacial clefting is unknown but has been associated with genetic syndromes (there are 171 syndromes associated with cleft lip alone) and environmental factors (alcohol; smoking; folic acid deficiency; medications—​steroid, phenytoin, and retinoic acid; high altitude).

14

10 4

13 12 1 211 3

9

8 0 1

2 3

7

6

4

7

5

30 14 13 12 0 1 2

11 3

10 4

9 8

3

7

4 5

6

Encephalocele An encephalocele is a congenital condition arising as a result of herniation of the intracranial contents through an abnormal defect in the skull base. It occurs in 1:5000 live births. The exact aetiology is unknown but may be multifactorial—​ genetic, environmental, racial, and paternal. Encephaloceles are classified based on the contents within the protrusion as meningocele (meninges alone), meningoencephalocele (meninges and brain), or meningoencephalocystocele (meninges, brain, and ventricles), or

0

123

30

Fig. 6.1.18  Tessier’s classification. This article was adapted from Plastic Surgery, J C McCarthy (Ed), Copyright Elsevier (1990).

681

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SECTION 6  Craniofacial and cleft

Box 6.1.3  Descriptive classification system of encephaloceles   I Occipital encephalocele. II Encephalocele of the cranial vault: A Interfrontal. B Anterior fontanelle. C Interparietal. D Posterior fontanelle. E Temporal. III Fontoethmoidal encephalocele: A Nasofrontal. B Nasoethmoidal. C Naso-​orbital. IV  Basal encephalocele: Transethmoidal. A B Sphenoethmoidal. C Transsphenoidal. D Fronotosphenoidal/​spheno-​orbital. Source data from Suwanwela C, Suwanwela N (1972) A morphological classification of sincipital encephalomeningoceles. J Neurosurg 36:202–211

upon their position on the skull as basal or sincipital. Suwanwela and Suwanwela (1972) developed a descriptive classification system of encephaloceles based on their site (Box 6.1.3). Clinical presentation depends on the site of the lesion and can range from an asymptomatic facial mass, proptosis, and visual disturbances, to upper airway obstruction in basal lesions.

REFERENCES Agochukwu NB, Solomon BD, Doherty ES, et al. Palatal and oral manifestations of Muenke syndrome (FGFR3-​related craniosynostosis). J Craniofac Surg 2012a;23:664–​8. Agochukwu NB, Solomon BD, Muenke M. Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses. Childs Nerv Syst 2012b;28:1447–​63. Aviv RI, Rodger E, Hall CM. Craniosynostosis. Clin Radiol 2002;57:93–​102. Bottero L, Lajeunie E, Arnaud E, et al. Functional outcome after surgery for trigonocephaly. Plast Reconstr Surg 1998;102:952–​8. Chen H. Carpenter syndrome. In:  Atlas of Genetic Diagnosis and Counseling, pp. 275–​8. New York: Springer, 2012. Cohen MM Jr. Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. Am J Med Genet 1993;45:300–​7. DeMyer W. The median cleft face syndrome. Differential diagnosis of cranium bifidum occultum, hypertelorism, and median cleft nose, lip, and palate. Neurology 1967;17:961–​71. Duhamel B. Morphogenè Pathologique. Paris: Masson, 1966. Eppley BL, van Aalst JA, Robey A, et  al. The spectrum of orofacial clefting. Plast Reconstr Surg 2005;115:101e–​14e. Foo R, Guo Y, McDonald-​McGinn DM, et al. The natural history of patients treated for TWIST1-​confirmed Saethre-​Chotzen syndrome. Plast Reconstr Surg 2009;124:2085–​95. Gonsalez S, Hayward R, Jones B, Lane R. Upper airway obstruction and raised intracranial pressure in children with craniosynostosis. Eur Respir J 1997;10:367–​75. GreerWalkerD.MalformationsoftheFace.Edinburgh: Livingstone,  1961.

Hansen M, Mulliken JB. Frontal plagiocephaly diagnosis and treatment. Clin Plast Surg 1994;21:543–​54. Jenkins D, Seelow D, Jehee FS, et al. RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-​ suture development and obesity. Am J Hum Genet 2007;80:1162–​70. Karfík V. [Proposed classification of rare congenital cleft defects of the face]. Rozhl Chir 1966;45:518–​22. Lajeunie E, Le Merrrer M, Bonaïti-​Pellie C, et  al. Genetic study of scaphocephaly. Am J Med Genet 1996;62:282–​5. Mazzola RF. Congenital malformations in the frontonasal area: their pathogenesis and classification. Clin Plast Surg 1976;3:573–​609. Muenke M, Gripp KW, McDonald-​McGinn DM, et al. A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome. Am J Hum Genet 1997;60:555–​64. Muenke M, Schell U, Hehr A, et al. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet 1994;8:269–​74. Mulliken JB, Vander Woude DL, Hansen M, et al. Analysis of posterior plagiocephaly: deformational versus synostotic. Plast Reconstr Surg 1999;103:371. Otto AW. Lehrbuch der pathologischen anatomie des meuchen und der thiere. Vol. 1. Berlin: Ruecker, 1830. Pfeifer G. [Development disorders of the face as classification problem]. Dtsch Zahn Mund Kieferheilkd Zentralbl Gesamte 1967;48:22–​40. Pfeifer G. Systematik und Morphologie der kraniofazialen Anomalien. Fortschr Kiefer Gesichtschir 1974;18:1. Renier D, Lajeunie E, Arnaud E, Marchac D. Management of craniosynostoses. Childs Nerv Syst 2000;16:546–​658. Sedano HO, Cohen MM Jr, Jirasek J, et  al. Frontonasal dysplasia. J Pediatr 1970;76:906–​13. Sidoti EJ Jr, Marsh JL, Marty-​Grames L, et  al. Long-​term studies of metopic synostosis: frequency of cognitive impairment and behavioral disturbances. Plast Reconstr Surg 1996;97:276–​81. Suwanwela C, Suwanwela N. A morphological classification of sincipital encephalomeningoceles. J Neurosurg 1972;36:202–​11. Tamburrini G, Caldarelli M, Massimi L, et  al. Intracranial pressure monitoring in children with single suture and complex craniosynostosis: a review. Childs Nerv Syst 2005;21:913–​21. Taullard JC. ‘El arco de cupido’ desde el punto di vista embriológico. Sem Med 1961;118:292–​5. Taylor WJ, Hayward RD, Lasjaunias P, et al. Enigma of raised intracranial pressure in patients with complex craniosynostosis: the role of abnormal intracranial venous drainage. J Neurosurg 2001;94: 377–​85. Tessier P. Anatomical classification facial, cranio-​facial and latero-​ facial clefts. J Maxillofac Surg 1976;4:69–​92. Thompson DNP, Harkness W, Jones B, et  al. Subdural intracranial pressure monitoring in craniosynostosis:  its role in surgical management. Childs Nerv Syst 1995a;11:269–​75. Thompson DNP, Malcolm GP, Jones BM, et al. Intracranial pressure in single suture craniosynostosis. Paediatr Neurosurg 1995b;22: 235–​75. Tuite GF, Chong W, Evanson J, et al. The effectiveness of papilledema as an indicator of raised intracranial pressure in children with craniosynostosis. Neurosurgery 1996;38:272–​8. Tunte W, Lenz W. Zur Haufigkeit und Mutationstrares des Apert-​ syndroms. Hum Genet 1967; 4:104–​11. Twigg SR, Lloyd D, Jenkins D, et  al. Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype

6.1  Classification of craniofacial anomalies

associated with defective lateralization. Am J Hum Genet 2012; 91:897–​905. Upton J. Apert syndrome. Classification and pathological anatomy of limb anomalies. Clin Plast Surg 1991;18:321–​55. van der Meulen J. Metopic synostosis. Childs Nerv Syst 2012;28:1359–​67. van der Meulen, JC, Mazzola R, Vermey-​Keers C, et  al. A morphogenetic classification of craniofacial malformations. Plast Reconstr Surg 1983;71:560–​72. van der Meulen J, van der Hulst R, van Adrichem L, et al. The increase of metopic synostosis: a pan-​European observation. J Craniofac Surg 2009;20:283–​6.

Virchow R. Über den Cretinismus, namentlich in Franken und über pathologische Schädelformen. Verh Phys Med Ges (Wurzburg) 1885;2:230–​71. Warschausky S, Angobaldo J, Kewman D, et al. Early development of infants with untreated metopic craniosynostosis. Plast Reconstr Surg 2005;115:1518–​23. Whitaker LA, Pashayan H, Reichman, J. A proposed new classification of craniofacial anomalies. Cleft Palate J 1981;18:161–​76. Wilkie AO, Slaney SF, Oldridge M, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 1995;9:165–​72.

683

6.2

Embryology of craniofacial skeleton Mark S. Lloyd

Cleft lip and palate embryology Cleft lip The development of the lip and palate involves a complex series of events that require close coordination of programmes for cell migration, growth, differentiation, and apoptosis (Marazita and Mooney, 2004). During the first 2 weeks of life, the human embryo resembles a flat disc. In the third week, this disc changes shape with the cranial region expanding and the neural tube elongating so that the disc morphs into a lightbulb shape. The neural tube lengthens during this time, bending in on itself bringing the more bulbous cranial end and longer cylindrical caudal ends into closer proximity. A  process of rapid neural growth causes further bending of the neural tube until in the fourth week of life the embryo resembles a horseshoe-​shaped cylinder (Merritt, 2005). Neural crest cells grow and migrate from the first branchial arch to form the five facial structures or primordia by the start of week 4.  These structures are the frontonasal prominence, the bilateral maxillary prominences, and the bilateral mandibular prominences (Fig. 6.2.1). The frontonasal prominence forms the forehead, nose, philtrum, and central part of the upper lip. The maxillary prominences form the lateral sides of the primitive mouth, nasolabial region, and malar region of the cheek. The mandibular process makes up the caudal part of the mouth. Formation of the nasal placodes (ectodermal thickenings) by the end of the fourth week of embryogenesis divides the lower portion of the frontonasal prominence into paired medial and lateral nasal prominences (Fig. 6.2.1) (Mossey et al., 2009). The placodes deepen and sink to form the nasal pits, acting as precursors to the nose, nostrils, and associated cartilaginous structures. The medial nasal prominences and the area above the primitive mouth continue to

grow and eventually merge with each other to form a vertical depression in the upper lip—​the philtrum. During the eighth week, the maxillary processes on each side of the mouth grow forward and fuse with the lower edges of the lateral nasal prominences which eventually form the nasolacrimal groove. The maxillary processes continue to extend below the nasal pits to reach and merge with medial nasal prominences to form the upper lip. The philtrum column is formed by fusion of the maxillary process and the medial nasal prominences of the frontonasal process. Normally, mesodermal tissue migrates from the first branchial arch and reinforces the fusion between the maxillary process and medial nasal prominence in development of the lip, with failure of this process causing a cleft lip (Fig. 6.2.2). If failed closure occurs on one side, a unilateral cleft lip develops and if both sides are affected, a bilateral cleft lip occurs.

Cleft palate The palate forms in the fifth week of gestation and continues to develop through to the twelfth week with the critical stage occurring between weeks 6 and 9 where the maxillary prominences merge with the medial nasal prominences beneath the nasal pits. This forms a wedge-​shaped mass of mesenchymal tissue which grows to separate the future nostrils from the upper lip and becomes the median palatine process or primary palate. The primary palate is located immediately behind the maxillary gingival alveolus and extends to the incisive foramen. In the sixth week of gestation, two mesenchymal projections develop called the lateral palatine shelves. These grow from the lateral walls of the primitive mouth and initially lie vertically under the tongue. Development of the mandible causes the tongue to move downward, allowing the palatal shelves to grow towards each other

686

SECTION 6  Craniofacial and cleft

4 weeks (28 days) Nasal placode Ruptured oropharyngeal membrane

Lens placode Nasal pit Branchial arches

Otic pit

Heart prominence Foregut Frontal view

Lateral view

4½ weeks (33 days) Cervical sinus

Eye

Lateral nasal prominence Nasolacrimal groove

Auricular hillocks

5 weeks (40 days) Eyelid Medial nasal prominence

Eyelid Stomodeum

External acoustic meatus

10 weeks (70 days)

Auricle of external ear

Philtrum of lip

Frontonasal prominence

Maxillary prominence

Mandibular prominence

Fig. 6.2.1  Normal embryology of the face between weeks 4 and 10 when cleft lip and palate occur. This article was published in Atlas of Neonatology: A Companion to Diseases of the Newborn, David A. Clark MD, Copyright Elsevier (2000).

and elevate to a horizontal position in the seventh week of gestation. The palatal shelves fuse to form a midline epithelial seam which then degenerates to allow mesenchymal continuity across the palate. The palate mesenchyme then differentiates into bony and muscular elements that correlate with the position of the hard and soft palate respectively. In addition to fusing in the midline, the secondary

palate fuses with the primary palate and the posterior part of the nasal septum around the ninth week of gestation. These processes of fusion are complete by the tenth to twelfth week of gestation and bone extends from the maxillae and palatine bones into the palatal shelves forming the hard palate (Fig. 6.2.3). A  cleft palate occurs when this process of fusion fails. The development of the secondary

6.2  Embryology of craniofacial skeleton

palate behind the incisive foramen divides the oronasal space into separate oral and nasal cavities, allowing mastication and respiration to take place simultaneously. In summary, although cleft lip and cleft palate often occur together, they have different embryological origins. Cleft lip results from a failed merging of the maxillary and medial nasal prominences on one or both sides. Cleft palate results from failure of the lateral palatine processes to meet and fuse with each other. Cleft palate is more frequently associated with a syndrome, whereas cleft lip is most often an isolated defect.

Craniosynostosis

Fig. 6.2.2  The embryological origins of a unilateral cleft lip. (A) Normal embryo at 5 weeks of gestation. (B) Embryo at 6 weeks with a persistent labial groove on the left side. (A1) Horizontal cross-​section illustrating the grooves between the maxillary prominences and the medial nasal prominences that are merging. (B1) Horizontal cross-​section; arrows point to the grooves filling gradually on the right side after the mesenchymal tissue proliferates. (C) Embryo at 7 weeks. (D) Embryo at 10 weeks with a left complete unilateral cleft lip. (C1) Horizontal cross-​ section showing how the merged epithelium on the right between the nasal prominences has been almost completely pushed out due to the persistent labial grove. (D1) Horizontal section shows the persistent labial groove formed from the stretching of the epithelium tissue and breakdown of this tissue resulting in a complete unilateral cleft lip. This article was published in Color Atlas of Clinical Embryology, Moore KL, Persaud VN, Shiota K, Copyright Elsevier (2000).

(a)

(b)

The skull of the embryo starts developing between days 23 and 26 of gestation. It can be divided into the neurocranium, which surrounds the brain and develops from the surrounding mesenchyme, and the viscerocranium, which is derived from the first three branchial arches and forms the facial skeleton. The neurocranium can be further subdivided into the cranial base; the chondrocranium, which refers to the cranial base bones that originate from the paraxial mesoderm and undergo endochondral ossification (Fig. 6.2.4); and the desmocranium, also known as the calvaria or cranial vault, which undergoes intramembranous ossification (Tubbs et al., 2011). Calvaria is Latin for ‘upper part of the head’. The connective and skeletal tissue of the neck, face, ansd skull formed in humans derives from the neural crest cells. The calvarial sutures are bands of fibrous connective tissue that prevent premature bone separation and allow for uniform growth of the cranium during brain development. As the cerebral and cerebellar hemispheres grow, the calvarial bones are drawn outward partly by the expanding meninges with the dura mater playing a dominant role. The dura mater has an outer layer that is osteogenic and is responsible for the production of the inner table of each flat bone of the cranial vault. The growing brain does not actually push the bones outward since this would create an untenable compressive force on vascular osteogenic tissues. Rather, each flat bone is suspended, with the existing traction forces within a widespread spider’s web of collagenous fibres of the enlarging inner (meningeal) and outer (cutaneous) periosteal layers. As these membranes grow in an ectocranial direction ahead of the expanding brain, the bones are carried with them and thus displaced. The fifth week of gestation marks the chondrocranial

(c)

(d)

(e)

Fig. 6.2.3  (a) Cleft lip and alveolus. (b) Cleft palate. (c) Incomplete unilateral cleft lip and palate. (d) Complete unilateral cleft lip and palate. (e) Complete bilateral cleft lip and palate. This article was published in Orthodontics and Occlusal Management, W. C. Shaw, Copyright Elsevier (1993).

687

688

SECTION 6  Craniofacial and cleft

Cranium

Neurocranium (Protective case around brain)

Viscerocranium (Skeleton of face)

Nasomaxillary Complex

Mandible

Cranial vault (Desmocranium)

Cranial base (Chondrocranium)

Fig. 6.2.4  Subdivisions of the neurocranium.

base, the vault, and facial bone foundations. The spheno-​occipital bone is the initial site of cranial base chondrification in the seventh week and reaches a peak at about the tenth week (Fig. 6.2.5) (Di Ieva et al., 2014). Craniosynostosis involves the failure of the signalling system that governs the processes of growth and differentiation at the sutural

margins. In most cases this appears to occur after suture formation although sutural growth may be affected very early in fetal life (Morriss-​Kay and Wilkie, 2005). It has been thought that failure of formation and maintenance of normal functional sutures could be due to events at the time of formation of the neural crest–​mesoderm boundary (see Chapter 6.3).

Supraoccipital cartilage Foramen magnum Jugular foramen

Occipital bone

Hypoglossal canal Internal auditory meatus

Meckel’s cartilage

Trigeminal passage Carotid foramen Sup. orbital fissure

Dorsum sellae Parietal cartilage

Optic canal Sphenoid bone Cribriform plate

Frontal cartilage Ethmoid bone Nasal bone

Fig. 6.2.5  Cranial view of the skull base during the twelfth week of fetal development. Reproduced with permission from Antonio Di Ieva, Emiliano Bruner, Thomas Haider et al., Skull base embryology: a multidisciplinary review, Child’s Nervous System, Volume 30, Issue 6, pp.991–​1000, Copyright © 2014 Springer Nature.

6.2  Embryology of craniofacial skeleton

REFERENCES Di Ieva A, Bruner E, Haider T, et al. Skull base embryology: a multidisciplinary review. Childs Nerv Syst 2014;30:991–​1000. Marazita ML, Mooney MP. Current concepts in the embryology and genetics of cleft lip and cleft palate. Clin Plast Surg 2004;31:125–​40. Merritt L. Part 1. Understanding the embryology and genetics of cleft lip and palate. Adv Neonatal Care 2005;5:64–​71.

Morriss-​Kay GM, Wilkie AO. Growth of the normal skull vault and its alteration in craniosynostosis; insights from human genetics and experimental studies. J Anat 2005;207:637–​53. Mossey PA, Little J, Munger RG, et  al. Cleft lip and palate. Lancet 2009;374:1773–​85. Tubbs RS, Bosmia AN, Cohen-​Gadol AA. The human calvaria: a review of embryology, anatomy, pathology, and molecular development. Childs Nerv Syst 2011;28:23–​31.

689

6.3

Genetics of craniofacial anomalies Andrew O.M. Wilkie

Introduction The birth of a child with a craniofacial malformation is usually an unexpected and devastating event for the parents. One of the first questions asked is ‘Why did this happen?’ Later, they may go on to ask ‘Could this happen again and if so, can it be avoided?’ A clinical genetics assessment can make an important contribution to answering these and other questions. In general, craniofacial malformations represent defects in embryogenesis, which can arise either from altered genetic information (abnormal developmental programming of the embryo), environmental insult (disruption of development), or a combination of adverse genetic and environmental factors. The clinical geneticist’s approach is primarily directed towards deciding which of these scenarios is most likely to be correct and, if a specific genetic cause is suspected, to advising on the most appropriate genetic tests to perform.

Types of craniofacial anomalies and their genetic contributions Excluding isolated clefts of the lip and palate, the major types of craniofacial anomaly can be classified into (1) craniosynostosis, (2) facial microsomias or dysostoses, (3) frontonasal dysplasias or major facial clefts, and (4)  calvarial and scalp defects. The craniofacial phenotype may present either as an isolated anomaly, or be accompanied by additional features indicating a syndrome. A family history or parental consanguinity increases the chance of an underlying genetic cause. However, most craniofacial disorders present sporadically, irrespective of whether they have a genetic, environmental, or in utero origin. It is often difficult therefore to identify whether a craniofacial defect in a specific patient has an underlying genetic cause. Intensive genetic investigations over the past 20 years have allowed the classification of craniofacial disorders to be refined greatly. Table 6.3.1, which includes the most common and important genetic diagnoses to consider as well as some of the rarer ones, summarizes this information. Each of the major diagnostic categories is summarized in the following sections, followed by the clinical approach to genetic diagnosis in craniofacial malformations through history, examination, and investigations.

Craniosynostosis Craniosynostosis (premature fusion of the cranial sutures) affects approximately 1 in 2250 children. A specific genetic cause can be identified in one-​quarter of cases. The most common genetic diagnoses collectively are syndromes attributable to mutations in the fibroblast growth factor receptor 2 gene (FGFR2) (Crouzon, Pfeiffer, and Apert syndromes). These syndromes are characterized by bicoronal or multisuture craniosynostosis and midface hypoplasia, which may be associated with specific complications including exposure keratitis or breathing difficulties related to choanal stenosis or atresia, or tracheal abnormalities. They are distinguished by examination of the hands and feet which are normal in Crouzon syndrome; in Pfeiffer syndrome, there are broad, radially deviated thumbs; and in Apert syndrome, cutaneous and bony syndactyly. Saethre–​Chotzen syndrome (mutations in TWIST1) and Muenke syndrome (specific p.Pro250Arg (abbreviated P250R) mutation encoded by the FGFR3 gene) are also common. In each, the coronal sutures are usually affected, either unilaterally or bilaterally. Saethre–​Chotzen syndrome is the more distinctive condition, characterized by upper eyelid ptosis, blocked tear ducts, low frontal hairline, and small ears with a prominent horizontal crus helicis. Milder cases can be confused with Muenke syndrome, which is frequently complicated by low-​frequency hearing loss, which should be monitored by audiology. The other distinctive syndrome that presents relatively frequently is craniofrontonasal syndrome (CFNS). This shows X-​linked inheritance, but, except in the case of very rare male mosaic cases, only females present with the classical features of the condition (summarized in Table 6.3.1) (Johnson and Wilkie, 2011). In many cases of what clinically appears to be non-​syndromic coronal craniosynostosis, a specific genetic cause can be identified, especially in bilateral cases (60%), although 30% of unicoronal cases also have a genetic explanation, most often with the Muenke P250R mutation or a mutation in TCF12 (Wilkie et al., 2010; Sharma et al., 2013). Specific gene mutations are much less frequently identified in single-​suture metopic and sagittal synostosis, but when this is accompanied by significant developmental delay, learning disability, or dysmorphic features, an underlying chromosomal abnormality should be sought or excluded. Genetic defects result in abnormal tissue boundary formation or altered osteogenesis-​differentiation

Mandibulofacial dysostosis (MFD)

Craniosynostosis (CRS)

Endothelin 1 Endothelin receptor type A

AD

AR/​ AD

MFD with alopecia

Auriculocondylar syndrome 3

Auriculocondylar syndrome 2

Auriculocondylar syndrome 1

MFD with microcephaly (Guion–​Almeida type)

Richieri–​Costa syndrome

Burn–​McKeown syndrome

EDNRA

Nager syndrome

EDN1

AD/​ AR

AD

AD

AR

AR

AR

AD

Acrofacial dysostosis, Cincinnati type

Phospholipase C, beta-​4

Splicing factor 3b, subunit 4

SF3B4

AD

Treacher Collins syndrome 2

Treacher Collins syndrome 3

G protein, alpha-​inhibiting 3

Polymerase (RNA) I polypeptide A

POLR1A

AD/​AR

AR

PLCB4

Polymerase (RNA) I polypeptide D

POLR1D

Treacher Collins syndrome 1

Craniosynostosis and dental anomalies

GNAI3

Polymerase (RNA) I polypeptide C

POLR1C

AD

AR

Elongation factor Tu GTP binding domain containing 2

Treacher Collins-​Franceschetti syndrome 1 (Treacle)

TCOF1

Antley–​Bixler syndrome

Carpenter syndrome

EFTUD2

Interleukin 11 receptor, alpha

IL11RA

AR

AR

Eukaryotic translation initiation factor 4A3

Cytochrome P450 oxidoreductase

POR

CFNS

EIF4A3

Ras-​associated protein Rab23

RAB23

XLD, male sparing

ERF-​associated craniosynostosis (CRS4)

Miller syndrome

Ephrin-​B1

EFNB1

AD

TCF12-​associated coronal synostosis (CRS3)

Thioredoxin-​like 4A

Ets2 repressor factor

ERF

AD

Saethre–​Chotzen syndrome

Pfeiffer syndrome (mild form)

Dihydroorotate dehydrogenase

Transcription factor 12

TCF12

AD

AD

Maxillary to mandibular transformation, alopecia

AD presentation with isolated question-​mark ears

Microcephaly

Median cleft of mandible, radial and tibial hypoplasia

Choanal atresia/​stenosis

Postaxial deficiency of limbs

Pierre Robin sequence, rib defects

Radial limb anomalies

Variable limb anomalies

Normal limbs

Normal limbs

Normal limbs

Delayed tooth eruption, supernumerary teeth

Ambiguous genitalia, bowed femora, elbow ankylosis

Polysyndactyly, congenital heart disease

Hypertelorism, grooved nasal tip, nipple asymmetry, longitudinal nail splits

May appear non-​syndromic or resemble mild Crouzon syndrome

May appear non-​syndromic or resemble mild Saethre–​Chotzen syndrome

Low frontal hairline, ptosis, blocked tear ducts, small ears with prominent horizontal crus helicis

Broad thumbs/​great toes, cutaneous syndactyly of feet

Choanal stenosis, hydrocephalus, acanthosis nigricans

TXNL4A

Twist homologue 1

TWIST1

Low-​frequency hearing loss

Crouzon syndrome with acanthosis nigricans

Ditto, complex syndactyly of hands/​feet

Apert syndrome Muenke syndrome

Ditto, broad thumbs/​great toes

Pfeiffer syndrome

DHODH

Fibroblast growth factor receptor, type 1

FGFR1

AD

Crouzonoid facies

Additional clinical features

Crouzon syndrome

Clinical disorder(s)

Cerebrocostomandibular syndrome

Fibroblast growth factor receptor, type 3

FGFR3

AD

Inheritance pattern

SNRPB

Fibroblast growth factor receptor, type 2

Encoded protein

FGFR2

Type of craniofacial Gene anomaly symbol

Table 6.3.1  Genes mutated in craniofacial anomaly syndromes

692

Aristaless-​like homeobox 1 Aristaless-​like homeobox 3 Aristaless-​like homeobox 4 Zinc finger SWIM domain-​containing protein 6 Runt-​related, 2 Muscle segment homeobox-​2 Aristaless-​like 4

ALX1

ALX3

ALX4

ZSWIM6

RUNX2

MSX2

ALX4 AR

Dedicator of cytokinesis 6 Notch, Drosophila, homolog of,

DOCK6

NOTCH1 AD

AD

ARHGAP31 Rho GTPase-​activating protein 31

AD

AD

AD

AD

AR

AR

AR

Sperm antigen with calponin homology and AD coiled-​coil domains 1-​like

SPECC1L

XLD

Midline 1 ring finger gene

MID1

AD, autosomal dominant; AR, autosomal recessive.

Scalp defects

Widened sutures, parietal foramina

Frontonasal dysplasia (FND)

Adams–​Oliver syndrome 5

Adams–​Oliver syndrome 3

Adams–​Oliver syndrome 1

Parietal foramina 2

Parietal foramina 1

Cleidocranial dysostosis

Acromelic frontonasal dysostosis

ALX4-​associated FND2

Frontorhiny (FND1)

ALX1-​associated FND3

Opitz G/​BBB syndrome 2

Opitz G/​BBB syndrome 1

Transverse limb deficiency, cardiac or vascular defects

Transverse limb deficiency, neurological, eye and cardiac defects

Transverse limb deficiency, occasional skull defects

Note, recessive mutations cause FND

Absent or hypoplastic clavicles, supernumerary teeth

Parietal foramina, tibial hemimelia, polydactyly

Parietal foramina, alopecia

Prominent philtral pillars

Orofacial clefting

Laryngo-​tracheo-​oesophageal anomalies, cleft lip/​palate, hypospadias

693

694

SECTION 6  Craniofacial and cleft

balance in the cranial sutures; intrauterine fetal head constraint may be a frequent precipitant in non-​syndromic cases.

Oculo-​auriculo-​vertebral spectrum and mandibulofacial dysostoses Hypoplasia of the mandible or maxilla may occur symmetrically or asymmetrically, and may commonly be accompanied by abnormality of the ears, facial tags, oral clefting, and abnormalities of the eyes including microphthalmia, epibulbar dermoids, and notches (colobomas) of the lower eyelids. The most common of these conditions are the facial microsomias, which include hemifacial microsomia (maxillary or mandibular asymmetry, preauricular tags or pits, and microtia, which may be associated with hearing loss) and Goldenhar syndrome (associated with epibulbar dermoids and cervical vertebral abnormalities, summarized by the term oculo-​auriculo-​vertebral spectrum (OAVS)), with a birth prevalence of up to 1 in 3500. These usually occur sporadically and probably arise from insults to embryonic development (such as stapedial artery haemorrhage or hypovolaemia) occurring at 4–​8 weeks of fetal development. Miscellaneous chromosomal abnormalities are identified in some cases, especially in those more severely affected (Beleza-​Meireles et al., 2014). The most common genetic cause of mandibulofacial dysostosis (MFD) is Treacher Collins–​Franceschetti syndrome 1 (TCS1), an autosomal dominant disorder caused by mutations in the TCOF1 gene. The features are characteristically symmetrical compared with the microsomias. Hypoplasia of the zygomatic bones is associated with lower eyelid colobomas; the ears are hypoplastic, hearing loss is frequent, and neurodevelopment and limb extremities are usually normal. TCS1 needs to be distinguished from many other rarer MFDs (Table 6.3.1). Clinical criteria to distinguish them include abnormalities of the limbs (acrofacial dysostoses, including Miller and Nager syndromes), presence of microcephaly (MFD with microcephaly), or thoracic vertebral defects (cerebrocostomandibular syndrome). The genes mutated in MFDs mostly affect proteins involved in fundamental cellular processes of ribosome biogenesis or splicing of messenger RNA, and mutations are associated with death of neural crest cells from which facial tissues arise (Lehalle et  al., 2015). Distinct from these are an intriguing group of disorders associated with abnormalities of endothelin signalling. These auriculocondylar syndromes cause homeotic transformations whereby the lower jaw is reprogrammed to develop with the identity of the upper jaw (causing auriculocondylar syndromes), and vice versa (Gordon et al., 2015). Abnormal pinnae accompanied by branchial cysts and renal abnormalities suggest one of the branchio-​ oto-​renal syndromes (mutations in EYA1 and SIX5).

Frontonasal malformations and major facial clefts These are rare disorders with the common characteristic of widely spaced eyes (hypertelorism). The majority of these are sporadic and probably mostly arise as developmental disorders or disruptions. For example, they may be associated with frontal or ethmoidal encephalocoeles (part of the neural tube defect spectrum), or severe facial clefts, which are probably disruptions of embryonic development and may be associated with clefts of the orbit and abnormalities of the orbital globe and eye socket (Tan and Mulliken, 1997).

Asymmetry is usual in these acquired disorders. The most common genetically determined frontonasal dysostoses/​dysplasias (FNDs) are associated with CFNS, and Opitz G/​BBB syndrome, which is X-​ linked (mutations in MID1) with a rarer autosomal dominant form (mutations in SPECC1L). Acromelic FND is caused by new mutations in the ZSWIM6 gene. Rare recessive causes of FND, which vary markedly in severity, include recessive mutations in three members of the ALX transcription factor family (Table 6.3.1).

Calvarial and scalp defects Cleidocranial dysplasia, an autosomal dominant condition associated with mutations in RUNX2, is the most common genetic disorder associated with calvarial defects (late closing fontanelles accompanied by diastasis of the midline sutures, aplasia or hypoplasia of the clavicles, and dental abnormalities with supernumerary teeth). Mutations in MSX2 and ALX4 cause isolated parietal foramina or cranium bifidum. The natural history is for the bony defects to close progressively with time and surgery is usually contraindicated. A surgically important congenital disorder affecting the scalp epidermis is aplasia cutis congenita (ACC), which occurs in up to 1 in 3000 births and is often accompanied by terminal transverse limb defects (Adams–​Oliver syndrome). The underlying skull bones are rarely affected. ACC is very heterogeneous genetically, with mutations in seven genes recently identified causing ACC or Adams–​ Oliver syndrome (Marneros, 2015). These genes influence a variety of developmental pathways affecting cell division, cell adhesion, or vascular development. The characteristic distribution of pathology may be due to some vulnerability of extremities (apical scalp and limbs) during fetal development.

Clinical approach Family history Consanguinity and the presence of any craniofacial features in other individuals in family are relevant; consider variable expressivity of a shared predisposition. Multiple affected individuals may signal one of the classical Mendelian patterns of inheritance: autosomal dominant (vertical transmission, both sexes equally affected), autosomal recessive (affected individuals usually in a single sibship, increased rate of consanguinity in parents), or X-​ linked recessive (affected males, females are carriers, no male-​to-​ male transmission). Note, however, that a negative family history is the norm and does not exclude a genetic origin (sporadic cases can be caused, for example, by new mutations or by autosomal recessive disease in small sibships).

Pregnancy history Any deviation from normal pregnancy may be relevant. Previous pregnancies (craniosynostosis is more frequent in primiparity) or the assisted reproduction should be identified. Teratogen exposure, for example, to anticonvulsants (metopic synostosis is associated with fetal valproate syndrome) or antimitotics (methotrexate embryopathy resembles Miller syndrome), may be relevant. Episodes of bleeding or serious illnesses (haemorrhage or fetal hypovolaemia may trigger OAVS), oligohydramnios, multiple pregnancy, abnormal fetal lie (intrauterine constraint predisposes

6.3  Genetics of craniofacial anomalies

Table 6.3.2  Examples of characteristic features on examination of different craniofacial syndromes System

Clinical feature

Differential diagnosis

Facies

Prominent eyes, relative hypoplasia of midface, prominent nose (Couzonoid facies)

Crouzon, Pfeiffer, Apert syndromes, ERF-​related craniosynostosis

Ears

Symmetrically hypoplastic

Treacher Collins and related syndromes

Question-​mark (detached lobules)

Auriculocondylar syndrome

Asymmetrically hypoplastic ± facial nubbins

Hemifacial microsomia/​Goldenhar syndrome/​OAVS

Small with prominent crus helicis

Saethre–​Chotzen syndrome

Eyes

Epibulbar dermoid

Goldenhar syndrome

Dental

Supernumerary teeth

Cleidocranial dysplasia

Cervical spine

Short neck, limited mobility

Klippel–​Feil anomaly (Goldenhar syndrome/​OAVS)

Heart

Congenital heart disease

Carpenter syndrome

Hands/​feet

Syndactyly without polydactyly

Apert syndrome

Polysyndactyly

Carpenter syndrome (with CRS) Acromelic FND

Broad thumbs and great toes

Pfeiffer syndrome

Radial hypoplasia

Nager syndrome Baller–​Gerold syndrome

Ulnar hypoplasia

Miller syndrome, Fetal aminopterin syndrome

Longitudinal splitting of finger and toenails

CFNS

Terminal transverse deficiency

Adams–​Oliver syndrome

to craniosynostosis), delivery (obstructed labour frequently associated with craniosynostosis, but as a consequence rather than cause, which is important to explain to parents) should also be sought. Extreme prematurity is associated with dolichocephalic head shape and may sometimes trigger craniosynostosis.

Postnatal history Growth, sensory functions, and developmental milestones are assessed.

Examination Examination and classification of the craniofacial deformity should be accompanied by a search for additional physical features suggestive of a syndrome. These might occur in the craniofacial region or be extracranial (e.g. characteristic abnormalities of the limbs). Selected features characteristically associated with different craniofacial syndromes are summarized in Table 6.3.2.

Genetic investigations The advice of a clinical geneticist should be sought. When there is strong clinical suspicion of mutation in a particular gene, then targeted DNA sequencing can be requested to detect mutations (such as substitutions and insertions and deletions of a few base pairs) in specific genes at nucleotide resolution. DNA sequencing is, however, unsuitable if a heterozygous deletion in a specific gene is suspected; in these cases, multiplex ligation-​dependent probe amplification or similar method is required to estimate gene dosage. With rapid advances in technology, increasing knowledge of the genetic complexity of disorders, and falling costs, genome-​ wide analyses are increasingly frequently requested in a routine diagnostic setting. Array comparative genomic hybridization (a

method to identify deletions or duplications of the chromosomes) has already largely superseded conventional karyotyping. High-​ throughput DNA sequencing, covering the coding part of the genome (exome) or even the entire genome, has catalysed many recent discoveries (Twigg and Wilkie, 2015), and clinical implementation is probably imminent.

REFERENCES Beleza-​Meireles A, Clayton-​Smith J, Saraiva JM, et al. Oculo-​auriculo-​ vertebral spectrum: a review of the literature and genetic update. J Med Genet 2014;51:635–​45. Gordon CT, Weaver KN, Zechi-​Ceide RM, et  al. Mutations in the endothelin receptor type A cause mandibulofacial dysostosis with alopecia. Am J Hum Genet 2015;96:519–​31. Johnson D, Wilkie AOM. Craniosynostosis. Eur J Hum Genet 2011;19:369–​76. Lehalle D, Wieczorek D, Zechi-​Ceide RM, et  al. A review of craniofacial disorders caused by spliceosomal defects. Clin Genet 2015;88:405–​15. Marneros AG. Genetics of aplasia cutis reveal novel regulators of skin morphogenesis. J Invest Dermatol 2015;135:666–​72. Sharma VP, Fenwick AL, Brockop MS, et  al. Mutations in TCF12, encoding a basic helix-​loop-​helix partner of TWIST1, are a frequent cause of coronal craniosynostosis. Nat Genet 2013;45:304–​7. Tan ST, Mulliken JB. Hypertelorism: nosologic analysis of 90 patients. Plast Reconstr Surg 1997;99:317–​27. Twigg SR, Wilkie AO. New insights into craniofacial malformations. Hum Mol Genet 2015;24:R50–​9. Wilkie AOM, Byren JC, Hurst JA, et al. Prevalence and complications of single-​ gene and chromosomal disorders in craniosynostosis. Pediatrics 2010;126:e391–​400.

695

6.4

Assessment of patients with craniosynostosis Nicholas White

Cranial growth The stimulus for growth of the cranium comes from the expanding brain which grows rapidly in the first years of life. This rapid brain growth has to be accommodated by an equal expansion in the size of the skull, which reaches 90% of its final adult size by the age of 3 years (Table 6.4.1). The cranial vault consists of frontal, parietal, temporal, and occipital bones which are separated from each other by the metopic, sagittal, right and left coronal, and right and left lambdoid sutures. These sutures allow gradual displacement of the individual bones allowing the underlying brain to expand. In order to avoid large gaps, developing new bone is deposited at the margins of the bones adjacent to the sutures. Bone deposition and resorption also takes place on the outer and inner surfaces of the bones to produce changes in their curvature and thickness. The cranial sutures only remain open while brain growth is taking place. If brain growth ceases then cranial growth will also stop and the cranial sutures will be replaced by bone. The term craniosynostosis denotes the pathological partial or complete absence of one or more cranial sutures which manifests as abnormal skull growth (Cohen, 2000). Although it is often referred to as premature fusion this is misleading as only the metopic suture fuses in the normal physiological state (Bajwa et al., 2013). The remaining sutures change and mature in macroscopic and microscopic form during growth but remain present.

Abnormal development of the skull results in an altered head shape Absence of a suture restricts growth perpendicular to that suture and produces compensatory changes elsewhere in the cranium. Table 6.4.1  Head circumference during growth

This may result in an overall reduction in cranial volume and a change in head shape which is characteristic depending on the suture involved. These are summarized in Table 6.4.2. Absence of the sagittal suture impairs expansion of cranial growth transversely, which is compensated for by excessive anteroposterior length. This gives the appearance of a long, narrow shape that resembles a boat, hence the term scaphocephaly. Additionally, there is frontal bossing, a sagittal ridge, bitemporal hollowing, and an occipital prominence (bullet). Unilateral coronal synostosis has recession of the supraorbital area on the affected side with compensatory bossing on the opposite side. In addition to this, there can be marked facial asymmetry. The term plagiocephaly (twisted head) can be used to describe a number of single-​or multisuture craniosynostoses or non-​pathological conditions such as deformational plagiocephaly (moulding). So, the term frontal plagiocephaly is best used to describe unilateral coronal synostosis and occipital plagiocephaly for unilambdoid synostosis. In bilateral coronal synostosis, the characteristic appearance of brachycephaly consists of a symmetrical deformity with reduction in the anterior growth of the forehead and compensatory widening of the cranium in the temporal region and increased vertical height of the cranium (turricephaly). Craniums of those with metopic synostosis have a symmetrical deformity with a narrow, pointed forehead known as trigonocephaly. In addition, there is lateral recession of the forehead with compensatory growth in the parietal region. To diagnose and manage children with craniosynostosis one must understand the consequences of abnormal skull growth. Table 6.4.2  Types of craniosynostosis and their characteristic head shapes Suture fusion

Head shape

Age

Male (cm)

Female (cm)

Approximate adult size (%)

Sagittal

Scaphocephaly

Birth

36

34

64

Metopic

Trigonocephaly

1 year

46

44

82

Unicoronal

Frontal plagiocephaly

3 years

50

48

89

Bicoronal

Brachycephaly

Adult

56

54

100

Unilambdoid

Occipital plagiocephaly

698

SECTION 6  Craniofacial and cleft

Presentation and consequences of craniosynostosis Parents presenting with a child with an abnormal head shape are usually anxious and their fears are often amplified by having seen several healthcare professionals prior to attending a craniofacial clinic. It is often necessary to distinguish a synostotic from a deformational change in head shape. This is described in more detail later in this chapter. For those with craniosynostosis, the characteristic phenotypical expression, described previously, is the basis of diagnosis. The correct diagnosis enables the craniofacial team to provide the patient and their family with appropriate treatment. In addition to altered head shape, the consequences of craniosynostosis, in particular for syndromic patients, need to be assessed during the initial presentation. This needs to be done in a systematic manner by history, examination, and specific investigations. The consequences of craniosynostosis can be divided into cosmetic and functional sequelae. As well as altered head shape due to atypical cranial growth, the cosmetic sequelae can also be altered facial appearance due to abnormal facial growth. This is particularly true in syndromic craniosynostosis and asymmetrical deformities (such as unicoronal synostosis). Cephalocranial disproportion is the main functional concern for patients with craniosynostosis. This can cause raised intracranial pressure (ICP) and cerebellar tonsillar descent. A mismatch of a restricted cranial volume with a normal brain volume leading to raised ICP and then impaired cerebral function is, however, a very simple model (Gault et al., 1992). The relationship between cephalocranial disproportion, raised ICP, and functional impairment is complex and has to take into account many other factors such as hydrocephalus, venous hypertension, and anatomical variants found in syndromic craniosynostosis such as narrow jugular foramina and a wide foramen magnum (Rich et al., 2003). As well as overt raised ICP, other more subtle functional impairments such as speech and language delays, motor developmental delays, and cognitive delays may be present. The consequence of not treating patients with craniosynostosis indicates the risks of raised ICP. Contemporary practice is to offer all patients treatment; this means that there is a lack of recent evidence. However, studies do exist that show the functional impairment caused by craniosynostosis (see Chapter 6.5). The earliest report, from 1913, describes 21% of the children at a school for the blind having craniosynostosis (Larsen, 1913). In 1958, a study of 171 cases of untreated craniosynostosis found that 26 had papilloedema; 33, optic atrophy; 85, headaches; 29, epilepsy; and 42, decreased intelligence (Bertelsen, 1958). More recently, children with unoperated craniosynostosis have been shown to have reduced IQ (Marchac and Renier, 1987). Other functional problems include the need for eye protection due to exorbitism caused by forehead recession and midface hypoplasia. Midface hypoplasia can also cause peripheral sleep apnoea or feeding issues. Children with Apert syndrome need assessment of their hand function due to their syndactyly. Hearing loss is associated with conditions such as Pro250Arg mutation (Muenke syndrome). These all need to be assessed during the initial presentation.

birth events such as gestation period and type of delivery. Preterm babies can have small heads with soft cranial bones which are easily deformed, especially during difficult instrumental deliveries. An antenatal history determines the presence of maternal epilepsy and sodium valproate use, or fetal alcohol syndrome—​both are causes of metopic synostosis. Family history includes all siblings, a past family history of skull surgery, and consanguineous relationships. Enquiry about head shape at birth and the immediate succeeding days is important. A history of immediate and progressive concern is in keeping with craniosynostosis whereas shape change in the weeks following birth is more indicative of deformational change. Feeding and sleep patterns should be assessed. Poor sleep in breastfed babies may indicate synostosis while deformational change is more likely in bottle-​fed good sleepers due to a repetitive sleeping position. A developmental history should be taken. Delayed development may indicate raised ICP. Also, there is a correlation between late sitting due to motor delay and deformational plagiocephaly.

Examination The examination of a child with suspected craniosynostosis is based on the pattern recognition of several characteristic head shapes. A  full head-​to-​toe examination is also performed; the head, neck, digits, toes, and spine require examination. The structures of the head and neck include skull base organs such as the ears, eyes, and nose; the occlusal plane and examination of the neck with range of movement and palpation of the sternocleidomastoid muscles. Presence of calvarial ridges, masses, skin pits, and accessory tags should be noted. The measurement of head circumference is recorded and plotted on a growth chart. Cephalic index, a tool developed by anthropologists for assessment of disarticulated skulls, is measured using a Bertillon calliper. In its fullest expression, it consists of three indices—​breadth/​ height, width/​height, and breadth/​length. The last is the only one regularly used in clinical practice and while repeatable and reliable, it is only able to provide a two-​dimensional description of a three-​ dimensional whole. It is the ratio of the maximum breadth of the head (biparietal distance) divided by the maximum length (anteroposterior distance) multiplied by 100 (Fig. 6.4.1). It is useful in the diagnosis of sagittal and bicoronal synostosis.

Cephalic index = Max breadth/length x 100 Width (Supramastoid crest) Length (Glabella to occiput) • 83% – Brachycephaly

History Altered head shape is either noticed at birth or during early infancy; the deformity is more subtle early on. History must include primary

Fig. 6.4.1  Cephalic index.

6.4  Assessment of patients with craniosynostosis

Distinguishing posterior deformational plagiocephaly from unilateral lambdoid synostosis The various forms of plagiocephaly need to be distinguished from each other. Anterior plagiocephaly results from unicoronal synostosis. Posterior plagiocephaly is caused by unilambdoid synostosis, deformational plagiocephaly, and plagiocephaly caused by torticollis. Deformational plagiocephaly, which is common and a frequent reason for referral (Losee and Mason, 2005), needs to be distinguished from the extremely low-​incidence unilambdoid craniosynostosis (Kalra and Walker, 2012). Deformational plagiocephaly (also known as moulding) is caused by an external force on the skull during or after birth. Most commonly, it is due to a supine positioning of a baby while sleeping with the head facing to the left or the right, resulting in a deformation force on one side of the occiput. The child is otherwise well, with normal development; however, there is a subgroup of children whose deformational plagiocephaly is secondary to another underlying condition which has resulted in them spending a long time lying in a supine position in their first months of life. The history usually suggests a normal head shape at birth with gradual development of plagiocephaly over the first 3 months of life, which then starts to improve as the child’s motor development results in better head control. Upon examination, the head size is normal, there is superior/​posterior flattening of the occiput and frontal bossing on the affected side. There is a parallelogram-​shaped head with the ear on the affected side moving anteriorly (Bruneteau and Mulliken, 1992). The appearance of unilambdoid synostosis, however, is of a normal sized or small head, inferior/​posterior occipital flattening, recessed forehead on the affected side, a compensatory contralateral occipital bulge, and a trapezoid-​shaped head with the ears set at different heights in the coronal axis with the affected side lower (Fig. 6.4.2). A  skull X-​ray will show sutures present in deformational plagiocephaly and absent in unilambdoid craniosynostosis; in equivocal cases, three-​dimensional computed tomography will provide the definitive diagnosis. The differences between deformational plagiocephaly and unilambdoid synostosis are summarized in Table 6.4.3.

Ipsilateral frontal bossing

Ipsilateral ear displaced anteriorly Contralateral occipital bossing

Ipsilateral occipitoparietal flattening

moulding

Fig. 6.4.2  Moulding versus unilambdoid.

Deformational plagiocephaly is a self-​correcting condition that requires no intervention whereas some cases of unilambdoid cranio­ synostosis may benefit from surgery. Torticollis is another cause of plagiocephaly. It is an abnormal neck position resulting in the head being tilted to one side. It has a variety of causes, which can include muscular, ocular, or cervical torticollis. The most common presentation is muscular torticollis. The aetiology is unknown, but the current theory is that it results from abnormal intrauterine positioning, leading to intramuscular compartment syndrome and ischaemic injury of the sternomastoid muscle. This leads to fibrosis and contracture. A mass (sometimes referred to as a sternocleidomastoid tumour) is present in the neck and gradually disappears by the age of 8 months. The muscle can remain fibrotic and shortened. The condition is treated primarily by physiotherapy. About 5–​10% of cases fail to respond to stretching and require surgical release of the muscle (Tang et al., 2002). Ocular torticollis arises from a complex squint due to orbital asymmetry or dystopia with one orbit in a superior position compared to the other. The head is tilted to one side to keep the apparent visual horizon at the same level. An example of this is untreated unicoronal synostosis in an adolescent or adult. Cervical torticollis is due to a cervical spine abnormality which alters the head position. In a suspected case of unilambdoid synostosis or severe deformational plagiocephaly, all these types of torticollis need to be excluded by clinical examination.

Specific investigations Apart from history, examination, a photographic record, and measurement of head circumference, further investigations are generally not warranted outside a craniofacial service for an initial assessment of a new patient. However, if there is clinical suspicion of sequelae of craniosynostosis then this needs to be investigated further. These are most commonly seen in patients with syndromic craniosynostosis and require the management and investigation by a multidisciplinary team.

Contralateral frontal bossing

Contralateral parietal bossing

Ipsilateral ear displaced posteriorly

Ipsilateral occipitoparietal flattening unilambdoid

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SECTION 6  Craniofacial and cleft

Table 6.4.3  Features of deformational plagiocephaly versus unilambdoid plagiocephaly Deformational plagiocephaly

Unilambdoid synostosis

Head size

Normal

Normal or small

Head shape

Parallelogram

Trapezoid

Posterior flattening

Superior/​occipital

Inferior/​parietal

Forehead

Ipsilateral bossing contralateral recession

Contralateral bossing ipsilateral recession

Ear displacement

Affected side anterior

Affected side inferior or posterior

Skull X-​ray

Sutures present

Sutures absent

Imaging Imaging is the mainstay of craniosynostosis investigation. Skull X-​rays have only a limited role in the diagnosis of craniosynostosis. Normally three views are taken: anterior–​posterior, posterior–​anterior, and lateral. Absent cranial sutures are shown as a sclerotic line whereas patent sutures appear as a gap. Skull X-​rays may differentiate craniosynostosis from deformational plagiocephaly as the presence of all the cranial sutures excludes craniosynostosis. Skull X-​rays of preterm and young babies are, however, notoriously difficult to interpret and a diagnosis based on an early skull X-​ray should be treated with caution. Historically, two features of skull X-​rays have been used to describe aspects of craniosynostosis. The first is a copper-​beaten appearance (Fig. 6.4.3). This is due to thinning of the cranial bones secondary to a constant pressure being exerted on the inner surface from the expanding brain. It is a feature of chronic, raised ICP, yet its absence does not exclude raised ICP. The harlequin sign on an anteroposterior skull X-​ray is a feature of unicoronal synostosis (Fig. 6.4.4). It describes the elevation of the ipsilateral lesser wing of the sphenoid, with posterior displacement of the superior and lateral rims of the orbit. The definitive radiological investigation of craniosynostosis performed in most craniofacial centres is a computed tomography scan of the head and facial bones with three-​dimensional reconstruction, using a low-​irradiation protocol. Although computed tomography rarely provides additional information in non-​syndromic, single-​ suture craniosynostosis and most diagnoses are made clinically, it helps delineate the exact pattern of synostosis in patients with multisuture problems, aids surgical planning, and occasionally identifies unexpected anomalies (Cerovac et al., 2002).

(a)

Fig. 6.4.3  Copper beaten skull X-​ray.

(b)

Magnetic resonance imaging provides better visualization of soft tissue anomalies but is rarely needed in sporadic craniosynostosis, being of more utility in syndromic variants. It is particularly of use for assessing brain parenchyma to help diagnose cases of secondary craniosynostosis. It is also of greater utility for detecting cerebellar tonsillar descent (Fig. 6.4.5).

Investigation of raised intracranial pressure Concerns over raised ICP are elicited by history and examination. Headaches, waking at night, and developmental delay are apparent from the history. Microcephaly, a tense anterior fontanelle, a syndromic phenotype, and multisuture synostosis are found by examination. Raised ICP is more frequent in syndromic synostosis (60%) than non-​syndromic synostosis (14%) and multisuture synostosis (45%) compared to single-​suture disease (9%) (Renier, 1989). The first-​line investigation should be computed tomography or magnetic resonance imaging. Following this, fundoscopy should be considered to assess for papilloedema—​optic disc swelling caused by increased ICP. The swelling is usually bilateral and in the case of craniosynostosis is a late sign, occurring following chronically raised ICP. Fundoscopy should be performed by a trained ophthalmologist with the pupils dilated. The signs of papilloedema seen with an ophthalmoscope include venous engorgement, loss of venous pulsation, haemorrhages over the optic disc, and blurring of the optic margins. In equivocal cases, invasive monitoring should be considered. ICP fluctuates:  rising with exertion and agitation, falling with sleep and a vertical posture. In a normal adult the ICP is 7–​15 mmHg. There is no clear definition of raised ICP in a child

6.4  Assessment of patients with craniosynostosis

(a)

(b)

Fig. 6.4.4  (a) Harlequin sign on an anteroposterior skull X-​ray of a child with right unicoronal synostosis. (b) Posteroanterior three-​dimensional computed tomography scan.

with craniosynostosis but values of 15–​20  mmHg are commonly used (Tamburrini et  al., 2004). Measurement is by a transcranial pressure device (ICP bolt) which is placed under a general anaesthetic then connected to a monitor. The bolt is usually used for 24 hours but may be needed for several days. ICP monitoring is considered to be a safe. However, there are potential risks of bleeding, infection, and epilepsy. An alternative method of recording raised ICP is through the use of visual evoked potentials (VEPs) (Mursch et al., 1998). The VEP tests the function of the visual pathway from the retina by measuring conduction from the optic nerve through the optic chiasm and optic radiations to the occipital cortex. Electrical potentials initiated by

Fig. 6.4.5  Magnetic resonance imaging of cerebellar tonsillar decent.

visual stimuli are recorded by electroencephalographic electrodes on the occiput. With raised ICP, optic nerve swelling reduces the conduction time.

Cerebellar tonsillar descent and Chiari malformation In patients with craniosynostosis, a complex combination of chronic, raised ICP, a small posterior fossa due to brachycephaly or pansynostosis, and an enlarged foramen magnum (sometimes found in syndromic craniosynostosis) can cause descent of the cerebellum below the level of the foramen magnum (Fig. 6.4.5). The term hindbrain herniation tends to be used to describe an acute, acquired event such as an extradural haematoma causing cerebellar descent. The term Chiari malformation has a specific meaning in neurosurgery and is divided into four types. Type I  is the most common and the least severe. The hallmark is caudal displacement of peg-​like cerebellar tonsils below the level of the foramen magnum with resultant impaction against the foramen magnum, compression of the cervicomedullary junction by the ectopic tonsils, and interruption of normal flow of cerebrospinal fluid through the region. The Chiari type II malformation is less common, more severe, and almost invariably associated with a myelomeningocele. Because of its greater severity, it becomes symptomatic in infancy or early childhood. Its hallmark is caudal displacement of lower brainstem (medulla, pons, fourth ventricle) through the foramen magnum. Symptoms arise from dysfunction of the brainstem and lower cranial nerves. Chiari type III and IV malformations are exceedingly rare and generally incompatible with life. The type III malformation refers to herniation of cerebellum into a high cervical myelomeningocele, whereas type IV refers to cerebellar agenesis. Importantly, it is not at all clear that the four types of Chiari malformation represent a disease continuum corresponding to a single disorder. The four types (particularly types III and IV) are increasingly believed to have different pathogenesis and share little in common other than their names. Patients with craniosynostosis may also have congenital type I or II Chiari malformations as opposed to cerebellar tonsillar descent as a result of cephalocranial disproportion which creates a complex clinical picture. Symptoms can include headache and neck pain (worsened by coughing or the Valsalva manoeuvre), cerebellar symptoms such as impaired motor coordination, and lower brainstem symptoms including dysarthria

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SECTION 6  Craniofacial and cleft

and dysphagia. In infants, signs of brainstem dysfunction predominate with swallowing or feeding difficulties, stridor, apnoea, and a weak cry. Treatment is surgical; in patients with isolated Chiari malformations, foramen magnum decompression is the most frequent treatment. However, in those patients with craniosynostosis where the cerebellar descent is due to cephalocranial disproportion then expansion of the posterior fossa needs to be considered (see Chapter 6.6) (White et al., 2009).

Multidisciplinary care of the child with craniosynostosis It is now known and understood that children who have cranio­ synostosis require the facilities and expertise of a varied team of healthcare professionals for their diagnosis and treatment in a modern, dedicated paediatric setting. The wide variety of potential problems found in children with craniosynostosis, particularly syndromic craniosynostosis, makes it necessary for them to be cared for by a large number of medical and surgical specialities including craniofacial surgeons, neurosurgeons, otolaryngologists, dentists, speech and language therapists, ophthalmologists, psychologists, and geneticists.

Genetics The genetic basis of craniosynostosis is dealt with in Chapter 6.3. The role of the clinical geneticist in the outpatient setting plays an important role. They contribute to both diagnosis and counselling of the family. Genetic testing is not indicated in patients with single-​ suture craniosynostosis in whom there are no associated abnormalities or other concerns. In addition, patients and their parents can be recruited into research programmes if there is no known genotype for their condition.

Airway Different respiratory problems arise at different ages in children with syndromic craniosynostosis. They are best managed by a team consisting of both ear, nose, and throat surgeons and respiratory physicians. Newborn children can have nasal obstruction due to midface hypoplasia or they can have more distal airway obstruction due to choanal atresia or a sleeve trachea. These are best dealt with by positioning or a nasopharyngeal airway. In the worst cases tracheostomy has to be considered. As the child gets older, oropharyngeal airway obstruction can be caused by enlargement of the tonsils or adenoids which may need removing. As the patients pass the age of 5 years they may develop peripheral (or obstructive) sleep apnoea as a result of their midface hypoplasia. However, it can be difficult to distinguish this from central sleep apnoea due to recurrent raised ICP. In these cases sleep studies under the guidance of a respiratory physician are invaluable. Definitive management of peripheral sleep

apnoea caused by midface hypoplasia is by Le Fort III advancement which is dealt with in Chapter 6.6.

Eyes The role of the ophthalmologist falls into three areas: screening, eye protection, and assessment for papilloedema. Ophthalmological screening should be an integral part of the evaluation of all patients with craniosynostosis because of the high incidence of abnormal findings such as amblyopia, strabismus, and hypermetropia. These abnormal eye findings are more common in asymmetrical or unilateral synostoses than symmetrical or bilateral synostoses. Due to forehead retrusion and midface hypoplasia, exorbitism may develop leading to exposure of the eyes. The initial management of these should be non-​surgical with barrier or antibiotic gel. First-​line surgical management is by lateral tarsorrhaphy and definitive surgical management by fronto-​orbital advancement and remodelling or midface advancement.

Development The purpose of treating a child with craniosynostosis is to maximize their potential. Surgery addresses both functional (cephalocranial disproportion) and cosmetic concerns. However, a child’s development is complex and so developmental assessments and monitoring are required. One of the most sensitive measurements of development is a speech and language ability as language delay is common in craniosynostosis (Korpilahti et al., 2012). This can be done from 3  years onwards and possibly from as early as 18  months. As the child gets older, psychologists can monitor behaviour from 5 years up and cognitive function from 7 years (Sidoti et al., 1996). Delayed milestones in any of these could be a sign of the development of raised ICP.

REFERENCES Bajwa M, Srinivasan D, Nishikawa H, et  al. Normal fusion of the metopic suture: an analysis of 337 paediatric computed tomography scans of the head. J Cranio Surg 2013;24:1201–​5. Bruneteau RJ, Mulliken JB. Frontal plagiocephaly:  synostotic, compensational or deformational. Plast Reconstr Surg 1992;89: 21–​31. Bertelsen TI. The mental symptoms and their cause. Acta Ophthalmol 1958;36:112–​16. Cerovac S, Neil-​Dwyer JG, Rich P, et al. Are routine preoperative CT scans necessary in the management of single suture craniosynostosis? Br J Neurosurg 2002;16:348–​54. Cohen MM. Sutural biology. In:  Cohen MM, Maclean RE (eds) Craniosynostosis:  Diagnosis, Evaluation and Management, pp. 11–​ 23. New York: Oxford University Press, 2000. Gault DT, Renier D, Marchac D, et al. Intracranial pressure and intracranial volume in children with craniosynostosis. Plast Reconstr Surg 1992;90:377–​81.

6.4  Assessment of patients with craniosynostosis

Kalra R, Walker ML. Posterior plagiocephaly. Childs Nerv Syst 2012;28:1389–​93. Korpilahti P, Saarinen P, Hukki J. Deficient language acquisition in children with single suture craniosynostosis and deformational posterior plagiocephaly. Childs Nerv Syst 2012;28:419–​25. Larsen H. Die Schädeldeformität mit Augensymptomen. Klin Monatsbl Augenheilkd 1913;51:145–​69. Losee JE, Mason AC. Deformational plagiocephaly: diagnosis, prevention, and treatment. Clin Plast Surg 2005;32:53–​64. Marchac D, Renier D. Treatment of craniosynostosis in infancy. Clin Plast Surg 1987;14:61–​72. Mursch K, Brockman K, Lang JK, et al. Visual evoked potentials in 52 children requiring surgery for craniosynostosis. Paediatr Neurosurg 1998;29:320–​3. Renier D. Intracranial pressure in craniosynostosis: pre-​and post-​ operative recordings—​ correlation with functional results. In: Persing J, Edgerton MT, Jane JA (eds) Scientific Foundations and

Surgical Treatment of Craniosynostosis, pp. 263–​9. Baltimore, MD: Williams and Wilkins, 1989. Rich PM, Cox TC, Hayward RD. The jugular foramen in complex and syndromic craniosynostosis and its relationship to intracranial pressure. Am J Neuroradiol 2003;24:45–​51. Sidoti EJ Jr, Marsh JL, Marty-​Grames L, et  al. Long-​term studies of metopic synostosis: frequency of cognitive impairment and behavioral disturbances. Plast Reconstr Surg 1996;97:276–​81. Tamburrini G, Di Rocco C, Velardi F, et  al. Prolonged intracranial pressure monitoring in non-​traumatic paediatric neurosurgical disease. Med Sci Monit 2004;10:53–​63. Tang SF, Hsu KH, Wong AM, et  al. Longitudinal followup study of ultrasonography in congenital muscular torticollis. Clin Orthop Relat Res 2002;403:179–​85. White N, Evans M, Dover MS, et  al. Posterior calvarial vault expansion using distraction osteogenesis. Childs Nerv System 2009;25:231–​6.

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6.5

Non-​syndromic  craniosynostosis Christian Duncan and Hiroshi Nishikawa

Introduction What is non-​syndromic craniosynostosis? Craniosynostosis is defined as the premature fusion of a skull suture and has an incidence of approximately 1:2000 live births. Historically, craniosynostosis was subdivided into primary and secondary synostosis. Further subclassifications included syndromic/​ non-​syndromic and single/​multisuture. Primary craniosynostosis, defined as premature fusion of a skull suture in a patient with normal brain growth, had been recognized by Sommerling and was characterized by Virchow (1851) who stated that skull growth, under normal circumstances, takes place perpendicular to an open suture, and that when a suture is fused, the growth vector of the skull then takes place parallel to the fused suture such that characteristic head shapes are the outcome (Figs. 6.5.1–​6.5.5). Based on this observation, it is possible to identify the pattern of suture fusion from clinical examination of the various characteristic head shapes in patients who present with craniosynostosis. This is straightforward with most of the single-​suture synostoses such as sagittal, metopic, and unicoronal synostosis which give rise to scaphocephaly, trigonocephaly, and anterior synostotic plagiocephaly, respectively. The only single-​suture synostosis that can be difficult to diagnose is unilateral lambdoid synostosis which gives rise to posterior synostotic plagiocephaly. It is rare and has a range of presentations

but it is nevertheless an important clinical entity because, like unicoronal craniosynostosis, it can be associated with facial asymmetry later in life and it is necessary to be able to distinguish it from the more common posterior deformational plagiocephaly. The approximate incidences of the various craniosynostoses together with presentation are summarized in Table 6.5.1. Multisuture synostoses also give rise to characteristic head shapes, which, with experience, are readily identifiable by experienced clinicians using clinical examination alone (see Chapter 6.6). While, in the past, single-​suture craniosynostosis was classified as ‘non-​syndromic’, advances in genetic analysis have shown that this may not be the case in a proportion of these cases, just as some multisuture presentations may also be non-​syndromic. This particularly applies to unicoronal craniosynostosis along with some metopic and bicoronal synostosis (Johnson and Wilkie, 2011). Given the higher rate of syndromic association in these patients, along with the tendency to require late surgery for facial scoliosis in unicoronal and unilambdoid patients, this cohort should be regarded as a more complex subset.

The natural history of sporadic or single-​suture craniosynostosis The main consequence of untreated single-​suture synostosis is a progressive change in head shape during the major period of brain growth in the first 5 years of life with the maximal impact being in

Fig. 6.5.1  Typical features of the scaphocephalic skull include a long skull with narrowed width, a tall, bossed forehead, a posterior bullet and variable changes to the bregma/vertex height. Anatomical model images courtesy of 3D Systems.

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SECTION 6  Craniofacial and cleft

Fig. 6.5.2  Typical features of the trigonocephalic skull include a midline frontal keel, backward sloping frontal bones, scalloping of the lateral brow ridges and narrowing of the interfrontozygomatic distance. Anatomical model images courtesy of 3D Systems.

Fig. 6.5.3  Typical features of the bicoronal skull include shortening in the AP dimension with widening of the biparietal dimension. In addition, turricephaly, rounding of the top of the skull and hypertelorbitism and constriction above the supraorbital bar and shallow orbits may occur. Anatomical model images courtesy of 3D Systems.

Fig. 6.5.4  Typical features of the unicoronal skull include flattening of the forehead on the fused side with overgrowth on the non fused side, complex orbital asymmetry with a tall narrowed orbit on the fused side and a wider less tall orbit on the non fused side, nasal deviation away from the fusion, temporal bossing on the side of the fusion and an occlusal cant. Anatomical model images courtesy of 3D Systems.

Fig. 6.5.5  Typical features of the lambdoid synostosis skull are vary variable but may include include ridging and mastoid bossing on the fused side, overgrowth of the parietal eminence, especially on the non fused side, facial scoliosis and nasal twisting away from the fused side but in a more subtle way than in the unicoronal patient. In addition, the vertex of the skull may be lower than the bregma as a result of compensatory overgrowth in the anterior skull. Anatomical model images courtesy of 3D Systems.

6.5 Non-syndromic craniosynostosis

Table 6.5.1  Approximate incidences of craniosynostosis Sagittal

40–​55%

Coronal

20–​25%

Metopic

5–​15%

Lambdoid

0–​5%

Reprinted from Clinical Radiology, Volume 68, issue 3, Nagaraja S, Anslow P, Winter B, Craniosynostosis, pp. 284–​92, Copyright (2013), with permission from Elsevier.

the first 2–​3  years. Asymmetric craniosynostosis (i.e. unicoronal and unilambdoid) have the additional consequence of inducing a facial scoliosis throughout the period of facial growth with the outcome that patients may present with evolving orbital dystopia, nasal deviation, generalized facial asymmetry, occlusal cant, and ocular torticollis. All craniosynostosis, left untreated, is thought to carry an elevated risk of raised intracranial pressure (ICP) as a consequence of brain growth in a constrained skull, giving rise to craniocerebral disproportion. The estimated risk of raised ICP is given as approximately 10% for a single fused suture based to a great extent on work by Renier and colleagues (2000). However, the range of risk is subject to extensive discussion including a late risk of 25% in isolated sagittal synostosis (Wall et al., 2014) where raised ICP occurred in the absence of clinical findings such as headaches, papilloedema, visual field loss, and developmental delay which are all traditionally thought to be the consequence of ongoing untreated raised ICP. The current consensus is that raised ICP is a credible concern. The evidence for this is based on historical series indicating high rates of blindness and developmental delay in untreated patients with craniosynostosis (Larsen, 1913)  and modern observations linking raised ICP to visual pathway changes (Liasis et al., 2003; Thompson et al., 2006) together with improvements or reductions in incidence following vault expansion. The importance of raised ICP is not yet fully understood but its consequences in the infant should be taken seriously until better information is available. Other associated problems, particularly of metopic and sagittal synostosis, include a possible 60% incidence of speech, motor, or other developmental delay (Kelleher et al., 2006) with at least a 30% incidence of speech delay in isolated sagittal synostosis (Shipster et al., 2003). High incidences of speech and other delays have been identified in isolated metopic synostosis with the burden of impact on the syndromic variants, but are still significant in the non-​ syndromic population (Kini et al., 2010).

What are the aims of surgery in sporadic craniosynostosis? The aims of corrective surgery for sporadic or single-​suture synostosis are summarized in Box 6.5.1. The first concern is aesthetic correction

Box 6.5.1  Aims of surgery for craniosynostosis • Allow normal brain growth. • Protect from raised ICP. • Improve psychosocial functioning by normalizing aesthetics. • Optimize growth vectors of skull base organs.

of the cranial vault such that normal integration in society can take place. There is an expectation that surgical intervention is beneficial for psychosocial functioning because involvement and engagement with peer groups is important for young people and concerns about appearance, bullying, and teasing can be serious impediments to development and maximization of potentials later in life. The second reason for seeking surgery is concern about raised ICP and its possible effects on the brain. The craniofacial consensus is that a significant driver of raised ICP is craniocerebral disproportion (Hayward and Nischal, 2004)  and that once adequate vault volume has been achieved, the risk of raised ICP drops but does not disappear completely, for which reason ongoing monitoring is required. It should be noted that there are other contributors to raised ICP including factors that contribute to venous hypertension and hydrocephalus (see Chapter 6.6) and these should always be considered where vault expansion has failed to correct the ICP. Lastly, surgery, particularly in the unicoronal and unilambdoid groups, may maximize the potential for normal facial growth in the expectation that the late complex surgical interventions needed to manage facial scoliosis (secondary to untreated craniosynostosis) can be avoided (Hilling et al., 2006). Whether, and to what extent, the face untwists following unicoronal synostosis correction is the subject of some debate. Hansen and colleagues (1997) contend that cranial surgery does not influence facial growth, based on the data from three small groups of patients. The wider consensus contends that there is a benefit to facial growth in vault remodelling, although the extent of benefit is unpredictable. This probably depends on the pattern of the craniosynostosis and the degree of skull base involvement (Dundulis et al., 2004). Based on the likelihood that, in a worst-​case scenario, the risk of raised ICP lies somewhere between 10% and 25%, it follows that the majority of patients, particularly in the metopic and sagittal groups, will incur the risk of surgery in return for the psychosocial benefit of normalized appearance. Given the risk profiles of the surgery, it follows that aesthetic outcomes are important and need to be carefully evaluated. The major goal of management is to eventually allow the patient to interact with and blend into a crowd of unaffected people.

Operative management Treatment of scaphocephaly Sagittal synostosis is the commonest form of craniosynostosis with an incidence of about 1:4000 births and it was the first craniosynostosis to be treated surgically by strip craniectomy (Lane, 1892). At present, sagittal synostosis is managed both by the widest range of surgical communities, often in a unidisciplinary way, and with a bewildering array of surgical correction methods. An added consideration is that of all the sporadic craniosynostoses, sagittal synostosis has the most variable range of presentations with some patients who have no scaphocephaly (Morritt et al., 2010) and others presenting with multiple variations (David et al., 2009). Although there are many operative interventions described, they can be classified as passive, active, or dynamic. Also, surgery can be categorized according to the type of access or approach. With the advent of minimal access surgery, endoscopic (Jimenez and Barone, 2012) or short scar (Massimi et al., 2007) techniques have evolved.

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SECTION 6  Craniofacial and cleft

Active cranioplasty methods can also be compressive (Boulos et al., 2004) or decompressive, while passive cranioplasty techniques are often supplemented with a helmet orthosis in order to assure a satisfactory aesthetic outcome.

Passive scaphocephaly correction Passive correction of scaphocephaly consists of a group of operations whereby brain drive is harnessed as the primary mode of correction of head shape following release of a constricting fused suture. The earliest passive operation was isolated strip craniectomy, first performed in the 1890s and still used by some practitioners until the late twentieth century. For some patients, strip craniectomy gave satisfactory results, at least according to cranial index measurements (Murray et  al., 2007). However, these outcomes were never reliable enough, nor were the more global aesthetic problems of scaphocephaly sufficiently addressed. For this reason, strip craniectomy was supplemented with more extensive lateral craniectomies such as extended strip craniectomy, pi craniectomy,

and extended pi craniectomy with some attempting radical morcelization of the calvarium and replacement on the dural surface (Goodrich, 2004). Brain expansion plays a key role in all of these operations. With 60% of brain growth complete in the first year of life, and the majority of that in the first 6 months, early intervention when using passive surgery techniques is mandatory because the slowing brain growth in the second 6 months of life lacks the velocity to drive passive shape change—​indeed, bone healing probably occurs prior to any significant change with the outcome that further brain growth merely drives relapse of the scaphocephalic head shape. In one study (Kandasamy et al., 2011), normal cephalic index measurements were achieved in long-​ term follow-​up of extended strip craniectomy and lateral microbarrel staving (Fig. 6.5.6) in those operated on before 6 months of age while this was achieved in almost none operated on after 6 months. Many passive cranioplasty techniques are supplemented by use of an orthotic helmet, which is usually worn for 23 hours a day until the patient is a year old.

Fig. 6.5.6  Standard views of preoperative and 2-​year follow-​up outcome taken from 3dMD® (Atlanta, GA, USA) images in a patient undergoing passive surgery by strip craniectomy, lateral barrel staving, and posterior expansion at age 4.5 months. Cephalic index changed from 68 to 89, normal head circumference and a normal overall skull morphology was achieved.

6.5 Non-syndromic craniosynostosis

Minimal access cranioplasty The timing and osteotomy of minimal access cranioplasty is the same as for any other passive operation. The two main techniques, as discussed previously, are the endoscopic route popularized by Jimenez and short scar techniques described by Di Rocco. In both cases, the extent of osteotomy is limited by the practicalities of the access and orthotic helmets are therefore used. Proponents of the techniques cite advantages in terms of scarring, blood loss, and duration of recovery (Jimenez and Barone, 2013). Uptake has been limited because experience of this technique has not been uniform and there are concerns that a number of these patients may experience significant bleeds, venous air embolism, respiratory complications, and intensive care unit admissions (Meier et al., 2011).

Active cranioplasty The need to achieve an acceptable aesthetic outcome combined with the tendency for scaphocephaly patients to be referred later than 6  months (Chatterjee et  al., 2009)  has driven the development of different approaches based on removal of bone, remodelling, and

replacement in different positions that are held with fixation. This can be done either in a completely decompressive way, or incorporating some compression in an anteroposterior direction in order to create artificial brain drive which is allowed to discharge posterolaterally via large lateral decompressions to encourage biparietal widening in the correct zone of the skull. There are many active cranioplasty operations in use, however, all have either anterior, middle, or posterior vault components and only when all three parts are addressed should the operation be termed a ‘total vault remodelling’. When less than all three components are treated, the surgery is called ‘subtotal vault remodelling’. The techniques require control and understanding of all forms of osteotomy and fixation in order to achieve the desired outcome and some judgement is required in order to maximize benefit versus risk for the patient. Optimal patient positioning on the operating table also needs careful consideration. In practice, many extended active vault procedures incorporate extensive remodelling of bone, repositioning of bone, and judicious use of localized compression to achieve the desired outcome (Fig. 6.5.7). Timing for these operations is variable

Fig. 6.5.7  Standard views of preoperative and 2-​year follow-​up outcome taken from 3dMD® (Atlanta, GA, USA) images in a patient undergoing total calvarial remodelling by a modified Melbourne technique comprising adjustment of the vertex, lowering of the forehead, and adjustment of the hairline in a 15-​month-​old child. Cephalic index changed from 60 to 75 with normal head circumference and a normal overall skull morphology was achieved. Normal outcomes depend on an individualized operative approach depending on the presentation, careful judgement of osteotomies, and control of soft tissues.

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SECTION 6  Craniofacial and cleft

method. The surgery allows aesthetic change of the forehead and an increase of the intracranial volume. The timing of surgery remains very variable again, as discussed by Fearon (2014). The surgical philosophy is to remodel the deformed shapes of both forehead and the supraorbital bar. After exposure of the upper orbits and frontal bone via an extensive bicoronal scalp flap, the fronto-​orbital area can be removed and the remodelling carried out off-​table. The whole assembly can be fixed with sutures or absorbable plates. The use of permanent metal plates or wires is avoided as they have the potential to migrate to undesired locations as a result of the growing brain. The degree of advancement depends on how tight the brain appears to be but there are also the constraints of skin closure. A common strategy is to compensate for the regressional forces that exist to return the head shape back to its preoperative synostotic appearance. Therefore, the fronto-​orbital assembly is often fixed and remodelled, not to create a normal baby forehead, but one that will be appropriate for a future calvarial volume both for the developing brain and to reflect a better approximation of the adult position (Lwin et al., 2011).

Postoperative care Fig. 6.5.8  The principles employed in spring-​mediated cranioplasty. The springs were fabricated on-​table and were removed 6 months postoperatively. With permission from Claes Lauritzen.

with some authorities arguing that aesthetic outcome is better if they are delayed until 12 months of age or more based on better control of outcome through surgery on a skull which is growing less quickly (Fearon, 2011). Others claim equivalent outcomes when they are done from 6 months of age onwards.

Dynamic or mechanically assisted cranioplasty The most recent addition to the surgical options for scaphocephaly and other vault expansion techniques involves use of mechanical devices to generate the necessary change following limited osteotomies. Spring-​mediated cranioplasty for sagittal synostosis and other sutures was introduced by Lauritzen and colleagues (2008) and has enjoyed some popularity. The concept involves limited osteotomies where bone is to be moved, often via short scars, and insertion of a spring, either prefabricated or manufactured in the operating room, with footplates on either side of the osteotomy pushing the bones apart. The springs provide immediate and then sustained distraction forces across the bone cuts (Fig. 6.5.8). They are left in situ until full spring expansion and stable bone consolidation has been achieved. They are then removed via the original scar at a separate operation. Proponents claim shorter hospital stays, lower transfusion, and good aesthetic results. However, independent assessment of aesthetic outcome and comparison with either norms or with other types of surgery have yet to take place and as Fearon (2014) observes, there is currently no trial evidence which guides a surgeon to an ideal technique.

Treatment of metopic, unicoronal, and bicoronal craniosynostosis Fronto-​orbital remodelling For the other single-​suture craniosynostosis, fronto-​orbital remodelling with or without advancement is the most widely used surgical

Postoperatively, it is the practice of many units to monitor the patient awake and non-​ventilated in a high-​dependency environment so that so that neuro-​observations can be carried out. The most dangerous early complication is either an extradural or subdural bleed. Dural tears should always be repaired peroperatively and certainly cerebrospinal fluid (CSF) leaks postoperatively are problematic. However, persistent CSF leak is relatively rare in fronto-​orbital remodelling and is not as critical in terms of morbidity as with frontofacial procedures when the nasal cavity can be in continuity with the anterior cranial fossa.

Distinguishing posterior deformational plagiocephaly from unilateral lambdoid synostosis Posterior deformational plagiocephaly is one of the commonest presentations to craniofacial units. It occurs in up to 48% of live births and is a cause of significant anxiety for parents (Littlefield et al., 2004). By contrast, posterior skull flattening secondary to unilateral lambdoid synostosis is rare, comprising less than 5% of presentations (Nagaraja et al., 2013) and may be associated with raised ICP and facial scoliosis (Al-​Jabri and Eccles, 2014). For this reason, it is important to be able to distinguish the two as complex surgical pathways may be required for the synostotic presentation while none are needed for deformational plagiocephaly. As in all conditions, history is key to distinguishing the two presentations and a comprehensive review of the comparison between the two was provided by Mulliken and colleagues (1999). History consistent with deformational change includes babies who are normal at birth and evolve posterior flatness in the first 6–​8 weeks of life, are good sleepers with a repetitive sleeping position, and are bottle fed. Other historical features include prematurity, multiparity, intrauterine gestational constraint, assisted birth with sternomastoid injury, and improvement or stabilization in condition after the child has sat up. Clinical findings in posterior deformational plagiocephaly are consistent. They present with posterior flatness always associated with ipsilateral anterior translocation of the ear, ipsilateral frontal

6.5 Non-syndromic craniosynostosis

bossing and a lack of facial scoliosis with the nose lying perpendicular to the horizontal axis, and no orbital dystopia or significant asymmetry. In spite of these specific morphological changes, gross morphology remains generally normal with an appropriate relative position of the vertex, bregma, and frontal and parietal eminences along with normal head circumference. Lambdoid synostosis, by contrast, often presents with an established head shape change at birth, does not improve with time but evolves, and is independent of sleep or feeding pattern and developmental progress. Examination findings can be both subtle and variable with no one finding providing incontrovertible evidence of fusion. As Fearon (2011) observes, the ear, for example, can be transposed in any direction horizontally or vertically on the fused side. Features of concern include posterior flattening associated with a lambdoid ridge, an occipito-​mastoid boss and changes of general calvarial morphology with altered vertex height, a displaced parietal eminence on the fused side with overgrowth on the non-​fused side, and facial scoliosis, including nasal deviation and occlusal cant. Given the difficulties in distinguishing the two presentations, radiological investigations are often required if doubt about the presentation exists. Surgery should be considered for unilateral lambdoid synostosis because of the risk of raised ICP and where evolving facial scoliosis is a concern but a reasonable balance of risks also needs to be considered because of the vascular anatomy underlying the posterior calvarium and the subtle presentation. Management of posterior deformational flattening is more controversial because it is considered to be a self-​limiting condition with resolution occurring naturally over a variable period between the first 2 years and about the first decade of life. Parental anxiety often drives a search for a more interventional approach and the options include advice sheets about repositioning and tummy time when awake, use of orthotic pillows or mattresses, and orthotic helmets. Helmet therapy in particular has proved popular. The theory behind helmet therapy involves either the application of pressure at certain areas of the growing skull to force its growth in a particular direction to compensate for the deformational shape, or protection of deformed areas from further deformational change. Advocates claim significant improvements in head shape in relatively short treatment periods but at high initial financial cost for the helmet fitting and follow-​up adjustments, a high need for compliance with the helmet being worn 23 hours a day, and a need to present early as helmet therapy after the age of 12 months is accepted as not being of value. Critics of helmet therapy point to the difficulty in ascribing improvement to a helmet in a self-​limiting condition, the lack of unbiased data confirming the benefits of helmets, the high cost, and the unknown implications of wearing a helmet for such a large part of the day at a critical time in paediatric development. Although there are many publications supporting the use of helmets (Moss, 1997; Pollack, 1997; Kelly, 1999) the only randomized trial to date indicated negligible benefit (Collett, 2014) and, at the time of writing, sufficient advantage of helmet therapy over, for example, less expensive mattress therapy (Sillifant et al., 2014), cannot be confirmed.

Complications The most serious early complication is a major postoperative intracranial bleed. These are rare but can be catastrophic and emergency return to theatre is lifesaving. The close postoperative neurosurgical monitoring of all these cases is therefore essential. All dural tears

should be repaired peroperatively but persistent CSF leak requires intervention. Infection is also surprisingly rare, but wound-​healing problems do occur and sometimes result from tight scalp closure due to surgical calvarial volume expansion. Although in the majority of cases an aesthetic improvement can be demonstrated, a late complication includes regression back to the original head shape. This may occur despite standard techniques and in some cases may reflect an occult syndrome or in rare cases surgery being mistakenly carried out for secondary craniosynostosis when there was no brain drive present. Generally, all calvarial and fronto-​orbital surgery before the age of 2 years relies on the natural bone-​forming potential of the dura. Bony gaps left by the reconstruction will normally fill with new bone but this becomes increasingly problematic when calvarial surgery is carried out for older patients. Certainly, dural tears with CSF leaks, infection, and dead space will discourage new bone formation. If the calvarial defect is significant (especially if present over the midline where the sagittal sinus or the torcula is situated), a cranioplasty may be required.

REFERENCES Al-​Jabri T, Eccles S. Surgical correction for unilateral lambdoid synostosis: a systematic review. J Craniofac Surg 2014;25:1266–​72. Boulos PT, Lin KYK, Jane JA, et al. Correction of sagittal synostosis using a modified pi method. Clin Plast Surg 2004;31:489–​98,  vii. Chatterjee JS, Mahmoud M, Karthikeyan S, et al. Referral pattern and surgical outcome of sagittal synostosis. J Plast Reconstr Aesthet Surg 2009;62:211–​15. Collett BR. Helmet therapy for positional plagiocephaly and brachycephaly. BMJ 2014;348:g2906. David L, Glazier S, Pyle J, et  al. Classification system for sagittal craniosynostosis. J Craniofac Surg 2009;20:279–​82. Dundulis JA, Becker DB, Govier DP, et al. Coronal ring involvement in patients treated for unilateral coronal craniosynostosis. Plast Reconstr Surg 2004;114:1695–​703. Fearon JA. Evidence-​based medicine: craniosynostosis. Plast Reconstr Surg 2014;133:1261–​75. Fearon JA. Discussion: temporal hollowing following surgical correction of unicoronal synostosis. Plast Reconstr Surg 2011;128:241–​2. Goodrich JT. Craniofacial surgery:  complications and their prevention. Semin Pediatr Neurol 2004;11:288–​300. Hansen M, Padwa BL, Scott RM, et  al. Synostotic frontal plagiocephaly: anthropometric comparison of three techniques for surgical correction. Plast Reconstr Surg 1997;100:1387–​95. Hayward R, Nischal KK. Management of raised intracranial pressure. In: Hayward R, Jones B, Dunaway D, et al. (eds). The Clinical Management of Craniosynostosis, pp. 137–​60. London:  MacKeith Press, 2004. Hilling DE, Mathijssen IMJ, Mulder PGH, et  al. Long-​term aesthetic results of frontoorbital correction for frontal plagiocephaly. J Neurosurg 2006;105:21–​5. Jimenez DF, Barone CM. Endoscopic technique for sagittal synostosis. Childs Nerv Syst 2012;28:1333–​9. Jimenez DF, Barone CM. Early treatment of coronal synostosis with endoscopy-​assisted craniectomy and postoperative cranial orthosis therapy: 16-​year experience. J Neurosurg Pediatr 2013;12:207–​19. Johnson D, Wilkie AOM. Craniosynostosis. Eur J Hum Genet 2011;19:369–​76.

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Kandasamy J, Anderson K, Dunne J, et al. Treatment of scaphocephaly with combined vertex craniectomy and bilateral microbarrel staving. J Craniofac Surg 2011;22:42–​6. Kelleher MO, Murray DJ, McGillivary A, et al. Behavioral, developmental, and educational problems in children with nonsyndromic trigonocephaly. J Neurosurg 2006;105:382–​4. Kelly KM, Littlefield TR, Pomatto JK, et al. Cranial growth unrestricted during treatment of deformational plagiocephaly. Pediatr Neurosurg 1999;30:193–​9. Kini U, Hurst JA, Byren JC, et al. Etiological heterogeneity and clinical characteristics of metopic synostosis: evidence from a tertiary craniofacial unit. Am J Med Genet A 2010;152A:1383–​9. Lane LC. Pioneer craniectomy for relief of the mental imbecility due to premature sutural closure and microcephalus. JAMA 1892;18:49–​50, Larsen H. Die Schädeldeformität mit Augensymptomen. Klin Monatbl Augenheilkd 1913;51:145. Lauritzen CGK, Davis C, Ivarsson A, et al. The evolving role of springs in craniofacial surgery:  the first 100 clinical cases. Plast Reconstr Surg 2008;121:545–​54. Liasis A, Thompson DA, Hayward R, et  al. Sustained raised intracranial pressure implicated only by pattern reversal visual evoked potentials after cranial vault expansion surgery. Pediatr Neurosurg 2003;39:75–​80. Littlefield TR, Saba NM, Kelly KM. On the current incidence of deformational plagiocephaly:  an estimation based on prospective registration at a single center. Semin Pediatr Neurol 2004;11:301–​4. Lwin CT-​TJW, Richardson D, Duncan C, et  al. Relapse in fronto-​ orbital advancement: a pilot study. J Craniofac Surg 2011;22:214–​6. Massimi L, Tamburrini G, Caldarelli M, et al. Effectiveness of a limited invasive scalp approach in the correction of sagittal craniosynostosis. Childs Nerv Syst 2007;23:1389–​401. Meier PM, Goobie SM, DiNardo JA, et al. Endoscopic strip craniectomy in early infancy: the initial five years of anesthesia experience. Anesth Analg 2011;112:407–​14.

Morritt DG, Yeh F-​JJ, Wall SA, et al. Management of isolated sagittal synostosis in the absence of scaphocephaly: a series of eight cases. Plast Reconstr Surg 2010;126:572–​80. Moss SD. Nonsurgical, nonorthotic treatment of occipital plagiocephaly: what is the natural history of the misshapen neonatal head? J Neurosurg 1997;87:667–​70. Mulliken JB, Vander Woude DL, Hansen M, et al. Analysis of posterior plagiocephaly: deformational versus synostotic. Plast Reconstr Surg 1999;103:371–​80. Murray DJ, Kelleher MO, McGillivary A, et al. Sagittal synostosis: a review of 53 cases of sagittal suturectomy in one unit. J Plast Reconstr Aesthet Surg 2007;60:991–​7. Nagaraja S, Anslow P, Winter B. Craniosynostosis. Clin Radiol 2013;68:284–​92. Pollack IF, Losken HW, Fasick P. Diagnosis and management of posterior plagiocephaly. Pediatrics 1997;99:180–​5. Renier D, Lajeunie E, Arnaud E, et al. Management of craniosynostoses. Childs Nerv Syst 2000;16:645–​58. Shipster C, Hearst D, Somerville A, et al. Speech, language, and cognitive development in children with isolated sagittal synostosis. Dev Med Child Neurol 2003;45:34–​43. Sillifant P, Vaiude P, Bruce S et  al. Positional plagiocephaly:  experience with a passive orthotic mattress. J Craniofac Surg 2014;25: 1365–​8. Thompson DA, Liasis A, Hardy S, et al. Prevalence of abnormal pattern reversal visual evoked potentials in craniosynostosis. Plast Reconstr Surg 2006;118:184–​92. Wall SA, Thomas GPL, Johnson D, et  al. The preoperative incidence of raised intracranial pressure in nonsyndromic sagittal craniosynostosis is underestimated in the literature. J Neurosurg Pediatr 2014;14:674–​81. Virchow R. Ueber den cretinismus, namentlich in Franken, und euber pathologische Schadelformen. Verh Phys Med Gesamle Wurzburg 1851;2:230–​71.

6.6

Syndromic craniosynostosis Stephen Dover and Martin Evans

Introduction Syndromic craniosynostoses result from a complex interaction between genetic factors, molecular and cellular events, as well as mechanical and deformational forces. They can all have secondary effects on growth and development (Buchman and Muraszko, 2007). Approximately 180 craniofacial syndromes have been identified and according to Agochukwu and colleagues (2012), 15% of all craniosynostoses are syndromic. They are due to genetic mutations and among the most common are mutations in the fibroblast growth factor receptor 2 gene (FGFR2). Multidisciplinary care for craniofacial patients is considered the optimal model of care and is based on the concept of management during childhood, the transition into adulthood, and finally support and treatment throughout adulthood. When initially assessing a syndromic craniosynostotic patient, the clinician should be aware of the potential sequelae of the systemic disorders and make provisions to investigate and treat as appropriate. An inflexible treatment plan is unhelpful because of the variety of phenotypes seen in craniofacial syndromes—​each patient should be individually evaluated, starting with a thorough history and examination. Most surgical craniofacial interventions in young syndromic patients aim for symptom relief and prevention. However, since most surgical procedures cannot address the inherently abnormal growth patterns, repeat surgery is often required in this group as they grow. This will be discussed later in the chapter and is pertinent to the discussion of early mid-​facial surgery. The phenotypic variation within a syndrome cohort means the outcomes of surgery may vary despite the application of similar surgical interventions.

Assessment of a craniofacial infant In a multidisciplinary craniofacial clinic, assessment involves seamless review and subspecialty investigation to address continuously the needs of the syndromic patient. These patients require prompt investigation and management whereas in non-​syndromic cases the timing of surgery is less critical.

Craniofacial growth in the syndromic infant Head circumference is a simple but helpful measurement, with an increase alerting the clinician to the possibility of hydrocephalus or compensatory distortion secondary to the craniosynostosis. Conversely, the smaller head might indicate intrinsic failure of the brain to grow and might indicate lack of brain drive causing compensatory craniosynostosis. The trend of head circumference measurements over time may be the first indication, along with closure of the anterior fontanelle, of premature skull suture fusion, especially if multiple sutures are implicated. A knowledge of craniofacial growth in the infant and child guides the timing of surgical interventions. There is differential growth of the calvarium and of the facial structures, the former (Fig. 6.6.1) showing a steep increase in the first 2 years of life, continuing into the third year (a 38% increase in circumference). This is due to brain growth, the volume of which increases by 300% in the first year of life (Cohen and Wexler, 1997) meaning that interventions to release the fused calvarial bones and create room for an expanding, developing brain must be considered during this active growth period. Conversely, facial growth commences a period of active growth from 7 years onwards until skeletal maturity. Maturity occurs in a cranio-​caudal direction. This influences the timing of surgery for facial deformity, although acute problems such as airway or ophthalmic complications may override such consideration.

Feeding issues in syndromic craniosynostosis Feeding problems within this cohort are common (Pereira, 2005) for many reasons. These problems may compromise physical development and may also contribute to impaired parental bonding, which is well recognized in this group of patients. Clinical nurse specialists provide close support and can engage other allied health professional such as nutritionists and occupational therapists when required. Feeding may be impaired by: • Abnormal orofacial anatomy. • Upper airway obstruction. • Visual impairment. • Motor issues or delayed development.

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SECTION 6  Craniofacial and cleft

Head circumference-for-age percentiles: Boys, birth to 36 months

54 21

95th 90th

52 20

75th

50

48

50th 25th

19

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18

44 17 42

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38

36

15

14

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34

20%

13 32

12 30 cm

in Birth

3

6

9

12

15

18

21

24

27

30

33

36

Age (months)

Fig. 6.6.1  Growth chart for plotting of head circumference. HMSO.

• Malformations of the central nervous system. • Respiratory or cardiac issues. • Gastrointestinal difficulties. There may be considerable abnormality of the orofacial anatomy. The aetiology in some cases may be identified early, for example, cleft palate which affects up to 50% of patients with Apert syndrome. It should not be forgotten, however, that any structural changes to this region, such as retrogenia or hypoplasia of the midface can lead to difficulty in establishing normal swallowing and chewing actions during the multiphase swallowing process.

Similarly, early surgery such as a monobloc advancement for emergent airway problems or ophthalmic issues can have a considerable effect on the swallowing and feeding apparatus which may initially be detrimental. Upper airway obstruction can impair swallowing and aspiration of foods can lead to respiratory infection and lung parenchyma damage. Pereira and colleagues (2009), using videofluoroscopy, established that more than half of patients with Apert syndrome aspirate when swallowing. This may also contribute to the failure to thrive seen in the group.

6.6 Non-syndromic craniosynostosis

Visual perception of foods and feeding during infancy in syndromic craniosynostosis patients may also be compromised (see Chapter 6.4). Delay in motor development may cause difficulties in all phases of the swallowing process and again this can lead to significant ongoing feeding and nutrition problems.

Raised intracranial pressure in syndromic craniosynostosis According to Tamburrini and colleagues (2012), raised intracranial pressure (ICP) affects up to 67% of complex craniosynostoses. Raised ICP is complex in its pathogenesis and incompletely understood but is thought to be due to an interaction between craniocephalic mismatch, venous hypertension, and cerebrospinal fluid (CSF) flow dynamic disorders. None of these factors can be considered in isolation and various strategies are employed to manage raised ICP. Fig. 6.6.2 shows how raised ICP and problems in CSF flow dynamics are thought to be implicated in developmental delay (hearing, vision, and airway are also strongly related). The craniocephalic mismatch describes the developing brain constrained in the poorly expanding cranial vault due to craniosynostosis. However, the simplistic historical view that the number of fused sutures is proportional to the ICP does not hold up to examination. De Jong and colleagues’ study (2012) showed that intracranial volume was not reduced in syndromic craniosynostotic children compared to non-​syndromic controls. For this reason, while a calvarial procedure to release the fused bones in craniosynostosis seems appropriate, it does not in all cases lead to a permanent or even temporary reduction in ICP. CSF flow dynamics in syndromic craniosynostosis vary depending upon the particular syndrome. Ventricular dilatation but not true hydrocephalus is common. Active hydrocephalus has been reported in up to 15% of craniosynostotic children. In Crouzon syndrome, this is more prevalent and is thought to be related to the effect of skull base synchondrosis fusion, leading to stenosis of skull base foramina. Also, posterior fossa growth can be restricted due to lambdoid sutural fusion. This is thought to contribute to the raised venous pressure (venous hypertension) and this itself then causes an increase in CSF hydrostatic pressure.

Visual problems

Hearing deficit

Airway obstruction

Developmental Delay

Raised ICP

Fig. 6.6.3  The reduction in patency of jugular foramina in a computed tomography scan of a pansynostotic skull.

In contrast, Apert syndrome has late closure of the skull base and posterior cranial fossa sutures and these patients are noted to be less affected by hydrocephalus. Venous hypertension is also the result of changes to skull base and cranial vault venous circulation. Stenosis of skull base foramina can compromise venous drainage out of the brain in syndromic patients. See Fig. 6.6.3 and Fig. 6.6.4.

Chiari I malformation and syndromic craniosynostosis There is link between syndromic craniosynostosis and the development of a Chiari I  malformation, particularly in Crouzon and Pfeiffer syndromes but rarely Apert syndrome. The development of Chiari I  malformation (cerebellar tonsillar descent of ≥5 mm) is thought to be related to the premature closure of the cranial base and lambdoid sutures. It is believed that this closure or narrowing of skull base foramina and the hypoplastic posterior cranial fossa causes venous hypertension and raised ICP and this combined with CSF flow dynamic changes leads to development of a Chiari I malformation and potentially syrinx formation in the spinal cord. Symptoms, including headache and neck pain, may be difficult to diagnose in the syndromic infant and child. (For management, see ‘Surgical management of syndromic craniosynostosis’.)

Hydrocephalus

Obstructive sleep apnoea Fig. 6.6.2  Graph showing how raised ICP and problems in CSF flow dynamics are thought to be implicated in developmental delay. HMSO.

Obstructive upper airway pathology in syndromic craniosynostosis is well recognized. Hayward and Gonsalez (2005) showed a

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SECTION 6  Craniofacial and cleft

Fig. 6.6.4  The development of abnormal collateral circulation in response to reduced venous outflow in the skull base in a pansynostotic patient.

relationship between obstructive breathing during sleep and ICP and consequently cerebral perfusion pressure. This chronic reduction in cerebral perfusion pressure, which is not autoregulated, may have a detrimental effect on the developing brain and so efforts should be made to mitigate it. The management of obstructive sleep apnoea includes the following interventions: • Choanal dilatation. • Continuous positive airway pressure (CPAP). • Palatal surgery. • Adenotonsillectomy. • Midface advancement. • Tracheostomy.

One of the fundamental issues affecting many syndromic patients is inadequate orbital volume and the shallow shape of the orbit in the presence of a normal volume of orbital content and eye. This can lead to exorbitism and potential dislocation of the globe. This might require urgent intervention to either close the eyelids temporarily and hence protect the orbital contents or provide a larger depth to the orbit. Surgical options to increase orbital volume either involve a Le Fort III osteotomy which addresses the floor and lateral wall of the orbit, a fronto-​orbital procedure which addresses the supraorbital and lateral orbital region, or a combination of the two. A monobloc-​type procedure addresses the whole orbital volume as well as potentially allowing expansion of the developing brain. These procedures will be discussed further. See Fig. 6.6.5 and Fig. 6.6.6.

Adenotonsillectomy alone is usually insufficient to correct upper airways-​related obstructive sleep apnoea as the midface hypoplasia decreases all upper airway spaces significantly. CPAP has some beneficial effect although tolerance in children is poor. Midface advancement is helpful in opening the upper respiratory spaces but in syndromic craniosynostosis, patients may not obtain a reduction in obstructive sleep apnoea, and, for instance, decannulation of a tracheostomy is not always possible after this surgery. Witherow and colleagues (2008) showed that only 6 of 14 patients who underwent a monobloc procedure with distraction osteogenesis showed a resolution in their obstructive sleep apnoea postoperatively (measured by decannulation or cessation of CPAP), despite anatomical airway enlargement being achieved. Conversely, Nelson and co-​ workers (2008) demonstrated that with midfacial advancement, 11 of 15 patients who were CPAP or tracheostomy dependent preoperatively, were able to discontinue respiratory support postoperatively.

Ophthalmic problems and syndromic craniosynostosis Ocular difficulties in syndromic craniosynostosis can occur early and require urgent intervention. Chronic problems need planned management.

Fig. 6.6.5  Exorbitism in a patient with Crouzon syndrome. A shallow orbit and excess scleral show due to lack of support of the lower lid complex is seen.

6.6 Non-syndromic craniosynostosis

osteotomy or monobloc are used to manage urgent orbital, airway, or ICP problems. Monobloc is used when the triad of raised ICP, ocular problems, and airway problems present together. In the second group, intervention is more able to be scheduled and involves the elective control of the shape of the craniofacial skeleton in order to allow optimum development of brain and eyes and to maintain an adequate airway. Also included in this group are those patients with Chiari I malformation, who require management. This group will include all of the procedures listed previously as well as the posterior calvarial expansion procedure, a recently developed procedure. Treatment algorithms are best understood by considering both the child’s age and the urgency of the intervention.

Age 0–​3 years

Fig. 6.6.6  The same patient as in Fig. 6.6.5 following advancement of the midface at le Fort III level (with distraction osteogenesis).

Children with syndromic craniosynostosis are also prone to other ocular issues such as strabismus (squint), refractive errors, and, more rarely, ocular muscle hypoplasia or abnormal insertion. See Fig. 6.6.7.

Surgical management of syndromic craniosynostosis Surgical management of these patients has evolved over the past 50 years and while there is no consensus on which operations are preferred, there is an understanding among craniofacial surgeons that there are two groups of patients. The first group needs urgent or emergency surgery in order to preserve organ function. Cranial decompression procedures can be carried out in order to manage malignant raised ICP. Le Fort III

In syndromic patients with raised ICP, urgent decompressive craniectomy is required. This involves the removal of restrictive and constrictive plates of calvarial bone. Historically, these bone plates were lifted with osteotomes then replaced on the expanding dura without fixation. In this way, the brain under pressure was able to expand and form the new position upon which the floating bones would lie. In patients with raised pressure, removal of calvarial bone carries a high risk of dural tear and CSF leaks. Also, expanding brain tissue within the dura following release of the bone plates could make skin closure of the bicoronal wound difficult. Finally, the syndromic craniosynostotic patient is predisposed to early postoperative bone fusion, which can lead to recurrence of raised ICP. Therefore, either total craniectomy with resection of bone plates (leaving the brain unprotected) may be required (or ensure that any replaced bone has significant exposed dura around it prior to scalp closure). The procedure is often repeated in severe phenotypes as refusion and regeneration of excised bone occurs. See Fig. 6.6.8. In syndromic patients who are at risk of raised ICP, and in particular those who have a brachycephalic deformity of the skull, expansion of the posterior skull has increasingly become accepted as the first-​line treatment. The technique of (dynamic) posterior calvarial expansion

Fig. 6.6.7  Late presenting and untreated patient with Saethre–​Chotzen syndrome showing severe supraorbital hypoplasia and shallow orbit.

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SECTION 6  Craniofacial and cleft

Fig. 6.6.8  Showing craniectomy with bony perforations.

by using distraction osteogenesis has been adopted in many craniofacial units worldwide. This procedure has several advantages over fronto-​orbital techniques in the young syndromic child. It is postulated that posterior calvarial expansion might reduce venous hypertension by addressing the crowded posterior fossa which in turn improves CSF flow and reduces ICP. It also has the added advantage of addressing only the posterior skull so that the fronto-​orbital region can be addressed more appropriately at a future date. See Fig. 6.6.9. In the syndromic infant, with no acute symptoms, fronto-​orbital advancement and remodelling (FOAR) is carried out to allow anterior calvarial expansion and further brain growth, to reduce exorbitism, and provide a more defined orbital shape. This is usually undertaken at 12–​15 months in the majority of syndromic and non-​syndromic patients. However, posterior calvarial expansion with distraction osteogenesis can delay and in some cases curtail the need for FOAR. See Fig. 6.6.10. A monobloc procedure is indicated when there is a combination of cranio-​volumetric disproportion causing raised ICP, exorbitism due to shallow orbits, and airway obstruction resulting from a constricted midface. The monobloc involves the simultaneous expansion

Fig. 6.6.9  Posterior calvarial osseodistraction. The distraction phase has been completed and bony consolidation is awaited.

of the anterior skull base with midface advancement at the Le Fort III level. The monobloc was first described by Ortiz-​Monasterio. The major disadvantage is that the anterior skull base is divided through the cribriform plate leaving the patients at risk of meningitis via a cranionasal communication. Anderl modified the technique so that the supraorbital bar and forehead were removed as one piece and the Le Fort III segment as a separate second bone fragment. The cribriform plate therefore retains its integrity. With the advent of distraction, the anterior skull base may require support from a pericranial flap, but in practice, it remains intact and the leaks associated with a single surgical advancement are not the problem they once were. See Fig. 6.6.11 and Fig. 6.6.12.

Age 3–​14 years Following the rapid brain growth of the first 3 years, the risk of developing raised ICP is reduced but does not resolve until late childhood. Hence, this group need ongoing surveillance for symptoms suggestive of raised ICP. They require intermittent scans and regular fundoscopy. Rarely, direct ICP measurements (using an intradural sensor, known as a bolt) may be needed.

Fig. 6.6.10  Supine positioned patient with Apert syndrome awaiting fronto-​orbital advancement to enhance the deficient anterior cranial fossa and supraorbital bar.

6.6 Non-syndromic craniosynostosis

Fronto-​orbital advancements are used in patients who have not previously had any frontal surgery, while repeat decompressive craniectomy is reserved for those patients with severe phenotypes who continue to show raised ICP and symptoms. Also, patients with ongoing airway problems (severe obstructive sleep apnoea), resistant to all other interventions and contributing to raised ICP, may require a midfacial osteotomy (Le Fort III) or a frontofacial advancement (monobloc). It is the policy of the authors’ unit that where possible any midfacial advancement should be delayed until skeletal maturity is reached, as it is well recognized that early frontofacial procedures usually need to be repeated if carried out at an early age. However, despite this ‘policy’, delay does not mean that midfacial surgery is not undertaken in this cohort and each case is judged on its merits and any evolving clinical signs.

Age 14 years onwards

Fig. 6.6.11  Computed tomography scan of postoperative monobloc (frontofacial advancement) procedure showing advancement achieved. Courtesy of Prof David Dunnaway, Great Ormond Street Hospital.

(a)

(b)

Fig. 6.6.12  Diagram illustrating the bone cuts and advancement of a monobloc osteotomy. Reproduced with permission from Charles HM Thorne, Geoffrey C. Gurtner, Kevin C Chung, Arun Gosain, Babak Mehrara, Peter Rubin, Scott L. Spear, Grabb and Smith’s Plastic Surgery, Sixth Edition, Wolters Kluwer Health, Copyright © 2007.

As these children approach skeletal maturity, midfacial advancement procedures are commonly performed for aesthetic rather than functional reasons. Comprehensive transition services are necessary as children approach adulthood. Psychologists who are part of the craniofacial multidisciplinary team and who already know the patients may be called upon to provide coping strategies as the syndromic patients enter the unforgiving adult world. Occasionally, the monobloc procedure is undertaken in adults who have not had previous surgery or in whom previous surgery was unsuccessful. A transcranial approach allows the orbital roof on each side to be exposed. In the conventional approach, the forehead remains attached to the Le Fort III midfacial segment, and both forehead and maxilla can be advanced simultaneously. Direct skeletal fixation of an external frame to the underlying bone is achieved with percutaneous wires passed through the pyriform rims and eyebrows to underlying plates, secured to the facial bones with screws. At the end of the consolidation period, the wires are withdrawn through the skin, the frame removed, and the plates and screws left in situ. See Fig. 6.6.13. Frontofacial advancement allows the face to be brought forward as a single unit. This presupposes that this will achieve the desired

Fig. 6.6.13  Le Fort III advancement by distraction osteogenesis in a patient with Crouzon syndrome. Pre-​distraction and post-​distraction views. Note orthodontic appliances in situ.

719

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SECTION 6  Craniofacial and cleft

facial balance. In practice, differential movements are often required between the upper midface, where maximum orbital volume is normally achieved by the age of 8 years, and the lower tooth-​bearing portion of the midface, where skeletal maturity and dentofacial relationship is not achieved until the late teenage years. To overcome this discrepancy, the midface can be segmentalized in terms of simultaneous surgery with advancement at the Le Fort III level being combined with advancement at the Le Fort I level. This can be achieved either by conventional advancement surgery alone or by the use of an external distractor frame offering differential traction on segments of the midface. Any midfacial surgery carried out in the teenage or adult age group is accompanied by presurgical orthodontics. More stable postoperative results are achieved if the occlusion or dental arches are aligned appropriately. In the authors’ experience, once a midface is advanced, either as one segment at Le Fort III or Le Fort II level, then it is usually necessary to undertake a mandibular osteotomy to produce an excellent and stable occlusion. This procedure, performed several months after the midfacial advancement, is a sagittal split osteotomy of the mandible with or without a genioplasty.

REFERENCES Agochukwu NB, Solomon BD, Muenke M. Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses. Childs Nerv Syst 2012;28:1447–​63.

Buchman SR, Muraszko K. Syndromic craniosynostosis. In:  Thaller S, Bradley JP, Garri JI (eds) Craniofacial Surgery, pp. 103–​ 26. New York: CRC Press, 2007. Cohen MM Jr, Wexler A. Craniofacial growth. In:  Ferraro JW (ed) Fundamentals of Maxillofacial Surgery, New York: Springer,  1997. de Jong T, Rijken BF, Lequin MH, et al. Brain and ventricular volume in patients with syndromic and complex craniosynostosis. Childs Nerv Syst 2012;28:137–​40. Hayward R, Gonsalez S. How low can you go? Intracranial pressure, cerebral perfusion pressure, and respiratory obstruction in children with complex craniosynostosis. J Neurosurg 2005;102(Suppl.  1): 16–​22. Nelson TE, Mulliken JB, Padwa BL. Effect of midfacial distraction on the obstructed airway in patients with syndromic bilateral coronal synostosis. J Oral Maxillofac Surg 2008:66:2318–​21. Pereira V. Feeding in syndromic craniosynostosis. In:  Hayward R, Jones B, Dunaway D, et  al. (eds) The Clinical Management of Craniosynostosis, pp. 311–​38. London: MacKeith Press; 2005. Pereira V, Sacher P, Ryan M, et  al. Dysphagia and nutrition problems in infants with Apert syndrome. Cleft Palate Craniofac J 2009;46:285–​91. Tamburrini G, Caldarelli M, Massimi L, et  al. Complex craniosynostoses: a review of the prominent clinical features and the related management strategies. Childs Nervous Syst 2012;28:1511–​23. Witherow H, Dunaway D, Evans R, et  al. Functional outcomes in monobloc advancement by distraction using the rigid external distractor device. Plast Reconstr Surg 2008;121:1311–​22.

6.7

Hypertelorism and orbital dystopia Aina V.H. Greig and David J. Dunaway

History ‘Ocular’ hypertelorism was a term used by D.M. Greig (1924) to describe two cases of congenital facial deformity with a ‘great breadth between the eyes’. ‘Ocular’ hypertelorism is a confusing term because it is tempting to incorrectly use interpupillary distance as a measure to indicate the distance between the eyes and the orbits. If a patient has a wide divergent squint (exotropia) and a normal orbital relationship, the interpupillary distance is much wider than the interorbital distance. Interpupillary distance therefore cannot be used to measure how far apart the orbits are. ‘Orbital’ hypertelorism, the preferred term, is defined as an abnormally wide distance between the orbits, measured at the dacryon (Table 6.7.1). It is a physical finding often associated with other cranial and facial malformations.

Classification of orbital hypertelorism The normal range for interorbital distance for women is 18.5–​29.5 mm and 19.5–​30.7  mm for men (Günther, 1933). Günther also demonstrated that the intercanthal distance was 7–​8  mm greater than the

Table 6.7.1 Definitions Hypertelorism (orbital Increased interorbital distance from dacryon to hypertelorism, teleorbitism, dacryon, with increased distance between lateral hypertelorbitism) orbits Pseudohypertelorism (interorbital hypertelorism)

Increased interorbital distance from dacryon to dacryon, but normal distance between lateral orbits

Telecanthus

Lateral displacement of medial canthi

Orbital dystopia

Any abnormal position of the bony orbit and contents (Tessier, 1981). Orbital dystopia in horizontal and vertical planes is termed orbital hypertelorism and vertical orbital dystopia respectively (Raposo do Amaral and Bradley, 2007). Orbital dystopia in an anteroposterior plane is associated with syndromic craniosynostosis

Dacryon

The point of junction between the maxillary, lacrimal, and frontal bones on the medial orbital wall

interorbital distance. Hansman (1966) measured interorbital distance on radiographs for both sexes from birth to the age of 25 years and established normal ranges. Waitzman and Posnick conducted similar measurements using computed tomography (Posnick, 1992; Waitzman et al., 1992). The average interorbital distance in adult females is 25 mm and in adult males is 28 mm. Tessier classified orbital hypertelorism in adults according to interorbital distance as first degree, 30–​34 mm; second degree, greater than 34 mm with normal shape and orientation of the orbits; and third degree, greater than 40 mm (Tessier, 1972). Tan and Mulliken (1997) graded hypertelorism in children as first degree (interorbital bony distance of 2–​4 standard deviations (SD) above the mean), second degree, (+4.1–​8 SD), and third degree, (>8 SD).

Management of patients with hypertelorism The diagnosis, management, and treatment of patients with craniofacial anomalies and hypertelorism require a team-​based approach. Interdisciplinary craniofacial teams are commonly composed of members with expertise in anaesthesia, craniofacial plastic surgery, dentistry, genetics, hand surgery, intensive care, neurosurgery, nursing, ophthalmology, oral and maxillofacial surgery, orthodontics, otolaryngology, paediatrics, prosthodontics, psychology, public health, radiology, social work, and speech-​ language pathology. Given the inherent complexities of patients with craniofacial anomalies, ideally care is best provided by such a team within centres managing a sufficient number of affected patients.

Craniofacial assessment Enquiry should be made of difficulties experienced in pregnancy, exposure to teratogens, and a family history of genetic abnormalities. The child’s current weight and birth weight should be plotted on a growth chart. An evaluation of the child’s airway, feeding, eye protection, and the presence of elevated intracranial pressure (ICP) should be made. Difficulty breathing, choking or vomiting on feeds, failure of adequate eyelid closure during sleep, or irritability may justify acute intervention.

Pathological anatomy of orbital hypertelorism Patients with an increased interorbital distance have an associated horizontal widening of the ethmoid sinuses. The optic foramina and

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SECTION 6  Craniofacial and cleft

canals are often a relatively normal distance apart, and orbital divergence increases from the apices to the orbital rims (Converse et al., 1970). It is therefore possible to surgically move the orbit without damaging the optic nerves. The roof of the ethmoid sinuses may be enlarged, but the width of the cribriform plate is not usually increased. This permits correction of orbital hypertelorism without damaging the cribriform plate or olfactory nerves (Converse et al., 1970; McCarthy, 1990).

Causes of orbital hypertelorism Frontonasal malformation Sedano and colleagues (1970) introduced the term frontonasal dysplasia, describing four facies: A, B, C, and D. All facies exhibit hypertelorism, which is usually symmetrical, with a broad nasal root. Facies A  consists of a median nasal groove with tip bifidity. Facies B comprises a deep median facial groove (minor form), or true clefting of the nose or both nose and upper lip or palate (major form). Facies C is typified by unilateral or bilateral notching of the ala nasi. Facies D is a combination of facies B (major form) and facies C. Rugose frontonasal malformation, a fifth subgroup described by Tan and Mulliken (1997), has characteristic corrugated nasal skin overlying fibrofatty tissue, a short and broad columella, with an obtuse columella–​labial angle. In 1998, Sedano and Gorlin proposed the description ‘frontonasal malformation’, which has become the preferred term. Frontonasal malformation has variable midline facial defects, which can include a widow’s peak, median cleft lip, broad nasal tip, median cleft upper lip and premaxilla, median cleft palate, anterior cranium bifidum occultum, and hypertelorism. The primary anomalies can be thought of as a developmental field defect. If the nasal capsule fails to develop properly, the primitive brain vesicle fills the space normally occupied by the capsule. This results in anterior cranium bifidum occultum, a morphokinetic arrest of movement of the orbits and failed formation of the nasal tip. Hereditary transmission of frontonasal malformation has not been documented (Sedano and Gorlin, 1988). Craniofrontonasal dysplasia Craniofrontonasal dysplasia is a rare syndrome caused by a mutation in the ephrin-​B1 (EFNB1) gene and can arise de novo or be inherited. Carriage is X-​linked, and females are more frequently and more severely affected. Craniofrontonasal dysplasia includes coronal synostosis and frontonasal anomalies in association with various craniofacial and extracranial anomalies, which include hypertelorism (frequently asymmetrical), a broad nasal bridge and tip, frontal bossing from coronal synostosis, and brachycephaly. Coronal synostosis may be unilateral or bilateral and is not always present. Patients have characteristic thick, dry, curly, or frizzy hair; narrow, sloping shoulders; and longitudinal ridging or splitting of fingernails or toenails. Other associated anomalies include intellectual disability, corpus callosum abnormalities, ophthalmic problems (down-​slanting palpebral fissures, blepharoptosis, amblyopia, strabismus, nystagmus), cleft lip and palate, a high-​arched palate; shoulder abnormalities (shortened, webbed neck, high and prominent scapulae, small or absent clavicles, axillary webbing, pectus excavatum), and hand and foot abnormalities (clinodactyly, syndactyly, brachydactyly, polydactyly, or a broad thumb or great toe). Other anomalies include pelvic kidney, vesicoureteric reflux, diaphragmatic hernia, seizure disorder, and ventricular

septal defects (Cohen, 1979; Tan and Mulliken, 1997; Kawamoto et al., 2007). Craniofacial clefts Tessier (1976) devised an orbitocentric classification of craniofacial clefts, numbering them from 0 to 14 (in addition to cleft number 30 of the midline of the mandible). Paramedian craniofacial clefts, for example, Tessier clefts 1,13; 2,12; 3,13, often present with asymmetrical orbital hypertelorism and orbital dystopia (Tessier, 1972, 1976; David et al., 1989; Eppley et al., 2005; Monasterio and Taylor, 2008). Patients may have multiple skeletal and soft tissue anomalies along the zone of the cleft, including encephalocoeles and extracranial anomalies including acrosyndactyly, constriction rings, scoliosis, and vertebral anomalies (Tan and Mulliken, 1997). Posnick (2000) summarized the general principles for treatment of craniofacial clefts, based on Kawamoto’s (2007) recommendations. Each craniofacial cleft is unique and varies in expression, thus hindering attempts towards standard management protocols. Early treatment is indicated when crisis intervention is necessary to treat serious functional problems including obstructive sleep apnoea, corneal exposure, visual pathway dysfunction, and elevated ICP. Clefting of the soft tissues generally involves all layers. Hypoplastic tissue along the edges of the cleft must be discarded to gain stable wound closure. Skeletal reconstruction is also required for bony defects (Posnick, 2000). Patients with cleft lip or palate Syndromic and non-​syndromic patients with cleft lip and palate, especially those with bilateral clefts, may display hypertelorism (Moss, 1965; Tan and Mulliken, 1997; Anchlia et al., 2011). Syndromic craniosynostosis Patients with Apert, Crouzon, or Pfeiffer syndrome can display hypertelorism, characterized by a negative canthal axis (lateral canthus lower than medial) and counter-​rotated orbits. Primary ophthalmic findings in Apert, Crouzon, and Pfeiffer syndromes include exorbitism due to shallow orbits, increased interpupillary distance, strabismus, refractive error, iris colobomas, cataracts, nasolacrimal duct obstruction, and ptosis (Hammerton, 1995). Major causes of visual loss are amblyopia, exposure keratopathy, and optic atrophy, due to elevated ICP (Harb and Kran, 2005). Patients with syndromic craniosynostosis must undergo regular ophthalmological assessment. Midface hypoplasia is pronounced in the central face, resulting in a biconcave appearance in midsagittal (vertical) and axial (horizontal) planes. There may be serious functional problems including obstructive sleep apnoea, corneal exposure, visual pathway dysfunction, and elevated ICP (Tessier, 1971; A.V. Greig et al., 2013).

Radiological imaging Computed tomography with three-​ dimensional reconstruction using both bone and soft tissue windows is the most useful investigation to examine the patency of cranial sutures (Branson and Shroff, 2011). The interorbital distance (dacryon—​dacryon) delineates the severity of hypertelorism and the lateral orbital distance will distinguish pseudo from true hypertelorism. The shape of the orbit and the position of the permanent central incisor and canine roots determine a surgical plan. Magnetic resonance imaging

6.7  Hypertelorism and orbital dystopia

provides detail of intracranial anatomy (craniocerebral disproportion, ventriculomegaly, corpus callosum agenesis, a Chiari malformation, or syrinx should be noted) but visualization of cranial sutures is limited.

Surgical management of hypertelorism True hypertelorism is generally treated by transcranial osteotomies that allow translocation of the complete anterior orbit. Several techniques have been described.

Box osteotomies Box osteotomies mobilize the orbits by combining extracranial and intracranial approaches. A box osteotomy (Fig. 6.7.1) mobilizes the entire anterior orbit from the surrounding craniofacial skeleton. It can be performed in adults and in children providing the permanent canine root has descended far enough to allow the infraorbital osteotomy. Permanent dentition is commonly sufficiently erupted by 9 years of age, but because of the abnormal facial anatomy associated with hypertelorism, it is often possible to perform box osteotomies at a younger age. Box osteotomies can be modified for use in young children; the infraorbital osteotomy is made at the level of the infraorbital foramen, rather than caudal to it, as is usual in older patients. The maxillary sinus is high in the maxilla in young children, as the descent of the sinus coincides with eruption of permanent teeth. Box osteotomies can be used to correct most types of hypertelorism and are particularly useful with facial asymmetry with an element of vertical orbital dystopia. They do not change the occlusion. Box osteotomies generally translocate rather than rotate the orbit, which is a key difference from the orbital movement produced by facial bipartition. Surgical technique 1. A bicoronal incision is performed and a D-​shaped frontal craniotomy undertaken. The dura is freed from the anterior cranial fossa floor, sparing the cribriform plate.

(a)

Fig. 6.7.1  Box osteotomies.

2. Dissection is continued to expose the zygomatic arches and upper maxilla. The periorbita are freed in a subperiosteal plane from the roof, medial and lateral walls of the orbits as far back as the junction of the posterior and middle thirds of the orbits. The anterior limbs of the medial canthal tendons are left attached to bone. 3. Access for the infraorbital osteotomies is either by a lower lid or intraoral approach. 4. The sites of the osteotomies are shown in Fig. 6.7.1. A central section of bone is removed from the nose and glabella region to allow medialization of the orbits. If there is soft tissue excess, then it may be necessary to resect this with a midline incision along the nasal dorsum to the nasal tip. The mucosa over the superior septum and the superior turbinates is preserved to preserve olfaction. 5. The orbits are then translocated medially and held in situ with wires, plates, and screws. 6. The nasal dorsum is reconstructed with a cranial bone graft. 7. It is important to resuspend the soft tissues at the end of the procedure, paying particular attention to the lateral canthi and malar region.

Facial bipartition In 1979, van der Meulen described the median fasciotomy (van der Meulen, 1979). Tessier (1985) refined this technique into the classical facial bipartition which was originally described for the treatment of hypertelorism. Facial bipartition allows correction of hypertelorism, orbital realignment, and unfolding of the central concavity of the face. The procedure rotates the two halves of the face together around an axis at the level of the hard palate. While narrowing the face at the orbital level, it widens the upper dental arch, which can be an advantage in craniosynostosis and frontonasal malformation, but a distinct disadvantage if the occlusion is normal preoperatively. The bipartition is not indicated in some asymmetric cases or where there is vertical orbital dystopia. A facial bipartition does not threaten the roots of the canines, but requires adequate space between the central incisor roots to allow the midline maxillary osteotomy (Fig. 6.7.2).

(b)

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SECTION 6  Craniofacial and cleft

Fig. 6.7.2  Pre-​and postoperative three-​dimensional computed tomography scans of a patient undergoing facial bipartition. Note the wide hypertelorism, bifid nose, and midline encephalocoele. The encephalocoele defect has been corrected with cranial bone graft and the nasal dorsum has been reconstructed with a dorsal midline cranial bone graft to the nose.

Surgical technique 1. Access is undertaken as described in steps 1–​3 of the box osteotomy technique. An intraoral approach is always required whereas lower eyelid incisions are unnecessary. 2. The orbits and midfacial skeleton are separated from the skull base by a monobloc osteotomy (Fig 6.7.3) (see Chapter 6.6). 3. Once the monobloc segment is mobilized, a wedge-​shaped bony segment is removed from the glabella region.

4. The midline osteotomy is completed by dividing the alveolus and hard palate in the midline. 5. The orbits and facial skeleton are rotated medially and held with wires, plates, and screws. 6. The nasal dorsum is reconstructed with a cranial bone graft (Fig. 6.7.2). 7. The soft tissues are resuspended, paying attention to the lateral canthi and malar region.

6.7  Hypertelorism and orbital dystopia

(a)

(b)

Fig. 6.7.3  Facial bipartition.

Nasal deformity correction Structural nasal deformities are also addressed at the time of hypertelorism correction (Fig. 6.7.2). Techniques include nasal monobloc osteotomy to correct nasal deviation, bone grafts to augment the nasal dorsum, and open tip rhinoplasty to correct nasal tip bifidity. Further surgery to correct residual deformity is performed after nasal growth is complete at 16 years.

Facial bipartition and monobloc distraction This combined procedure addresses both hypertelorism and syndromic craniosynostosis (A.V. Greig et al., 2013). Distraction osteogenesis allows large stable advancements (Fearon, 2005; Shetye et al., 2010) and has proved effective in the very young (Polley et al., 1995; Witherow et al., 2008b).

Causes of pseudohypertelorism Meningoencephalocoeles A meningoencephalocoele, with occipital, parietal, basal, and sincipital types, is a congenital herniation of the brain and meninges through a craniofacial skeletal defect. Sincipital meningo­ encephalocoeles were subdivided by Suwanwela and Suwanwela into frontoethmoidal (nasofrontal, nasoethmoidal, naso-​orbital), interfrontal, and craniofacial clefts (Suwanwela and Suwanwela, 1972). David and colleagues (1984) described the skeletal and soft tissue morphology of frontoethmoidal meningoencephalocoeles with three-​dimensional computed tomography scans. In all cases, the cranial end of the defect was in the anterior cranial fossa at the site of the foramen cecum at the junction of the frontal and ethmoid bones. The facial component of the defect determined the subclassification:  nasofrontal (at the junction of the frontal and nasal bones), nasoethmoidal (between the nasal bones and nasal cartilages), and naso-​orbital (through the medial orbital wall). Frontoethmoidal encephalocoeles can be corrected at the same time as orbital translocation surgery for hypertelorism (McCarthy, 1990). Exposure is via a combined extracranial and intracranial

route. The dura is opened and the cerebral herniation conserved as much as possible. The neck of the encephalocoele is transected and the dural defect is repaired. The orbits are translocated and any remaining bony defect at the site of the encephalocoele is reconstructed with cranial bone graft. As encephalocoeles cause pseudohypertelorism, it is sometimes possible to correct the orbital deformity by medializing the medial orbital walls only and leaving the orbital floor, roof, and lateral wall intact. Midline dermoids Facial dermoids are congenital developmental malformations derived from ectodermal and mesodermal origins. They contain skin adnexal structures, which differentiate them from epidermoid cysts. Nasal dermoid sinus cysts are rare, with an incidence of 1 in 20,000–​40,000. They are commonly found anywhere from the glabella to the base of the columella. There may be a deep extension of a tract to the underlying periosteum and, occasionally, an intracranial extension. This can make surgical excision unexpectedly hazardous with the danger of causing a cerebrospinal fluid leak, in addition to complications of meningitis and cerebral abscess, if left untreated. The incidence of extensions to the cribriform plate has been reported as between 12% and 45%. Patients presenting with dermoid cysts in the midline require magnetic resonance imaging to delineate the anatomy and also to exclude a midline cranial defect, which can be associated with pseudohypertelorism (Moses et  al., 2015). Radiological features are either indirect (deformed or bifid crista galli, widened foramen caecum, cribriform plate defect) or direct (identification of intracranial lesions) (Sreetharan et al., 2007). Anterior skull base tumours Many different kinds of neoplasms can potentially involve the craniofacial skeleton, and tumour growth can cause pseudohypertelorism. Examples include fibrous dysplasia, simple osteomas, benign angiofibromas, neural tumours (meningiomas with extracranial erosion, encapsulated neurofibromas, schwannomas, and neurilemmomas), osteogenic sarcomas, and rhabdomyosarcomas (Hunt and Hobar, 2003).

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SECTION 6  Craniofacial and cleft

Table 6.7.2  Causes of vertical orbital dystopia Congenital

Acquired

Facial clefts Craniofacial microsomia Craniosynostosis Vascular malformations

Table 6.7.3  Sequence of craniofacial surgical procedures in hypertelorism Age

Procedure

6 months to 3 years

Crisis intervention (ICP, orbital protection, airway), cranial vault expansion, midfacial or frontofacial advancement

4–​8 years

Correction of midface deformities, primary and secondary cranial vault procedures, and adjunctive procedures

9–​12 years

Correction of midface deformities, secondary cranial vault procedures, and adjunctive procedures

13–​17 years

Late correction of midface deformities. Adjunctive procedures, e.g. rhinoplasty and orthodontic therapy

Over 17 years

Orthognathic surgery

Trauma Tumours

Fibrous dysplasia Neurofibromatosis Osteoma Angiofibroma Neural tumours Osteogenic sarcomas Rhabdomyosarcomas

Naso-​orbitoethmoid fractures Telecanthus secondary to trauma, with lateral displacement of the medial canthus, can give the appearance of abnormal widening between the orbits (Tessier, 1972). See Chapter 7.7.

Vertical orbital dystopia In this condition, the orbits lie at differing vertical levels. The causes are outlined in Table 6.7.2. The condition should not be confused with ocular dystopia where the globes are at differing levels within a normally positioned orbit. Correction involves a vertical translocation of the orbit with a modified (usually unilateral) box osteotomy (Fig. 6.7.4). Lateral orbital translocation is usually tolerated very well, but vertical movements can lead to persistent diplopia. See Table 6.7.3 for the sequence of craniofacial surgical procedures in hypertelorism.

Complications of surgery for hypertelorism Patients undergoing corrective surgery for hypertelorism showed exotropia or exophoria preoperatively whereas postoperatively,

(a)

there was a tendency for esotropia in one study (McCarthy et al., 1990). It was found at about 6 months postoperatively and so the authors recommended delaying corrective strabismus surgery until 6 months after hypertelorism surgery as the strabismus tended to stabilize by this time. Early series evaluating complications for all types of craniofacial surgery quoted mortality rates of 1–​2% (Whitaker et al., 1979; Poole, 1988). A more recent multicentre review, showed mortality had fallen to 0.1% for transcranial procedures and 0.3% for subcranial procedures (Arnaud et al., 2007). Mortality rates of 0.11% for all craniofacial procedures undertaken in the last 5  years has been reported (Dunaway et al., 2012). Higher mortality rates are associated with frontofacial advancement, demonstrating greater risks with major surgery (Fearon and Whitaker, 1993; Arnaud et al., 2007; Witherow et  al., 2008a; Czerwinski et  al., 2010; Dunaway et al., 2012). The risk of death or significant morbidity most commonly arises from bleeding (either exsanguination or postoperative intracranial bleeding) or less frequently, postoperative airway complications. Well-​defined protocols and strategies for addressing perioperative blood loss are important (Czerwinski et al., 2010). See Table 6.7.4.

(b)

Fig. 6.7.4  Unilateral box osteotomy for vertical orbital translocation with bone graft inset into maxilla.

6.7  Hypertelorism and orbital dystopia

Table 6.7.4  Complications of craniofacial surgical procedures Early

Bleeding Airway Infection, e.g. meningitis Neurosurgical, e.g. stroke, elevated ICP Cerebrospinal fluid leak (Dunaway et al., 2012) Blindness

Intermediate

Bone loss, e.g. frontal bone (Dunaway et al., 2012; A.V. Greig et al., 2012) Osteomyelitis/​sequestrum Plate infections Strabismus and diplopia

Late

Mucocoele (Dunaway et al., 2012) Late bone loss Relapse Seizures (McCarthy et al., 1995; Dunaway et al., 2012; A.V. Greig et al., 2013) Premature ageing (Tulasne and Tessier, 1986; Warren et al., 2012) Effects of radiation exposure from multiple CTs (Domeshek et al., 2009)

Conclusion The complex functional and anatomical problems caused by hypertelorism mandate treatment by a dedicated multidisciplinary team. Through collaboration with this team, the craniofacial surgeon can make informed decisions about the timing of surgery and the use of different surgical techniques.

REFERENCES Anchlia S, Rao KS, Bonanthaya K, et al. Ophthalmic considerations in cleft lip and palate patients. J Maxillofac Oral Surg 2011;10: 14–​19. Arnaud E, Marchac D, Renier D. Reduction of morbidity of the frontofacial monobloc advancement in children by the use of internal distraction. Plast Reconstr Surg 2007;120:1009–​26. Branson HM, Shroff MM. Craniosynostosis and 3-​dimensional computed tomography. Semin Ultrasound CT MR 2011;32:569–​77. Cohen MM Jr. Craniofrontonasal dysplasia. Birth Defects Orig Artic Ser 1979;15:85–​9. Converse JM, Ransohoff J, Mathews ES, et  al. Ocular hypertelorism and pseudohypertelorism. Advances in surgical treatment. Plast Reconstr Surg 1970;45:1–​13. Czerwinski M, Hopper RA, Gruss J, et al. Major morbidity and mortality rates in craniofacial surgery: an analysis of 8101 major procedures. Plast Reconstr Surg 2010;126:181–​6. David DJ, Moore MH, Cooter RD. Tessier clefts revisited with a third dimension. Cleft Palate J 1989;26:163–​84. David DJ, Sheffield L, Simpson D, et  al. Fronto-​ ethmoidal meningoencephaloceles: morphology and treatment. Br J Plast Surg 1984;37:271–​84. Domeshek LF, Mukundan S Jr, Yoshizumi T, et al. Increasing concern regarding computed tomography irradiation in craniofacial surgery. Plast Reconstr Surg 2009;123:1313–​20. Dunaway DJ, Britto JA, Abela C, et al. Complications of frontofacial advancement. Childs Nerv Syst 2012;28:1571–​6. Eppley BL, Van Aalst JA, Robey A, et  al. The spectrum of orofacial clefting. Plast Reconstr Surg 2005;115:101e–​14e.

Fearon JA. Halo distraction of the Le Fort III in syndromic craniosynostosis:  a long-​ term assessment. Plast Reconstr Surg 2005;115:1524–​36. Fearon JA, Whitaker LA. Complications with facial advancement:  a comparison between the Le Fort III and monobloc advancements. Plast Reconstr Surg 1993;91:990–​5. Greig AV, Britto JA, Abela C, et  al. Correcting the typical Apert face:  combining bipartition with monobloc distraction. Plast Reconstr Surg 2013;131:219e–​30e. Greig AV, Davidson EH, Grayson BH, et  al. Complications of craniofacial midface distraction:  10-​year review. Plast Reconstr Surg 2012;130:371e–​2e. Greig DM. Hypertelorism: a hitherto undifferentiated congenital craniofacial deformity. Edinburgh Med J 1924;31:560. Günther, H. Konstitutionelle Anomalien des Augenabstandes und der Interorbitalbreite. Virchows Arch Pathol Anat 1933;290:373. Hammerton M. The ophthalmic features of Pfeiffer syndrome. In:  Marchac D (ed) Craniofacial Surgery:  Proceedings of the Sixth International Congress of the International Society of Cranio-​Facial Surgery, pp. 157–​9. Bologna: Monduzzi Editore, 1995. Hansman CF. Growth of interorbital distance and skull thickness as observed in roentgenographic measurements. Radiology 1966;86:87–​96. Harb E, Kran B. Pfeiffer syndrome: systemic and ocular implications. Optometry 2005;76:352–​62. Hunt JA, Hobar PC. Common craniofacial anomalies: conditions of craniofacial atrophy/​hypoplasia and neoplasia. Plast Reconstr Surg 2003;111:1497–​508. Kawamoto HK, Heller JB, Heller MM, et  al. Craniofrontonasal dysplasia:  a surgical treatment algorithm. Plast Reconstr Surg 2007;120:1943–​56. McCarthy JG, Glasberg SB, Cutting CB, et al. Twenty-​year experience with early surgery for craniosynostosis: II. The craniofacial synostosis syndromes and pansynostosis—​results and unsolved problems. Plast Reconstr Surg 1995;96:284–​95. McCarthy JG, Thorne CHM, Wood-​Smith, D. Principles of craniofacial surgery: orbital hypertelorism. In: McCarthy JG (ed) Plastic Surgery, pp. 2982–​3002. Philadelphia, PA: WB Saunders Company, 1990. Monasterio FO, Taylor JA. Major craniofacial clefts:  case series and treatment philosophy. Plast Reconstr Surg 2008;122:534–​43. Moses MA, Green BC, Cugno S, et  al. The management of midline frontonasal dermoids:  a review of 55 cases at a tertiary referral center and a protocol for treatment. Plast Reconstr Surg 2015;135: 187–​96. Moss ML. Hypertelorism and cleft palate deformity. Acta Anat 1965;61:547. Polley JW, Figueroa AA, Charbel FT, et al. Monobloc craniomaxillofacial distraction osteogenesis in a newborn with severe craniofacial synostosis: a preliminary report. J Craniofac Surg 1995;6:421–​3. Poole MD. Complications in craniofacial surgery. Br J Plast Surg 1988;41:608–​13. Posnick JC. Rare craniofacial clefts:  evaluation and treatment. In:  Posnick JC (ed) Craniofacial and Maxillofacial Surgery in Children and Young Adults, pp. 487–​502. Philadelphia, PA:  WB Saunders Company, 2000. Raposo do Amaral CE, Bradley JP. Orbital dystopia. In:  Thaller SR, Bradley JP, Garri JI (eds) Craniofacial Surgery, pp. 143–​52. New York: CRC Press, 2007. Sedano HO, Cohen MM Jr, Jirasek J, et  al. Frontonasal dysplasia. J Pediatr 1970;76:906–​13.

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Sedano HO, Gorlin RJ. Frontonasal malformation as a field defect and in syndromic associations. Oral Surg Oral Med Oral Pathol 1988;65:704–​10. Shetye PR, Kapadia H, Grayson BH, et al. A 10-​year study of skeletal stability and growth of the midface following Le Fort III advancement in syndromic craniosynostosis. Plast Reconstr Surg 2010;126:973–​81. Sreetharan V, Kangesu L, Sommerlad BC. Atypical congenital dermoids of the face: a 25-​year experience. J Plast Reconstr Aesthet Surg 2007;60:1025–​9. Suwanwela C, Suwanwela, N. A morphological classification of sincipital encephalomeningoceles. J Neurosurg 1972;36:201–​11. Tan ST, Mulliken JB. Hypertelorism: nosologic analysis of 90 patients. Plast Reconstr Surg 1997;99:317–​27. Tessier P. The definitive plastic surgical treatment of the severe facial deformities of craniofacial dysostosis, Crouzon and Apert disease. Plast Reconstr Surg 1971;48:419. Tessier P. Orbital hypertelorism. I.  Successive surgical attempts. Material and methods. Causes and mechanisms. Scand J Plast Reconstr Surg 1972;6:135–​55. Tessier P. Anatomical classification facial, cranio-​facial and latero-​ facial clefts. J Maxillofac Surg 1976;4:69–​92. Tessier P. Apert syndrome: Acrocephalosyndactyly type 1. In: Caronni EP (ed) Craniofacial surgery, pp. 280–​ 303. Boston, MA:  Little Brown, 1985.

Tessier P, Rougier J, Hervouet F, et  al. Congenital orbital dystopias. In:  Plastic Surgery of the Orbit and Eyelids:  Report of the French Society of Ophthalmology, pp. 191–​9. New  York, USA:  Masson Publishing, 1981. Tulasne JF, Tessier PL. Long-​term results of Le Fort III advancement in Crouzon’s syndrome. Cleft Palate J 1986;23(Suppl. 1):102–​9. van der Meulen JC. Medial faciotomy. Br J Plast Surg 1979;32: 339–​42. Waitzman AA, Posnick JC, Armstrong DC, et  al. Craniofacial skeletal measurements based on computed tomography:  Part II. Normal values and growth trends. Cleft Palate Craniofac J 1992;29: 118–​28. Warren SM, Shetye PR, Obaid SI, et  al. Long-​term evaluation of midface position after Le Fort III advancement:  a 20-​plus-​year follow-​up. Plast Reconstr Surg 2012;129:234–​42. Whitaker LA, Munro IR, Salyer KE, et al. Combined report of problems and complications in 793 craniofacial operations. Plast Reconstr Surg 1979;64:198–​203. Witherow H, Dunaway D, Evans R, et  al. Functional outcomes in monobloc advancement by distraction using the rigid external distractor device. Plast Reconstr Surg 2008a;121:1311–​22. Witherow H, Thiessen F, Evans R, et al. Relapse following frontofacial advancement using the rigid external distractor. J Craniofac Surg 2008b;19:113–​20.

6.8

Orofacial clefts Embryology, epidemiology, and genetics David R. FitzPatrick

Introduction Cleft lip with or without cleft palate (CL(P)) and cleft palate (CP) only are aetiologically distinct subgroups of common human malformations caused by failure of growth or fusion of the embryonic facial processes that form the primary and secondary palate, respectively. The prevalence of these malformations is around 1.5 per 1000 births in Caucasian populations. A higher birth prevalence of CL(P) is observed in populations of South-​East Asian decent and a lower birth prevalence in populations of recent African descent. In a minority of cleft cases, chromosomal aberrations, single-​gene defects, or environmental causes can be identified. In most affected individuals, genetic factors play a role but the number and nature of these genes and the extent of their interaction with environmental factors are unknown. The identification of the genes and genomic loci involved in non-​syndromal human clefts has required many different approaches including linkage analysis, genome-​wide association studies, candidate gene sequencing, and, more recently, genome-​wide sequencing technologies.

Embryology The Carnegie system (Table 6.8.1) allows developmental, stage-​ specific, comparisons between human embryos and other vertebrate species (Streeter, 1942, 1945, 1948; O’Rahilly and Müller, 1987). Carnegie staging is used throughout this chapter since most studies of vertebrate craniofacial development use non-​human species with species-​specific embryonic size and gestational periods. The available data on human embryos has yielded no major discrepancies in the anatomical, histochemical (Andersen and Matthiessen, 1967), or transcriptional (Cai et al., 2005) aspects of primary and secondary palate development with that available from non-​human mammalian species.

The primary palate and upper lip The pharyngeal arches are symmetrically paired bars of tissue that arise ventral to the hindbrain in the human at stages 10–​12

(Bartelmez and Evans, 1926). Each consists of a mesenchymal core, partly derived from migratory cranial neural crest, covered externally by surface ectoderm and internally by epithelium of endodermal origin (Sulik and Schoenwolf, 1984). Although three to four pharyngeal arches appear in a rostrocaudal sequence in human embryos (O’Rahilly and Müller, 1987) only the first and second arch contribute directly to facial structures. Differential growth within the first arch forms a ‘c’ shape. The dorsal part of the arch (the maxillary process) forms the rostral arm of the ‘c’ and the ventral part (the mandibular process) forms the caudal arm. By stage 12 the primitive mouth or stomodeum has been formed, bordered superiorly by the frontal process, laterally by the maxillary processes and inferiorly by the mandibular processes (Fig. 6.8.1). In stage 13, the mandibular processes enlarge, grow medially, and merge in the midline to form the lower lip and mandible. The paired maxillary and mandibular processes together with the frontal process will form all of the facial structures. In the first half of the twentieth century, many embryologists, most notably Frazer (Frazer and Baxter, 1953), believed that the upper lip was formed in the human embryo by fusion of the maxillary processes in the midline. Wax plate reconstruction (Warbrick, 1960) and scanning electron micrography (Sulik and Schoenwolf, 1984)  subsequently demonstrated convincingly that the upper lip is formed by fusion of the medial end of the maxillary processes with the medial and lateral nasal prominences of the frontal process at stage 17 (Fig. 6.8.1) (Vukojevic et al., 2012). The exact mechanism of fusion is not known but the initial outgrowth of the processes requires both WNT and FGF signalling (Jin et al., 2012) and the fusion event is dependent on SHH and BMP signalling (Hu et al., 2015).

Formation of the secondary palate Following closure of the primary palate at stage 17, the oral cavity is roofed by the frontal process, walled by two lateral maxillary processes, floored by the merged first arches, and occupied by the enlarging tongue and the developing nasal septum. It communicates dorsally with the foregut and ventrally with the amniotic cavity via the mouth and the nares. Development of the secondary palate is phenotypically similar in all mammalian species studied (Ferguson,

730

SECTION 6  Craniofacial and cleft

Table 6.8.1  Carnegie staging of human embryos Carnegie stage

Age (days)

Size (mm)

Major features

1

1

0.1

Fertilization

2

1.5

0.1

2–​16 cells

3

4

0.1

Blastocyst

4

5

0.1

Attaching blastocyst

5

7

0.1

Implantation

6

13

0.2

Chorionic villi formation, primitive streak

7

16

0.4

Notochord formation

8

18

1.25

Gastrulation, neural fold formation

9

20

2

Somite formation

10

22

2.75

Start of neural tube fusion

11

24

3.5

Optic vesicle formation, anterior neuropore closes

12

26

4

Upper limb buds appear

13

28

5

Lower limb buds, lens disc, and otic vesicle appear

14

32

6

Optic cup appears

15

33

8

Formation of nasal pit, hand plate, and future cerebral hemispheres

16

37

9.5

Auricular hillocks and foot plate appears

17

41

12.5

Finger rays distinct, nasofrontal groove appears

18

44

15

Ossification begins, eyelid folds

19

47.5

17

Trunk elongating and straightening

20

50.5

20

Upper limbs longer and bent at elbow

21

52

23

Fingers longer, hands approach each other

22

54

25.5

Eyelids and external ears more distinct

23

56.5

29

External genitalia well developed

Reproduced with permission from Streeter, G.L., Description of age group XI., Contrib Embryol Carnegie Instn, Volume 30, pp. 211–​245., Copyright © 1942 Carnegie Institution. Reproduced with permission from O’Rahilly, R. & Müller, F., Developmental stages in human embryos: including a revision of Streeter's “horizons” and a survey of the Carnegie Collection, Carnegie Institution of Washington, Washington, DC, Copyright © 1987.

CS12

CS13

CS14

CS15

CS16

fusion of mandibular processes

CS17

CS18

CS19

CS20

CS22

fusion of primary palate Frontal Process

Second Pharyngeal Arch

Maxillary Process

Lateral Nasal Process

Mandibular Process

Medial Nasal Process

Fig. 6.8.1  Development of craniofacial structures in human embryos. Optical projection tomography images of human embryos between Carnegie stages 12 and 22 with colours representing specific facial structures indicated in the key. Kathleen K. Sulik, Ph.D., Emeritus Professor, University of North Carolina.

6.8  Orofacial clefts: embryology, epidemiology, and genetics

1988) and can be summarized as initiation of the palate primordia, initially vertical growth of the palatal shelves, subsequent elevation and approximation of the shelves, fusion of the medial edge epithelia to form an epithelial seam, followed by disruption of the seam establishing mesenchymal continuity (Fig. 6.8.2).

The palatal primordia and vertical growth In stage 18, the palatal shelves arise from the bilateral maxillary processes as distinct ridges of mesenchymal cells associated with craniopharyngeal ectoderm (Greene and Pratt, 1976). An ultrastructural study of shelf initiation in hamster embryos (Shah, 1984)  showed a change in epithelial phenotype from simple cuboidal before the appearance of palatal shelves to a bilayer with flattened cells covering a layer of irregularly shaped cells in early palatal shelves. It would seem likely that the initiation of palatal shelf growth, at least in part, is controlled by epithelial–​mesenchymal tissue interaction, although the physiochemical nature of these signals is poorly understood. With rapid vertical growth, the shelves achieve their full length prior to elevation. This growth on either side of the tongue is the result of proliferation of mesenchyme (Fig. 6.8.2b) (Ferguson, 1987).

Mechanisms of shelf elevation In the stage 20 embryo, a remarkable reorientation of the palatal shelves occurs; as both shelves rapidly elevate, they come into apposition above the tongue. The origin of the intrinsic force of elevation has been the subject of much debate and is almost certainly

(a)

multifactorial (Ferguson, 1977; Sandham, 1985a, 1985b; Almaidhan et al., 2014). At a cellular level, regional differences in orientation of growth within the densely packed anterior mesenchyme are associated with a rapid, all-​or-​nothing, rotational elevation while the posterior regions display a more fluid remodelling. Contractile proteins, actin and myosin, have been localized to cytoplasmic, non-​muscle contractile systems on the oral and nasal sides of the murine vertical palatal shelves. Incubation of pre-​elevation palatal shelves with adenosine triphosphate causes condensation of cytoplasmic actomyosin complexes which results in almost complete elevation of the anterior palate. The ability of certain neurotransmitters to stimulate (serotonin and acetylcholine) and inhibit (gamma-​aminobutyric acid) shelf elevation in cultured murine palates is thought to be mediated via mesenchymal cell contractility and matrix degradation (Zimmerman and Wee, 1984). Posteriorly, expansion of a mesenchymal gel matrix produces a force which is then directed by local proliferative changes in the oral epithelial component and bundles of type I collagen (Ferguson, 1987) which produces a more fluid reorientation. Other factors with a possible role in shelf elevation include the mechanical effect of substantial vertical head growth with little lateral growth, straightening of the flexed cartilaginous, cranial base, pressure changes produced by fetal mouth opening, swallowing movements, and hiccupping (Ferguson, 1988).

Fusion of the shelves Almost immediately after elevation, the medial edge epithelia (MEE) of both shelves come into contact above the tongue. In the mouse

(b)

palatal shelf (PS) tongue

(c)

tongue

(d)

PS PS

midline epithelial seam (MES)

medial edge epithelium (MEE) tongue tongue

Fig. 6.8.2  Diagrammatic representation of the normal stages of mammalian palatogenesis. (a) At stage 18, the palatal shelves (PS) become visible as ridges on the maxillary processes. (b) The palatal shelves grow vertically down the side of the tongue (to), reaching their full length by stage 21. (c) In stage 22, reorientation of the palatal shelves brings them into apposition above the tongue. (d) The palatal shelves fuse in the midline at stage 23.

731

732

SECTION 6  Craniofacial and cleft

embryo, fusion begins at the border of the anterior and middle thirds of the secondary palate in the region of the second rugae (Sakamoto et al., 1989) with formation of the midline epithelial seam (MES) and proceeds in both anterior and posterior directions until completion by stage 23. The final process of fusion involves disruption of the MES to establish mesenchymal continuity. Prior to elevation, the MEE is a bilayer consisting of a surface squamous layer (periderm) overlying a glycogen-​rich cuboidal cell layer in contact with an intact basal lamina. The cells are connected both within and between layers, by numerous small desmosomes. After elevation, but prior to midline contact, the cells in the peridermal layer of the MEE lose their intercellular connections, become irregularly shaped, and are shed from the outer surface. In mouse embryos, the basal layer of the MEE shows continued heavy staining for glycogen, abundant rough endoplasmic reticulum, and occasional mitotic figures (Fitchett and Hay, 1989). As the MEE fuse to form the MES, the mechanism of initial adherence is thought to be the formation of glycoconjugates on ‘sticky’ cell surfaces. However, the MEE will only adhere to one another and not to other oral epithelial surfaces. The MES is formed by specific and rapid construction of desmosomal components.

Disruption of the midline epithelial seam The mechanism of disruption of the MES has been controversial. Programmed cell death was initially thought to be involved but epithelial-​to-​mesenchymal transformation is now considered to be the primary mechanism of MES disruption. Dramatic changes in morphology of the remaining mammalian palatal epithelia occur immediately after the disruption of the MES. The nasal epithelium differentiates into pseudostratified ciliated columnar cells and the oral epithelium into stratified squamous cells (Sharpe and Ferguson, 1988). Epithelial–​ mesenchymal recombination techniques have shown that epithelial differentiation in the palatal shelves, both within and across species, is controlled by the underlying mesenchyme. TGF-​β signalling is required for successful completion of MES disruption (Huang et al., 2011; Hu et al., 2014; Iwata et al., 2014; Liu et al., 2014; Lane et al., 2015).

The post-​fusion palate There are very few studies of the ultrastructural or biochemical processes involved in mesenchymal differentiation after disruption of the MES. It is known that the subsequent differentiation of the ectomesenchyme must be regionally specified as the anterior portion (hard palate) undergoes membranous ossification and the mesenchyme of the posterior palate differentiates to myoblasts and forms the musculature of the soft palate, (tensor veli palatini, musculus uvulae, etc.), the nature of the physiochemical signals determining this polarity is, however, unknown.

Epidemiology The two major subgroups of facial clefts, CL(P) and CP, have been considered as separate genetic and developmental entities. This distinction has been informed both by embryological studies and family recurrence data. Poul Fogh-​Andersen (1942) was the first to recognize these genetic differences in a large study of Danish families with one member or more affected with cleft lip (CL), CP, or both. He

reported that siblings of patients with CL(P) have a higher incidence of CL and of CL and CP, but not of CP and that this homogeneity of defect recurrence also occurred in the siblings of CP patients. All subsequent work has essentially confirmed these findings. However, exceptions exist to this recurrence phenomenon; families with van der Woude syndrome can have both types of facial cleft associated with lip pits, segregating with the gene (Woolf, 1971). Woolf (1971) also showed a small but convincing increase in the incidence of CP occurring in the families of a large cohort of patients with CL(P).

Birth incidence Facial clefts are predominantly non-​lethal malformations that are usually obvious at birth or in early neonatal life with surgical treatment as the only therapeutic option. These characteristics should aid the estimation of accurate birth prevalence figures for CL(P) and CP using either birth certificates or hospital records as their main sources of ascertaining the affected individuals. However, it has been estimated that in up to one-​third of cases the presence of the facial cleft will not be recorded on birth records or neonatal discharge forms (Shapiro, 1976). Other studies have shown that up to 20% of infants with facial clefts will die prior to operation or before the cleft is recognized (Drillien et al., 1966; FitzPatrick et al., 1994). It must be assumed, therefore, that using either of the previously mentioned methods alone would lead to significant under-​ascertainment of facial cleft cases. From published reports, the average birth prevalence of facial clefting in Caucasian populations is 1 per 1000 total births for CL(P) and 1 per 2000 total births for CP. Significant racial differences in birth prevalence of facial clefts exist:  peoples of South-​East Asian origin have a higher total birth prevalence while a lower birth prevalence is found in families of recent African decent (Canfield et al., 2006; Lidral et  al., 2008). These inter-​racial variations are mostly accounted for by differences in the CL(P) birth prevalence, which range from 0.42 per 1000 total births in African Americans, to 2.7 per 1000 total births in Indigenous Canadian populations. No major racial differences are apparent in the CP group. The racial differences in CL(P) birth prevalence are likely to have a genetic basis. An extensive study from Hawaii has shown that the children of Japanese immigrants continue to have an increased birth prevalence of CL(P). The offspring of Caucasian–​Japanese couples have intermediate birth prevalence, suggesting that the racial differences are independent of environment (Ching and Chung, 1974). The sex ratios differ significantly between the facial cleft groups and vary with severity of the cleft, the number of affected siblings in a family, and racial origin. In most populations CL(P) occurs more frequently in males than females with an average male-​to-​female ratio of 2:1. The male excess in the CL(P) group becomes more apparent with increasing severity of cleft and less apparent when more than one sibling is affected in the family (Niswander et al., 1972). There would appear to be a slight excess of affected females in the CP group. In African Americans, there is no overall significant sex difference in CL(P) or CP. No generally accepted explanation for these sex differences exists, although differences do exist between the sexes in the timing of critical developmental stages during craniofacial development. The difference in laterality within the CL group has also proved to be a consistent and puzzling finding. Of unilateral CL (85% of all CL), two thirds have left-​sided defects regardless of sex, race, and

6.8  Orofacial clefts: embryology, epidemiology, and genetics

severity of defect. No convincing explanation for these differences has been advanced.

Family studies Poul Fogh-​Andersen’s classic study of 703 probands with CL, CP, or both, showed a sixfold increase in the incidence of facial clefting in their third-​degree relatives or closer (Fogh-​Andersen, 1942). All subsequent studies have confirmed this familial clustering. Twin studies have shown a significantly higher concordance of clefts in monozygotic compared to dizygotic pairs, the heritability (h2) has been estimated at 0.35 (i.e. 35% of the difference between those with clefts and those without maybe attributable to genetic factors) (Hay and Wehrung, 1970). The statistical and molecular techniques available for analyses of family data in non-​Mendelian diseases have improved greatly over the last 30 years. A multifactorial model with an oligogenetic contribution is generally accepted in non-​syndromal clefting (Farrall and Holder, 1992; FitzPatrick and Farrall, 1993). The use of genome-​wide association studies has identified individual loci that are robustly associated with CL(P) but none of these variants are as yet of clinical utility in prediction of genetic risks in healthy populations (Beaty et al., 2010; Birnbaum et al., 2009; Mangold et al., 2010; Ludwig et al., 2012). A variant altering the cis-​regulation of the gene that causes van der Woude syndrome, IRF6 (Table 6.8.2), appears to be a major contributor in South-​East Asian populations (Rahimov et al., 2008). In European populations, a variant of unknown function on 8q24 has been identified (Birnbaum et al., 2009).

Aetiology of facial clefts Both CL(P) and CP are anomalies with remarkably heterogeneous aetiologies. Well-​ characterized unifactorial aetiologies (chromosomal, single gene, and teratogenic) can be identified in a minority of cases but no specific cause can be identified in most affected individuals. For CP in particular, such aetiological heterogeneity is not surprising given the developmental complexity of palatogenesis. The

processes of palate development could be interrupted at many different stages by a wide variety of factors. The number and nature of these disruptive factors is not known but genetic and teratogenic studies are providing useful clues.

Environmental factors Many specific environmental factors have been implicated in facial clefting. Shprintzen and colleagues (1985) estimated that 4% of orofacial clefting was due to specific teratogenic agents, of which fetal alcohol syndrome was the most common (75%) entity. Deficiencies of specific vitamins, particularly folic acid, have been postulated as contributing to CL(P) and CP; however, no firm causative link has been established to date.

Chromosomal anomalies causing clefts Both CL(P) and CP are common in trisomies of chromosomes 13 (Patau syndrome) and 18 (Edwards syndrome). In CL(P), deletions of 1q21–​25, 4p16–​15, 4q31–​35, and 7q34–​35 are non-​randomly associated with this malformation (Brewer et al., 1998). The likely causative dosage-​sensitive gene at 1q21–​25 is IRF6 and at 7q34–​35 is SHH. For CP, deletions of 2q32, 4p16–​13, and 4q31–​35 were identified. SATB2 is the likely causative gene in the 2q32 deletions (Brewer et al., 1998). Microdeletion of 22q11.2 (velo-​cardio-​facial syndrome, DiGeorge syndrome) is an infrequent but significant cause of CP and submucous CP.

Single-​gene defects Over 300 different disease entities with facial clefting as a feature are listed in the Online Mendelian Inheritance in Man database (http://​www.ncbi.nlm.nih.gov/​omim/​). In spite of the large number of single-​gene defects described, as a group they represent a relatively small proportion of individuals within the facial cleft population. The major syndrome entities and their associated clinical features and molecular pathologies are summarized in Table 6.8.2. Robin sequence (micrognathia, U-​shaped CP, and glossoptosis) is an important subset of CP as syndrome diagnoses can be made in over half the cases. The primary defect in Robin

Table 6.8.2  Major syndromes associated with CL(P) and CP Cleft type

Syndrome

Inheritance

Genes

Clinical features

CL(P) and CP

Van der Woude

AD

IRF6

Bilateral severe cleft, lip pits

Popliteal pterygium

AD

IRF6

Large joint pterygia, syndactyly, lip pits, CL(P)

Ectrodactyly–​ectodermal dysplasia–​clefting (EEC)

AD

TP73

Split hand, split foot, ectodermal dysplasia, CL(P)

3MC

AR

MASP1 COLEC11

Intellectual disability, facial dysmorphism, micropenis, growth failure, hearing loss

Treacher Collins

AD

TCOF1

Lower lid coloboma, hypoplasia of the zygoma, microtia

Marshall–​Stickler

AD

COL2A1 COL11A1 COL11A2

Wide joints, myopia, deafness, Robin sequence or isolated cleft palate

SOX9-​associated CP

AD

SOX9

Robin sequence or isolated cleft palate, campomelic dysplasia

SATB2-​associated CP

AD

SATB2

Robin sequence or isolated cleft palate, long fingers, intellectual disability, dysmorphic facies

Velo-​cardio-​facial

AD Chromosomal

TBX1 22q11.2

Cardiac malformations, dysmorphic facies, long fingers, immunological problems

CL(P)

CP

AD, autosomal dominant; AR, autosomal recessive.

733

734

SECTION 6  Craniofacial and cleft

sequence is thought to be mandibular hypoplasia, with glossal obstruction of palate closure.

REFERENCES Almaidhan A, Cesario J, Landin Malt A, et al. Neural crest-​specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation. BMC Dev Biol 2014;14:3. Andersen H, Matthiessen M. Histochemistry of the early development of the human central face and nasal cavity with special reference to the movements and fusion of the palatine processes. Cells Tissues Organs 1967;68:473–​508. Bartelmez GW, Evans HM. Development of the Human Embryo During the Period of Somite Formation, Including Embryos with 2 to 16 Pairs of Somites. Washington, DC:  Carnegie Institution of Washington, 1926. Beaty TH, Murray JC, Marazita ML, et al. A genome-​wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet 2010;42:525–​9. Birnbaum S, Ludwig KU, Reutter H, et al. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nat Genet 2009;41:473–​7. Brewer C, Holloway S, Zawalnyski P, et al. A chromosomal deletion map of human malformations. Am J Hum Genet 1998;63:1153–​9. Cai J, Ash D, Kotch LE, et  al. Gene expression in pharyngeal arch 1 during human embryonic development. Hum Mol Genet 2005;14:903–​12. Canfield MA, Honein MA, Yuskiv N, et al. National estimates and race/​ ethnic-​specific variation of selected birth defects in the United States, 1999–​2001. Birth Defects Res A Clin Mol Teratol 2006;76:747–​56. Ching GH, Chung CS. A genetic study of cleft lip and palate in Hawaii. I. Interracial crosses. Am J Hum Genet 1974;26:162–​76. Drillien CM, Ingram TTS, Wilkinson EM. The Causes and Natural History of Cleft Lip and Palate. Edinburgh: E. & S. Livingstone, 1966. Farrall M, Holder S. Familial recurrence-​pattern analysis of cleft lip with or without cleft palate. Am J Hum Genet 1992;50:270–​7. Ferguson MW. The mechanism of palatal shelf elevation and the pathogenesis of cleft palate. Virchows Arch A  Pathol Anat Histol 1977;375:97–​113. Ferguson MW. Palate development: mechanisms and malformations. Ir J Med Sci 1987;156:309–​15. Ferguson MW. Palate development. Development 1988;103(Suppl.): 41–​60. Fitchett JE, Hay ED. Medial edge epithelium transforms to mesenchyme after embryonic palatal shelves fuse. Dev Biol 1989;131:455–​74. FitzPatrick D, Farrall M. An estimation of the number of susceptibility loci for isolated cleft palate. J Craniofac Genet Dev Biol 1993;13:230–​5. FitzPatrick DR, Raine PA, Boorman JG. Facial clefts in the west of Scotland in the period 1980–​1984: epidemiology and genetic diagnoses. J Med Genet 1994;31:126–​9. Fogh-​Andersen P. Inheritance of Harelip and Cleft Palate: Contribution to the Elucidation of the Etiology of the Congenital Clefts of the Face. Copenhagen: Nyt Nordisk forlag, A. Busck, 1942. Frazer JES, Baxter JS. Frazer’s Manual of Embryology: The Development of the Human Body. London: Bailliere, Tindall and Cox, 1953. Greene RM, Pratt RM. Developmental aspects of secondary palate formation. J Embryol Exp Morphol 1976;36:225–​45. Hay S, Wehrung DA. Congenital malformations in twins. Am J Hum Genet 1970;22:662–​78.

Hu D, Young NM, Li X, et al. A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face. Development 2015;142:567–​74. Hu L, Liu J, Li Z, et al. TGFβ3 regulates periderm removal through ΔNp63 in the developing palate. J Cell Physiol 2015;230:1212–​25. Huang X, Yokota T, Iwata J, et al. TGF-​beta-​mediated FASL-​Fas-​caspase pathway is crucial during palatogenesis. J Dent Res 2011;90:981–​7. Iwata J, Suzuki A, Yokota T, et  al. TGFbeta regulates epithelial-​ mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate. Development 2014;141:909–​17. Jin YR, Han XH, Taketo MM, et al. Wnt9b-​dependent FGF signaling is crucial for outgrowth of the nasal and maxillary processes during upper jaw and lip development. Development 2012;139:1821–​30. Lane J, Yumoto K, Azhar M, et al. Tak1, Smad4 and Trim33 redundantly mediate TGF-​beta3 signaling during palate development. Dev Biol 2015;398:231–​41. Lidral AC, Moreno LM, Bullard SA. Genetic factors and orofacial clefting. Semin Orthod 2008;14:103–​14. Liu X, Zhang H, Gao L, et al. Negative interplay of retinoic acid and TGF-​beta signaling mediated by TG-​interacting factor to modulate mouse embryonic palate mesenchymal-​cell proliferation. Birth Defects Res B Dev Reprod Toxicol 2014;101:403–​9. Ludwig KU, Mangold E, Herms S, et al. Genome-​wide meta-​analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nat Genet 2012;44:968–​71. Mangold E, Ludwig KU, Birnbaum S, et al. Genome-​wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate. Nat Genet 2010;42:24–​6. Niswander JD, MacLean CJ, Chung CS, et al. Sex ratio and cleft lip with or without cleft palate. Lancet 1972;2:858–​60. O’Rahilly R, Müller F. Developmental Stages in Human Embryos: Including a Revision of Streeter’s “Horizons” and a Survey of the Carnegie Collection. Washington, DC: Carnegie Institution of Washington, 1987. Rahimov F, Marazita ML, Visel A, et al. Disruption of an AP-​2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet 2008;40:1341–​7 Sakamoto MK, Nakamura K, Handa J, et al. Morphogenesis of the secondary palate in mouse embryos with special reference to the development of rugae. Anat Rec 1989;223:299–​310 Sandham A. Embryonic head posture and palatal shelf elevation. Early Hum Dev 1985a;11:69–​73. Sandham A. Embryonic facial vertical dimension and its relationship to palatal shelf elevation. Early Hum Dev 1985b;12:241–​5. Shah RM. Morphological, cellular, and biochemical aspects of differentiation of normal and teratogen-​treated palate in hamster and chick embryos. Curr Top Dev Biol 1984;19:103–​35. Shapiro BL. The genetics of cleft lip and palate. In: Stewart RE, Prescott GH (eds) Oral Facial Genetics, pp. 473–​99. St. Louis, MO:  CV Mosby, 1976. Sharpe PM, Ferguson MW. Mesenchymal influences on epithelial differentiation in developing systems. J Cell Sci Suppl 1988;10:195–​230. Shprintzen RJ, Siegel-​Sadewitz VL, Amato J, et al. Anomalies associated with cleft lip, cleft palate, or both. Am J Med Genet 1985;20:585–​95. Streeter GL. Description of age group XI. Contrib Embryol Carnegie Instn 1942;30:211–​45. Streeter GL. Descriptions of age group XIII, embryos 4 or 5 mm long, and age group XIV, period of indentation of the lens vesicle. Contrib Embryol Carnegie Inst 1945;31:27–​64. Streeter GL. Description of age groups XV, XVI, XVII and XVIII being the third issue of a survey of the Carnegie collection. Contrib Embryol 1948;32:133–​203.

6.8  Orofacial clefts: embryology, epidemiology, and genetics

Sulik KK, Schoenwolf GC. Highlights of craniofacial morphogenesis in mammalian embryos, as revealed by scanning electron microscopy. Scan Electron Microsc 1985:1735–​52. Vukojevic K, Kero D, Novakovic J, et al. Cell proliferation and apoptosis in the fusion of human primary and secondary palates. Eur J Oral Sci 2012;120:283–​91.

Warbrick JG. The early development of the nasal cavity and upper lip in the human embryo. J Anat 1960;94:351–​62. Woolf CM. Congenital cleft lip. A genetic study of 496 propositi. J Med Genet 1971;8:65–​83. Zimmerman EF, Wee EL. Role of neurotransmitters in palate development. Curr Top Dev Biol 1984;19:37–​63.

735

6.9

Classification, evaluation, and management of the neonate with a cleft David C.G. Sainsbury

Introduction This chapter considers the classification of clefts, the implications of antenatal diagnosis, and the evaluation and management of a neonate with a cleft. Airway management and feeding in such a newborn will be discussed. This chapter, which primarily deals with typical orofacial clefts (OFCs), uses the following abbreviations: cleft palate only, without cleft lip (CP); cleft lip only, without cleft palate (CL); cleft lip with or without cleft palate (CL(P)); cleft lip and cleft palate (CLP); submucous cleft palate (SMCP). Atypical OFCs, including Tessier oblique and midline clefts, are covered in Chapter 6.1.

completeness. One description of a Simonart’s band is a soft tissue bridge, without muscle, spanning the upper most aspect of the lip cleft, with a complete alveolar cleft. Atypical OFCs (Tessier 0–​4) may involve the lip and alar rim (Tessier 3), or extend cephalad beside the nose (Tessier 4).

Alveolus Alveolar anomalies range from dimples, to grooves, through to complete clefts with premaxillary displacement to the non-​cleft side in unilateral cases. Minor defects may resolve with growth. Regardless of the anomaly, there may be dental defects.

Palate

Classification of orofacial clefts Landmarks established during embryological development aid OFC classification. The primary palate, anterior to the incisive foramen, includes the lip, alveolus, and anterior hard palate. The secondary palate, posterior to the incisive foramen, includes the remaining hard and soft palate (see Chapter 6.8). Although every individual with an OFC is unique, a broad classification includes CL (21%), CP (33%), and CLP (46%). Subclassification is based upon laterality, completeness, and syndromal presence. Clefts may be left unilateral, right unilateral, or bilateral (typical ratio 6:3:1). Bilateral clefts may be symmetrical or asymmetrical.

Lip CL becomes more severe from anterior to posterior (i.e. from the vermilion margin cephalad towards the nose and posteriorly to the alveolus). Completeness is subdivided into microform (also known as forme fruste), incomplete, or complete (Fig. 6.9.1). Microform lip features include mucosal indentation, vermilion notching, white roll disruption, philtral skin furrowing, nasal sill flattening, and alar displacement and involve under a quarter of lip height (Yuzuriha and Mulliken, 2008). Complete CL involves the entire lip, from the vermilion border to the nasal floor. Incomplete CL (with an intact nasal sill) lies between the microform and complete phenotypes. A  Simonart’s band, arising in 30%, may complicate establishing

Palatal clefts generally become more severe from posterior to anterior, that is, from the uvula towards the anterior hard palate (Hodgkinson et  al., 2005). The exception is a congenital fistula, appearing as a palatal hole, presumed to be due to embryological disruption. The spectrum ranges from occult and overt SMCP, incomplete soft palatal cleft, incomplete secondary palatal cleft, complete secondary palatal cleft, through to bilateral CP. Veau (1931) provided a simple and practical classification (Table 6.9.1). Randall and colleagues (2000) classified palatal length (Table 6.9.2). Hard palate appearance determines laterality. In the unilateral phenotype, the cleft involves one side of the midline, exposing one side of the vomer, while the other palatal shelf is joined to the nasal septum. In a bilateral cleft, neither palatal shelf has fused with the nasal septum, yielding a wider central defect with the vomer visible on both sides and suspended superiorly. Uvula clefting is observed in 2% of children, although only 0.3% have a completely bifid uvula. If a bifid uvula is potentially contributing to a speech disorder then prompt referral to a specialist cleft centre is required (Swan et  al., 2015). The absence of bifid uvula does not exclude SMCP. In SMCP there is velar musculature diastasis, but unlike CP, the palatal mucosa is intact (Fig. 6.9.1b) (Val Aalst et al., 2008). SMCP can be a challenging diagnosis and may remain undetected until the child is sufficiently mature to develop hypernasal speech exposing the underlying velopharyngeal insufficiency.

738

SECTION 6  Craniofacial and cleft

Primary palatal clefts

a

b

c

a

d

b

e

c

f

g

d

e

Secondary palatal clefts

a

b

c

e

d

Combined palatal clefts Unilateral

a

b

c

d

Bilateral

a

b

c

d

e

Fig. 6.9.1  (a) Range of severity of primary palatal clefts (anterior to the incisive foramen). (b) Range of severity of secondary palate clefts (posterior to the incisive foramen). (c) Range of severity of combined palatal clefts. Reproduced with permission from Samuel Berkowitz, Cleft Lip and Palate. Diagnosis and Management, Second Edition, Springer Nature, Copyright © 2005.

Table 6.9.1  Veau classification of cleft palate Grade

Cleft extent

I

Soft palate

II

Soft and hard palate

III

Soft and hard palate, unilateral CLP

IV

Soft and hard palate, bilateral CLP

Reproduced with permission from Victor Veau, Chirurgien de l’Hǒpital des Enfants assistés, with the collaboration of Mme. S. Borel, Paris: Masson et Cie. Fr. 140, Copyright © 1931.

Table 6.9.2  Randall classification of velar length Grade

Description

I

Normal (uvula below adenoids)

II

Uvula at posterior half of adenoids

III

Uvula at anterior half of adenoids

IV

Uvula anterior to adenoids

Reproduced with permission from Randall P, LaRossa D, McWilliams BJ et al., Palatal length in cleft palate as a predictor of speech outcome, Plastic and Reconstructive Surgery, Volume 106, Issue 6, pp.1254–​1259, Copyright © 2000 Wolters Kluwer Health, Inc.

6.9  Classification, evaluation, and management of the neonate with a cleft

Right

Left

1 1 2 3 4 5 6 7 8 9

Right lip Right alveolus Right hard palate anterior to incisive foramen Left lip Left alveolus Left hard palate anterior to incisive foramen Anterior hard palate Posterior hard palate Soft palate

4 5

2 3

6 7 8 9

Each anatomical unit is allocated a box on the Y; stippling of the box indicates a cleft in that area, cross-hatching indicates a submucous cleft. The circle between boxes 3, 6 and 7 represents the incisive foramen.

Fig. 6.9.2  Kernahan’s striped Y. Reproduced with permission from Desmond Kernahan, The striped Y—​a symbolic classification for cleft lip and palate, Plastic and Reconstructive Surgery, Volume 47, Issue 5, pp. 469–​470, Copyright © 1971 Wolters Kluwer Health, Inc.

Kernahan’s striped Y diagrammatically analogizes CLP to the letter Y (Fig. 6.9.2). The palindromic LAHSHAL acronym (Fig. 6.9.3), adapted by the Royal College of Surgeons by removing one ‘H’, has produced a common, simplified system. This is generally suitable, although the modified version cannot document bilateral hard palate clefts.

Antenatal diagnosis Antenatal OFC diagnosis, especially CL, is increasingly common. Loozen and colleagues (2015) from Utrecht, the Netherlands, found 76.9% concordance of prenatal cleft diagnosis from transabdominal ultrasound scanning with subsequent postnatal findings. CP was frequently missed; consequently, cleft underestimation occurred in 19.4%. In 3.7%, the extent was overestimated. No mistakes were Right

Left

L

L

Lip

Lip

A

A

Alveolus

Alveolus

H

Hard Palate

S

Soft Palate

The mouth is conceptualised as six units (right lip, right alveolus, hard palate, soft palate, left alveolus and left lip). The code is transcribed as if looking at the patient. Capital letters denote complete clefts, lowercase letters denote incomplete clefts; a dot denotes no cleft. An incomplete cleft of the secondary palate is ..hS..; a complete left CL and incomplete left alveolar cleft would be ....aL

made in differentiating bilateral from unilateral clefts. Visualizing CP ultrasonically is difficult but may be inferred from CL width. Following antenatal diagnosis, parents are often understandably shocked. Mothers, in particular, often encounter emotions otherwise experienced at birth—​guilt, anxiety, shock, anger, denial, and loss of control. Telephone contact with the cleft team should be made before the parents leave the scanning department or within 24 hours. Thereby an appointment with a cleft specialist nurse (CSN) can be made to counsel, support, and impart expert and appropriate information regarding facial appearance or other fears. Parents receiving late information may consult the Internet; incorrect web-​ based information may exacerbate parental anxiety (Hodgkinson et al., 2005). The CSN plays an important role in allowing parents to understand and manage feelings without the challenges of caring for a newborn baby. Images of children with similar visible facial differences, before and after surgical correction, are helpful, placing the cleft into context. A study in the United Kingdom found 85% of parents felt antenatal diagnosis facilitated psychological preparation, 89% were glad they knew the diagnosis prior to birth, and 92% never contemplated pregnancy termination (Davalbhakta and Hall, 2000). Accurately ascertaining the nature of the cleft with further gestational scans, including three-​dimensional imaging, assists the family in visualizing their child, informs about probable timing and nature of surgery, and helps with feeding considerations. The CSN can construct a postnatal management plan prior to the birth by liaising with the community midwife, health visitor, and other healthcare professionals. Further parental support may be gained from the cleft team in the specialist clinic, parental support groups including CLAPA (Cleft Lip and Palate Association; a United Kingdom-​wide voluntary organization helping those with CL(P)), or local groups and mentor families.

Evaluation and management of the neonate with a cleft A neonate with an OFC requires evaluation and management from a dedicated multidisciplinary team. Assessment evaluates any anomalies, provides a baseline for ongoing assessments, and may institute specialist referral. A syndrome, of which over 400 are listed, is identified in 21–​37% of patients. Comorbidities include cardiovascular (24–​51%), musculoskeletal, facial dysmorphia, or genitourinary anomalies (Hodgkinson et  al., 2005). Children with CP are more likely to have associated syndromes, rather than CL(P) and are often of a lower birth weight. Often the first time the primary surgeon within the cleft team sees the neonate is the first out-​patient clinic appointment at 4–​6 weeks of age. The baby and parents will probably have been seen by the CSN and paediatric teams on a number of occasions before then. If the situation allows, a history and examination is performed. The surgeon or other cleft team members may see the infant earlier, including in the early postnatal period. Regardless, problems regarding the airway, breathing, and circulation take priority.

Fig. 6.9.3  The LAHSAL system.

History

Kriens O. (1989). LAHSHAL: a concise documentation system for cleft lip, alveolus, and palate diagnoses, in What is a Cleft Lip and Palate?: A Multidisciplinary Update, ed Kriens O., editor. (New York, NY: Thieme Medical Publishers), 30–​34.

Often this information has already been collected by the CSN but it is worth confirming with the family.

739

740

SECTION 6  Craniofacial and cleft

Demographics and diagnosis Following introductions, record the parent’s names, the baby’s age and sex, current cleft diagnosis in words, and LAHSAL code. It should be noted whether an antenatal diagnosis was made. Pregnancy, birth, and postnatal period The gestation duration, any issues during the pregnancy for mother or baby, along with the birthing history should be determined. If the baby was induced or delivered by Caesarean section, the indication for this should be noted. The postnatal history should be obtained; was there admission to the special care baby unit and how long was the hospital stay? Were any problems identified on the baby check (especially cardiac and hearing)? Are the family coping and is there evidence of postnatal depression? Airway Does the baby make any loud noises while asleep, is there any snoring or apnoeas? If there are apnoeas, how often do they occur and how long do they last? Is there any associated pallor or cyanosis? Feeding What was the baby’s birth weight and what is it now? The Personal Child Health Record (the Red Book in the United Kingdom) allows identification of which centile the baby is on using the standard weight curves. Ask about the means of feeding and whether there are any associated problems (prolonged feeding, small volumes, choking, nasal regurgitation, or reflux). Other areas Enquire about medications and allergies. Ask about the presence of a family history of clefting and other medical problems. A family tree may be helpful. Often families have gone through an emotional and demanding time. It is worth congratulating the family on how well they have done. This fosters rapport with the parents, invaluable for establishing trust in a probable long-​term relationship with the cleft team.

Examination Determine alertness, hydration, and nutritional status. Assess for any facial dysmorphia (ocular dystopia, hypertelorism, nasal or oral anomalies, any asymmetry or abnormal movement) or craniofacial abnormality (head size, shape, and symmetry). In particular assess the mandible for micrognathia and retrognathia. Either look at the Personal Child Health Record to see where the head circumference lies on the standard growth curve or measure and do the same. A CL might be immediately obvious but microform variants can be subtle

(furrow or scar traversing the lip, cutaneous roll imperfections, slight vertical lip shortness). Note laterality, completeness (height of lip involved, e.g. two-​thirds of lip height), cant of the Cupid’s bow, lateral lip element vertical height, presence of a Simonart’s band, and any associated nasal deformity (Table 6.9.3). Observe lip and facial movement to assess facial nerve integrity and assess any abnormal attachments of orbicularis oris. Look for lower lip pits (associated with van der Woude syndrome, popliteal pterygium syndrome, oral–​ facial–​ digital syndrome, and ankyloblepharon filiforme adnatum). Ear abnormalities (overfolded or squared-​ off helices; cupped, microtic, and prominent ears; preauricular pits or tags; and narrow external auditory meati) may be suggestive of 22q11 deletion, Treacher Collins syndrome, or Goldenhar syndrome (McDonald-​McGinn et al., 2013). Distinction must be made between a true median CL with a midline, inverted V-​shaped notch and a wide cleft with a flat nose and absent columella caused by premaxillary agenesis. A true median or midline cleft, is rare, usually affecting just the vermilion border but the alveolus may be involved. It is often associated with syndromes, including Ellis–​van Creveld syndrome and oral–​facial–​digital spectrum. Conversely, the wide midline CL and midline alveolar ridge due to premaxillary agenesis is characteristic of the holoprosencephaly spectrum of cerebral anomalies, which is associated with significant developmental delay and premature mortality requiring early specialist genetic assessment to aid care and counselling. Oral examination requires direct visual inspection of the palate (Royal College of Paediatrics and Child Health 2014; Butterworth et al., 2017). One way of achieving a safe and reasonable view is to sit opposite a parent with your knees held together and touching the parent’s knees. Ask the parent to hold the baby with the baby facing them; lower the baby so that their head is resting on your knees. You may require the parent or an assistant to gently hold the baby’s arms. Assess tongue size and position. Use a torch and a tongue depressor to gently push the tongue to the floor of the mouth to gain a good view. Stabilize the child’s head with gentle pressure from your thenar eminences on the child’s cheeks. Look for the presence of CP (completeness, width, shape, laterality). A bifid uvula or zona pellucida (pale-​bluish area in the soft palate midline due to velar muscular diastasis) suggests SMCP (see Fig. 6.13.1). Look for an alveolar cleft or groove, assessing alveolar cleft width and any collapse (palatal displacement of the lateral maxillary segment) and neonatal teeth. The CL width and extent of alveolar arch collapse influences surgical planning and correlates with the challenge and tension of lip and nose repair and the extent of nasal deformity (Hopper et al., 2007). In a bilateral CL, the protrusion and rotation of the premaxilla should be assessed. Insert a gloved finger into the mouth and palpate for a posterior hard palate notch; assess the gag reflex and sucking ability.

Table 6.9.3  Degrees of nasal deformity

a

Mild

Moderate

Severe

Alar base displacement

Lateral

Lateral and posterior

Lateral and posterior

Alar rim contour

Normal

+/​− Recurvatum deformity

Recurvatum deformity

Columella shortening

Minimal

Moderate

Severe

Dome projection

Normal

Depressed

Underprojecteda

Complete lower lateral cartilage collapse. Reproduced with permission from Hopper RA, Cutting CB, Grayson BH, Grabb and Smith’s Plastic Surgery, Sixth Edition, Wolters Kluwer Health, Philadelphia, Copyright © 2006.

6.9  Classification, evaluation, and management of the neonate with a cleft

Complete a systematic head-​to-​toe examination including an examination of the hands and feet, assessment of respiratory effort, and cardiovascular system; a paediatrician may fulfil this role. Major anomalies may have already been detected during the antenatal ultrasound scans or during the baby check. Referral to a geneticist should be considered in children with a cleft and other malformations.

Robin sequence Particular attention should be paid to identifying Robin sequence (RS) (Fig. 6.9.4), defined at the first Consensus meeting (Latter and Thomas, 2014) as subjective assessment of micrognathia, subjective assessment of glossoptosis (retroplaced and retroverted tongue), and total or partial upper airway obstruction which may be associated with feeding problems and, in up to 90% of children, CP (classically wide and U-​shaped but may be V-​shaped) (Evans et al., 2011). A suspected diagnosis of RS should prompt immediate referral to the regional cleft team so that the CSN can conduct an expeditious assessment. Neonates with RS are at risk of upper airway obstruction and feeding difficulties. Both are interlinked with the severity varying between infants. Airway obstruction is believed to be a result of the tongue falling posteriorly into the hypopharynx, thus occluding the airway at the epiglottis. The tongue often lies between the palatal shelves with the uvula lying either side. Tongue retraction may be aggravated when the neonate is distressed. The airway obstruction is usually not life-​threatening, although is occasionally.

(a)

The tongue’s position and CP may lead to poor sucking and swallowing resulting in decreased food intake, prolonged oral feeding (>30 minutes), fatigue, choking, vomiting, or regurgitation. With respiratory obstruction the majority of the neonate’s energy may be spent breathing. In conjunction with the feeding problems this could result in failure to thrive (FTT) and protein-​calorie malnutrition. By about 6 months, most infants outgrow these difficulties due to maturation of neuromuscular tongue control and mandibular growth. Fifty per cent of babies with RS have an associated syndrome such as Stickler syndrome (type 2 collagen abnormality with myopia, retinal detachment, and glaucoma) or 22q11 deletion syndrome. All children with RS should be referred to an ophthalmologist (to assess retinal status). Genetic analysis (karyotype, fluorescent in situ hybridization, or comparative genomic hybridization test for 22q11) should be considered.

Airway, breathing, and circulation The airway is the first concern in a neonate with a cleft. Infants with RS, in particular, require close observation. To facilitate airway management, respiratory effort and effectiveness should be assessed during sleep and wakefulness and in a variety of positions (Box 6.9.1). These babies often need more sleep. All babies with RS should be assessed for a sleep-​related breathing disorder with at least continuous oxygen saturation monitoring and preferably

(b)

Fig. 6.9.4  Baby with Robin sequence (note the micrognathia, nasopharyngeal airway, and nasogastric tube). © Newcastle Upon Tyne Hospitals NHS Foundation Trust.

741

742

SECTION 6  Craniofacial and cleft

Box 6.9.1  Assessment of respiratory status • Presence of tracheal tug. • Presence of audible stertor. • Presence of sternal or intercostal recession. • Presence of abnormal oxygen or carbon dioxide saturation levels. • Tongue position. • Tachycardia. • Presence of neck extension.

carbon dioxide monitoring (Royal College of Paediatrics and Child Health, 2009). This should be performed within the first month of life and repeated at 3–​6 months of age unless there are signs of upper airway obstruction which mandates prompt assessment. There may be airway deterioration at 4–​8 weeks. The reasons for this are unclear but maybe due to anatomical changes with growth, FTT, and increased energy expenditure from increasing alertness and activity. Wilson and colleagues (2000) found that out of ten infants with upper airway obstruction, only two presented with symptoms on day 1. Seven were felt not to have upper airway obstruction in

the neonatal period, but developed signs between 24 and 51 days (mean 36.6 days). A key message is that FTT in infants with Robin sequence should be attributed to airway obstruction unless proven otherwise. There is an increasing awareness of the deleterious effect of chronic, even subclinical, hypoxia on neonatal brain development (Bass et al., 2004). Initial airway management involves lateral or prone positioning allowing the mandible and tongue to fall anteriorly, thus minimizing tongue-​base airway obstruction. Positioning alone is successful in over half of infants with RS (Evans et al., 2011). See Fig. 6.9.5. A nasopharyngeal airway (NPA) is usually the next step in airway management. Box 6.9.2 highlights the factors indicating whether a NPA is the treatment of choice. Parents can be safely taught to insert and manage a NPA at home. If these infants cannot be managed with a NPA then nasal continuous positive airway pressure or bi-​level positive airway pressure may be indicated. Should this fail then tracheostomy may be considered. Tracheostomy should not be undertaken lightly; it requires 24-​hour care for suctioning (placing considerable strain upon relationships), prevents swimming, and is associated with significant morbidity and possibly death (Bath and

Initial meeting with parents Verbal and written information provided

PRIMARY ASSESSMENT

• • • • • • •

Airway Breathing Circulation Disability Exposure Feeding Growth

ALL INFANTS

• •

Minimal handling NG feed only for the initial 48 hours

AGREE PLANS FOR Can the infant be nursed without an airway?

NO

YES

AGREE PLANS FOR

• • • • • • • •

Feeding Posture and sleep Contact Liaison Resuscitation Further assessment Professional liaison Family liaison

Fig. 6.9.5  Overview of care plan for a baby with Robin sequence. Adapted from Latter and Thomas, Trent Regional Cleft Lip and Palate Network Guidelines 2014.

• • • • • • •

Airway adjunct Feeding Posture and sleep Contact Liaison Resuscitation Further assessment

• •

Professional liaison Family liaison

6.9  Classification, evaluation, and management of the neonate with a cleft

Bull, 1997; Kremer et al., 2002). Some units perform neonatal mandibular distraction or tongue lip adhesion (Viezel-Mathieu et al., 2016; Hsieh and Woo, 2019).

the initial 48 hours postpartum, receive only essential care, and be fed exclusively nasogastrically. A gag reflex must be present before commencing oral feeds. Parents should participate early in nasogastric feeding to enable competent feeding and tube insertion which may be continued on discharge. High-​calorie feeds may be required. Reflux is also a feature of RS, particularly during nasogastric feeding. Antireflux medication and raising the baby’s head during a feed may help. On discharge, the CSN will closely observe the baby and family to reassess the airway and feeding skills (including planned removal of the nasogastric tube when safe and appropriate). Weight gain, the best indicator of airway adequacy, is closely monitored (Anderson et al., 2007).

Feeding

Hearing assessment

An inadequate airway heightens the aspiration risk during oral feeding. Only following a full assessment by the CSN and respiratory status stabilization can attention be turned to nutrition. The feeding assessment should be performed within the first 24 hours of diagnosis, preferably within the first day of life (Clinical Standards Advisory Group, 1998). For effective feeding, the soft palate must elevate and occlude the nasopharynx from the oropharynx, and the lips form a competent seal around the nipple or teat. Functional tongue movement is important; compressing the teat against the oral roof in bottle feeding or rippling along the breast base aiding milk expression during breastfeeding. The completeness of the cleft usually correlates with feeding ability. With only soft palate involvement there is often normal sucking although support with assisted feeding is often required. Neonates with CLP, with oronasal communication, usually struggle to generate sufficient negative intraoral pressure for effective milk expression from breast or bottle. A CL hinders the seal the lips should make around the teat or nipple, mitigating the stabilization the lips can offer and making it harder to maintain appropriate teat or nipple orientation. Neonates with incomplete or microform CL normally feed without any problems. Prolonged feeding times due to impaired sucking and inadequate nutritional intake (more energy is expended than ingested) is common, leading to weight loss and FTT. Indeed, babies with a late CP diagnosis often present with FTT (Hodgkinson et al., 2005; Butterworth et al., 2017). A feeding assessment by the CSN should be carried out prior to the introduction of assisted feeding. Successful feeding should be relaxed and positive; infants experiencing traumatic feeds may develop feeding aversion. Parental preference and medical problems should be considered to enable adoption of a suitable and safe feeding method. For a baby with an incomplete CL, all feedings options are available. In a baby with an isolated CP or CLP, it will be difficult for a baby to exclusively breast feed. Therefore support will be given from the CSN to allow the mother’s expressed breast milk to be given via an assisted feeding bottle. This is a soft bottle which parents are taught to squeeze whilst babies are sucking. Alternatively, the Dr Brown’s specialty feeding bottles may be used. These are fully vented to create a positive-pressure flow for vacuum free feeding. A breast pump can be provided to parents to aid this process. Alternatively, formula milk can be used. For a baby with a microform or incomplete CL, all feeding options are likely to be available. Babies with RS are often more challenging to feed. They easily fatigue, and when tired are unable to hold the tongue forwards, causing breathing difficulties. Babies with RS should be rested for

The abnormal insertion of the tensor and levator veli palatini is believed to contribute to serous otitis media (glue ear) (van Aalst et al., 2008). The multiple syndromes associated with OFCs, including Stickler and van der Woude syndromes, may cause sensorineural hearing loss. Hearing assessment by automated otoacoustic emission or automated auditory brainstem response should be conducted at birth and throughout childhood as required.

Box 6.9.2  Potential benefits of a nasopharyngeal airway • Reduces the need for surgical intervention. • Relieves airway obstruction. • Enables oral feeding. • Prevents faltering growth. • Improves bonding by facilitating normal handling and positioning.

Conclusion Numerous classifications, including LAHSAL and Kernahan’s striped Y, aid organizing the heterogeneous nature of OFCs. Antenatal diagnosis occurs in approximately 80% of births and is more accurate for diagnosing CL than CP. Most parents find antenatal diagnosis beneficial for psychological adjustment and planning prior to the birth. Airway assessment is vital in neonates with a cleft. Most, even those with severe RS, can be managed non-​ surgically with lateral or prone positioning, a NPA and supplemental oxygen. Sleep studies are an important means of assessing the airway. Feeding is a major concern in babies with a cleft; early feeding intervention and parental education is important. The CSN plays a key role in allaying parental anxiety and providing accurate information and practical advice particularly around airway management and feeding. Other conditions, including RS, 22q11 deletion syndrome, Stickler syndrome, and van der Woude syndrome, must be identified early in conjunction with the cleft multidisciplinary team. Genetic analysis, opthalmological assessment and psychological support should be considered.

REFERENCES Anderson K, Cole A, Chuo C, et  al. Home management of upper airway obstruction in Pierre Robin sequence using a nasopharyngeal airway. Cleft Palate Craniofac J 2007;44;269–​72. Bass JL, Corwin M, Gozal D, et al. The effect of chronic or intermittent hypoxia on cognition in childhood: a review of the evidence. Pediatrics 2004;114:805–​16. Butterworth S, Sainsbury D, Hodgkinson P. Faltering growth in children: improving early detection of cleft palate. BMJ 2017;359:j5082. Bath AP, Bull PD. Management of upper airway obstruction in Pierre Robin sequence. J Laryngol Otol 1997;111:1155–​7. Clinical Standards Advisory Group (CSAG). Cleft Lip and/​ or Palate:  Report of a CSAG Committee. London:  The Stationery Office, 1998.

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Davalbhakta A, Hall PN. The impact of antenatal diagnosis on the effectiveness and timing of counselling for cleft lip and palate. Br J Plast Surg 2000;53:298–​301. Evans KN, Sie KC, Hopper RA, et  al. Robin sequence:  from diagnosis to development of an effective management plan. Pediatrics 2011;127;936–​48. Hodgkinson PD, Brown S, Duncan D, et al. Management of children with cleft lip and palate. Fetal Matern Med Rev 2005;16:1–​27. Hopper RA, Cutting CB, Grayson BH. Cleft lip and palate. In: Thorne CH (ed) Grabb and Smith’s Plastic Surgery, 6th ed, pp. 201–​25. Philadelphia, PA:  Wolters Kluwer Health/​Lippincott Williams & Wilkins, 2006. Hsieh ST, Woo AS. Pierre Robin Sequence. Clin Plast Surg. 2019;46: 249–59. Kremer B, Botos-​Kremer AI, Eckel HE, et al. Indications, complications and surgical techniques for pediatric tracheostomies: an update. J Pediatr Surg 2002;37:1556–​62. Latter K, Thomas D. Guidelines for the treatment and management of infants with Pierre Robin Sequence. Presented at Trent Regional Cleft Lip and Palate Network, Nottingham, United Kingdom, December 2014. Loozen CS, Maarse W, Manten GT, et  al. The accuracy of prenatal ultrasound in determining the type of orofacial cleft. Prenat Diagn 2015;35:652–​5. McDonald-​McGinn DM, Emanuel BS, Zackai EH. 22q11.2 deletion syndrome. GeneReviews® http://​www.ncbi.nlm.nih.gov/​books/​ NBK1523

Randall P, LaRossa D, McWilliams BJ, et  al. Palatal length in cleft palate as a predictor of speech outcome. Plast Reconstr Surg 2000;106:1254–​9. Royal College of Paediatrics and Child Health. Working Party on Sleep Physiology and Respiratory Control Disorders in Children. London: Royal College of Paediatrics and Child Health, 2009. Royal College of Paediatrics and Child Health. Palate examination: identification of cleft palate in the newborn—best practice guide, 2014. Accessed at: www.rcpch.ac.uk/resources/palate-examinationidentification-cleft-palate-newborn-best-practice-guide Swan MC, Luscombe C, Goodacre TEE. A plea to exclude the bifid uvula in the child with speech impairment. BMJ 2015;350; h2318. Van Aalst JA, Kolappa KK, Sadove M. Nonsyndromic cleft palate. Plast Reconstr Surg 2008;121:1–​14. Veau V. Chirurgien de l’Hǒpital des Enfants assistés, with the collaboration of Mme. S. Borel. Paris: Masson et Cie, 1931. Viezel-Mathieu A, Safran T, Gilardino MS. A Systematic Review of the Effectiveness of Tongue Lip Adhesion in Improving Airway Obstruction in Children With Pierre Robin Sequence. J Craniofac Surg 2016;27:1453–56. Wilson AC, Moore DJ, Moore MH, et al. Late presentation of upper airway obstruction in Pierre Robin sequence. Arch Dis Child 2010;83:435–​8. Yuzuriha S, Mulliken JB. Minor-​ form, microform, and mini-​ microform cleft lip: anatomical features, operative techniques, and revisions. Plast Reconstr Surg 2008;122:1485–​93.

6.10

Primary management of cleft lip and palate Jason Neil-​Dwyer

Introduction Cleft lip and palate is a condition with the potential to impact the lifetime of a patient, affecting overall health, appearance, communication, facial growth, hearing, eating, dental health, and psychological well-​being. To effectively manage these multiple effects, the treatment of cleft lip and/​or palate requires involvement of multiple healthcare specialists. This multidisciplinary management is difficult to coordinate so is often delivered by extended multidisciplinary healthcare teams. The early management of a child with a cleft lip and/​or palate centres on the well-​being of the child. The focus is on feeding, breathing, and managing medical comorbidities. Care can require extensive input from paediatric medical specialists, and needs to occur prior to any surgical management of the cleft lip or palate. This chapter will discuss the surgical and perisurgical management of the primary cleft lip and/​or palate including manipulation of the cleft lip prior to definitive surgery, primary lip surgery, primary palate surgery, and primary closure of the alveolar cleft with an assumption of medical well-​being.

Primary management of the cleft lip Cleft lip is a predominantly aesthetic issue; it does not impair physiological health. In its unrepaired state, it has a significant functional effect precluding normal psychosocial interaction in society, so that repair is a norm in all but very isolated geographic populations. Many different protocols and techniques exist for cleft lip management as the optimal treatment is not yet agreed.

Manipulation of cleft lip prior to definitive surgery In the untreated patient with a complete cleft lip, the most obvious feature is the distance between the segments of the lip involved in the cleft, and the resultant deformity of the nose. How to make the segments meet is one of the primary challenges of surgery. The degree of surgical manipulation of tissues to close a cleft increases with width;

there is concern over the impact of this on long-​term growth of the maxilla and face. Various non-​surgical and surgical techniques have been developed to narrow the cleft prior to surgery, taking advantage of the potential to mould the facial skeleton in infancy, thus reducing the dissection in subsequent primary lip repair. Non-​surgical Taping The simplest manipulation of the cleft has been to apply tension across the cleft using some form of taping of the soft tissues on either side of the cleft (Brown, 1905). This varies from single strips of tape to specially produced elasticated tapes or arrangements of elasticated bands secured with tape. Taping has the advantages of being easy to manage by parents and of low cost. The disadvantage is that taping collapses the maxillary components of the cleft in an uncontrolled fashion, resulting in unfavourable alveolar arch positions. Presurgical orthopaedics To address the shortcomings of taping, additional techniques have developed to control the bony segment positions during narrowing of the cleft (McNeil, 1950). The combination of narrowing the cleft with bony segment control is known as presurgical orthopaedics. Passive presurgical orthopaedics uses adjunctive taping to narrow the cleft, while active presurgical orthopaedics applies forces directly to the bony segments of the cleft maxilla with no taping (Winters and Hurwitz, 1995). These techniques require a custom-​fitted oral plate to guide the bony segments. The plate must lie snugly on the alveolar segments of the cleft, so one of the primary challenges in presurgical orthopaedics is to take an oral mould of the alveolar segments in a neonate with a cleft as the successful moulding must be started early. Taking a mould in a neonate has a risk of the moulding material becoming free in the airway with ensuing complications so requires experience and suitable facilities. Any plates require frequent modification due to the child growing and the segments moving so these techniques can have a significant clinical burden in the first 3–​4 months of a child’s life involving up to weekly visits.

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SECTION 6  Craniofacial and cleft Passive presurgical orthopaedics Passive presurgical orthopaedics involves a simple moulded oral plate combined with some form of taping. The plate is gradually adjusted to guide the alveolar segments into the desired position as the cleft is narrowed by the taping. Studies have failed to demonstrate an advantage to this compared to no passive presurgical orthopaedics for multiple outcomes including facial growth and appearance (Bongaarts et al., 2009). Active presurgical orthopaedics  Active presurgical orthopaedics involves a moulded plate that is pinned into the two segments of the maxilla either side of the cleft. The plate is in two segments which are gradually brought together into the desired position by turning a screw mechanism that the parents activate daily; this narrows the cleft and aligns the alveolar arches without a need for taping. The most well-​known version of this is the Latham device, which is predominantly used by some cleft centre treatment protocols in the United States (Latham et  al., 1976). Studies have questioned whether the active presurgical orthopaedics protocols result in an unfavourable alveolar arch position in the longer term (Matic and Power, 2008). Nasoalveolar moulding (NAM) Following the previously mentioned studies suggesting presurgical orthopaedics has no significant effect on outcomes, many teams have adopted NAM as a method to manipulate the cleft lip and nose prior to surgery (Grayson et al., 1993). A criticism of the lack of effect on appearance of the presurgical orthopaedic techniques was that they did not help with nasal appearance which was a significant contributor to appearance and not optimally corrected for surgery. NAM takes a passive presurgical orthopaedic set-​up of a passive oral plate and facial soft tissue taping adding a small moulding prong to the front of the plate that can be adjusted to push the nose into a better shape as the cleft closes. NAM has been widely adopted internationally, there are some early observational studies showing a benefit in bilateral cleft lip for columella length (Lee et al., 2008), but many teams are awaiting clear evidence of benefit given the studies on passive NAM. Some case-​control studies show no difference for facial growth in unilateral cleft lip with or without NAM (Peanchitlertkajorn et al., 2018).

Surgical Lip adhesion A lip adhesion is where a little dissection of the lip is done at a first early procedure, and the edges of the cleft are just incised and joined with no attention to normalizing the appearance (Randall, 1965). The principle is that this then applies a narrowing force to the cleft, and when the segments have narrowed, a definitive cosmetic surgical repair of the lip can be done. This scheme can be considered akin to biological taping. The advantage over taping is that it is not dependent on parental capacity. The disadvantages are that it requires an anaesthetic and that the segments are uncontrolled. There are not currently any comparative studies for lip adhesions outcomes with any other modality. It is still practised around the world.

Cleft lip repair A cleft lip repair aims to address the appearance effects of a cleft lip. To understand cleft lip surgery, it is helpful to understand the normal anatomy of the lip and the cleft lip deformity. Anatomy of a lip The normal lip is composed of several clearly identified anatomical areas. It is a muscular structure overlaid with a layer of subcutaneous tissues, skin, and mucosa. The muscle, orbicularis oris, gives the lip its gross shape. It is described in two parts: pars marginalis in the vermillion and pars peripheralis in the rest of the lip (Fig. 6.10.1). The pars peripheralis has some fibres crossing the midline to insert into the dermis on the opposite side. This is the architectural basis for the philtral ridges (Nicolau, 1983). The philtral dimple reflects absence of this dermal insertion. The combined superficial reticular extensions of the levator labii superioris, zygomaticus minor, and zygomaticus major insert into the medial philtrum ridge with the pars peripheralis. This creates a slight upwards pull forming the Cupid’s bow shape. The pars marginalis is a continuous band across the lip, curling upward at the anterior part of the muscle, in the shape of a hook, forming the white roll. This muscular anatomy defines the upper lip aesthetics (Fig. 6.10.2) with a philtrum and two triangles of lateral skin, a white roll defining

Pars peripheralis of orbicularis oris Inserting into ipsilateral philtral column Pars peripheralis of orbicularis oris Inserting into contralateral philtral column Pars marginalis of orbicularis oris

Fig. 6.10.1  The anatomy of orbicularis oris muscle. Illustrating the two different insertions of the pars peripheralis into the dermis of the philtral the ipsilateral and contralateral philtral columns that creates the philtral dimple.

6.10  Primary management of cleft lip and palate

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4

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Philtrum Upper nasolabial skin Nasal footplates and columella Alar base Nostril sill White roll Lateral lip dry vermillion Philtral dry vermillion Peak cupids bow (corresponds to Noordhoff's point in cleft lip repair)

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1. 2. 3. 4. 5. 6. 7. 8.

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Fig. 6.10.2  The aesthetic subunits of the nasolabial area.

the border between skin and vermillion, and a vermillion based on two lateral triangular segments building to a Cupid’s bow peak. Medial to this, the height of the vermillion reduces slightly until the midline.

is greater in complete clefts as lateral and medial bony segments also move. These anatomical abnormalities cause the characteristic deformity of cleft lip:

Cleft lip deformity

• Progressive reduction in lip height on the cleft side of the midline and medial to Noordhoff ’s point, creating a notch in incomplete cleft lips and lip height shortening into the cleft in complete cleft lips. • Progressive reduction in dry vermillion height on the cleft side of the midline and medial to Noordhoff ’s point adding to the above-​ mentioned effect. • Deviation of the nasal tip over to the non-​cleft side. • Depression of the cleft alar cartilage dome. • An open angle between the medial and lateral crura of the lower lateral cartilage on the cleft side that increases with the degree of clefting. • Retroplacement of the maxilla on the cleft side. • Shorter columella on the cleft side so the columella is slanted toward the non-​cleft side. • Inferior displacement of the medial crus within the columella. • Dislocation of the caudal septum to the non-​cleft side of the nasal spine. • Inferior rotation of the alar cartilage on the cleft side.

The cleft lip as is a not just a gap in the tissues, but the tissues have malformed and subsequently been subject to deformational forces from the malformed muscles (Fig. 6.10.3). The tissues on the non-​cleft side have a normal orbicularis muscle until the midline. Beyond this the muscle diverts superiorly towards the columella, inserting into the periosteum of the premaxilla and caudal septum. In the lateral segment, there is a point on the lip, lateral to which the mass of the orbicularis in the pars marginalis and pars peripheralis is normal. This point is defined as Noordhoff ’s point (Noordhoff, 1997), it the point where both the maximum height of the dry vermillion and a well-​formed white roll coincide. Medial to this the orbicularis oris muscle travels towards the alar base, becoming progressively more hypoplastic as it approaches the alar base. The muscle inserts into the periosteum of the piriform aperture and the alar base. This abnormal muscular anatomy means that contraction of the orbicularis in utero exerts a medializing force on the medial segment and a lateralizing, retrogressive force (via the muscles of facial expression and buccinator) on the lateral segment. The tissue of the nose on the cleft side although not directly involved in the clefting process bridges this area which is therefore progressively deformed by the relative displacement of the segments. This displacement is present in the soft tissues of all cleft lips, but

(a)

(b)

In a bilateral cleft lip, the same effect on both sides causes a large, flat, and bifid nasal tip because both alae are depressed, rotated downward, and spread apart with opening of the angle of the crura of the lower lateral cartilages.

Pars peripheralis of orbicularis oris Inserting into ipsilateral philtral column Pars peripheralis of orbicularis oris Inserting into contralateral philtral column Pars marginalis of orbicularis oris

Fig. 6.10.3  (a) A complete cleft lip. (b) Schematic to show muscle anatomy in a complete cleft lip.

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SECTION 6  Craniofacial and cleft

Components of a cleft lip repair From an understanding of the anatomy and the deformity, the potential aims of repairing a cleft lip can be outlined: 1. To join the medial and lateral lip segments preserving the natural landmarks creating the lip appearance. 2. Where possible to minimize the use of the hypoplastic tissues adjacent to the cleft in constructing the lip. 3. Preserving the projected width of the philtrum at the level of the white roll. 4. Preserving Noordhoff ’s point in the lateral element so it becomes the peak of the Cupid’s bow which is the base of the philtral column. 5. Planning surgery so that the lines of union of medial and lateral segments should lie on the natural anatomical lines of the lip subunits. 6. Realigning the orbicularis oris muscle from its abnormal position and joining it anatomically in its full height. 7. Deficit in the cleft-​side philtral height, so levelling the Cupid’s bow by lengthening the lip down using tissue from the lateral segment. 8. Correcting the deficit in dry vermillion height below the cleft-​side philtrum. 9. Creating nostril margins of equal circumference and symmetric alar bases. 10. Matching nostril sill structure to the non-​cleft side as closely as possible.

flap of dry vermillion from the lateral element is inserted into an incision along the wet–​dry vermillion junction up to the midline beneath the cleft-​side philtral element. Muscle repair As the malformation of the orbicularis muscle creates much of the contour of the cleft lip deformity prior to repair, so the form of the muscle after any surgery will significantly contribute to the form of the repaired lip. Anatomical muscle reconstruction is advocated to give the lip the correct bulk and contour, as skin is felt to offer little restriction to the lip in the longer term (Randall et al., 1974). Full muscle reconstruction involves dissection of the muscle from its abnormal insertions in the cleft lip both medially and laterally. The muscle is then turned down to lie horizontally across the lip, matching the upper border, white roll, and the wet–​dry junction which aligns all the anatomical segments of the muscle. In modern cleft lip repairs, this happens with most skin incision patterns and is thought important for a good lip form. The unique anatomy of the muscles in the philtrum are challenging to reproduce with many suggested methods (Rogers et al., 2014); most suggested techniques suggest only conservative, if any, dissection of orbicularis in the philtrum. Nose repair

Normalization of the cleft nose can be attempted at the time of lip repair, but as this is not standard practice in all surgeries, it is addressed separately in techniques of nose repair. Cleft lip repair therefore aims to establish a level lip with a balanced vermillion, a symmetrical nasal base appearance with the resultant scars approximating as nearly as possible to the lines of natural anatomical structure in the normal lip appearance.

Correction of the cleft nose deformity is one of the more challenging aspects of cleft lip surgery. The ideal nasal correction would correct the form of the nose and retain its shape through growth to maturity. Concerns developed regarding early surgery following marked changes in maxillary growth of rabbits after septal resection (Sarnat and Wexler, 1969), leading it to be suggested that major septal work and cartilaginous dissection negatively affected nasal growth, but these issues have not been proven. No studies have suggested that minor manipulations (without resection) of the nasal tip or nasal base interfere with future nasal growth (McComb and Coghlan, 1996). For this reason, most modern cleft lip repairs include some degree of attempt primarily to correct the nasal deformity.

Skin repair

Unilateral cleft lip repair

The repair of the lip skin, is the primary focus of the surgical techniques of cleft lip repair. Multiple different patterns of skin incision have been described. Mirault (1844) first described the foundation of modern cleft lip techniques, by incising the medial cleft element to turn it down, inserting tissue from the lateral element to fill the resulting defect. Many of the earlier techniques did not respect the anatomically defined boundaries of the lip, until the work of Millard with the rotation advancement repair (Millard, 1960), so that most modern techniques of cleft lip repair aim to have scars that as far as possible align with the anatomical subunits of the lip (Fisher, 2005)  (Fig. 6.10.2). Descriptions of skin incision techniques have dominated the literature, but many of the challenges of achieving a symmetrical result arise from a need to address other aspects of the malformation and deformity. Vermillion repair The dry vermillion under the cleft-​ side philtral element is hypoplastic. This appearance can be addressed by augmentation with excess dry vermillion medial to Noordhoff ’s point on the lateral lip element. There are several techniques for this but Noordhoff ’s triangular flap is the commonest (Noordhoff, 1997), where a triangular

The literature contains many descriptions of methods to repair the unilateral cleft lip. All techniques must address the deformity in terms of skin, vermillion, muscle, and nose, but this is often not made explicit in descriptions. Most of the repairs are classified according to the skin incisions. Modern cleft surgery techniques tend to respect the anatomical structure of the lip, but differ in how they turn the vermillion border down to make a level lip; these can be broadly classified as superior or inferior lip lengthening techniques. Many surgeons use hybrid techniques that amalgamate components of eponymous repairs. The following description is not intended to be exhaustive but addresses the major repairs in use currently. Superior lip lengthening techniques These techniques involve an incision in the upper lip, usually below the columella, that allows the philtrum to be turned down and a lateral segment of skin advanced into the resulting defect in a subcolumella position; therefore, they disrupt the philtral lines just below the columella. Rotation advancement after  Millard  Millard first described the technique in 1960. It involves a curved incision in the medial lip

6.10  Primary management of cleft lip and palate

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Fig. 6.10.4  A cleft lip repair using a superior lip lengthening technique—​the Millard cleft lip repair. (a) Skin markings for repair. (b) Line of scars following repair.

element (Fig. 6.10.4). The incision passes along the junction of the lip and columella until the philtrum can be rotated down enough to level the Cupid’s bow of the lip. The incision under the columella does not need to extend beyond the non-​cleft side philtrum as the lip is normal beyond this point, and this violates an aesthetic boundary resulting in an unfavourable appearance. The resulting defect is filled with a large advancement flap from the lateral lip segment. If incision to the non-​cleft columella does not allow enough downwards rotation of the lip to create a level Cupid’s bow, a ‘back-​ cut’ down the lip medial to the non-​cleft philtral column is done until the lip is level. Advancement of lateral lip tissue into the resulting defect creates a non-​anatomical disruption of the upper philtral form that can be noticeable—​this is a criticism of the technique (Fisher, 2005). The technique is popular as it allows a ‘cut and go’ approach to correcting the deformity, with the upper incision tailored to the amount of downwards rotation required to level the lip. The tissue lateral to the rotation incision is called the ‘C-​flap’; it is used to reconstruct the nostril sill. The original descriptions of the technique included an incision around the base of the cleft-​side alar base that could result in a small nostril; Millard described variations avoiding this incision. Modified rotation advancement  The rotation advancement repair is widely practised in cleft repair; many modifications have been proposed, these are the most influential in current practice. In an international survey, 84% of respondents used a version of the rotation advancement (Weinfeld et al., 2005). Mohler repair  To address the asymmetry of the scars in the upper lip compared to the non-​cleft philtral column of Millard’s technique, Mohler (1987) proposed a popular modification. The curved incision on the edge of the cleft is continued up into the columella rather than along the lip columella, there is then a back-​cut at 90° to this incision back down to the columella crease. This allows a V-​to-​Y advancement of some columella tissue down into the lip giving a scar more symmetrical to the non-​cleft side, at the expense of narrowing the columella. Noordhoff repair  In order to avoid a back-​cut down the non-​cleft philtrum, Noordhoff describes that if when this point is reached there is insufficient rotation of the lip downwards, a small incision is made above the white roll. A small triangle of lateral lip skin is introduced into this defect. The triangle scar does not match the non-​cleft philtrum but is inconspicuous in this position compared

to the appearance of a classic Millard back-​cut. The technique includes Noordhoff ’s lateral dry vermillion flap. Inferior lip lengthening techniques Inferior triangle repair of  Tennison–​Randall Tennison (1952) first proposed levelling the Cupid’s bow by making an incision across the lower philtrum perpendicular to the cleft edge until the lip rotated down, and introducing a triangle of skin from the lateral lip element into the resultant defect. Randall (1959) refined the technique by using measurements to tailor the height of the lateral triangle to the needed lengthening, which reduced the tendency to over-​lengthening. The technique was popular as it easily achieves good length to the lip and the scar mirrors the non-​cleft philtral column in the upper philtrum, but the triangular flap does not follow anatomical landmarks in the prominent lower philtrum so is often noticeable. Anatomical subunit repair  Fisher (2005) described the anatomical subunit repair which can be considered an update addressing some of the shortcomings of the Tennison–​Randall procedure (Fig. 6.10.5). The upper scar is planned to mirror the non-​cleft philtral column. Lip length is achieved by two manoeuvres:  a Rose–​ Thompson lengthening is made just above the white roll by straightening two incisions at an angle to each other, and a small measured triangle is inserted from the lateral lip element just above the white roll. The technique includes Noordhoff ’s dry vermillion flap. Fisher’s technique minimizes the size of the inferior triangle and places it in a position where there is a natural contour depression just above the white roll; both reduce the visibility of the scar, although it can still be visible as it does not match the form of the non-​cleft philtral column. Fisher’s technique involves planning with careful measurement of anatomical landmarks and precise design of the incisions based on this, which has made it popular as a counterpoint to the ‘cut and go’ approach of the rotation advancement techniques. Nasal surgery techniques Primary correction of the nose at the time of cleft lip repair is often attempted. It is important to recognize that the techniques of NAM are advocated to at least partially correct the nasal form, and may be used as a preliminary intervention prior to surgery. The techniques of nasal correction can be categorized.

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SECTION 6  Craniofacial and cleft

(a)

(b)

Fig. 6.10.5  A cleft lip repair using an inferior lip lengthening technique—​the Fisher cleft lip repair. (a) Skin markings for repair. (b) Line of scars following repair.

Adjustment of nasal cartilages  Closed correction  McComb (1975) proposed dissection from the lateral element of the cleft-​side upper and lower lateral cartilages with dissection from the medial element of the domal area. The cleft-​side lower lateral cartilage is then elevated, moved medially, and flexed at the genu by placing one or two sutures supporting it to the nasal bridge. These have become known as McComb sutures and can be either non-​absorbable material that is removed or longer term absorbable material such as PDS®. Long-​term studies have suggested the effects of McComb primary rhinoplasty are lasting (McComb, 1985)

Non-​surgical

Open correction  The alar cartilages at the time of primary nasal repair are delicate and there is a concern that closed techniques may result in unrecognized trauma. The results of closed techniques are not consistent so some authors advocate an open approach to cleft nasal deformity using techniques like the Tajima nasal correction. Some early results suggest this may give a better outcome (Tajima, 1990).

Techniques of bilateral cleft lip repair

Nasal septal repositioning  Repositioning of the septum from its dislocated position on the non-​cleft side of the nasal spine is carried out by some surgeons.

Bilateral cleft lip repair The bilateral cleft lip deformity presents a major challenge to surgical correction and has been extensively discussed by Mulliken (2001). The anatomical malformation and deformity of the lateral lip segment is repeated on both sides and the central lip element, the premaxilla and prolabium, are often markedly in advance of the lateral elements. This makes achieving closure of bilateral cleft lip challenging, particularly to achieve a full-​height joining of the orbicularis muscles in the midline. The prolabial segment has a short height in comparison to the lateral lip elements with little dry vermillion, which must therefore be augmented by lateral segment dry vermillion. The nose in bilateral cleft lip is often widely bifid with splaying of the tip cartilages and a separation of the medial crura of the lower lateral cartilages with an appearance of marked shortening of the columella. Surgical corrections attempt to address these additional aspects with varying degrees of success. Procedures to reduce the displacement of the cleft elements Due to the challenges of bilateral cleft lip repair, attempts are often made to reduce the discrepancy between the components of the lip.

Many bilateral cleft lip treatment protocols use preliminary non-​ surgical methods to reposition the cleft elements prior to surgery. Simple techniques such as taping, or more complex, bilateral NAM may be used. Some reports suggest NAM in bilateral cleft lips improves long-​term nasal form (Lee et al., 2008). Primary bilateral lip adhesion Primary bilateral lip adhesion can be used to allow the lip elements to move closer together prior to definitive lip repair.

Modified Millard Millard (1967) described a primary bilateral cleft lip repair that respected the anatomical forms in the normal lip. Mulliken (2001) has subsequently modified and popularized the method (Fig. 6.10.6) and versions of this operation are widely practised for bilateral cleft lip repair. These repairs discard the prolabial segment dry vermillion, reconstruct the philtrum using a columella base philtral flap, with the lateral lip elements contributing the white roll and dry vermillion elements inferior to the philtrum. Various open and closed primary nasal corrections are advocated. Manchester repair Manchester (1965) described using the entire prolabial height and dry and wet vermillion as the philtral segment reconstruction (Fig. 6.10.7). This involved reconstructing the muscles underneath this band of tissue. The technique can result in a deficit of dry vermillion under the philtrum.

Timing of primary cleft lip repair Timing of cleft lip repair is less variable than palate repair. Many treatment protocols describe lip closure at 3–​5  months. If non-​ surgical manipulation of the cleft is performed initially, this will dictate the timing of surgery, as the manipulated segments need to reach their planned position. Neonatal cleft lip repair is possible (Harris et al., 2010). Evidence of benefits and safety remain inconclusive so it is not widely practised currently (Stephens et al., 1997).

6.10  Primary management of cleft lip and palate

(a)

(b)

Fig. 6.10.6  A bilateral cleft lip repair: modified Millard after Mulliken. (a) Skin incision markings. (b) Position of scars after repair.

Primary management of the cleft palate Cleft palate repair A cleft palate repair aims to create a functional palate. To understand cleft palate surgery, it is helpful to understand the normal anatomy of the palate and the anatomy of the cleft palate. Anatomy of the palate The anterior palate is the hard palate; this is formed by the palatine process of the maxilla and the palatine part of the sphenoid. The greater and lesser palatine neurovascular bundles traverse the greater and lesser palatine foramina. The periosteum of the palatine bones is continuous with the tensor aponeurosis in the soft palate. There are four paired muscles that form the bulk of the soft palate (Fig. 6.10.8): levator veli palatini, tensor veli palatini, palatoglossus, and palatopharyngeus. Musculus uvulae is a midline structure with doubtful function. The levator is a cylindrical muscle that originates from the skull base and runs in the lateral wall of the nasopharynx to enter the velum, where it fans out to form a muscular sling with the contralateral levator; this lies in the middle 50% of the soft palate (Rohan and Turner, 1956). A small number of levator fibres originate from the under-​surface of the fibrocartilaginous part of the Eustachian tube. Levator palatini elevates and closes the palate against the wall of the nasopharynx.

(a)

Tensor veli palatini originates from the Eustachian tube and passes inferiorly before becoming tendinous as it passes around the hamulus into the palate where it fans out into the tensor aponeurosis which meets the contralateral tensor aponeurosis. Tensor veli palatini is in the anterior 50% of the palate. Contraction of tensor veli palatini tenses the aponeurosis but the functional significance of this is disputed. Palatopharyngeus runs from the pharyngeal wall via the posterior tonsillar pillar into the palate where it meets with the contralateral palatopharyngeus. It also inserts into the fascia overlying levator palatini. Palatoglossus runs from the tongue via the anterior tonsillar pillar into the palate. Palatoglossus and palatopharyngeus are palatal depressors. Together, levator, palatoglossus, and palatopharyngeus form a complex providing fine palatal control for speech and swallowing (Moon, 1994). Cleft palate anatomy In the cleft hard palate, a gap in the maxillary bones permits direct communication between the oral and nasal cavities. This can be unilateral or bilateral. In clefts involving the soft palate, the muscles of the palate are affected (Fig. 6.10.8). The muscles originate normally but the fibres of the levator veli palatini, palatopharyngeus, and palatoglossus converge to form a compact bundle that sweeps forwards inserting into the posterior nasal hemispine and medial margin of the bony cleft, sometimes referred to as Veau’s muscle. There is also a reduced palatal aponeurosis that

(b)

Fig. 6.10.7  A bilateral cleft lip repair: modified Manchester repair. (a) Skin incision markings. (b) Position of scars after repair.

751

752

SECTION 6  Craniofacial and cleft

(a)

(b)

Tensor veli palatini muscle Tensor veli palatini aponeurosis Laevator veli palatini Palatoglossus Palatopharyngeus

Fig. 6.10.8  Schematics of paired palatal musculature. (a) Normal anatomy. (b) Cleft palate anatomy.

lies touching the lateral edge of the Veau’s muscle (Maue-​Dickson and Dickson, 1980).

decision-​making regarding the selection of techniques for cleft palate repair.

Components of a cleft palate repair

Oral mucosa repair

The aim of cleft hard palate repair is to produce separation of the nasal cavity from the oral cavity. Soft palate repair must restore normal function; the soft palate opens for breathing and some speech sounds, but closes to separate oral cavity from the nasal cavity for suction, swallowing, and most consonant sounds in speech. Thus, the functional effects of a cleft palate are;

The oral mucosa of the palate is considered in two parts: the hard palate and the soft palate. The hard palate mucosa is tightly adherent to the underlying bones. In most of the palate this is a simple flat relationship, but around the greater palatine foramen the mucoperiosteal attachment is complex and lies at the posterolateral hard palate. Reducing tension of closure in the posterior hard palate requires mobilization of this area which can be challenging. This is an area where palatal breakdown with fistula is a risk. Some surgical techniques try to address this. Simple mucoperiosteal repair  As the palate is not flat, the palatal shelves lie at an angle to the horizontal, and in many narrow clefts, simple mobilization of the mucoperiosteum via an incision at the edge of the cleft is sufficient to allow midline closure. Palatal flap repairs  In wider clefts or those where the palatal shelves are closer to horizontal, achieving tension-​free closure with simple mobilization is not possible. In such situations, palatal flaps can be used to close the palatal mucosa. These techniques leave an area or palatal bone to heal by secondary intention, carrying a potential to inhibit palatal growth.

1. Inability to generate effective suction, which makes breastfeeding impossible and requires assisted feeding techniques for bottle-​feeding (see previous chapter). 2. Inability to close off the nasal cavity from the oral cavity during swallowing, which produces regurgitation into the nasal cavity of food at the initiation of a swallow. Children can still swallow, but liquids may appear out of the nostrils. 3. In speech with a non-​functioning palate, inability to close the nasopharynx from the oropharynx impairs productions of most consonants. Phonation of ‘m’, ‘n’, and the vowel sounds is unaffected. Intelligibility of speech is severely affected. 4. Inability to close the nose of from the oral cavity when attempting to blow, markedly reducing the pressure generated. It is therefore standard practice to repair a cleft palate with the primary aim of producing normal speech production, ability to suck, ability to blow, and stop nasal regurgitation of food. Repair of a cleft palate involves closure of the oral and nasal mucosa. In addition, some surgeons believe it is important to specifically repair the palatal musculature to maximize palatal function. The palate is also a growing structure; this is not a function so much as a property of the tissues. There is concern that surgery, particularly some surgical manoeuvers in the hard palate such as extensive dissection and leaving areas of exposed bone to heal by secondary intention, reduce the growth potential of the bony hard palate. This is an additional concern that is factored into the

Bipedicled repairs • Von Langenbeck palatoplasty:  von Langenbeck palatoplasty (von Langenbeck, 1864)  involves elevating mucoperiosteal bipedicled flaps based on the greater palatine artery and making a releasing incision at the junction of the palate and alveolar mucosa (Fig. 6.10.9). The flap is advanced medially and the resulting lateral defects are left to heal by secondary intention. • Medial von Langenbeck palatoplasty: Piggott and Murison (1992), concerned that elevation of the greater palatine artery within the flaps may devascularize the palatal bone, proposed bipedicled flaps based medial to the greater palatine pedicle. This technique has not been widely adopted.

6.10  Primary management of cleft lip and palate

(a)

(b)

Fig. 6.10.9  Von Langenbeck cleft palate repair. (a) Markings for incisions. (b) After repair.

Islanded repair  Veau–​Wardill–​Kilner palatoplasty Based on the observation of a short palate after some von Langenbeck repairs. The Veau–​Wardill–​Kilner palatoplasty raises the anterior palatal mucosa as a posteriorly based pedicled flap on the greater palatine artery. These flaps are then intentionally sutured posterior to their donor sites, leaving an area of exposed palatal bone anteriorly. This procedure can cause marked scarring from secondary intention healing and a growth disturbance in reported in some series (Palmer et al., 1969) but not others (Choudhary et al., 2003). Two-​flap palatoplasty The two-​flap palatoplasty (Bardach et al., 1967) elevates the entire palatal mucoperiosteum as a posteriorly based flap incised at the gingivopalatal junction (Fig. 6.10.10). The flaps are then sutured in the midline and resutured as much as possible to the gingiva from the front posteriorly without creating tension. The procedure results in defects similar to the von Langenbeck palatoplasty, but can address the very anterior extent of a primary palatal cleft more effectively. Nasal mucosa repair This layer is closed directly by mobilization of the nasal floor mucoperiosteum. This mobilization is usually out to the lateral wall of the nasal cavity to help advance the mucosa. To help closure, the incision at the edge of the cleft may be biased orally to give a little more tissue, as additional procedures to help with nasal closure of

the hard palate are not common. The mucoperiosteum is mobilized off the septum and vomer to allow the two layers of mucosa to be closed. Historically, some repairs did not formally repair the nasal floor mucoperiosteum, with only oral closure. Palatal musculature repair The abnormal orientation of the palatal muscles in the cleft soft palate and their attachment to the hard palate can be addressed surgically. This is by surgical dissection of the muscles—​intravelar veloplasty (IVV) (Kriens, 1969). The procedure varies from simple release of the conjoined palatal muscular insertion on the hard palate and midline joining, to complete dissection of the individual levator muscles to rejoin them across the midline (Flores et  al., 2010). Sommerlad (2003) popularized a microscope assisted procedure to release the conjoined muscle off the hard palate, release it off the oral and nasal mucosal layers, and release the attached tensor aponeurosis off the hard palate and medial to hamulus, the muscles can then be retroposed into the posterior third of the soft palate where they are repaired. Not all surgeons agree IVV is a required adjunct in the surgical repair of the cleft palate. There are few studies that compare cleft palate repair with and without an IVV. A cohort study by Marsh and colleagues (1989) reported 60% of those whose cleft was repaired without IVV required secondary surgery to improve speech whereas

753

754

SECTION 6  Craniofacial and cleft

(a)

(b)

Fig. 6.10.10  Bardach cleft palate repair. (a) Markings for incisions. (b) After repair.

69% of those who underwent IVV required secondary surgery—​a non-​significant difference although the study was only powered to detect differences greater than 10%. Sommerlad (2003) reported a cohort study of cleft palate repairs using microsurgical IVV with a minimum follow-​ up of 10 years. Secondary surgery rate for speech problems was 4.6–​10.2% depending on experience. The fistula repair rate was 15%. IVV is also an integral part of the Furlow palatoplasty which is widely practised internationally in cleft palate repair with reports in large cohort studies of rates of secondary surgery for speech of 8.1% and a fistula rate of 5.2% (Jackson et al., 2013). Primary palatal lengthening procedures A recurrent observation of cleft palate following repair, especially in patients with speech difficulties, is that the soft palate is short. This is felt to be both intrinsic because the palatal shelves are small, but also extrinsic as by closing the palate in the midline the palate tends to shorten. This has led to proposing lengthening the soft palate as part of the primary palatal closure. Furlow palatoplasty Furlow (1986) proposed incorporating opposing Z-​plasties into the oral and nasal mucosa in primary palatoplasty (Fig. 6.10.11). The opposing Z-​plasty design allows reorientation of the abnormal palatal muscles into the posterior palate which is a form in IVV as well as lengthening the palate. Z-​plasty requires lateral laxity that is utilized for lengthening. This is problematic in cleft palate as there is a deficit in lateral width. Modifications

of the Furlow palatoplasty which add releasing incisions lateral to the soft palate orally allow the soft palate oral mucosa to advance medially been published to allow use of the procedure in all widths of cleft (Jackson et al., 2013). These procedures involve extensive soft palate dissection. Staged palate repairs Several treatment protocols address the hard and soft palate in a staged fashion. Hard palate then soft palate This protocol is common in the United Kingdom having been popularized by Sommerlad (2009). It is used in cases where there is both a cleft lip and cleft hard palate. It involves: • Anterior inferiorly based vomerine flap: a single-​layer closure can be achieved in the hard palate by incising the mucosa between the nasal septal mucosa and oral mucosa, then elevating a superiorly based mucoperiosteal flap which is sutured to an incision on the hard palate cleft margin (Pichler, 1926) (Fig. 6.10.12). • Simple soft palate closure: once the area has healed, the soft palate is closed directly, usually with an additional IVV (Sommerlad, 2003). Soft palate then hard palate There are multiple descriptions of primary closure of the soft palate followed by delayed hard palate closure. These techniques are advocated to minimize palatal growth disturbance. Studies have demonstrated that delaying the hard palate

6.10  Primary management of cleft lip and palate

(a)

(b)

A B B A

Fig. 6.10.11  Furlow cleft palate repair. (a) Markings for incisions. (b) After repair: note that the flaps A and B have been transposed in a Z-​plasty which lengthens the soft palate.

closure beyond a year impacts the quality of the speech outcomes. At this stage there is no benefit in terms of growth.

Timing of primary cleft palate repair The optimum timing of cleft palate repair remains unclear. Surgery after 1  year is associated with poor speech articulations such as glottal or pharyngeal articulation (Dorf and Curtin, 1982). The only randomized trial on speech and maxillary growth (Ysunza, 1998) in unilateral cleft lip and palates repaired at 6 or 12 months suggested less compensatory articulations in the younger age of repair group but no difference in maxillary growth. This finding of improved outcome with earlier repair has been supported by multiple cohort studies since. The better speech outcomes that follow early palate surgery should be considered alongside concerns over the growth of the maxilla in cleft lip and palate patients. Delayed closure of the hard palate, performed in adolescence, benefits maxillary growth (Lilja et al., 2006), but at the expense of significant speech articulation errors. Many protocols advocate completion of cleft palate closure in the medically fit child by 12  months of age—​several protocols advocating an age as low as 6 months—​accepting growth disturbances can be successfully treated orthodontically or surgically, but

entrenched late compensatory speech articulation frequently cannot (Sell and Grunwell, 1990).

Primary management of the alveolar cleft Alveolar bone grafting A cleft occurs in the alveolus due to a failure of fusion of the medial and lateral palatine processes, which usually fuse to form the primary palate anterior to the incisive foramen. The alveolus is the specialized bone of the maxilla in which the tooth buds arise. In the sixth week of development, the oral epithelium thickens to form the dental laminae; these grow into the underlying mesenchyme which becomes the maxilla to form the tooth buds of both the deciduous and permanent teeth. The teeth neighbouring the cleft are commonly affected by the cleft. About a fifth of patients have extra teeth in the cleft and over half have missing teeth. Tooth eruption is delayed around the cleft by a mean of 18  months. In addition, the occlusion of the teeth may be altered in any plane. The dental phenotype and occlusal issues mean that considerable orthodontic manipulation of dental anatomy in the cleft is required to provide a functional and aesthetic occlusion; providing viable bone to allow

755

756

SECTION 6  Craniofacial and cleft

(a)

(b)

Fig. 6.10.12  Superiorly based vomerine flap repair of hard palate. (a) Markings for incisions. Arrows show movement of resulting superior vomerine flap. (b) After repair: note the deep surface of the vomerine flap exposed orally as well as the bony surface of the vomer.

future orthodontic treatment is the primary aim of alveolar bone grafting. Alveolar bone grafting is a relatively recent introduction to cleft care, gaining widespread practice after the 1950s (Weissler et  al., 2016). Initially, this was predominantly primary alveolar bone grafting in deciduous dentition (Brauer et al., 1962), but due to concerns over primary bone grafts not growing with the child’s skull and teeth not erupting through the graft (Pickrell et al., 1968), secondary grafting during the period of mixed dentition became the preferred practice (Boyne and Sands, 1976).

Components of alveolar cleft repair Alveolar bone graft, unlike cleft lip or cleft palate surgery, must address bone replacement as well as oral and nasal mucosa. Nasal mucosa repair In most alveolar bone graft procedures, the nasal mucosa is directly closed linearly after mobilization from the cleft edges and nasal floor. A complete, robust closure of the nasal mucosa is necessary to allow revascularization of the bone graft; exposed graft will not take. Oral mucosa repair Teeth need to erupt through gingival mucosa, so techniques have developed to move adjacent gingival mucosa across the cleft. The commonest technique is a sliding buccal gingival flap from the lesser segment that reaches the first molar posteriorly where a back-​cut

allows mesial transposition (Fig. 6.10.13), as described by Bergland and colleagues (1986). Bone repair Bone is required to allow eruption at the correct level and to provide durable root foundation. The functional stress of the erupted teeth on the grafted bone maintains the bone stock which would otherwise be subject to reabsorption. This means that sufficient bone volume in the cleft is an important factor in long-​term success as judged by orthodontic outcome. Bone graft is often also placed under the nasal base on the cleft side as there is a volume deficit which gives a characteristic appearance. The amount of bone required and the alignment of the alveolus are often manipulated in the period prior to the surgery using orthodontic appliances to expand the constricted and collapsed maxillary segments.

Alveolar cleft repair Primary periosteoplasty and gingivoperiosteoplasty In this procedure, the periosteum over the alveolus is directly closed at the time of primary cleft lip surgery. The lack of distensible tissue over the alveolus means this procedure is only possible when presurgical orthopaedics have successfully aligned the alveolar cleft segments and they approximate each other. Primary gingivoperiosteoplasty is advocated because it reduces the need for secondary bone grafting; the best series report 72% of patients

6.10  Primary management of cleft lip and palate

(a)

Other sites of autogenous bone graft donors include cranial, mandibular symphyseal, and tibial bone but all have donor site morbidity that has limited their widespread adoption. Timing

(b)

Timing within the mixed dentition period is debated. Early secondary grafting defined as grafting performed before canine eruption is better than late secondary grafting (Ozawa et  al., 2007). Grafting before the cleft canine eruption means it can erupt into the grafted cleft, functionally stressing the bone so maintaining bone volume. Late secondary grafting after canine eruption is less successful (Bergland et al., 1986). The surgeon must therefore collaborate with an orthodontist to time the surgery based on an assessment of development of the cleft canine, usually by radiography.

Author’s preferred primary cleft protocols (c)

Table 6.10.1 shows the agreed cleft protocols and techniques in the author’s service as an example of how a primary cleft surgery protocol is built up.

Table 6.10.1  Author’s example of how a primary cleft surgery protocol is built up

Fig. 6.10.13  Abyholm alveolar bone graft. (a) Markings for incisions. Arrow shows direction of transposition of gingival flap. (b) Flaps retracted superiorly showing inlay bone graft in yellow. (c) Flap transposed over bone graft with bone over alveolus laterally left exposed to mucosalize.

Condition

Technique

Timing

Isolated unilateral cleft lip

Fisher subunit repair

3 months

Complete unilateral cleft lip and palate

Fisher subunit cleft lip repair

McComb nasal correction Inferiorly based vomerine flap hard palate repair McComb nasal correction

avoid secondary grafting. The procedure remains controversial as some studies have shown it is a predictor of poor long-​term growth outcomes in the form of adverse dental arch form (Hsieh et  al., 2012) and the requirement for presurgical orthopaedics.

Direct simple repair of palate or von Langenbeck palatoplasty

Alveolar bone graft is an inlay graft between the osseous segments of the maxilla, which is different to an onlay graft which most studies of cranial bone grafting have examined. Animal models of inlay cranial bone grafting show volume increases when either endochondral or membranous bone is grafted but the increase is greater with endochondral cancellous bone (Sugg et  al., 2013). This has been demonstrated in the superiority of cancellous iliac crest over cranial bone for secondary alveolar grafts (Sadove et al., 1990). Autogenous iliac crest is the commonest donor for alveolar bone grafting and has become the gold standard by which other grafts are judged. It is easy to access and can provide large quantities of cancellous bone. Due to its higher content of osteogenic cells, cancellous bone is thought to be superior to corticocancellous bone. Cancellous bone graft is revascularized within 3 weeks unlike that of cortical bone, which maintains volume by creeping substitution (Denny et al., 1999).

6–​9 months

Sommerlad intravelar veloplasty Abyholm alveolar bone graft

8–​11 years old depending on canine development

Fisher subunit bilateral lip repair (modified Mulliken)

3 months

Secondary bone grafting Bone sources

3 months

Isolated bilateral cleft lip

McComb nasal correction Complete bilateral cleft lip and palate

Fisher subunit bilateral lip repair (modified Mulliken)

3 months

Inferiorly based vomerine flap hard palate repair McComb nasal correction Direct simple repair of palate or von Langenbeck palatoplasty

6–​9 months

Sommerlad intravelar veloplasty

Cleft palate

Abyholm alveolar bone graft

8–​11 years old depending on canine development

Direct simple repair of palate or von Langenbeck palatoplasty

6–​9 months

Sommerlad intravelar veloplasty

757

758

SECTION 6  Craniofacial and cleft

REFERENCES Bardach J. Rozszczepy Warqi Gornej i Podniebienia. Warszawa, Panstwowy Zaklad Wydawnictw Lekarskich, 1967. Bergland O, Semb G, Abyholm FE. Elimination of the residual alveolar cleft by secondary bone grafting and subsequent orthodontic treatment. Cleft Palate J 1986;23:175–​205. Bongaarts CA, Prahl-​ Andersen B, Bronkhorst EM, et  al. Infant orthopedics and facial growth in complete unilateral cleft lip and palate until six years of age (Dutchcleft). Cleft Palate Craniofac J 2009;46:654–​63. Boyne PJ, Sands NR. Combined orthodontic-​surgical management of residual palato-​alveolar cleft defects. Am J Orthod 1976;70:20–​37. Brauer RO, Cronin TD, Reaves EL. Early maxillary orthopedics, orthodontia and alveolar bone grafting in complete clefts of the palate. Plast Reconstr Surg Transplant Bull 1962;29:625–​41. Brown GVI. A system for the surgical correction of harelip and cleft palate. JAMA 1905;44:848–​59. Choudhary S, Cadier MA, Shinn DL, et  al. Effect of Veau-​Wardill-​ Kilner type of cleft palate repair on long-​term midfacial growth. Plast Reconstr Surg 2003;111:576–​82. Denny AD, Talisman R, Bonawitz SC. Secondary alveolar bone grafting using milled cranial bone graft: a retrospective study of a consecutive series of 100 patients. Cleft Palate Craniofac J 1999;36:144–​53. Dorf DS, Curtin JW. Early cleft palate repair and speech outcome. Plast Reconstr Surg 1982;70:74–​81. Fisher DM. Unilateral cleft lip repair: an anatomical sub-​unit approximation technique. Plast Reconstr Surg 2005;116:61–​71. Flores RL, Jones BL, Bernstein J, et al. Tensor veli palatini preservation, transection, and transection with tensor tenopexy during cleft palate repair and its effects on eustachian tube function. Plast Reconstr Surg 2010;125:282–​9. Furlow LT Jr. Cleft palate repair by double opposing Z-​plasty. Plast Reconstr Surg 1986;78:724–​38. Grayson BH, Cutting C, Wood R. Preoperative columella lengthening in bilateral cleft lip and palate. Plast Reconstr Surg 1993;92:1422–​3. Harris PA, Oliver NK, Slater P, et al. Safety of neonatal cleft lip repair. J Plast Surg Hand Surg 2010;44:231–​6. Hsieh YJ, Liao YF, Shetty A. Predictors of poor dental arch relationship in young children with unilateral cleft lip and palate. Clin Oral Investig 2012;16:1261–​6. Jackson O, Stransky CA, Jawad AF, et  al. The Children’s Hospital of Philadelphia modification of the Furlow double-​ opposing Z-​ palatoplasty:  30-​year experience and long-​term speech outcomes. Plast Reconstr Surg 2013;132:613–​22. Kriens OB. An anatomical approach to veloplasty. Plast Reconstr Surg 1969;43:29–​41. Latham RA, Kusy RP, Georgiade NG. An extraorally activated expansion appliance for cleft palate infants. Cleft Palate J 1976;13: 253–​61. Lee CT, Garfinkle JS, Warren SM, et  al. Nasoalveolar molding improves appearance of children with bilateral cleft lip-​cleft palate. Plast Reconstr Surg 2008;122:1131–​7. Lilja J, Mars M, Elander A, et al. Analysis of dental arch relationships in Swedish unilateral cleft lip and palate subjects: 20-​year longitudinal consecutive series treated with delayed hard palate closure. Cleft Palate Craniofac J 2006;43:606–​11. Manchester WM. The repair of bilateral cleft lip and palate Br J Surg 1965;52:878–​82. Marsh JL, Grames LM, Holtman B. Intravelar veloplasty: a prospective study. Cleft Palate J. 1989;26:46–​50.

Matic DB, Power SM. Evaluating the success of gingivoperiosteoplasty versus secondary bone grafting in patients with unilateral clefts. Plast Reconstr Surg 2008;121:1343–​53. Maue-​Dickson W, Dickson DR. Anatomy and physiology related to cleft palate: current research and clinical implications. Plast Reconstr Surg 1980;65:83–​90. McComb H. Treatment of the unilateral cleft lip nose. Plast Reconstr Surg 1975;55:596–​601. McComb H. Primary correction of unilateral cleft lip nasal deformity: a 10-​year review. Plast Reconstr Surg 1985;75:791–​9. McComb HK, Coghlan BA. Primary repair of the unilateral cleft lip nose:  completion of a longitudinal study. Cleft Palate Craniofac J 1996;33:23–​31. McNeil CK. Orthodontic procedures in the treatment of congenital cleft palate. Dent Rec (London) 1950;70:126–​32. Millard DR Jr. Complete unilateral clefts of the lip. Plast Reconstr Surg 1960;25:595–​605. Millard DR. Bilateral cleft lip and a primary forked flap: a preliminary report. Plast Reconstr Surg 1967;39:59–​65. Mirault G. Deux lettres sur l’operation du bec-​ delievre. J Chir 1844;2:257. Mohler LR. Unilateral cleft lip repair. Plast Reconstr Surg 1987;80:511–​17. Moon JB. Coordination of velopharyngeal muscle activity during positioning of the soft palate. Cleft Palate Craniofac J 1994:31:45–​55. Mulliken JB. Primary repair of bilateral complete cleft lip and nasal deformity. Plast Reconstr Surg 2001;108:181–​94. Murison MS, Pigott RW. Medial Langenbeck: experience of a modified von Langenbeck repair of the cleft palate. A preliminary report. Br J Plast Surg 1992;45  454–​9. Nicolau PJ. The orbicularis oris muscle: a functional approach to its repair in the cleft lip. Br J Plast Surg 1983;36:141–​53. Noordhoff MS. The Surgical Technique for the Unilateral Cleft Lip-​Nasal Deformity. Taipei, Taiwan:  Noordhoff Craniofacial Foundation; 1997. Ozawa T, Omura S, Fukuyama E, et  al. Factors influencing secondary alveolar bone grafting in cleft lip and palate patients: prospective analysis using CT image analyzer. Cleft Palate Craniofac J 2007;44:286–​91. Palmer CR, Hamlen M, Ross RB, et al. Cleft palate repair: comparison of the results of two surgical techniques. Can J Surg 1969;12:32–​9. Peanchitlertkajorn S, Mercado A, Daskalogiannakis J, et  al. An intercenter comparison of dental arch relationships and craniofacial form including a center using nasoalveolar molding. Cleft Palate Craniofac J 2018;55:821–​9. Pichler H. Uber Lippen und Gaumenspalten. Dtsch Z Chir 1926;195:104–​7. Pickrell K, Quinn G, Massengill R. Primary bone grafting of the maxilla in clefts of the lip and palate: a four-​year study. Plast Reconstr Surg 1968;41:438–​43. Randall P. A triangular flap operation for the primary repair of unilateral clefts of the lip. Plast Reconstr Surg 1959;23:331–​47. Randall P. A lip adhesion operation in cleft lip surgery. Plast Reconstr Surg 1965;35:371–​6. Randall P, Whitaker LA, LaRossa D. The importance of muscle reconstruction in primary and secondary cleft lip repair. Plast Reconstr Surg 1974;54:316–​23. Rogers CR, Meara JG, Mulliken JB. The philtrum in cleft lip:  review of anatomy and techniques for construction. J Craniofac Surg 2014;25:9–​13. Rohan RF, Turner L. The levator veli palati muscle. J Anat 1956;90:153.

6.10  Primary management of cleft lip and palate

Sadove AM, Nelson CL, Eppley BL, et al. An evaluation of calvarial and iliac donor sites in alveolar cleft grafting. Cleft Palate J 1990;27:225–​8. Sarnat BG, Wexler MR. Longitudinal development of upper facial deformity after septal resection in growing rabbits. Br J Plast Surg 1969;120:313–​23. Sell DA, Grunwell P. Speech results following late palatal surgery in previously unoperated Sri Lankan adolescents with cleft palate. Cleft Palate J 1990;27:162–​8. Sommerlad BC. A technique for cleft palate repair. Plast Reconstr Surg 2003;112:1542–​8. Sommerlad BC. Cleft palate repair. In:  Losee JE, Kirschner R (eds) ComprehensiveCleftCare,pp.399–​412.New York: McGraw-​Hill,  2009. Stephens P, Saunders P, Bingham R. Neonatal cleft lip repair: a retrospective review of anaesthetic complications. Paediatr Anaesth 1997;7:33–​6. Sugg KB, Rosenthal AH, Ozaki W, et al. Quantitative comparison of volume maintenance between inlay and onlay bone grafts in the craniofacial skeleton. Plast Reconstr Surg 2013;131:1014–​21.

Tajima S. Follow-​up results of the unilateral primary cleft lip operation with special reference to primary nasal correction by the author’s method. Facial Plast Surg 1990;7:97–​104. Tennison CW. The repair of the unilateral cleft lip by the stencil method. Plast Reconstr Surg 1952;9:115–​20. von Langenbeck B. Weitere Erfahrungen im Gebiete der Uranoplastik mittels Ablosung des mucosperiostalen Gaumenuberzuges. Arch Klin Chir 1864;5:1–​70. Weinfeld AB, Hollier LH, Spira M, et al. International trends in the treatment of cleft lip and palate. Clin Plast Surg 2005;32:19–​23. Weissler EH, Paine KM, Ahmed MK, et al. Alveolar bone grafting and cleft lip and palate: a review. Plast Reconstr Surg 2016;138:1287–​95. Winters JC, Hurwitz DJ. Presurgical orthopedics in the surgical management of unilateral cleft lip and palate. Plast Reconstr Surg 1995;95:755–​64. Ysunza A. A speech outcome and maxillary growth in patients with unilateral complete cleft lip/​palate operated on at 6 versus 12 months of age. Plast Reconstr Surg 1998:102;675–​9.

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6.11

Outcome assessment in cleft lip and palate surgery Marc C. Swan, Conrad J. Harrison, and Tim E.E. Goodacre

Introduction The domain of cleft surgery presents an exceptionally complex subject area when compared with those in which more ‘binary outcomes’ pertain for the health intervention concerned. Cleft care not only relates to multiple aspects of well-​being (appearance, social functioning, dental function, speech, and hearing) but also covers these across the fourth dimension of time—​from prenatal diagnosis throughout childhood development until the end of life. The effect of this complex array of concerns (that the best management protocols seek to address) is the generation of numerous interacting variables that can be exceptionally difficult to measure and evaluate when trying to determine the ‘best outcome’. Thus even determining the outcome for a simple intervention such as primary surgical repair, the use of an orthodontic device for jaw alignment, or therapeutic speech methods involves teasing out the single variable of interest from numerous other confounding factors that might have a bearing on the measurement. For all practical purposes, the complexity of cleft management is such that it may never be possible to sufficiently reduce outcome evaluation to the degree that will enable neat and tidy delineations of procedures to guide best practice across all aspects of care. The drive to address this subject has been rendered more urgent by two factors. Recently, the focus of much health delivery planning has, quite appropriately, moved towards ensuring that treatments are ‘evidence based’ as well as being considered the best possible by conventional wisdom. Much of this change in emphasis has been patient driven to counteract the more traditional physician-​ determined evaluation of what matters. Alongside this, the second driver has been the desire among those funding services to not only eliminate poor practice, but also to move towards the best value for money in a time of rapidly escalating costs—​as well as an explosion of new techniques and treatment methodologies. In this light, outcome evaluation is evolving along two lines. Until recently, the principal method has been to reduce outcomes to strictly defined and directly measurable variables in each subset of healthy well-​being. Examples of these, which will be described in more detail later, are the use of speech evaluation at set age points throughout development, using the Great Ormond Street Speech

Assessment (GOS.SP.ASS) instrument, and the classification of maxillary arch development at 5-​and 10-​year age points using the 5-​year index and the GOSLON yardstick (Mars et al., 1987; Atack et al., 1997; Sell et al., 1999). Such methodology is difficult to develop, and work continues across all areas to improve the reproducibility and validity of such ‘metrics’, along with understanding the appropriateness of using each outcome measure to define best practice. More recently, a different approach to outcome evaluation has developed to attempt to measure what matters most to the patients themselves. Such so-​called patient-​reported outcomes (PROs) have the distinct benefit of enabling the outcome of what might have been a complex series of treatment interventions to be evaluated at set time points with what can reasonably be assumed to be what matters most—​namely what the ‘consumer’ feels. Turning to the patient to rate the outcome of a physical intervention such as rhinoplasty for nasal deformity might seem to deliver a relatively ‘soft measure’ compared with a detailed measurement of the dimensions of deviation from a purported ‘norm’. However, in practice, case variability and the requirements of the patient themselves differ so much that a strong argument can be made for patient-​reported evaluation to be most relevant for all practical decision-​making. It could also be argued that the only valid means of teasing out the respective ‘pros and cons’ of something as complex as early hard palate closure versus delayed closure will be to evaluate PROs across all domains of speech, maxillary growth, and psychosocial impact, for groups adopting different protocols. In that way, those in whom early speech development has to some extent been necessarily sacrificed to deliver better maxillary development (with perhaps less surgical demand in later adolescence)—​and vice versa—​might have PROs recorded at set time points throughout childhood and into adult life. With sufficient numbers in each group, the best outcome from the consumer perspective might eventually be determined and questions that have vexed clinicians for generations might finally be answered. It is important to note that the generation of valid and reproducible PROs instruments is a lengthy process, involving structured interviewing of affected individuals and carers, item generation and testing, psychometric analysis, item reduction following field testing, and numerous other stages to ensure wide validity across all

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SECTION 6  Craniofacial and cleft

patient subtypes (race, age, social class, education, language, and so forth). A plethora of PRO measures in recent years has been generated by interest in this area, but there has been some degree of failure to recognize that generating such patient-oriented questions cannot simply be undertaken by clinicians dreaming up what they consider to be a set of the most relevant questions to ask.

Current outcome measures Facial appearance No agreed standard exists to evaluate aesthetic outcomes in cleft patients (Sharma et  al., 2012). While many surgeons consider direct clinical assessment as the ‘gold standard’, difficulty in performing reliable objective measurements with adequate inter-​rater and intra-​rater reliability pose significant limitations. Thus clinical photographic evaluation is now frequently used as it offers a quick, cheap, and straightforward means of evaluation. The use of ‘cropped’ two-​dimensional images of the nasolabial complex (in frontal, basal and lateral view) aims to limit the confounding effect of other facial features (such as subjective ‘cuteness’), with patients typically being assessed according to a five-​point ordinal scale (Asher-​McDade et al., 1991). Recently, the need for having expert assessors has been questioned, as scores assigned by lay-people in ‘crowdsourcing’ initiatives appear to correlate closely with those assigned by surgeons (Tse et al., 2016). Three-​dimensional photographs and videographic assessments have also been trialled but have hitherto not enjoyed widespread adoption (Morrant and Shaw, 1996; Trotman et al., 2000; Meyer-​Marcotty et al., 2010). The fact that symmetrical faces are perceived as being more attractive and that orofacial clefts have a tendency towards facial asymmetry, forms the basis of the SymNose analysis: a semi-​automated quantitative assessment based on analysing facial asymmetry from two-​dimensional images (Baudouin and Tiberghien, 2004; Pigott and Pigott, 2010). While this software provides quantitative data on symmetry, it can be difficult to interpret its significance in the absence of normative data from non-​cleft populations for this methodology.

Dentofacial measures Assessing the dental arch relationship in patients with unilateral cleft lip and palate is based on orthodontic plaster study models (though digital alternatives are being developed), and commonly utilizes the 5-​year index or, in 10-​year olds, the GOSLON Yardstick (Mars et al., 1987; Atack et al., 1997; Chawla et al., 2012). The modified Huddard–​ Bodenham scoring system is used by some and is applicable to all cleft types, while a yardstick specific to bilateral cleft lip and palate has also been developed (Tothill and Mossey, 2007; Okada Ozawa et al., 2011). The GOSLON Yardstick is applied to children who are in their early permanent (mixed) dentition and is designed to reflect the underlying skeletal relationship. It takes into consideration the anteroposterior arch relationship (i.e. class III malocclusion), the vertical incisor overbite relationship (i.e. anterior open bite), and the transverse arch relationship (i.e. crossbite). Scores range from 1 to 5, with 1 being scored as the best outcome and 4 and 5 being in the realms of requiring orthognathic correction. This method has been successfully validated and has been used in a number of inter-​centre comparison studies (Molsted et al., 2005; Hathaway et al., 2011).

Cleft surgery in the growing child is associated with the development of maxillary hypoplasia (Phillips et al., 2012). The skeletal relationship between the upper and lower jaws is assessed using the standardized lateral cephalogram to determine the key landmark points, from which the ANB (subspinale–​nasion–​supramentale), SNA (sella–​ nasion–​ subspinale), and SNB (sella–​ nasion–​ supramentale) angles are calculated. SNA describes the position of the maxilla, relative to the cranial base, while SNB refers to the relationship of the mandible to the cranial base. ANB specifies the relative position of the maxilla to the mandible, thereby enabling an assessment of jaw discrepancy. Normative cephalometric values are specific to age, sex, and race (Huang et al., 1998).

Speech measures Despite much work on the development of objective instruments to evaluate speech in relation to cleft palate and velopharyngeal function (such as nasometry and PERCI-​SARS), perceptual speech evaluation remains the ‘gold standard’. For now, this should be undertaken by appropriately trained speech and language therapists, although early research is exploring the potential for crowdsourcing speech assessments or automating the process through speech recognition software (Lohmander and Olsson, 2004; Sescleifer et al., 2020; Vucovich et al., 2017; Seaward et al., 2018). GOS.SP.ASS (Fig. 6.13.3) is a validated screening tool for quantifying the speech characteristics commonly associated with cleft palate and velopharyngeal dysfunction (Sell et al., 1999). This tool has been universally adopted in the United Kingdom. A revision of an earlier 1994 iteration, it provides a comprehensive yet practical tool for clinical assessment of resonance, nasal emission, nasal turbulence, and consonant production (Sell et  al., 1994). The Cleft Audit Protocol for Speech-​Augmented (CAPS-​A) is employed for clinical audit and research (John et al., 2006). This process is undertaken by therapists trained in the use of the protocol in order to render the results as valid and reproducible as possible (Sell et al., 2009). Global comparisons of speech outcomes can be notoriously difficult, particularly in the context of cross-​linguistic speech analysis. Attempts to eliminate the influence of language by focusing on the assessment of consonant articulation enables cross-linguistic evaluations to be made (Hutters and Henningsson, 2004; Henningsson et al., 2008). Universal parameters for reporting speech outcomes were adopted by the Eurocleft Speech Project that compared results from six European cleft centres using a specifically designed phonetic framework (Grunwell et al., 2000). The Scandcleft Project is using an alternate analysis known as the ‘percent consonants correct’ method, which has also been approved for speech analysis in the Timing of Primary Surgery for Cleft Palate (TOPS) Trial (Lohmander et al., 2009). Although capable of robustly assessing articulation outcomes and velopharyngeal dysfunction, the ability to evaluate intelligibility accurately is more contentious, thus meriting further work (Whitehill, 2002). Patient-​ reported measures of velopharyngeal outcome are being developed and are discussed briefly under the heading ‘Patient-​reported outcome measures’.

Psychological measures There is inevitably a considerable overlap between the objective evaluation of psychological aspects of health and patients’ own reports of outcome following treatment in general. This subject, therefore, is mainly covered under the heading of ‘Patient-​reported outcome measures’.

6.11  Outcome assessment in cleft lip and palate surgery

While some instruments have routinely been used to measure aspects of mental health, such as the Rosenberg Self-Esteem Scale and various scales rating depression (Rosenberg, 1965), these are more generic measures of psychological health and frequently have items that are irrelevant to conditions as specific as cleft. Similar problems beset the use of the Derriford Appearance Scale (DAS-​59) which was developed primarily for the evaluation of outcomes of cosmetic surgical procedures (Harris and Carr, 2001). The Strengths and Difficulties Questionnaire (SDQ) is a generic behavioural screening questionnaire for mental disorders in children (aged 3–​16 years); normative values are available for children in the United Kingdom which enables comparison with cleft patients (Goodman, 2001). The Orthognathic Quality of Life Scale (OQLS) is a condition-​ specific quality of life measure that assesses functional and appearance-​ related issues in patients with severe dentofacial deformity who are considering orthognathic treatment (Cunningham et al., 2000).

Audiological measures The association between hearing loss and cleft palate is well established and is usually conductive in nature due to middle ear effusions; late sequelae include tympanic scarring, adhesions, and perforation (Grant et al., 1988). In the United Kingdom, the frequency of hearing assessment is dictated by clinical need. At the 5-​yearly audit points, pure tone audiometry is used to identify hearing threshold levels and tympanography is used to establish tympanic membrane compliance. The use of ventilation tubes (grommets) and/​or hearing aids should also be documented.

Dental health and alveolar bone grafting outcomes It is known that patients with orofacial clefts are prone to poor dental health (Chapple and Nunn, 2001). A key global index used to assess the extent of dental caries is the Decayed, Missing, Filled Teeth score, which has been adopted by the World Health Organization (Klein and Palmer, 1938). It is based on clinical examination rather than radiographs. When expressed in lower case (dmft), the index refers to the primary dentition, while when in upper case notation (DMFT), it appertains to the secondary dentition. The assessment of outcome following secondary alveolar bone grafting is performed both clinically and radiographically (Guo et  al., 2011). Two scoring systems are in widespread use. One method focuses on the height of the interdental septum adjacent to the erupted canine, and is based on radiographs taken 12 months after grafting (Bergland et  al., 1986). An alternate approach is to compare the pre-​and postoperative anterior occlusal radiographs and grade the degree of ‘bone fill’ within the alveolar cleft; this can be applied at any time after bony integration has occurred (Kindelan et al., 1997). The latter index is commonly used in the United Kingdom as it can be employed prior to eruption of the permanent maxillary canine, although critics argue that a favourable early Kindelan score does not necessarily correlate with late clinical success (Seike et al., 2012).

Fistula rates Postoperative fistula rates vary widely in the reported literature (Hardwicke et al., 2014). Fistulae may be intentional or unplanned. In the example of a unilateral complete cleft lip and palate, the residual lingual-​alveolar and labio-​alveolar defect that remains patent until subsequent alveolar bone grafting is a planned event.

Unintended postoperative oronasal fistulae result from a failure of normal palatal wound healing usually as a consequence of unfavourable patient or surgical factors. The anatomical location of fistulae within the palate has been categorized by the Pittsburgh Fistula Classification System (Fig. 6.13.2); its widespread adoption has reduced reporting ambiguity in the literature (Smith et al., 2007). It is also helpful to consider fistulae as being either clinically asymptomatic (such as a pinhole fistula which does not require intervention) or symptomatic (i.e. one that causes significant nasal regurgitation or speech impairment that may necessitate surgical intervention).

Patient-​reported outcome measures An important division for PRO instruments is that between ‘generic’ questionnaires and ‘condition specific’ instruments. The former have been developed to evaluate health across all aspects of life, in order to set baselines for populations as a whole, and subsequently to enable valid comparisons between treated individuals and cohorts by measuring health variables before and after treatment. Some methods attempt to reduce health gain to single-​figure determinants—​the most well-​known perhaps being the QALY and the DALY (quality-​or disability-​adjusted life year, Arnesen and Nord, 1999). Although widely adopted by those who find the metric useful in evaluating treatments for planning purposes, these highly reductive measurements have strict limitations in validity and always need to be used alongside clear ‘health warnings’ when conclusions are reached. More refined and far more valid (and therefore useful) generic measures are those that use a carefully refined selection of questions to evaluate all aspects of a healthy life. A good example of this would be the Short Form 36-item (SF36) questionnaire which has items across eight domains of life including social and role functioning as well as pain and other functional matters (Ware et al., 1994). This instrument has been used alongside large population norms to assess the reported impact of diverse diseases and conditions, as well as the outcome of treatments. The clear problem with such tools is the lack of sensitivity that such ‘broad brush’ assessments embody. The subtleties of aspects of life affected by the presence of a cleft lip in an individual cannot be teased out adequately by these generic instruments, although there can be some value in their use when comparing the effectiveness of resource use for managing clefts in comparison with other conditions. There is therefore a clear need for condition specific outcome instruments. Recently, work has begun to appear around this area, including the development of the Child Oral Health Impact Profile (Broder et al., 2007) and the CLEFT-Q (Wong et al., 2013). The CLEFT-Q is a cleft-related, condition-specific instrument that measures aspects of appearance, facial function and quality of life. In contrast to legacy instruments, the CLEFT-Q has been developed with modern psychometric theory that enables the measurement of different health domains on precise, interval-level continua (akin to measuring temperature with a thermometer, or length with a ruler). Additionally, the statistical models that underpin this instrument’s development mean that briefer, personalized assessments are possible by selecting the most relevant questions for an individual, based on their previous responses, a process known as computerized adaptive testing (Harrison et al., 2019). While the CLEFT-Q has demonstrated excellent performance to-date in a large international field-test (Klassen et al., 2018), more research is needed to

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understand how to best interpret CLEFT-Q scores in clinical practice and research. For other, more specific domains of outcome, there are relatively few condition-​ specific measures currently extant. The Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) instrument has been validated to determine patient-​ reported evaluation of velopharyngeal insufficiency in speech (Skirko et al., 2013). It is not, as yet, widely used, and supplants the previous Velopharyngeal Insufficiency Quality of Life Inventory (VPIQL) instrument (Barr et al., 2007).

CUSUM methodology Cumulative sum (CUSUM) techniques are being increasingly adopted as a means of ‘real-​time’ monitoring of the outcome of surgical procedures, and are therefore a useful surrogate measure of surgical performance (Yap et al., 2007). CUSUM is a sequential analysis method that involves plotting a chart with the number of procedures in chronological order on the x-​axis and the cumulative number of a particular complication on the y-​axis. It enables trends in performance to be clearly demonstrated. Risk adjustment can be added to the chart in order to show the difference between what is expected based on patient risk factors and what is observed. It can be more constructive for teams and surgeons to concentrate on their best performances that can then be replicated (Argyris, 1991). Having gained acceptance in cardiac surgery circles, it has been applied as an early-​warning system to monitor outcomes in a burns intensive care setting (Roberts et al., 2013). In the context of cleft surgery, CUSUM can be used to identify longitudinal fluctuations in the secondary surgery rate resulting from, for example, palatal fistula repair or secondary speech surgery.

International outcome measures To date, there has been little effective standardization of outcome measure data collection, with teams throughout the world collecting and using datasets based on a wide variety of instruments. This has led to an inability to deliver valid comparisons between different management protocols or philosophical ideals surrounding treatment plans. A proposal from the International Consortium for Health Outcome Measures (Allori et al., 2017) has suggested a series of data points that could be internationally applicable and suitably shortened to enable widespread collection for international comparison. If this process succeeds in attracting a good proportion of global cleft team support, it would enable the more rapid accrual of valid data that would then enable answers to some of the questions that have beset cleft research for many years to be delivered in a shorter time frame.

Conclusion Cleft outcome measurement is a complex and rapidly evolving science. Recent crowdsourcing initiatives and advances in automatic assessment software have questioned the need for traditional ‘expert’ assessment. The last decade has also seen a paradigm shift towards patient-reported health measures, and this will enable us to capture the patent’s perspective in benchmarking exercises, studies of comparative treatment effectiveness and commissioning decisions. This

is a huge step towards better practice and a more caring means of managing this most challenging and diversely presenting condition.

REFERENCES Allori AC, Kelley T, Meara JG, et al. A Standard Set of Outcome Measures for the Comprehensive Appraisal of Cleft Care. Cleft Palate Craniofac J 2017;54(5):540–54. Argyris C. Teaching smart people how to learn. Harvard Bus Rev 1991;May–​June:99–​109. Arnesen T, Nord E. The value of DALY life: problems with ethics and validity of disability adjusted life years. BMJ 1999;319:1423–​5. Asher-​McDade C, Roberts C, Shaw WC, et  al. Development of a method for rating nasolabial appearance in patients with clefts of the lip and palate. Cleft Palate Craniofac J 1991;28:385–​90. Atack NE, Hathorn IS, Semb G, et al. A new index for assessing surgical outcome in unilateral cleft lip and palate subjects aged five: reproducibility and validity. Cleft Palate Craniofac J 1997;34:242–​6. Barr L, Thibeault SL, Muntz H, et al. Quality of life in children with velopharyngeal insufficiency. Arch Otolaryngol Head Neck Surg 2007;133:224–​9. Baudouin JY, Tiberghien G. Symmetry, averageness, and feature size in the facial attractiveness of women. Acta Psychol (Amst) 2004;117:313–​32. Bergland O, Semb G, Abyholm FE. Elimination of the residual alveolar cleft by secondary bone grafting and subsequent orthodontic treatment. Cleft Palate J 1986;23:175–​205. Broder HL, McGrath C, Cisneros GJ. Questionnaire development: face validity and item impact testing of the Child Oral Health Impact Profile. Community Dent Oral Epidemiol 2007;35(Suppl. 1):8–​19. Chapple JR, Nunn JH. The oral health of children with clefts of the lip, palate, or both. Cleft Palate Craniofac J 2001;38:525–​8. Chawla O, Deacon SA, Atack NE, et al. The 5-year-olds’ Index: determining the optimal format for rating dental arch relationships in unilateral cleft lip and palate. Eur J Orthod 2012;34:768–72. Cunningham SJ, Garratt AM, Hunt NP. Development of a condition-​ specific quality of life measure for patients with dentofacial deformity:  I. Reliability of the instrument. Community Dent Oral Epidemiol 2000;28:195–​201. Goodman R. Psychometric properties of the strengths and difficulties questionnaire. J Am Acad Child Adolesc Psychiatry 2001;40:1337–​45. Grant HR, Quiney RE, Mercer DM, et al. Cleft palate and glue ear. Arch Dis Child 1988;63:176–​9. Grunwell P, Brondsted K, Henningsson G, et  al. A six-​centre international study of the outcome of treatment in patients with clefts of the lip and palate: the results of a cross-​linguistic investigation of cleft palate speech. Scand J Plast Reconstr Surg Hand Surg 2000;34:219–​29. Guo J, Li C, Zhang Q, et al. Secondary bone grafting for alveolar cleft in children with cleft lip or cleft lip and palate. Cochrane Database Syst Rev 2011;6:CD008050. Hardwicke JT, Landini G, Richard BM. Fistula incidence after primary cleft palate repair: a systematic review of the literature. Plast Reconstr Surg 2014;134:618e–​27e. Harris DL, Carr AT. The Derriford Appearance Scale (DAS59):  a new psychometric scale for the evaluation of patients with disfigurements and aesthetic problems of appearance. Br J Plast Surg 2001;54:216–​22. Harrison CJ, Ottenhof MJ, Klassen AF, et al. Computerised adaptive testing accurately predicts CLEFT-Q scores by selecting fewer, more patient-focused questions. J Plast Reconstr Aesthet Surg 2019;72(11):1819–24.

6.11  Outcome assessment in cleft lip and palate surgery

Hathaway R, Daskalogiannakis J, Mercado A, et  al. The Americleft study: an inter-​center study of treatment outcomes for patients with unilateral cleft lip and palate part 2. Dental arch relationships. Cleft Palate Craniofac J 2011;48:244–​51. Henningsson G, Kuehn DP, Sell D, et al. Universal parameters for reporting speech outcomes in individuals with cleft palate. Cleft Palate Craniofac J 2008;45:1–​17. Huang WJ, Taylor RW, Dasanayake AP. Determining cephalometric norms for Caucasians and African Americans in Birmingham. Angle Orthod 1998;68:503–​11. Hutters B, Henningsson G. Speech outcome following treatment in cross-​linguistic cleft palate studies:  methodological implications. Cleft Palate Craniofac J 2004;41:544–​9. John A, Sell D, Sweeney T, et al. The cleft audit protocol for speech-​ augmented:  a validated and reliable measure for auditing cleft speech. Cleft Palate Craniofac J 2006;43:272–​88. Kindelan JD, Nashed RR, Bromige MR. Radiographic assessment of secondary autogenous alveolar bone grafting in cleft lip and palate patients. Cleft Palate Craniofac J 1997;34:195–​8. Klassen AF, Wong Riff KWY, Longmire NM, et al. Psychometric findings and normative values for the CLEFT-Q based on 2434 children and young adult patients with cleft lip and/or palate from 12 countries. CMAJ 2018;190(15):E455–E462. Klein H, Palmer CE. Studies on dental caries. Public Health Rep 1938;53:1685–​90. Lohmander A, Olsson M. Methodology for perceptual assessment of speech in patients with cleft palate: a critical review of the literature. Cleft Palate Craniofac J 2004;41:64–​70. Lohmander A, Willadsen E, Persson C, et al. Methodology for speech assessment in the Scandcleft project—​an international randomized clinical trial on palatal surgery: experiences from a pilot study. Cleft Palate Craniofac J 2009;46:347–​62. Mars M, Plint DA, Houston WJ, et  al. The Goslon Yardstick:  a new system of assessing dental arch relationships in children with unilateral clefts of the lip and palate. Cleft Palate J 1987;24:314–​22. Meyer-​Marcotty P, Alpers GW, Gerdes AB, et al. Impact of facial asymmetry in visual perception:  a 3-​dimensional data analysis. Am J Orthod Dentofacial Orthop 2010;137:168.e1–​8. Molsted K, Brattstrom V, Prahl-​Andersen B, et  al. The Eurocleft study: intercenter study of treatment outcome in patients with complete cleft lip and palate. Part 3: dental arch relationships. Cleft Palate Craniofac J 2005;42:78–​82. Morrant DG, Shaw WC. Use of standardized video recordings to assess cleft surgery outcome. Cleft Palate Craniofac J 1996;33:134–​42. Okada Ozawa T, Shaw W, Katsaros C, et al. A new yardstick for rating dental arch relationship in patients with complete bilateral cleft lip and palate. Cleft Palate Craniofac J 2011;48:167–​72. Phillips JH, Nish I, Daskalogiannakis J. Orthognathic surgery in cleft patients. Plast Reconstr Surg 2012;129:535e–​48e. Pigott RW, Pigott BB. Quantitative measurement of symmetry from photographs following surgery for unilateral cleft lip and palate. Cleft Palate Craniofac J 2010;47:363–​7.

Roberts G, Thorburn G, Collins D, et  al. Development and implementation of prospective outcome monitoring in a regional burns service using cumulative sum (CUSUM) techniques. Burns 2013; 39:571–​6. Rosenberg M. Society and the Adolescent Self-​ Image. Princeton, NJ: Princeton University Press, 1965. Seaward JR, Hallac RR, Vucovich M, et al. Improving the accuracy of automated cleft speech evaluation. J Craniomaxillofac Surg 2018;46(12):2022–26. Seike T, Hashimoto I, Matsumoto K, et al. Early postoperative evaluation of secondary bone grafting into the alveolar cleft and its effects on subsequent orthodontic treatment. J Med Invest 2012;59:152–​65. Sell D, Harding A, Grunwell P. A screening assessment of cleft palate speech (Great Ormond Street Speech Assessment). Eur J Disord Commun 1994;29:1–​15. Sell D, Harding A, Grunwell P. GOS.SP.ASS.’98:  an assessment for speech disorders associated with cleft palate and/​or velopharyngeal dysfunction (revised). Int J Lang Commun Disord 1999;34:17–​33. Sescleifer AM, Francoisse CA, Webber JC, et al. Transforming assessment of speech in children with cleft palate via online crowdsourcing. PLoS One 2020;15(1):e0227686. Sharma VP, Bella H, Cadier MM, et al. Outcomes in facial aesthetics in cleft lip and palate surgery: a systematic review. J Plast Reconstr Aesthet Surg 2012;65:1233–​45. Skirko JR, Weaver EM, Perkins JA, et al. Validity and responsiveness of VELO:  a velopharyngeal insufficiency quality of life measure. Otolaryngol Head Neck Surg 2013;149:304–​11. Smith DM, Vecchione L, Jiang S, et  al. The Pittsburgh Fistula Classification System: a standardized scheme for the description of palatal fistulas. Cleft Palate Craniofac J 2007;44:590–​4. Tothill C, Mossey PA. Assessment of arch constriction in patients with bilateral cleft lip and palate and isolated cleft palate: a pilot study. Eur J Orthod 2007;29:193–​7. Trotman CA, Faraway JJ, Essick GK. Three-​dimensional nasolabial displacement during movement in repaired cleft lip and palate patients. Plast Reconstr Surg 2000;105:1273–​83. Tse RW, Oh E, Gruss JS, et al. Crowdsourcing as a Novel Method to Evaluate Aesthetic Outcomes of Treatment for Unilateral Cleft Lip. Plast Reconstr Surg 2016;138(4):864–74. Vucovich M, Hallac RR, Kane AA, et al. Automated cleft speech evaluation using speech recognition. J Craniomaxillofac Surg 2017;45(8)1268–71. Ware JE, Kosinski M, Keller SD. SF-​36 Physical and Mental Health Summary Scales:  A User’s Manual. Boston, MA:  Health Institute, New England Medical Center, 1994. Whitehill TL. Assessing intelligibility in speakers with cleft palate: a critical review of the literature. Cleft Palate Craniofac J 2002;39:50–​8. Wong KW, Forrest CR, Goodacre TE, et  al. Measuring outcomes in craniofacial and pediatric plastic surgery. Clin Plast Surg 2013;40:305–​12. Yap CH, Colson ME, Watters DA. Cumulative sum techniques for surgeons: a brief review. ANZ J Surg 2007;77:583–​6.

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6.12

Secondary surgery in cleft lip and palate Peter D. Hodgkinson

Introduction Secondary surgery in patients with cleft lip and palate should be undertaken within an experienced cleft multidisciplinary cleft team (which includes surgeons, speech and language therapists, psychologists, orthodontists, and dentists) where such expertise is available. The requirements of patients considering secondary cleft surgery are more similar to the requirements of patients undergoing primary surgery than they are to other non-​cleft, facial surgery patients.

Secondary cleft lip and palate surgery Individuals with cleft lip and palate contemplating secondary surgery fall into two broad classes: • Planned secondary care or surgery: this group comprises patients who have been treated within a planned cleft care pathway and who have completed the treatment of the primary cleft problem (i.e. alveolar bone grafting, speech surgery, and palatal fistula surgery). Such patients may remain within the established care pathway or may have returned following completion of the primary cleft care pathway. • Unplanned secondary care or surgery:  this cohort includes the patients who return to cleft care with deficiencies of primary treatment, those who may have opted out of the care pathway prematurely, or those who did not have access to a coordinated multidisciplinary care pathway. The second group is more complex although for either group there is no standardized surgical package. An acceptable outcome for the unplanned secondary care group may be to achieve the position they would have reached had they followed a coordinated care pathway. Surgical procedures to improve speech, palatal integrity, and alveolar bone grafting may be required. These are considered elsewhere (see Chapter  6.10 and Chapter  6.13). For the planned secondary surgery group, the aim is to improve upon the outcome of the completed care pathway, and, although in this group the

starting position may be better, the level of expectation may be higher. In the unplanned group, facial growth is usually complete whereas patients in the planned group may or may not have completed facial growth. In these cases, additional psychological support for the patient and their family by the cleft team may be necessary. The severity and effects of the problem to be corrected and the timing of secondary procedures in relation to facial growth have to be carefully considered (Byrd and Beale, 2015). In most cases it is preferable to wait for growth to be complete. Nasal growth tends to cease in females at 12 years and males at 15 years (Akgüner et al., 1998). Facial skeletal maturity is achieved with maturation of the mandible at 16–​18 years in females and 18–​21 years in males (Sharma et al., 2014).

Multidisciplinary team assessment All patients initially require complete multidisciplinary assessment, including speech and language, dental, orthodontic, and surgical assessment. This is easier in the planned secondary care group but is no less essential. Additionally, all patients benefit from a complete diagnostic analysis including a psychological assessment. Psychological assessment can include consideration with the patient of the risks and benefits of secondary procedures, that is, ‘What will I get out of it?’ and ‘What are the physical, emotional, time and financial costs of this treatment?’ and an assessment with the surgical team of the timeliness and appropriateness of secondary procedures. The involvement of a clinical psychologist can identify any issues related, or unrelated, to the cleft that remain from childhood into adulthood. Additionally, appropriate levels of expectation can be set.

Surgical procedures Surgical procedures may need to be coordinated, or combined with orthodontics, speech assessment, and audiological and

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SECTION 6  Craniofacial and cleft

airway evaluations. Individual surgical procedures can on occasion be combined, for example, unilateral cleft lip re-​repair and nose revision, or may need to be undertaken sequentially. Surgical procedures need to be sequenced correctly and a long-​term plan made with the patient, for example, postponing rhinoplasty until after orthognathic surgery. Maxillary hypoplasia should be recognized as this may perpetuate secondary problems following primary lip repair. Such sequencing is reconciled with the wishes of the patient. Unilateral and bilateral cleft lip patients have more similarities than differences. In particular, almost all bilateral cleft lip babies have some asymmetry of their primary deformity and this remains into adulthood. Secondary surgical procedures appropriate to cleft lip and palate patients include: • Revision lip surgery. • Adjunctive alveolar and maxillary surgery. • Orthognathic surgery. • Revision nasal surgery. • Adjunctive facial procedures.

Revision lip surgery Common problems following cleft lip repair may be in relation to the form of the lip, the scar, or a combination of both and include: • Discontinuity or notching of the vermillion margin. • Differences in fullness of the vermillion and wet–​dry line mismatch with ulceration of exposed wet vermillion. • Vertically short lip. • Suture marks or wide irregular scar. • Blurring, discontinuity, or a step in the white roll at the mucocuta­ neous junction. • Hair-​bearing skin from the nose within the scar on the lip or within the buccal sulcus. • In bilateral clefts, retention of the central vermillion of the pro­ labial segment. In any lip in which secondary surgery is being considered, it is rare for there to be only one problem. Therefore, unless an isolated and specific cause of secondary lip deformity is identified, the most appropriate plan is often to undertake a complete re-​repair of the lip. Lip re-​repair is better performed when there are no adjacent orthodontic brackets. Preferably growth should be complete so that the lip scar does not have to expand with growth but can be considered from relatively early teenage years. A re-​repair based on a modified rotation advancement pattern is preferred by the author even if the original operation utilized a different system. Anatomical subunit approaches may also be used. At operation, the primary landmarks are usually identifiable on either side of the existing scar. It is not uncommon for aberrant attachments of the orbicularis oris to the anterior nasal spine and alar base to remain; observing the patient pouting and smiling can identify these. Notched lips are more often caused by tightness or shortness of the mucosal scar on the inner aspect of the lip than the cutaneous scar. There is often weakness of the orbicularis repair at the

vermillion margin. Commonly, there is inadequate repair of the superior end of the lip within the nostril sill. In bilateral cases, lip re-​repair is the preferred secondary procedure. Lack of transverse width of the upper lip requiring cross-​ lip transfer (Abbé flap; see Chapter 8.12) has not been identified in the author’s practice even in cases in which the prolabial skin has previously been completely excised. Bilateral lip re-​repair has been found to produce a superior aesthetic outcome even when, in a small number of cases, this has involved the removal of cross-​lip transferred tissue. The sequence for lip re-​repair includes: • Skin marking as for a primary lip repair using the ‘normal’ primary landmarks (particularly the white roll, Cupid’s bow, and red line) and incorporating a Z-​or hemi-​Z-​plasty into the vermillion. • Excision of the scar through the all three lip layers (skin, muscle, mucosa). • Extension of the lateral mucosal incision along the upper buccal sulcus. • Extension of the cutaneous incision around the alar base at the junction of lip and ala to allow access to the upper orbicularis oris fibres so that they can be redirected across the nostril sill. While others suggest this results in unsightly scarring, the author has not observed this. • Subperiosteal mobilization of the lateral and medial elements of the lip. • Repair of the mucosal surface. • Anatomical repair of the orbicularis oris. Particular emphasis is given to repairing muscle throughout the full lip height; from nasal sill superiorly, down to the red line (wet–​dry junction) inferiorly. Superiorly, the mobilized muscle fibres from beneath the nasal ala must be repaired across the nostril sill to the region of the anterior nasal spine. From the vermillion margin, inferiorly a two-​layered muscle repair should be performed: ■ From the vermilion to the red line, a deeper muscle layer should first be created. ■ From the nadir at the red line the repaired muscle should turn superiorly, and by a separate superficial muscle layer, ascend to the level of the white roll to reconstruct the J-​shape of the orbicularis oris thus recreating the pout at the vermilion tubercle (see section on ‘Anatomy and subunits’ in Chapter 8.12). • Skin repair—​most often using fine (7/​0 or 8/​0) absorbable sutures and glue. Even after lip re-​repair the vermillion on cleft or both sides may lack fullness. Fat transfer may be performed contemporaneously or subsequently (Niechajev, 2000; Crawford et al., 2010). It may need to be repeated. Occasionally, a dermal fat graft, usually from the groin, may be needed. For some patients, adjunctive lip procedures including medical tattooing of the lip line and dry needling of the scars may be helpful. In the few cases where a specific and single problem is identified, a minor lip revision may be performed (Byrd and Beale, 2015):

6.12  Secondary surgery in cleft lip and palate

• Minor vermilion mismatch (50% lip width) may be reconstructed with bipedicled, contralateral labial mucosal flaps. Two-​stage tongue flaps are described; the papillated dorsum yields suboptimal aesthetic results in contrast to reconstruction using vermilion or mucosa. Meshing techniques are reported when there is limited mucosa.

Full-​thickness lip reconstruction Small defects (less than one-​third width)

Fig. 8.12.3  Blood vessels of the lips.

avoided. Discrete skin-​only defects, especially in the upper lip, may be reconstructed with local flaps and full-​thickness skin grafts.

Vermilion reconstruction Small mucosa-​only defects may be reconstructed using labial mucosal advancement flaps (Coppit et al., 2004). The vermilion border is incised as much as is required from commissure to commissure and dissection performed between the submucosal glands and muscle to the gingivolabial sulcus. The flap is advanced to cover the exposed muscle. This can be performed as a V–​Y advancement flap or using tension-​relieving incisions (Fig. 8.12.4). Dermal grafting or lipofilling may ameliorate postoperative lip thinning or retraction. A  musculocutaneous V–​Y advancement flap followed

Fig. 8.12.4  V–​Y mucosal advancement flap.

Defects less than 25% of the lower lip width and 30% of the upper lip may be closed directly (Anvar et  al., 2007). However, up to 45% width lower lip defects have been reconstructed using full-​ thickness ‘V-​wedge’ incisions (Baumann and Robb, 2008). The angle of the vertex of the wedge should not exceed 30°, to minimize a standing cone, and the incision should not traverse the mental crease. If these criteria cannot be achieved a W-​plasty should be considered (McCarn and Park, 2005). Pentagonal techniques and barrel excisions are described (Figs. 8.12.5–​8.12.7). Direct closure and local tissue usage reduces donor-​site morbidity, provides optimal tissue texture and colour match, and is a single procedure, providing innervated, muscular continuity (Coppit et al., 2004).

Large defects (one-​to two-​thirds width defects) Defects between a quarter and two-​thirds of the total lip width may be reconstructed using cross-​lip flaps (Sabattini–​Abbé and Estlander flaps), circumoral rotation-​advancement flaps (Karapandzic, Gillies’ fan, and McGregor flaps), mucosal, and tongue flaps. Sabattini–​Abbé flap First described by Sabattini (1838) and popularized by Abbé (1898), this cross-​lip flap corrects central upper lip and, with the reversed type of flap, up to 50% lower lip width defects with an intact commissure (Fig. 8.12.8). By preserving muscle continuity and fibre alignment

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Fig. 8.12.5  V-​wedge excision and direct closure.

Fig. 8.12.6  W-​plasty and direct closure.

it facilitates sphincteric reconstruction. The flap should be approximately half the width and an identical height as the defect. The lateral reverse variation of this flap is usually supplied by the medial labial artery and, unlike the Estlander flap, the commissure does not move. It is applicable for reconstruction of lateral lower lip defects where direct closure is not possible. The philtrum position may move. The central reverse variation of this flap is often used for central lower lip defects with vascular supply typically coming from the lateral labial artery. As there is no significant venous drainage, sufficient tissue must be incorporated to aid venous return. A small cuff of muscle helps preserve the vascular pedicle. Preserving the labial artery, the flap is produced by full-​thickness incisions and rotated 180° into the defect. A soft diet is advisable before pedicle division after at least 2–​3 weeks of vascular ingrowth. Flap viability may be confirmed by clamping the pedicle prior to division.

touch, then temperature around 6–​18 months. Flaps may be hypersensitive but this usually settles after 1 year (Anvar et al., 2007).

Estlander flap (1872)

Karapandzic flap

This provides single-​stage commissure reconstruction by utilizing a full-​thickness commissural triangular flap, of equal height and one-​half the defect width, rotated from one lip to the other facilitating a proportional reduction in both lips (Fig. 8.12.9). Again, a muscular cuff is preserved at the rotation point to maintain flap vascularity. The vascular supply from the contralateral labial artery may be tenuous, oral animation and the modiolus may be distorted; commissuroplasty may be necessary later. Like all cross-​lip flaps, it is initially insensate. The order of sensory recovery is typically pain,

Karapandzic (1974) modified Gilles’ flap using a one-​ stage, circumoral flap for reconstructing central lower lip defects (Fig. 8.12.11). Radial incisions across the outer perioral area allow medial flap rotation-​advancement while preserving muscle innervation. Crucially, lip defect height should be translated into flap width. The literature is equivocal whether incisions should commence in the nasolabial fold or arise from the defect potentially running parallel to the nasolabial fold; both give acceptable donor-​site morbidity (Ong et al., 2005). Even flap thickness is important.

Gillies’ fan flap This myocutaneous flap of remaining lip and a component of adjacent ipsilateral lip, pivots at a point neighbouring the commissure (Fig. 8.12.10). In lower lip reconstruction, a full-​thickness fan shape emanates from the defect’s caudal aspect, continuing laterally around the commissure and cephalad into the nasolabial fold (McCarn and Park, 2005). A back-​cut towards the upper lip, without damaging the superior labial artery, facilitates rotation-​ advancement; Z-​ plasty may improve rotation. Gillies’ flap recruits greater tissue so minimizing the risk of microstomia. Neuromuscular recovery may not occur, leading to oral incompetence and a rounded commissure.

8.12 Lip reconstruction

Fig. 8.12.7  Direct closure using barrel excisions allows rotation and advancement of the cheek and lip to facilitate closure (Schuchardt procedure).

Unlike Gillies’ flap, the mucosa is cut only as much as necessary to allow closure; typically 1–​2 cm from the defect. The labial arteries and nerves are preserved by careful longitudinal spreading and blunt dissection before orbicularis fibre division. The completed reconstruction circularizes the existing sphincter allowing sphincteric sensation, functional competence, and preserves the cosmetically sensitive philtrum and modiolus. If used for large defect reconstruction (over two-​thirds lip width) microstomia may occur, at least initially. Care must be taken performing this technique following a neck dissection as the facial artery, and

(a)

therefore flap blood supply, may be compromised. It is best suited for central, rectangular defects with an intact commissure. It can reconstruct up to two-​thirds of the lower lip and half of the upper lip. Johanson’s step technique (1974) For lower lip reconstruction, this technique may be used unilaterally for lateral defects or bilaterally for central defects by creating step cuts along the labiomental folds (Fig. 8.12.12). These commence at the caudal defect margin becoming progressively smaller. The

(b)

Fig. 8.12.8  Sabattini–​Abbé flap. Wedge resections may allow sufficient lip advancement.

(c)

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SECTION 8  Head and neck surgery

Fig. 8.12.9  Estlander flap. (a)

(b)

Fig. 8.12.10  Gillies’ fan flap. (a)

Fig. 8.12.11  Karapandiz flap.

(b)

8.12 Lip reconstruction

(a)

(b)

Fig. 8.12.12  Johanson’s step technique.

last step incorporates standing cone excision as a triangular wedge. Sequential advancement of tissue ‘up’ the steps allows reconstruction and often preserves sensation, muscle innervation and fibre orientation. However, conspicuous scarring is documented. When used with other flaps it may close large defects (>50% lip width), otherwise microstomia may result. Roldán and colleagues (2007) reported superior aesthetic and functional results using the step technique alone or combined with a cross-​lip flap to reconstruct up to two-​thirds of the lower lip when compared to a Webster–​Bernard flap or direct closure.

lip defects. However, this admirable outcome may be acquired in defects one-​third to two-​thirds of lip width. It may be adynamic, resulting in poor oral competence; performing skin only Burow’s triangle excision may reduce neurovascular injury. Central lip incision notching and gingivobuccal sulcus effacement may occur. McGregor flap

To avoid microstomia, reconstruction of over two-​thirds of the lip usually requires recruitment of regional tissue.

McGregor’s (1983) modification of Gillies’ flap uses a rectangular myocutaneous flap of three equally sized squares, recruiting tissue to avoid microstomia (Fig. 8.12.14). Here, the pivot point is commissural, allowing the commissure to stay in an identical position. The medial flap margin becomes neovermilion. Therefore, the reconstructed lip lacks vermilion, but is repairable with a tongue or mucosal flap. Spinchteric function may be compromised as muscle fibres rotate 90°.

Webster–​Bernard flap

Cheek flaps

Bernard first reported lower lip reconstruction using cheek flap medial advancement. From the commissure a horizontal full or partial-​thickness incision is made half the length of the horizontal lip defect. Webster’s modification (Webster, 1960) utilizes excision of Burow’s triangles of standing cones at the superior (nasolabial fold) and inferior flap (labiomental crease) margins facilitating medial advancement of the lower lateral lip elements without cheek distortion (Fig. 8.12.13). Chin–​cheek junction skin laxity means the inferior incision can usually be advanced without resecting Burow’s triangles. Incisions are made down to the mucosa. The mucosa, while incised medially, need not be cut laterally as this stretches with tissue advancement, preserving the intraoral lining. Medially, mucosa maybe incised above the cutaneous flap to facilitate vermilion reconstruction. The vascular supply may be compromised in those undergoing neck dissection. While originally this technique was as a full-​thickness reconstruction, skin only excision may be performed. This technique is independent of the amount of residual lip; if performed bilaterally it may reconstruct total or subtotal lower

Large lip defects may be reconstructed using cheek flaps. Sliding lateral cheek flaps are limited by high-​morbidity, full-​thickness incisions traversing the cheek to the pretragal area and potential facial nerve and parotid duct damage. Often better are rotational flaps designed in the nasolabial fold as wide as the defect is high; if full thickness they relinquish upper lip innervation. Fujimori’s (1980) gate flap uses bilateral nasolabial flaps for total lower lip reconstruction.

Subtotal full-​thickness defects (more than two-​thirds  width)

Total lip reconstruction When over three-​quarters of the lip requires reconstruction, combined techniques or free tissue transfer may be required (Westreich et al., 2008).

Combined flaps Ong and colleagues (2005) reconstructed over 80% of the lower lip using combined bilobed and Karapandzic flaps. Excellent results are

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SECTION 8  Head and neck surgery

(a)

(b)

(c)

(d)

Fig. 8.12.13  Webster–​Bernard  flap.

reported following combined Karapandzic and Webster–​Bernard flaps to reconstruct 50–​90% defects of the lower lip (Westreich et al., 2008).

Regional flaps Trauma or widespread disease may prohibit local tissue use; regional flaps, including bipedicled submental or anterior scalp flaps, may be an option. These reconstruct vertical lip height and provide a platform for opposite lip abutment but are adynamic, having minimal substance or muscle. Deltopectoral and pectoralis major myocutaneous flaps are described for total lower lip reconstruction.

Free flaps The radial forearm flap, transferred with the palmaris longus tendon and attached to the modiolus, the orbicularis, or both for lip support, is well reported (Baumann and Robb, 2008). The tendon should be transected with 5 cm length at either end of the flap. Coaptation of a forearm cutaneous nerve to the mental or inferior alveolar nerve means this flap can be sensate. Total lower lip reconstruction has

been documented using a neurotendinofasciocutaneous anterolateral thigh flap, prefabricated free gracilis flap with tensor fascia lata, and parascapular flaps. Following resection, the cheek and lip divided ends retract. These should be placed under physiological tension allowing accurate three-​dimensional template design representing the mucosal and cutaneous deficit. A combined temporalis myoplasty may allow dynamic reconstruction.

Upper lip considerations The unique anatomical topography and male hair-​bearing skin pattern should be considered; scalp or neck hair-​bearing flaps can be utilized (McCarn and Park, 2005). Crescentic peri-​alar cheek excision facilitates upper lip flap advancement without distorting nasal tissue (Fig. 8.12.15) (Webster, 1955). In selected patients with upper lip cutaneous-​only defects, such flaps have reconstructed 35% width defects (Baumann and Robb, 2008). Sabattini–​Abbé flaps are often advantageous over other techniques by conserving the Cupid’s bow,

8.12 Lip reconstruction

(a)

(b)

(c)

(d)

Fig. 8.12.14  McGregor flap.

oral commissure, and modiolus—​key structures which are difficult to reconstruct.

Revisions Following extensive lip reconstruction and adjuvant treatment, patients may benefit from revisional surgery. The same reconstructive

(a)

(b)

Fig. 8.12.15  Webster’s crescentic peri-​alar cheek excision facilitates upper lip flap advancement.

principles apply in concert with appreciation of the patient’s aims. Facial artery musculomucosal flaps, mucosal advancement flaps, and tongue flaps may improve the vermilion. Gingivobuccal sulcus deepening by intraoral scar release and grafting may aid management of secretions and liquids. Lip and chin aesthetic units can be reconstructed with full-​thickness skin grafts. Commissuroplasty, using modified Estlander and Webster–​Bernard flaps, may correct microstomia or commissure rounding.

Conclusion Lips are vital functionally and socially for eating, speech, and intimate interaction. Reconstruction should observe the principles of anatomical subunit reconstruction and aesthetic proportion, while preserving oral continence and preventing microstomia. Meticulous anatomical alignment is important, particularly of the muscle and mucocutaneous junction. In smaller lip defects, direct closure and dynamic reconstructions, utilizing local tissue, often yield superior results. Large defects may require free tissue transfer which provides static lip support. Figs. 8.12.16–​8.12.18 provide a pragmatic reference for management options. The individual’s

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Superficial lip defects

Small, vermilion only

Small, crosses vermilion border

Large, confined to vermilion

Direct closure, secondary healing

Direct closure (accurate vermilion– cutaneous opposition)

Labial flap, mucosal graft

Fig. 8.12.16  Management of superficial lip defects without muscle involvement.

Upper lip defects

2/3

Sufficient adjacent lip/cheek tissue

Commissure

Karapandzic flap, Sabattini–Abbé flap

Karapandzic flap, Estlander flap

Central

Insufficient adjacent lip/cheek tissue

Commissure

Webster-BernardBurow flap +/– bilateral Abbé flap

Regional flap, free flap

Full-thickness nasolabial transposition flap

Fig. 8.12.17  Management of full-​thickness upper lip defects.

Lower lip defects

2/3

1/3–2/3

Central

Karapandzic flap, Sabattini–Abbé flap, Step flap

Sufficient adjacent lip/cheek tissue

Commissure

Microstomia unlikely

Microstomia likely

Webster–Bernard flap +/– bilateral Abbé flap Combined Karapandzic/ Webster-Bernard flap

Estlander flap, Karapandzic flap, Step flap

Fig. 8.12.18  Management of full-​thickness lower lip defects.

Gilles fan flap, nasolabial flap

Insufficient adjacent lip/cheek tissue

Regional flap, free flap

8.12 Lip reconstruction

defect, local tissues, and most importantly, the patient, may say something else.

REFERENCES Abbé R. A new plastic operation for the relief of deformity due to double harelip. Med Rec 1898;53:477. Anvar BA, Evans BCD, Evans GRD. Lip reconstruction. Plast Reconstr Surg 2007;120:57e–​64e. Baumann D, Robb G. Lip reconstructions. Semin Plast Surg 2008; 22:269–​80. Coppit GL, Lin DT, Burkey BB. Current concepts in lip reconstruction. Curr Opin Otolaryngol Head Neck Surg 2004;12:281–​7. Estlander JA. Eine methode aus der einen lippe substanzverluste der anderen zu ersetzen. Arch Klin Chir 1872;14:622–​6. Fujimori R. ‘Gate flap’ for the total reconstruction of the lower lip. Br J Plast Surg 1980;33:340–​5. Johanson B, Aspelund E, Breine U, et  al. Surgical treatment of non-​ traumatic lower lip lesions with special reference to the step technique. A follow-​up on 149 patients. Scand J Plast Reconstr Surg 1974;8:232–​40. Karapandzic M. Reconstruction of lip defects by local arterial flaps. Br J Plast Surg 1974;27:93–​7. McCarn KE, Park SS. Lip reconstruction. Facial Plast Surg Clinic North Am 2005;13:361–​80.

McGregor IA. Reconstruction of the lower lip. Br J Plast Surg 1983;36:40–​7. Ong WC, Lim J, Lim TC. A modification of the bilobed and Karapandzic flap used for reconstruction of the lower lip. Plast Reconstr Surg 2005;115:2154–​5. Roldán JC, Teschke M, Fritzer E, et  al. Reconstruction of the lower lip: rationale to preserve the aesthetic units of the face. Plast Reconstr Surg 2007;120:1231–​9. Sabattini P. Rinoplastica e Cheiliplastica operate sopra un solo individuo. Bull Sci Med (Bologna) 1838;10:387. Webster JP. Crescentic peri-​alar cheek excision for upper lip flap advancement with a short history of upper lip repair. Plast Reconstr Surg 1955;16:434–​58. Webster RC, Coffey RJ, Kelleher RE. Total and partial reconstruction of the lower lip with innervated muscle-​bearing flaps. Plast Reconstr Surg Transplant Bull 1960;25:360–​71. Westreich R, Meissner J, Reino A, et al. The use of combined Bernard-​ Webster and Karapandzic flaps for subtotal lower lip reconstruction. Plast Reconstr Surg 2008;121:340e–​1e. Yano K, Hosokawa K, Kubo T. Combined tongue flap and V-​Y advancement flap for lower lip defects. Br J Plast Surg 2005; 58:258–​62. Zide BM, Swift R. How to block and tackle the face. Plast Reconstr Surg 1998;101:840–​51.

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8.13 Cheek reconstruction

8.13

Cheek reconstruction Matthew Potter

Anatomy The bony foundations of the cheek are the zygoma forming the zygomatic arch, the maxilla, superiorly the orbital rim comprising nasal, maxillary, and lacrimal bones, and laterally the zygomaticofrontal suture. Inferiorly lies the body of the mandible and the mandibular alveolus. Suspended over the cheek lie the muscles of facial animation. These lie within the cheek fat as a panniculus carneosus. These are animated from the zygomatic, buccal, and marginal mandibular branches of the facial nerve. The facial muscles of animation lie external to the muscles of mastication. Masseter is the only palpable masticatory muscle within the cheek. It attaches to the angle of the mandible and gives definition to the frontal facial view. The sensory innervation to the cheek is that of the trigeminal nerve branches; infraorbital, zygomaticofacial, auriculotemporal, and mental nerves. Laterally, the cheek is filled with the parotid gland and its anterior accessory parotid gland. Overlying the parotid lies the superficial musculoaponeurotic system (SMAS). This is a superficial facial layer that separates the underlying parotid gland and muscles of facial expression from the overlying skin and subcutaneous fat. It is substantial laterally.

Aesthetics The cheek skin is anisotropic (Cox, 1942). Its position varies according to the pull of the underlying muscles. These impart areas of skin tension within the cheek due to the interaction of intrinsic and extrinsic forces. These resultant relaxed skin tension lines (RSTLs) are perpendicular to the orientation of underlying muscles of facial expression (Borges, 1984). They guide the surgeon to the placement of incision lines, which should be parallel to the RSTLs. The tension lines, skin quality, contour, and dermal thickness separate the cheek into four aesthetic units (Fig 8.13.1) (Gonzalez et al., 1954): • • • •

Medial subunit. Zygomatic subunit. Lateral subunit. Buccal subunit.

Zygomatic Medial

Lateral

Buccal

Fig. 8.13.1  The cheek is subdivided into four aesthetic subunits; the medial lying lateral to the nose and above the buccal subunit. The zygomatic subunit overlies the zygomatic arch and above the lateral subunit.

Reconstruction The sine qua non of all reconstruction is to provide a like-​for-​like reconstruction that maintains the function of all remaining parts. The aesthetics of reconstruction arguably take second place. Being prominent, however, cheek aesthetics are important. If possible, the use of local flaps provides optimum colour and texture match. However, large defects may well escape the remit of local transfer necessitating free tissue transfer as either skin or composite tissue including bone.

Reconstructive options Healing by secondary intention will arguably give the best aesthetic result. This takes time and an understanding, suitably educated patient with patient expectations managed from the outset. Areas that tolerate secondary intention well are those where scar contracture

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will not impair the function of moving parts such as lower eyelid and the lips. Areas that tolerate secondary intention well include the medial canthus, lateral nose, and preauricular area.

Direct closure It is essential that the surgeon observes the orientation of RSTLs as well as any skin folds such as the nasolabial fold or nasojugal fold. Enlarging defects to take the margin up to the aesthetic subunit border will provide a more aesthetic closure.

Skin grafts The most suitable donor sites for skin graft for the cheek are from neighbouring areas. These provide matched colour and also dermal thickness. The preauricular site is good and well hidden in the female but in the male moves hair-​bearing skin to the tragus with associated shaving issues. Other suitable areas include the postauricular sulcus, neck, or supraclavicular area.

Local flaps Local flaps ideally have their donor site scars placed within RSTLs. Common local flaps include:

The V–​Y advancement flap This is ideal for infraorbital or medial cheek defects (Sugg et  al., 2013). This flap should be sutured to periosteum to minimize

ectropion. Enlarging defects to the aesthetic subunit border and native skin creases will provide a more suitable aesthetic result (Fig. 8.13.2).

Staggered ellipse flap This is ideal for lateral cheek defects and utilizes laxity within the neck. Incisions are placed preauricularly and within a neck crease. They are discrete and well hidden. This flap will close defects up to 6–​7 cm pending laxity within the neck (Evans, 2000) (Fig. 8.13.3).

Cervico/​platysmal flap This is a posteriorly based flap that can be islanded on the superior thyroid artery perforator about the anterior aspect of the sternocleidomastoid muscle (Wilson et al., 2012) or taken as a pedicled flap if the patient has had a previous neck dissection. Either way skin can be recruited across the entire neck to the contralateral sternocleidomastoid. When transposed, the flap will reach to the zygomatic arch, the orbital rim (Fig. 8.13.4), the nose, and the upper lip. It will reach to any area within the cheek. It is thin and hair-​bearing in the male. The donor site is placed within a neck crease. Most patients have 6–​7 cm of skin excess within the neck allowing for ease of horizontal neck closure.

Cervicofacial flap This can be based either medially or laterally. A medially based flap is used for closing defects of the medial subunit mostly up to the width of an orbit (Mustardé, 1972). The flap is raised supra-​SMAS and continued into the neck either supra-​ or subplatysmal. The incision passes from the defect to the lateral brow to the preauricular area. The incision can be extended to a

Fig. 8.13.2  The V–​Y advancement flap is versatile in reconstructing medial cheek defects. It is ideal to have the medial margin of the flap within the nasolabial fold to minimize evident scarring. The flap is incised to the facial muscles. Once elevated, the flap may be secured to periosteum superiorly to minimize the chance of ectropion. Patients readily have periorbital bruising and swelling which should settle at a week.

8.13 Cheek reconstruction

Fig. 8.13.3  The staggered ellipse flap is exceptionally versatile in closing preauricular defects up to 6 cm in size. It transfers the defect from an area of limited skin laxity (the lateral cheek) to the neck where there commonly is greater than 6 cm of vertical laxity. Ideally the flap is raised in the sub-​SMAS/​ platysmal plane to maximize the vascularity. Where necessary, the ear lobule can be detached and sutured to the flap at the time of the initial closure or at a second stage if there is concern regarding flap vascularity.

neck crease. Larger flaps can be taken by recruiting postauricular skin (Fig. 8.13.5). The medially based flap has the disadvantage that the superior leading skin edge is thin. This skin is susceptible to bruising and subsequent necrosis and is often the most essential part of the

reconstruction. Secondary intention healing of this area and the resultant scar contracture may cause ectropion. Patients need to be aware of the resultant contusion and likely downtime (2 weeks). Patients’ expectations, through appropriate consent, need to be kept in line with this postoperative course.

Fig. 8.13.4  A posteriorly pedicled cervico/​platysmal flap used to reconstruct a full-​thickness defect following excision of a squamous cell carcinoma involving the medial, buccal, and zygomatic subunits of the cheek.

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Fig. 8.13.5  The cervicofacial flap is preferentially raised sub-​SMAS/​platysma. Where necessary this can be raised to the clavicle when reconstructing large defects. With significant cheek defects the medial part of the reconstruction can be grafted initially. The graft can be excised at a later date once the skin tension has eased. The flap can be sutured to the periorbita to minimize postoperative ectropion. Large flaps pass around the ear lobule to recruit postauricular skin.

A laterally based cervicofacial flap is used to reconstruct defects of the medial subunit. It is raised medial to lateral with the muscles of facial expression providing the deep plane of dissection. Its advantage is that its leading edge is thicker, more reliable, and less prone to necrosis. If large, the scars will traverse the mental area and are more noticeable. Traversing the neck recruits jowl and submental skin. While the deep plane facial muscles overlay and protect the

facial nerve, there are windows between the lip elevators in which the buccal branches of the facial nerve can be injured.

Submental artery perforator flap This flap is based on the submental artery and vein from the facial vessels. The flap’s tip is based in the contralateral neck over the contralateral anterior belly of digastric. The flap is raised from the

8.13 Cheek reconstruction

Fig. 8.13.6  The submental flap takes skin from under the mandible, islanded on the submental branch of the facial vessels. The pedicle is sufficient in length to allow any part of the cheek to be reconstructed. One needs to be cautious regarding nodal speed of cutaneous tumours as the flap takes nodes from level Ia of the neck. The flap should be raised taking the ipsilateral anterior belly of digastric. Taking this muscle allows for a more straightforward raise as well as including potential perforators to the overlying skin.

contralateral neck taking submental skin off the contralateral anterior belly of digastric and the mylohyoid muscles. The flap raising is continued by taking the ipsilateral anterior belly of digastric. The submental vessels are seen once the ipsilateral anterior belly of digastric is detached. The flap is islanded on the facial vessels which can be chased to the carotid and jugular vessels. The flap will reach any area of the cheek (Fig. 8.13.6).

Free flaps These are often the only solution in the reconstruction of large defects. Advantages: • More reliable (free flap failure rate 2–​3 years) facial palsy with absent fibrillations on EMG, and congenital facial palsy. Muscle procedures involve animating the face by either regional muscle transposition or free muscle transplant. When choosing between regional or free muscle flaps, factors to take into consideration include the age, general health, expectations and preferences of the patient, and surgeon experience. Regional muscle transposition A number of regional muscles have been used as pedicled transfers to reanimate the mouth, eyes, or both. The most commonly used muscles are the temporalis, masseter, and digastric. The advantages of regional muscle transposition

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include a single-​stage, relatively short procedure with predictable outcomes. Disadvantages include the potential lack of spontaneity and absence of emotional expression. Temporalis transfer  The temporalis muscle has been used for facial reanimation for many years. Its direction of pull is similar to that of the zygomaticus major and it is, therefore, useful for smile restoration. Gillies (1934) described a method of turning down the muscle with fascial extensions and attaching these extensions to the to the upper and lower lips. This technique is still in use today, but creates a significant bulge over the zygomatic arch. McLaughlin (1953) avoided this bulge by retaining the cranial attachments of the muscle but detaching the temporalis tendon from the coronoid process of the mandible. Fascial strips were then used to lengthen the tendon to reach the mouth. These strips could, however, stretch or potentially detach from the tendon. Labbé (1997) described a novel technique, the lengthening temporalis myoplasty, which is based up the intrinsic ability of the posterior fibres of the temporalis muscle to stretch, such that fascial extensions are not required for the tendon to reach the mouth. Labbé later introduced a modification to the technique, which required less dissection (Labbe and Huault, 2000). This procedure produces the best results of current temporalis transposition techniques. A major advantage of the temporalis muscle is the possibility to augment function in patients with partial facial palsy, or in patients who have suboptimal movement after free muscle transplant. Masseter transfer  Like the temporalis muscle, the masseter muscle is a muscle of mastication innervated by the mandibular division of the trigeminal nerve. It has a less favourable direction of pull than the temporalis, tending to produce a more lateral smile. Furthermore, transposition of the masseter can leave an unsightly depression at its former mandibular site of attachment. Because of this, it is rarely the first choice muscle transposition for facial reanimation. Instead, it is most often used when the temporalis is unavailable. Digastric transfer The digastric muscle has two bellies; a facial nerve innervated posterior belly, and a trigeminal nerve (via the nerve to the mylohyoid) innervated anterior belly, joined by an intermediate tendon. The anterior belly is, therefore, spared in facial palsy and may be used to animate the lower lip (Edgerton, 1965). Traditionally, the anterior belly is transposed to the lower lip, along with the intermediate tendon and at least half of the posterior belly, in a single operation (Conley et al., 1982). The procedure can also be performed in two stages, as described by Terzis and Kalantarian (2000), with cross-​facial nerve grafting in the first stage. In the second stage, the nerve graft is coapted to the nerve to the anterior belly of digastric before transfer to the lower lip. Digastric transfer is best performed in cases of isolated palsy of the marginal mandibular branch of the facial nerve. When performed in more globally paralysed patients, it can adversely affect oral continence. Free muscle transplant  Free muscle transplants are usually reserved for facial reanimation in relatively young, healthy patients. These procedures are traditionally performed in two stages. In the first stage, a cross-​facial nerve graft is inserted from the non-​paralysed to the paralysed side of the face. Muscle transplantation is performed 6–​12 months after the first stage, with microvascular anastomosis of the muscle vessels to vessels in the face and microneural coaptation of the muscle nerve to the cross-​facial nerve graft. The two-​stage free

muscle transplant using the contralateral facial nerve remains the gold standard in facial reanimation surgery, in that it is thought to be the only procedure that can provide a spontaneous, emotional smile. There are reports, however, of spontaneity being achieved in patients following both temporalis transfer and single-​stage free muscle transplants neurotized by the masseteric nerve. Whether or not such movements are truly emotional is open to debate. The potential disadvantages of free muscle transplants include excess bulk, tethering, and dimpling of overlying cheek skin, ipsilateral macrostomia, and unpredictable outcomes. The ideal muscle should have a reliable neurovascular pedicle, should not be too bulky, and should be relatively expendable. Although a wide variety of muscles have been used in facial reanimation surgery, most authors currently prefer the gracilis, the pectoralis minor, and the segmental latissimus dorsi.

Conclusion Many options exist for the management of facial palsy. Selection of the correct procedure is based upon an understanding of the patient’s requirements, the availability of ipsilateral nerve motors, and viable muscle targets. When applied correctly, surgical techniques can achieve good clinical outcomes.

REFERENCES Conley J, Baker DC, Selfe RW. Paralysis of the mandibular branch of the facial nerve. Plast Reconstr Surg 1982;70:569–​77. Edgerton MT. Digastric muscle transfer to correct deformity of the lower lip resulting from paralysis of the marginal branch of the facial nerve. Presented at the Meeting of the American Society of Plastic and Reconstructive Surgeons, Philadelphia, PA, October, 1965. Engström M, Berg T, Stjernquist-​Desatnik A, et al. Prednisolone and valaciclovir in Bell’s palsy:  a randomised, double-​blind, placebo-​ controlled, multicentre trial. Lancet Neurol 2008;7:993–​1000. Gardetto A, Kovacs P, Piegger J, et al. Direct coaption of extensive facial nerve defects after removal of the superficial part of the parotid gland: an anatomic study. Head and Neck 2002;24;1047–​53. Gillies H. Experiences with fascia lata grafts in the operative treatment of facial paralysis: (Section of Otology and Section of Laryngology). Proc R Soc Med 1934;27:1372–​82. Labbé D. Lengthening of temporalis myoplasty and reanimation of the lips. Technical notes [in French]. Ann Chir Plast Esthet 1997;42:44–​7. Labbé D, Huault M. Lengthening temporalis myoplasty and lip reanimation. Plast Reconstr Surg 2000;105:1289–​97. May M, Sobol SM, Mester SJ. Hypoglossal-​facial nerve interpositional-​ jump graft for facial reanimation without tongue atrophy. Otolaryngol Head Neck Surg 1991;104:818–​25. McLaughlin CR. Surgical support in permanent facial paralysis. Plast Reconstr Surg 1953;11:302–​14. Sullivan FM, Swan IR, Donnan PT, et al. Early treatment with prednisolone or acyclovir in Bell’s palsy. N Eng J Med 2007;357;16:1598–​607. Terzis JK, Kalantarian B. Microsurgical strategies in 74 patients for restoration of dynamic depressor muscle mechanism:  a neglected target in facial reanimation. Plast Reconstr Surg 2000;105:1917–​31. Terzis JK, Tzafetta K. The ‘babysitter’ procedure: minihypoglossal to facial nerve transfer and cross-​facial nerve grafting. Plast Reconstr Surg 2009;123:865–​76.

8.19

Radiology of the head and neck Ivan Zammit-​Maempel

Introduction Imaging plays an important role in the staging and follow-​up of head and neck tumours and evaluating neck masses. Radiologists also perform image-​guided biopsies, aspiration of collections within the neck, injection of botulinum toxin in postsurgical patients to reduce salivary flow or improve speech, and vascular stenting and embolization in cases of uncontrollable bleeding.

Ultrasonography Ultrasonography is quick, non-​invasive, readily available, cheap, and does not use ionizing radiation but is operator dependent. It is widely used in evaluating neck masses, the salivary and thyroid glands, and can be used to guide fine-​needle aspirations and biopsies. The verbal interaction with patients while placing the probe directly over a mass is an advantage compared to other cross-​sectional imaging (Zammit-​Maempel, 2015). Colour Doppler, elastography, and contrast agents are increasingly being used for characterization of masses (Ying et al., 2013).

Computed tomography Multislice computed tomography (CT) allows the neck to be scanned in a few seconds with high-​quality coronal and sagittal reconstructions. Its advantage over ultrasonography is in detecting masses or abscesses in the deep structures of the neck such as the retropharyngeal, prevertebral, and parapharyngeal spaces. Disadvantages include the use of ionizing radiation and artefact from swallowing or dental amalgam, but most modern scanners have built-​in radiation dose-​reduction features while gantry tilt can negate amalgam artefact. Intravenous iodinated contrast agents allow discrimination between normal tissues, inflammatory masses, and tumours. Dual-​source CT scanning, the latest breakthrough in CT technology, results in the acquisition of two image data sets in the same anatomical location with two different X-​ray spectra, thus allowing the analysis of energy-​dependent changes in the attenuation of different materials. This allows faster acquisition and sharper images and shows some promise in neck imaging (Vogl et al., 2012).

Magnetic resonance imaging The strengths of magnetic resonance imaging (MRI) are that it does not use ionizing radiation and produces images with very good soft

tissue contrast but is potentially claustrophobic and contraindicated in patients with ferromagnetic intraocular foreign bodies and certain patients with pacemakers, cochlear implants, cerebral artery aneurysm clips, and cardiac valve prostheses. The long acquisition times can result in images degraded by swallowing and movement artefact.

Positron emission tomography Positron emission tomography (PET) is a functional imaging technique that depicts tissue metabolic activity. All hypermetabolic cells, not just malignant cells, accumulate the commonly used tracer, fluorine-​18-​labelled 2-​fluoro-​2-​deoxy-​D-​glucose (FDG), resulting in increased activity as measured by standard uptake value. A major advance of PET has been the combination with CT, and more recently MRI, into a single scanner, allowing more accurate anatomical localization. It is important to note that structures including the nasal turbinates, lymphoid tissue in Waldeyer’s ring, the salivary glands, and cervical muscles normally show FDG uptake.

Plain radiographs Plain radiographs have a limited role in evaluating patient dentition, detecting ingested radio-​ opaque foreign bodies, and evaluating bone hard masses.

Lump in the neck The imaging of patients presenting with a neck lump depends on the clinical history, age of the patient, and location of the mass. Any adult presenting with a suspicious neck lump should be imaged. Ultrasound scanning can usually determine whether the mass is cystic or solid, if nodal whether it looks benign or malignant, and if not nodal may point to a specific diagnosis. Malignancy is suggested by a round rather than oval shape to the node, loss of the normal echogenic hilum, a hypoechoic appearance relative to the adjacent muscles, and by disorganized peripheral vascularity or exaggerated hilar flow (Fig. 8.19.1a). Once a node has been identified as pathological, fine-​needle aspiration can be performed (Fig. 8.19.1b). CT and MRI will allow the deeper extent of masses to be assessed. A cystic mass presenting at the angle of the mandible often causes confusion as a second branchial cleft cyst can resemble a completely

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(a)

(b)

Fig. 8.19.1  (a) A hypoechoic node with increased hilar vascularity (arrow) in non-​Hodgkin’s lymphoma. (b) A needle (arrow) traversing an abnormal node showing loss of the normal echogenic hilum. Cytology revealed melanoma.

necrotic node from a head and neck squamous cell carcinoma (SCC) or a papillary thyroid cancer. If the patient is over 40 years then metastatic SCC (Fig. 8.19.2a) needs exclusion. In a younger patient, the mass is likely to represent a branchial cleft cyst but papillary thyroid cancer needs consideration and it is essential to look for other cystic nodal masses (Fig. 8.19.2b) in levels III–​VI as the primary thyroid tumour is often very small and not detected by imaging (Wong et al., 2008). Paragangliomas are benign vascular tumours derived from primitive neural crest and occur anywhere along the carotid sheath. The carotid body tumour occurring at the carotid bifurcation, resulting in the characteristic splaying of the internal and external carotid arteries, is the commonest paraganglioma. Other common paragangliomas are the glomus vagale and glomus jugulare arising from the vagus nerve and jugular vein respectively. These tumours demonstrate intense contrast enhancement on both MRI and CT and often show a characteristic salt and pepper appearance on MRI

(a)

with the low-​signal ‘pepper’ appearance representing flow voids of feeding vessels (Fig. 8.19.3). Salivary gland masses are usually assessed by ultrasonography first, at which time fine-​needle aspiration can be performed, with CT or MRI (Fig. 8.19.4) reserved for patients with suspected involvement of the deep lobe of the parotid gland or to stage a proven malignant tumour. Thyroid gland masses should be initially evaluated by ultrasonography. Small thyroid nodules are very common and can be ignored if there are no worrying features such as microcalcification, marked hypoechogenicity, an irregular border, or a larger longitudinal than transverse dimension. CT is used in staging thyroid cancer and demonstrating tracheal narrowing or retrosternal extension in goitres. Lipomas are common in the head and neck and characteristically appear feathery on ultrasound scans and are of low attenuation on CT scans. They demonstrate high signal on T1 and T2 MRI that is lost on fat suppression sequences.

(b)

Fig. 8.19.2  (a) Low-​attenuation left level II nodal SCC mass (arrow) on contrast enhanced CT. (b) Right level IV cystic metastatic papillary thyroid cancer nodal mass (arrow) on contrast enhanced CT.

8.19  Radiology of the head and neck

Fig. 8.19.3  Axial STIR (short tau inversion recovery) MRI showing a glomus vagale as a high-​signal left carotid space mass with flow voids (arrow).

Fig. 8.19.5  Axial STIR (short tau inversion recovery) MRI showing a large, right-​sided superficial venous malformation containing a phlebolith (arrow).

Tuberculosis is commonly seen in the posterior triangle and supraclavicular groups, but may occasionally affect the pharynx or larynx. In the early stage, nodes may simply be enlarged but later the nodes adopt the classical matted appearance with central necrosis (Abdel Razek and Castillo, 2010). Low-​flow vascular malformations are commonly found in the masticator space with phleboliths seen in 22% of cases of haemangiomas (Fig. 8.19.5).

Imaging is essential to document the extent of the primary tumour, metastatic lymphadenopathy, or distant metastases. Many tumours are staged by CT as the chest and liver can be imaged at the same time as the neck, allowing the detection of distant metastases and any unsuspected bronchogenic carcinoma. MRI is useful

Fig. 8.19.4  Axial T2 MRI showing a large, high-​signal right parotid mass (arrow), surgically proven pleomorphic adenoma.

Fig. 8.19.6  Axial contrast-​enhanced CT showing a left floor of mouth tumour with associated mandibular destruction (arrow).

Head and neck cancer

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Many studies have shown a clear advantage of PET-​CT over conventional cross-​sectional imaging in patients presenting with a metastatic SCC node but no clinically overt primary tumour, the so-​called cancers of unknown primary site (Fig. 8.19.7). PET-​CT is also being routinely used in the post-​treatment patient with residual lymphadenopathy to identify patients who would benefit from neck dissection (Cashman et al., 2011).

Conclusion Imaging as a blanket screening examination should be discouraged as there is no substitute for meticulous clinical history and examination. Close cooperation between the surgeon and radiologist is the key to choosing the appropriate investigation.

REFERENCES

Fig. 8.19.7  Axial fused PET-​CT scan showing increased activity in a left level II node (single arrow) as well as within the clinically unsuspected primary tumour in the left base of tongue (double arrow).

for assessment of intracranial spread in the case of nasopharyngeal and other skull base tumours and for assessing oral cavity tumours if the CT images are degraded by dental amalgam artefact (de Bree et al., 2009). Diffusion-​weighted MRI may be useful in differentiating benign from malignant tumours, SCC from lymphoma, and recurrence from post-​radiotherapy change (Thoeny et al., 2012). Small primary tumours can be easily assessed clinically and may be difficult to see on imaging but CT or MRI can assess the size and location of larger tumours, any deep extension, or involvement of surrounding structures (Fig. 8.19.6). Lymph node status is one of the most important prognostic factors and studies have shown that imaging is more reliable than palpation (Bryson et al., 2012).

Abdel Razek AAK, Castillo M. Imaging appearance of granulomatous lesions of head and neck. Eur J Radiol 2010;76:52–​60. Bryson TC, Shah GV, Srinivasan A, et al. Cervical lymph node evaluation and diagnosis. Otolaryngol Clin North Am 2012;45:1363–​83. Cashman EC, MacMahon PJ, Shelly MJ, et al. Role of positron emission tomography-​computed tomography in head and neck cancer. Ann Otol Rhinol Laryngol 2011;120:593–​602. de Bree R, Castelijins JA, Hoekstra OS, et  al. Advances in imaging in the work-​ up of head and neck cancer patients. Oral Oncol 2009;45:930–​5. Thoeny HC, De Keyzer F, King AD. Diffusion-​weighted MR imaging in the head and neck. Radiology 2012;263:19–​32. Vogl TJ, Schulz B, Bauer RW, et  al. Dual-​energy CT applications in head and neck imaging. Am J Roentgenol 2012;199(Suppl.  5): 34–​9. Wong KT, Lee YYP, King AD, et al. Imaging of cystic or cyst-​like neck masses. Clin Radiol 2008;63:613–​22. Ying M, Bhatia KS, Lee YP, et al. Review of ultrasonography of malignant neck nodes: greyscale, Doppler, contrast enhancement and elastography. Cancer Imaging 2013;13:658–​69. Zammit-​ Maempel I. Imaging of the head and neck. Surgery 2015;33:627–​32.

8.20

Adjuvant therapy for head and neck cancers Charles Kelly

Introduction The non-​surgical management of head and neck cancer has changed over the last two decades with more emphasis given now to organ preservation and post-​treatment organ function. These two concepts do not necessarily go hand in hand but preserving an organ without preserving its function is pointless. In this period, for some head and neck cancers subsites, for example, oropharynx, the treatment model has moved away from primary surgery followed by planned, adjuvant radiotherapy, to one of primary chemoradiotherapy with the objective of greater organ and function preservation. This change in management strategy may be coming under further review now, with the introduction of transoral robotic surgery (TORS), where the treatment model may revert back to primary surgery with the question raised, whether highly selective TORS followed by highly selective adjuvant radiotherapy using the newer radiation technologies and techniques with intensity-​modulated radiotherapy (IMRT) or tomotherapy, with or without chemotherapy might optimize tumour control with minimal long-​term morbidity.

Multidisciplinary team meetings, shared decision-​making, and survivorship The decision for adjuvant or primary chemoradiotherapy is made in the multidisciplinary team (MDT) meeting. The main criticism of the MDT is that very few include the patient in the decision-​ making process and the patient and family are presented with a decision after the MDT discussion, which is thought to be the optimal management plan for that particular circumstance. These decisions may not consider patients’ preferences and objectives from treatment. In head and neck cancer, the prognostic outcomes and survival rates may be similar for surgery followed by planned adjuvant chemoradiotherapy when compared to primary chemoradiotherapy without surgery, but the potential long-​term morbidities can be very different. As more attention is now paid to potential survivorship issues, it is important for the patient’s surgeon and oncologist to inform, preferably together, patient, partner, and family of the cancer

management options with the associated potential morbidities so that the patient can make a fully informed decision. For example, voice preservation may be more important to a mid-​career opera singer than to an 80-​year-​old recluse who shuns social contact. Survivorship issues with the associated changes in quality of life are being recognized as being more and more important, as another aspect of personalized medicine. In the last decade, genomics has also led to more personalized treatment plans but this has not taken place in head and neck cancer as yet, unlike breast cancer or melanoma where genomics informs management plans to a much greater extent. There is no doubt, however, that genomics will play a greater role in the future, for example, defining those patients who will experience a more marked radiotherapy reaction for any given radiotherapy dose.

When is adjuvant chemoradiotherapy appropriate? The initial question when considering surgery and adjuvant radiotherapy or primary chemoradiotherapy, is whether functional organ preservation is possible. If it is, then for many head and neck sites, functional organ sparing should be attempted with chemoradiotherapy as primary treatment and any recurrence dealt with by surgical salvage. Several randomized controlled trials going back to the Veterans Affairs trials of the early 1990s have shown this treatment regimen to be effective (The Department of Veterans Affairs Laryngeal Cancer Study Group, 1991; Spaulding et al., 1994). In this seminal trial, patients with stage III or IV laryngeal cancer were randomized to have either total laryngectomy with regional node dissection and adjuvant radiotherapy, or to have induction chemotherapy with three cycles of cisplatin and fluorouracil (5FU) given three-​weekly. If there was no partial response after two cycles of chemotherapy, patients underwent laryngectomy and went on to have adjuvant radiotherapy. If at least a partial response was present, patients had a third cycle of chemotherapy as originally planned, and then went on to have a radical course of radiotherapy. Both groups had similar initial survival rates and there was no difference

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SECTION 8  Head and neck surgery

in survival with 10-​year follow-​up, showing that functional larynx preservation could be achieved without any compromise in survival. This landmark study encouraged functional organ preservation in advanced laryngeal and pharyngeal tumours. The other major indication for primary chemoradiotherapy is a clinical situation where primary surgery and adjuvant radiotherapy would give a lesser chance of cure such as in the treatment of nasopharyngeal cancer, where treatment with chemoradiotherapy is the standard of care. In T1 and T2 tumours, organ preservation has less of a role to play as surgical treatment carries less risk of functional loss and laser excision of an early laryngeal cancer or surgical treatment of an early lateral tongue cancer would be the treatment of choice. In most cases, these early cancers will not require any further adjuvant treatment, if there has been adequate surgical excision.

Indications for adjuvant therapy Adjuvant (Latin: ad-​‘towards’ + juvare ‘to help’) therapy is any treatment given to optimize the effect of the principal treatment, in this case surgery. Adjuvant therapy usually takes place after surgery but may be given before when it is known as neoadjuvant or induction treatment. Neoadjuvant treatment is usually given in the form of chemotherapy, with the objective of reducing the primary tumour volume or reducing the size of involved neck nodes. It may also make nodes mobile, if fixed, to allow for more optimal surgical removal. Induction chemotherapy has not been shown to improve survival if given before surgery, but there is some evidence that it may reduce the incidence of early metastatic disease (Moore et al., 2012). Radiotherapy is not often used for neoadjuvant treatment now before surgery as there is evidence that postoperative radiotherapy gives better local control than preoperative radiotherapy with the same survival outcomes (Marcial et al., 1988). Postsurgical radiotherapy is given with the objective of killing any residual cancer cells remaining after surgery and thus increasing the chance of local control. Radiotherapy, like surgery, is a local treatment and does not affect any malignant cells outside the radiotherapy volume, whereas in theory, adding chemotherapy may have a tumouricidal effect on any distant micrometastases. Adjuvant radiotherapy is indicated if there are positive or close surgical margins, if there has been spillage or potential spillage of tumour cells during operation, if there is a large malignant nodal mass, multiple nodes, or extracapsular spread present. The most important of these factors are microscopically involved resection margins and extracapsular spread, and there is evidence that adding chemotherapy to radiotherapy, in these clinical situations, is beneficial (Bernier et al., 2005). Radiotherapy in head and neck practice is almost always delivered as external beam radiotherapy, using a linear accelerator (Fig. 8.20.1). Advances in radiotherapy technologies and techniques now allow the use of intensity-​modulated radiotherapy (IMRT) or tomotherapy (Fig. 8.20.2), where radiation can be delivered to a sharply defined high-​dose volume around the tumour, with a much sharper cut-​off in dose and very rapid decrease in dose delivered outside the high-​dose volume, so giving much lower dose

Fig. 8.20.1  A linear accelerator. Modern linear accelerators allow the implementation of intensity-​modulated radiotherapy (see text for details).

to surrounding normal tissues, sparing ‘organs at risk’, which in the head and neck would include the spinal cord, brainstem, mandible, the constrictor muscles, and parotid and submandibular glands. Tomotherapy is a particular commercial delivery system for IMRT, but volume planning and beam production are essentially the same as for other linear accelerator-​delivered IMRT. Complicated three-​ dimensional volumes within patients can be built up by considering the radiotherapy beam as consisting of multiple beamlets coming from the machine head, similar to the separate pixels on a monitor screen. The intensity of photon energy in each beam light can be changed separately or ‘modulated’ while a linear accelerator head is moving around the patient in a spiral or an arc. Multileaf collimators (Fig. 8.20.3) are a series of extremely thin metal blocks, which are set at 90° to the beam in the machine head and can move in and out of the beam dynamically blocking parts of it, while moving around the patient. This allows complicated dose distribution patterns to be built up within very small volumes giving more conformity around the tumour and much reduced dose to organs at risk (Fig. 8.20.4). Precise radiotherapy volume planning, dose delivery, and quality assurance are needed with these techniques, as there is much less margin for error. Geographic miss of the tumour, or high-​dose errors to organs at risk, such as spinal cord and brainstem, can lead to a catastrophic outcome for the patient.

8.20  Adjuvant therapy for head and neck cancers

changes affecting microvasculature and connective tissue that is usually the limiting factor for the total radiotherapy dose that can be given.

Adjuvant chemotherapy in context

Fig. 8.20.2  Tomotherapy is a commercial IMRT delivery system, incorporating a CT scanner in the machine head, allowing for daily pretreatment CT scans for comparison with the original radiotherapy plan to facilitate very accurate setup for radiotherapy treatment.

Radiotherapy doses Conventional radical radiotherapy dose fractionation with or without chemotherapy in North America is 70 Gy in 35 daily fractions at 2 Gy per fraction, treating 5 days per week for 7 consecutive weeks with no treatment breaks. In the United Kingdom, a wider range of regimens have developed empirically in different centres, using fractionation regimens thought radiobiologically equivalent to the standard North American dose and fractionation. Centres in the United Kingdom have used 70 Gy/​35 fractions, 66 Gy/​33 fractions, 65 Gy/​30 fractions, and 55 Gy/​20 fractions over 4 weeks, that is, 2.75 Gy per day for radical dose regimens. The latter regimen would usually be used in small treatment volumes to minimize the acute radiation reaction. Most radiotherapy centres will try to complete treatment within 6 weeks, as it is known that cancer cells can undergo accelerated repopulation after 6 weeks of radiotherapy. For adjuvant radiotherapy, after surgery, dose fractionation schedules have included 50 Gy/​20 fractions, 60 Gy/​30 fractions, and 63 Gy/​30 fractions. Prophylactic doses (54 Gy in 30 fractions) can also be used, for example, to a clinically and radiologically uninvolved neck node chain where there is risk of microscopic spread. All patients may experience unpleasant acute radiotherapy reactions, but this acute morbidity is reversible and it is the late radiation

Chemotherapy by itself is not curative in head and neck cancer. It is used to increase cancer cell kill and to act as a radiosensitizer when given with radiotherapy and it can theoretically eradicate distant micrometastases. Chemotherapy can be used as an adjuvant therapy if radiotherapy is the primary treatment, where functional organ preservation is the objective. When it is given concurrently with radiotherapy, there is an approximately 8% survival benefit (Pignon et  al., 2000, 2007). Cisplatin alone is now considered as effective as cisplatin combined with 5FU, with less toxicity. The standard regimen is cisplatin 100 mg/​m2 given on days 1, 22, and 43 of the radiotherapy course, although it can be given in weekly or even daily schedules. Chemoradiotherapy is also given as an adjuvant treatment after surgery with the same indications as for adjuvant radiotherapy. Chemotherapy would not be given by itself after surgery as an adjuvant treatment. In the last decade there has been renewed interest in the use of neoadjuvant or induction chemotherapy with the introduction of taxane-​based regimens (Posner et  al., 2007; Vermorken et  al., 2007)  used with cisplatin and 5FU. Although these combinations can reduce tumour volume for definitive chemoradiotherapy, there is little evidence of improved survival (Garden, 2014; Zhang et al., 2015) and there is a concern that their use can impair completion of the subsequent definitive treatment (i.e. chemoradiotherapy) as well as causing a higher treatment-​related mortality. In practice, these taxane-​based regimes are only offered to patients with higher performance status and with few comorbidities. In recurrent head and neck cancer, especially where the patient may only have had surgery as treatment at initial presentation, radiotherapy or chemoradiotherapy can be indicated, if the recurrence is inoperable or given as adjuvant treatment, if further surgery is possible. If recurrence occurs shortly after primary radiotherapy or chemoradiotherapy treatment, then surgical salvage would be the most appropriate management as the early recurrence would suggest chemo-​or radiotherapy resistance. If recurrence occurs after chemoradiotherapy, but has taken place several years after initial treatment, then retreatment with chemoradiotherapy might be possible after review of the previous radiation dose to critical organs at risk, such as the spinal cord and brainstem, and also as to whether the cumulative radiation dose, enhanced or not by chemotherapy, could be tolerated by the tissues. In most of these cases, salvage surgery, if possible, would usually be considered more appropriate.

Chemotherapy in metastatic head and neck cancer In metastatic disease or in recurrent head and neck cancer where radical potentially curable treatment is not appropriate, palliative

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SECTION 8  Head and neck surgery

Fig. 8.20.3  A multileaf collimator. Multileaf collimators are alloy leaves, only millimetres wide but several millimetres thick, which allow free passage or blocking of parts of the radiotherapy beam as it emerges from the head of the linear accelerator, allowing for the synthesis of complex three-​dimensional dose distributions within the patient.

chemotherapy has an approximate 30% response rate. The most common drugs used are cisplatin or carboplatin combined with 5FU. These combinations have not shown a survival benefit over single-​agent cisplatin, but they do have a higher response rate and also a correspondingly higher toxicity. Palliative chemotherapy outcomes have not been compared to palliative radiotherapy or best supportive care alone.

Targeted biological therapies In patients with less physiological reserve or with more comorbidities, platinum-​containing regimens are still the optimal concurrent chemotherapy with primary or adjuvant radiotherapy, if such

regimens can be tolerated. In those patients where platinum is contraindicated, for example, in established renal impairment, cetuximab, which acts as an epidermal growth factor receptor (EGFR) inhibitor can be used. This is the first targeted biological agent for use in head and neck cancer. Patients using cetuximab may have an increased radiation reaction within the treatment field and can also develop an acne-​like rash outside of the field. When first introduced, cetuximab was marketed as having a relatively side effect-​free profile, but for some patients, the acne-​like rash may become intolerable causing discontinuation of the drug. Cetuximab with radiotherapy has been shown to improve survival compared to radiotherapy alone (Bonner et  al., 2006)  in the radical treatment of head and neck cancer. In the EXTREME trial (Rivera et al., 2009), patients with recurrent or metastatic head and neck cancer were randomized to platinum and 5FU, with or without cetuximab. Those patients receiving chemotherapy and cetuximab had a small but significant improvement in survival. Other biological targeting therapies are being used in clinical trials in head and neck cancer, such as erlotinib and gefitinib which are small-​molecule tyrosine kinase inhibitors and do not block EGFR on the cell membrane, but act on the EGFR pathways inside the cell. We are only at the start of exploring targeted biological therapies in head and neck cancer and in years to come targeted agents may mirror the advances made and already introduced into clinical practice in other cancer sites such as breast and lung cancer.

Future developments The development of TORS, the use of tomotherapy, IMRT, radiotherapy dose escalation, and the introduction of targeted biological agents should allow for improvements in the optimal management and use of the differing treatment options in head and neck cancer with better survival outcomes with less short-​term and long-​term morbidities and more attention given to survivorship issues. Future head and neck cancer patients should survive longer and in greater

Fig. 8.20.4  An intensity-​modulated head and neck radiotherapy plan showing a complex dose distribution in head neck cancer.

8.20  Adjuvant therapy for head and neck cancers

numbers, and hopefully with more patients cured. Further optimization and better balanced integration of currently established treatments will also benefit head and neck cancer patients.

REFERENCES Bernier J, Cooper JS, Pajak TF. Defining risk levels in locally advanced head and neck cancers:  a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843–​50. Bonner JA, Harari PM, Giralt J, et  al. Radiotherapy plus cetuximab for squamous-​cell carcinoma of the head and neck. N Engl J Med 2006;354:567–​78. Garden AS. The never-​ending story:  finding a role for neoadjuvant chemotherapy in the management of head and neck cancer. J Clin Oncol 2014;32:2685–​6. Marcial VA, Pajak TF, Kramer S, et al. Radiation Therapy Oncology Group (RTOG) studies in head and neck cancer. Semin Oncol 1988;15:39–​60. Moore EJ, Olsen SM, Laborde RR, et  al. Long-​term functional and oncological results of trans-​oral robotic surgery for oropharyngeal squamous cell carcinoma. Mayo Clin Proc 2012;87:219–​25. Pignon JP, Bourhis J, Domenge C, et  al. Chemotherapy added to locoregional treatment for head and neck squamous-​ cell carcinoma: three meta-​analyses of updated individual data. MACH-​NC

Collaborative Group. Meta-​Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000;355:949–​55. Pignon JP, le Maitre A, Bourhis J et al. Meta-​Analyses of Chemotherapy in Head and Neck Cancer (MACH-​NC):  an update. Int J Radiat Oncol Biol Phys 2007;69:S112–​14. Posner MR, Hershock DM, Blajman CR, et  al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:1705–​15. Rivera F, García-​Castaño A, Vega N, et  al. Cetuximab in metastatic or recurrent head and neck cancer: the EXTREME trial. Expert Rev Anticancer Ther 2009;9:1421–​8. Spaulding MB, Fischer SG, Wolf GT. Tumor response, toxicity, and survival after neoadjuvant organ-​preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 1994;12:1592–​9. The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324:1685–​90. Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357:1695–​704. Zhang LN, Gao YH, Lan X W et al. Effect of taxanes-​based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a large scale propensity-​matched study. Oral Oncol 2015;51:950–​6.

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SECTION 9

The chest and breast Section editors: Rodney Cooter, Nicola R. Dean, and Kieran Horgan

9.1 Embryology and development of the chest wall and breast  985 Quoc Lam 9.2 Deformities of the chest  991 Harvey Stern

9.10 TRAM flap breast reconstruction  1081 Janek S. Januszkiewicz 9.11 DIEP flap breast reconstruction  1093 Mark Ashton

9.3 Surgical anatomy of the breast  1001 Amy E. Jeeves

9.12 Alternative flaps for microsurgical breast reconstruction  1107 Hinne A. Rakhorst

9.4 Congenital deformities of the breast  1007 Michelle L. Lodge

9.13 The tissue-​engineered breast  1115 Wayne Morrison

9.5 Preoperative imaging for autologous breast reconstruction  1017 Mark Ashton and Iain Whitaker

9.14 Management of complications of microvascular abdominal flap breast reconstruction  1121 Marc A.M. Mureau

9.6 Breast malignancy: diagnosis and management  1025 Kieran Horgan, Barbara Dall, Rebecca Millican-​Slater, Russell Bramhall, Fiona MacNeill, David Dodwell, Indu Chaudhuri, and Sebastian Trainor

9.15 The nipple–​areolar complex  1133 Garry Buckland

9.7 Breast reconstruction: patient assessment  1053 Nicola R. Dean 9.8 Tissue expander and implant breast reconstruction  1063 Melissa A. Mueller, Emily G. Clark, and Gregory R.D. Evans 9.9 Latissimus dorsi breast reconstruction  1069 Mark A. Lee

9.16 Ancillary considerations in breast surgery  1145 Emily G. Clark, Melissa A. Mueller, and Gregory R.D. Evans 9.17 Anaesthesia and analgesia considerations in breast surgery  1151 Glenda Rudkin and Sarah Gardiner 9.18 Measuring outcomes in plastic surgery of the breast  1159 Nicola R. Dean, Rod Cooter, and Andrea L. Pusic

9.1

Embryology and development of the chest wall and breast Quoc Lam

Introduction The concepts of embryogenesis of the chest wall and breast are intimately related to our understanding, assessment, and treatment of common congenital anomalies of this region. The embryological development of this region follows a complex cascade of events involving differential gene expression, cell interactions, and cell signalling between precursor tissues. Although surgical embryology focuses on morphological development of the embryo and fetus, it is important to keep in mind the complex interplay of physical and chemical messengers required to propagate this morphological development. Development of the breast and thorax begins in the fourth week of gestation during the embryonic period (Fig. 9.1.1). At birth, the basic structures of the chest and breast are established. Both regions continue to develop through childhood, adolescence, and adulthood. The breast plays a complex functional and psychosocial role in the developing female. Plastic surgical approaches to congenital and acquired defects of the chest and breast should be sensitive to these developmental changes in order to balance form, function, and psychosocial development.

Chest wall embryology As the embryo folds in the fourth week producing lateral folds, mesoderm begins to organize into somites. The somites represent

Time line embryonic fetal stage In Utero Early development stage of the embryo

Embryonic period stage

Fetal stage

Fig. 9.1.1  In utero development of the breast—​the first 9 weeks.

40 segmental tissue blocks alongside the notochord, which then segregate into a dorsolateral subpopulation known as the dermomyotome fated to become muscular structures and a ventromedial subpopulation known as the sclerotome, which later differentiate into the vertebrae and ribs. The cells of the sclerotome mobilize to condense around the spinal cord forming ventral and lateral subdivisions, which differentiate into components of the bony vertebral column. Although there is some controversy in relation to the exact origin of the ribs, the consensus is that the ribs are a process of the vertebral bodies derived completely from the sclerotome (Huang et al., 2000). As the rib templates grow, they elongate, wrapping around the embryonic thorax as cartilaginous processes later to fuse with the sternum. The ribs ossify by endochondral ossification, beginning at the rib angle in the sixth week and continuing into the fetal period (Brochhausen et al., 2012). As the vertebrae differentiate segmentally, the dermomyotome separates into a myotome and a dermatome. A segmental nerve associates itself with the dermomyotome and this segmental pattern of sensory and motor innervation is maintained throughout life. The myotome further subdivides into an epimere, giving rise to the skeletal muscles of the back, and a hypomere, which differentiates into three layers giving rise to the lateral and anterior muscles of the thorax, namely the intercostals and muscles of the anterior abdominal wall. The sternum arises independently of the rib cage from paired vertical condensations of somatic mesoderm in the sixth week of development (Fig. 9.1.2). The paired sternal bars fuse in a craniocaudal direction to form a single cartilaginous sternal plate by the end of the tenth week. This cartilaginous precursor undergoes segmentation into six regions known as sternebrae. The most superior sternebrae becomes the manubrium. The second to fifth sternebrae form the body of the sternum and the sixth sternebrae forms the xiphoid process. Union of adjacent sternebrae occurs through ossification, which begins at 60 days and is complete by the time of birth. The xiphoid, however, does not ossify until later in life between the ages of 5 and 18 years. Problems related to fusion of the sternal bars or the sternebrae can lead to congenital sternal defects such as sternal clefts, ectopia

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SECTION 9  The chest and breast

Clavicle

Suprasternum

Clavicle Suprasternal cartilage

Presternum

Ribs

Ribs

Sternal bands

Sternal bars

Xiphoid process

Ossification centres

Fig. 9.1.2  Development of the sternum.

cordis, or even sternal agenesis. A severe congenital defect such as ectopia cordis implies incomplete closure of the ventral body during the folding of the embryo. A skin-​covered sternal defect on the other hand implies failure of fusion of the sternal bars (Sadler, 2000).

Pectus excavatum and pectus carinatum The embryological basis of pectus excavatum and pectus carinatum is less well understood. There exist many hypotheses suggesting either an intrinsic problem related to the sternum and embryo as well as extrinsic hypotheses, which implicate external causes such as intrauterine pressure (Brochhausen et  al., 2012). The most accepted view is an overgrowth or undergrowth potential of the ribs secondary to defective metabolism in the sternocostal cartilage (Brochhausen et al., 2012).

Stages of breast development Breast development occurs in four distinct phases separated by intervals of relatively little change (Fig. 9.1.3). After early in utero development, the newborn’s breast remains largely unchanged until puberty. Following puberty, the next period of dramatic change occurs when pregnancy induces functional maturity of the breast, culminating in lactation. Unless further pregnancy, lactation cycles occur, the breast once again remains relatively unchanged until the postmenopausal phase of involution and fat replacement.

Time line In utero

Puberty

33 weeks

Age 13 years

Pregnancy lactation

Fig. 9.1.3  Timeline of breast development.

Menopause

Embryonic stage of breast development The breast is derived from the ectoderm of the embryo. The first signs of breast development occur during the fourth to fifth week of gestation when symmetrical ectodermal thickenings known as mammary ridges form, extending from the axilla to the inner thigh (Fig. 9.1.4). By the end of the fifth week, most parts of this ridge have undergone apoptosis except for an area over the fourth intercostal space. Between the seventh and eighth week of gestation, the ectoderm of this region begins to proliferate and penetrate the underlying mesenchyme creating an elevated mammary crest. Between weeks 10 to 12, primary epithelial buds begin to differentiate from invading ectoderm extending into the mesenchyme as solid diverticula. By week 20, primary buds have given rise to secondary buds seen as cords invading the primitive breast. Through ongoing proliferation, elongation, repeated branching, and canalization, these secondary buds give rise to lactiferous ducts by 32 weeks of gestation. As the developing bud invaginates, it becomes enclosed within the layers of the superficial fascia (Costagliola et al., 2013). This is a key concept in our understanding of the normal anatomy of the developed breast, the development of tuberous breast deformity, as well as oncological breast cancer resection. As ductal elements develop, mesodermal tissues simultaneously evolve into the supporting structures such as the fibrous capsule, Cooper’s ligaments, and adipose tissue. These elements increase in density during the final weeks of gestation. Although development of the nipple–​areolar complex begins in the embryonic period, most changes occur during the fetal period. Smooth muscle first develops in the nipple–​areolar region between weeks 10–​12 (Hassiotou and Geddes, 2013). The smooth muscle of this region eventually assumes a circular and longitudinal arrangement of fibres towards the end of gestation (Javed and Lteif, 2013). During the fetal period, the epidermis at the site of the future nipple becomes depressed, forming the mammary pit. Lactiferous ducts drain into retro-​areola ampullae that converge onto the mammary pit. Ductal eventration onto the surface of the mammary pit, pigmentation, and development of Montgomery glands also occurs in the last 8 weeks of gestation. Further formation of the nipple occurs as a result of the interplay between ectodermal invagination and

9.1  Embryology and development of the chest wall and breast

Formation of the breast

Level of section C

Remnant of mammary crest, which produces primary mammary bud

Mammary crest

Fig. 9.1.4  In utero breast formation—​mammary crest and mammary bud.

underlying mesodermal expansion giving the infant nipple its characteristic everted appearance. Equally, the mammary vasculature has developed from early gestation from mesenchyme as primitive vessels to eventually become an organized concentric network supporting the development of skin, secretory gland, adipose tissue, and connective tissue commensurate with the overall development of the breast (Hassiotou and Geddes, 2013). At term, approximately 15–​20 lobes of glandular tissue exist, each with a lactiferous duct, which opens onto the mammary pit. The surrounding skin and fibrous suspensory ligaments of Cooper anchor the breast to the underlying pectoralis major fascia. This concept of early breast development is integral to our understanding of the spectrum of congenital breast conditions ranging from complete amastia to supernumerary breast tissue. In 5% of women, accessory glands or nipples may develop at any location along the mammary line (Schmidt, 1998). This is known as polythelia and is thought to be due to incomplete regression of the mammary ridge leading to additional foci of breast tissue. Polythelia may present as a supernumerary areola with or without a nipple. However, a nipple is never present in the absence of an areola (Schmidt, 1998). On the other hand, the complete absence of breast tissue or amastia is a rare condition believed to be a result of failure of the mammary ridge to develop in utero (Lin et al., 2000). Amastia occurs in three clinical contexts. It may present in association with a congenital ectodermal defect (Trier, 1965; Burck and Held, 1981), which is a sex-​linked recessive condition characterized by bilateral amastia and disordered growth of skin and its appendages, namely the survivable teeth and nails. It has also been associated with cleft lip and palate, microphthalmia, and corneal dysplasia (Burck and Held, 1981). Amastia may also present in the setting of Poland syndrome which presents with a spectrum of unilateral chest wall anomalies that can involve the thoracic cage and musculature as well as the breast and upper limb (Seyfer et al., 2010). Typically, there is an absent sternocostal head of the pectoralis major muscle, chest wall asymmetry, and breast hypoplasia. Poland syndrome is believed to be due to a vascular developmental anomaly during the critical sixth week of gestation, with hypoplasia of the subclavian artery (Bavinck et  al., 1986). This concept has been dubbed the subclavian artery

disruption sequence and implies a cascade of malformations due to compromised perfusion during development. It further implies that the more proximal the disruption, the more severe the clinical manifestation which could explain the findings in conditions such as Klippel–​Feil syndrome or Moebius syndrome (Bavinck et al., 1986). Finally, bilateral amastia can occur in isolation. This is rare and the condition has been reported in the setting of other craniofacial and musculoskeletal abnormalities outside the spectrum of known syndromes (Kowlessar and Orti, 1968; Wilson et al., 1972; Mathews, 1974; Lin et al., 2000). Athelia refers to the absence of a nipple in the presence of breast tissue. Amazia refers to the absence of breast tissue when a nipple is present. Both of these conditions are rare, but are useful descriptors as they display the great heterogeneity of presentation of congenital disorders of the breast. Within this spectrum of presentation, varying degrees of breast hypoplasia will exist. A severe breast hypoplasia may be difficult to distinguish from amazia, especially in the incompletely developed individual (Lin et al., 2000).

The infant breast The breast of the newborn is usually palpable with varying amounts of tissue and no significant differences between the sexes (Naccarato et  al., 2000). It often assumes an everted appearance due to ongoing mesodermal expansion. The nipple–​areolar complex continues to change with pigmentation becoming more prominent, while erectile smooth muscle continues to develop resulting in a more reactive nipple. Transient unilateral or bilateral breast enlargement associated with milk secretion is common and has been reported in up to 70% of term infants. This is thought to be related to falling levels of maternal oestrogens in the neonate stimulating prolactin production from the pituitary (McKiernan and Hull, 1981). The infant breast continues to develop until 2 years of age. Anbazhagan and colleagues (1991) have described the morphological and functional changes of the infant breast during this period, culminating in a branched ductal network lined with apocrine-​type epithelium with a well-​developed lobular system. The normal gland then remains quiescent from 2 years of age to puberty (Naccarato et al., 2000).

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988

SECTION 9  The chest and breast

Puberty Sexually dimorphic development of the breast begins at puberty under the influence of sex hormones, in particular oestrogen (Javed and Lteif, 2013). Development of the breast or thelarche is often the first secondary sexual characteristic to develop in females and occurs between 8 and 13 years of age. Tanner has described the most well-​accepted macroscopic stages of breast development in females; there are five Tanner stages from the prepubertal breast to the fully developed breast, characterized by an increase in volume, nipple and areolar size, and pigmentation (Marshall and Tanner, 1969). There are significant variations of breast development based on hormone levels, ethnicity, and a multitude of environmental factors. Early asymmetry during Tanner stages 2–​3 is common and often resolves by Tanner stage 4 (Dewhurst, 1981). Persistent asymmetry may occur for a variety of acquired or congenital reasons, which may warrant consideration of symmetrizing surgery once breast maturity has been established. The macroscopic evolution of the breast reflects the immense changes occurring in stromal, parenchymal, and ductal tissues. Fibrous and fatty tissues continue to expand, increasing the net volume of the breast. Ductal elongation and branching as acini develop into the surrounding stroma form individual terminal duct lobular units. These units mark functional maturity of the breast. With each menstrual cycle further development of ductal and lobuloalveolar tissue occurs, compounding gradual development until approximately 30 years of age (Hassiotou and Geddes, 2013). Oestrogen and progesterone are thought to be responsible for ductal elongation and side branching respectively, while progesterone and prolactin are believed to be responsible for lobuloalveolar development (Javed and Lteif, 2013). The process of puberty results in aesthetic as well as functional breast maturity. It then remains in this mature but inactive state until pregnancy. It is during this pubertal period that a tuberous breast deformity may become apparent. Features of a tuberous breast include hypoplasia of breast tissue, a narrow-​based breast footprint, a high inframammary fold, and wide nipple–​areolar complex herniating through a fascial constriction resulting in a tubular appearance. The anomaly may be unilateral or bilateral and can present with a wide spectrum of asymmetry and morphology (von Heimburg et  al., 1996; Grolleau et al., 1999). The aetiology of tuberous breast at present remains unknown and is the subject of much speculation. The normal shape of a breast relies on the delicate balance of hormone-​driven growth within the limits of anatomical fascial boundaries that are established during ectodermal invagination of underling mesenchyme. It is generally accepted that the features of a tuberous breast are produced by a combination of fascial anatomical anomalies leading to relative constriction as well as abnormal growth. The first of these is a fibrous constricting ring at the level of the periphery of the areola resulting in a herniated nipple–​areolar complex. The second is a thickening of the deep layer of the superficial fascia resulting in a strong adherence between the dermis and the chest wall at the breast base leading to a narrow-​based breast. The last, relates to a relative weakness of subareolar fascial support leading to an expanded nipple–​areolar complex as the breast continues to grow through the constricted ring (Costagliola et al., 2013).

Male puberty At puberty no further development of the breast occurs in the male due to rising testosterone concentrations. However, up to 40% of boys may develop transient gynaecomastia due to relative oestrogen dominance (Simmons, 1992). This physiological gynaecomastia may persist and present as a source of distress for a young man. Although there are many causes of persistent gynaecomastia in males, it is more commonly seen in overweight individuals. Obese males will have more adipose tissue in the pectoral region as well as relative oestrogen dominance as circulating testosterone is converted to oestrogen in adipose tissues (Dundar et al., 2005).

Pregnancy and lactation cycle, and involution Pregnancy marks the beginning of the final stage of breast maturation. Under the influence of circulating hormones, the breast is readied for lactation. This is seen as an increase in breast volume, as well as increase in size and pigmentation of the nipple–​areolar complex. At a cellular level, proliferation, expansion, and differentiation of ductal, stromal, and alveolar elements underpin the clinical changes seen. Following parturition, lactation proceeds primarily as a response to environmental stimuli and the withdrawal of circulating progesterone. The breast remains in this secretory state until cessation or significant reduction of breastfeeding occurs. In between pregnancies, the breast transitions to a resting non-​ lactating state until the next pregnancy lactation cycle (Hurley, 1989). If further pregnancies do not occur, the breast undergoes post-​lactational involution characterized by a decrease in volume of the breast and nipple–​areolar complex. In addition to post-​lactational involution, the breast undergoes a second phase of involution during menopause related to reduction of ovarian function. The breast becomes fat-​replaced as glandular tissue regresses and adipose tissue is deposited (Hutson et al., 1985). Changes related to ageing cause further loss of volume with laxity of skin and ligaments leading to empty ptotic breasts.

Conclusion An understanding of the embryology and development of the chest and breast is a useful scaffold underpinning our approaches to the common congenital and acquired conditions of this region. The female breast plays a complex, multifaceted role in a child’s development, through adolescence and adulthood. The changes that occur during puberty, pregnancy, lactation, and menopause play significant roles in clinical decision-​making when confronted with reconstruction of breast abnormalities.

REFERENCES Anbazhagan R, Bartek J, Monaghan P, et al. Growth and development of the human infant breast. Am J Anat 1991;192:407–​17.

9.1  Embryology and development of the chest wall and breast

Bavinck JNB, Weaver DD, Opitz JM, et  al. Subclavian artery supply disruption sequence:  hypothesis of a vascular etiology for Poland, Klippel-​Feil, and Möbius anomalies. Am J Med Genet 1986;23:903–​18. Brochhausen C, Turial S, Müller FK, et al. Pectus excavatum: history, hypotheses and treatment options. Interact Cardiovasc Thorac Surg 2012;14:801–​6. Burck U, Held KR. Athelia in a female infant heterozygous for anhidrotic ectodermal dysplasia. Clin Genet 1981;19:117–​21. Costagliola M, Atiyeh B, Rampillon F. Tuberous breast: revised classification and a new hypothesis for its development. Aesthetic Plast Surg 2013;37:896–​903. Dewhurst J. Gonadal dysgenesis and X chromosome deletion. BJOG 1981;88:944–​9. Dundar B, Dundar N, Erci T, et al. Leptin levels in boys with pubertal gynecomastia. J Pediatr Endocrinol Metab 2005;18:929–​34. Grolleau J-​L, Lanfrey E, Lavigne B, et al. Breast base anomalies: treatment strategy for tuberous breasts, minor deformities, and asymmetry. Plast Reconstr Surg 1999;104:2040–​8. Hassiotou F, Geddes D. Anatomy of the human mammary gland: current status of knowledge. Clin Anat 2013;26:29–​48. Huang R, Zhi Q, Schmidt C, et  al. Sclerotomal origin of the ribs. Development 2000;127:527–​32. Hurley W. Mammary gland function during involution. J Dairy Sci 1989;72:1637–​46. Hutson SW, Cowen PN, Bird CC. Morphometric studies of age related changes in normal human breast and their significance for evolution of mammary cancer. J Clin Pathol 1985;38:281–​7. Javed A, Lteif A. Development of the human breast. Semin Plast Surg 2013;27:5–​12.

Kowlessar M, Orti E. Complete breast absence in siblings. Am J Dis Child 1968;115:91–​2. Lin KY, Nguyen DB, Williams RM. Complete breast absence revisited. Plast Reconstr Surg 2000;106:98–​101. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–​303. Mathews J. Bilateral absence of breasts. N Y State J Med 1974;74:87. Mckiernan JF, Hull D. Breast development in the newborn. Arch Dis Child 1981;56:525–​9. Naccarato AG, Viacava P, Vignati S, et al. Bio-​morphological events in the development of the human female mammary gland from fetal age to puberty. Virchows Arch 2000;436:431–​8. Sadler, T. Embryology of the sternum. Chest Surg Clin North Am 2000;10:237–​44,  v. Schmidt H. Supernumerary nipples:  prevalence, size, sex and side predilection—​ a prospective clinical study. Eur J Pediatr 1998;157:821–​3. Seyfer AE, Fox JP, Hamilton CG. Poland syndrome:  evaluation and treatment of the chest wall in 63 patients. Plast Reconstr Surg 2010;126:902–​11. Simmons P. Diagnostic considerations in breast disorders of children and adolescents. Obstetr Gynecol Clin North Am 1992;19:91–​102. Trier WC. Case report and review of the literature. Plast Reconstr Surg 1965;36:430–​9. von Heimburg D, Exner K, Kruft S, et  al. The tuberous breast deformity:  classification and treatment. Br J Plast Surg 1996; 49:339–​45. Wilson MG, Hall E, Ebbin AJ. Dominant inheritance of absence of the breast. Humangenetik 1972;15:268–​70.

989

9.2

Deformities of the chest Harvey Stern

Introduction Deformities of the chest wall are classified into congenital and acquired conditions. Beyond that, they can be classified by their location, aetiology, or involved tissue type (Table 9.2.1).

Congenital conditions Pectus excavatum Pectus excavatum refers to a congenital and developmental abnormality characterized by a depression of the anterior chest wall, most commonly involving the body and xiphoid process of the sternum.

There is usually an associated concavity of the medial aspects of the costal cartilages which attach to the affected part of the sternum, and the shape may be symmetrical or asymmetrical. The associated anterior chest wall musculature is usually present but may be abnormal in shape, origin, and dimension on the affected sides. The incidence of pectus excavatum has been reported as being as high as 8 per 1000 live births, with boys generally affected more than girls and the deformity frequently apparent in the first 5 years of life (Fox et al., 2007). The severity of the defect is variable with the distance between sternum and vertebral column used as the criterion for classification. A distance of less than 5.0 cm is severe, 5–​7 cm is moderate, and greater than 7 cm is a mild deformity. Severe excavatum may be associated with impairment of cardiopulmonary function either due to limited pleural cavity volume, diminished venous return, or both.

Table 9.2.1  Methods of categorizing deformities of the chest Congenital

Anterior chest

Acquired

Depressions (excavatum)

Location

Manubrial, sternal

Protrusions (carinatum)

Anterior

Poland syndrome

Anterolateral

Midline clefts

Posterior

Jeune syndrome

Aetiology

Proteus syndrome

Trauma Infection

Osteomyelitis Soft tissue infection

Tumour Posterior chest

Spinal dysraphisms

Secondary

Diastematomyelia

Radiotherapy

Hemimyelia

Iatrogenic

Dermal sinus tract Neurenteric cyst

Primary

Surgical Non-​surgical

Tissue types involved

Soft tissue only

Teratoma

Skin ± subcutaneous fat All layers of soft tissue (bone exposed)

Skeletal

Fracture Bone defect

Full-​thickness of chest wall Lung

Hernia (pneumonocoele) Fistula

992

SECTION 9  The chest and breast

Broadly, the surgical approach to pectus excavatum may be either correction of the skeletal abnormality, or an attempt to camouflage it with a prosthesis or a transferred flap. The surgical approaches to correction of the excavatum in moderate or severe cases may either be based on the approach described by Ravitch (1949) which involves rib cartilage resection and sternal repositioning, with or without some form of sternal fixation, or be a variant of the minimally invasive Nuss approach. Sternal fixation methods have included the use of Steinmann pins, sutures, vascularized rib struts, polypropylene mesh, and rigid plate fixation. The minimally invasive approach described by Nuss and colleagues (1998) involved the placement of a malleable curved metallic bar deep to the ribs and sternum. The sternum is then forced anteriorly by inverting the bar to become convex anteriorly. The bar is fixed into position by lateral wiring to the ribs, and the bar subsequently removed at a later date. The Nuss approach is less effective in late adolescence and adult life, which has led to the description of blended approaches, with the placement of the bar supplemented with some costal cartilage incisions (Molik et  al., 2001; Schaarschmidt et al., 2002; Del Frari and Schwabegger, 2013). However, where the pectus deformity is mild, significant improvement may be achieved by the placement of a prosthesis, which in the male can be customized to fill the presternal hollow. In the female patient, mammary implants may be employed as an alternative to disguise the defect. The same potential complication associated with the placement of breast implants may be a feature of the use of presternal prostheses including capsule formation with subsequent potential contracture or calcification, infection, or extrusion. If a surgical decision is made to correct the deformity, there is no uniform agreement as to the correct timing. Resection in early childhood can lead to diminished growth of the thorax and chest wall constriction. Some advocate repairs between ages 6 and 8 years, whereas others favour delaying surgery until 12–​16  years of age. Morshuis and colleagues (1994) performed a high-​quality study of 147 patients with 8-​year follow-​up and found poorer than expected pulmonary function. Paradoxically, they found that patients often reported improved symptoms but with an objectively measured reduction in pulmonary capacity. The hypothesis for this paradox was that psychological and cardiac factors may be implicated in improved symptoms, rather than respiratory factors alone (Morshuis et al., 1994). Haller and colleagues (1996) reported a series of 12 children who underwent surgical correction under the age of 4 years. Their recommendation was to avoid operating on children less than 6 years of age.

Pectus carinatum Pectus carinatum occurs approximately one-​tenth as often as pectus excavatum. In this deformity there is sternal protrusion associated with depressions along the lateral aspects of the chest resulting in a bowed-​out appearance. Usually there are no associated cardiac or pulmonary abnormalities but there may be symptoms of intermittent, sharp chest pain (van Aalst et al., 2009). Reconstructive surgery typically involves the use of a modified Ravitch approach but the use of an external prosthesis applying continuous pressure to the anterior chest to effect remodelling of the thoracic cage has also been described (Frey et al., 2006).

Poland syndrome This syndrome, initially described in 1841 by Poland, includes absence of the sternocostal head of the pectoralis major muscle, pectoralis minor muscle, and syndactyly of the ipsilateral hand (Poland, 1841). The syndrome is now recognized as being associated with the absence of multiple ribs, athelia or amastia, breast hypoplasia, hypoplasia or absence of the ipsilateral latissimus dorsi muscle, and possible brachysyndactyly. Treatment options vary in parallel with the differing manifestations of the syndrome. Possible surgical manoeuvres include pedicled latissimus dorsi muscle or myocutaneous flaps (Longaker et al., 1997), assuming that preoperative assessment has confirmed the presence of this functional muscle. Prostheses may be employed alone or in combination with flaps (Marks and Iacobucci, 2000). In the female patient, a breast implant is typically also required, sometimes after preliminary tissue expansion. Free microvascular tissue transfer may also be required, particularly in the absence of an ipsilateral latissimus dorsi flap, or to achieve breast reconstruction in the female patient without the use of a prosthesis. Seyfer and colleagues (2010) classify Poland syndrome as ‘simple’ or ‘complex’ and describe treatment algorithms and outcomes in these two categories of cases.

Acquired conditions Defects of the chest may be considered from a variety of aspects. The defect may be classified according to its anatomical location, by its aetiology, or by the tissue plane or planes affected. Each of these approaches is pertinent in the clinical assessment of the defect and the formulation of a reconstructive plan. The anatomical location of the defect may be midline anterior (manubrial, sternal, or both), anterior, anterolateral, or posterior. The anatomical location will be significant as it will influence respiratory function, aesthetics, and reconstructive optional considerations. For example, a midline anterior skeletal defect may result following management of sternal osteomyelitis with no consistently proven deleterious effect on respiratory function. In contrast, reconstruction of a soft tissue defect in this location may be frequently exposed in many styles of clothing and therefore important aesthetically. Skeletal repair at the anterior and particularly anterolateral aspects of the chest will have a greater impact on respiratory function, as well as aesthetic significance as the platform upon which the female breast will be positioned. Aetiology of a specific defect will determine the surgical approach undertaken both in terms of the handling of the tissue at the defect and the degree of urgency with which the defect is created or repaired. Aetiologies of chest wall defects include trauma, infection, osteomyelitis, tumour (primary or secondary), radiotherapy, and iatrogenic or surgical. The aetiological classification forms the structure for the discussion of specific acquired chest wall defects and their management.

Trauma The relevant assessment of the traumatic chest defect includes the history of the type of trauma, tissue planes involved, underlying lung function or injury, anatomical location and extent, and the age and background medical condition of the patient. Traumatic defects which involve the underlying skeleton will almost certainly be initially treated under the care of a cardiothoracic unit, or as combined

9.2  Deformities of the chest

care between cardiothoracic and plastic surgical teams. The management principles of the traumatic chest wound are the same as for any other location: early effective debridement of all contaminated and non-​viable tissue, skeletal stabilization, where required, and well-​ vascularized soft tissue cover. Management of the visceral contents of the chest would clearly be the domain of the cardiothoracic surgical team and may dictate aspects of the reconstruction, including timing or complexity. As for any other multidisciplinary team involvement there should be early and detailed liaison to ensure that the surgical treatment plan formulated by either service does not compromise the potential options available to the other team. High-​ velocity injuries will create more extensive regional tissue damage which may reduce locoregional reconstructive options.

Infection Infections may be considered to be acute or chronic, affecting a variety of tissue planes, with or without suppuration, and with or without involvement of the underlying body cavity. The most common forms of infection in the chest with which the plastic surgeon may be involved are those of the sternum or mediastinum following sternotomy, and the management of post-​pneumonectomy space infection. The plastic surgeon may also become involved in the management of other, more localized, destructive infective processes, such as those resulting from septic emboli. Osteomyelitis Median sternotomy provides uncomplicated access for most cardiac surgical procedures. Sternotomy infection with or without underlying mediastinitis, with or without sternal instability, may complicate the recovery of a patient already compromised by multisystem disease. The incidence of such infections is between 0.2% and 10% (Jurkiewicz et al., 1980; Jones et al., 1997; Landes et al., 2007; Cabbabe and Cabbabe, 2009) with an associated mortality rate of between 10% and 25% using current surgical approaches. In the early years following the introduction of median sternotomy as an approach for cardiac surgery, infections were managed by techniques such as box-​ wiring and systems of continuous closed irrigation/​drainage and these approaches did reduce mortality. More recently, surgical debridement and flap repairs have become accepted techniques because they have significantly lowered mortality rates and reduced hospital stay. The omentum flap described by Lee and colleagues (1976) was the first vascularized flap significantly to change the management of deep sternal wound infection. Jurkiewicz and co-​workers (1980) advocated the use of a muscle flap, which remains the standard of care in the modern management of deep sternal wound infection. The muscle flaps commonly employed include rectus abdominis, pectoralis major which may be mobilized as an advancement, transposition, or turn-​over flap, and latissimus dorsi. These muscles may be employed as muscle only, myocutaneous, alone or in combinations. The degree of urgency to assess and manage post-​sternotomy infections will be influenced by the postoperative interval before the infection becomes clinically apparent. An acute presentation, with a greater potential for an underlying mediastinal infection, should be assessed within 24 hours with the initial surgical debridement occurring soon after unless the general medical condition of the patient precludes general anaesthesia. Initial debridement may be performed by a plastic surgeon or by their cardiothoracic colleagues, but in either circumstance, a thorough debridement of all contaminated

and non-​viable material should occur. A  delayed presentation of chronic osteomyelitis, months or even years after surgery, allows a more considered approach. At the time of initial debridement of acute cases, the sternotomy wound is reopened and all suture material, bone wax, and sternal fixation material should be removed. Microbiology swabs are taken from both subcutaneous and mediastinal planes. Thorough debridement of all layers of soft tissue and skeleton are performed to remove all infected or non-​viable material. Any skeletal tissue removed is submitted to microbiology, and where this extends to costal cartilage, specimens should be submitted from beyond the limits of the required debridement to confirm removal of infected material. Copious irrigation with normal saline or antibacterial solutions is performed and moist dressings applied. Systemic antibiotic management is guided by an infectious diseases specialist. A dressing regimen is established on the ward with a definitive repair of the wound carried out when the sternotomy defect displays clear evidence of improvement and where the patient has a therapeutic blood level of appropriate, culture-​specific, antibiotics. In most sternotomy infections there is a minimum of 3–​4 days between initial debridement and suitable circumstances for delayed closure. Techniques of secondary repair are largely dictated by the amount and quality of the residual sternum. If adequate bone stock remains, secondary sternal repair may be achieved using polydioxanone (PDS®) interrupted sutures (Perkins et al., 1996a), rigid plate internal fixation (Cicilioni et al., 2005), approximating bone clamp systems (Levin et  al., 2010), or a combination plate and wire techniques (Chase et al., 1999). Most of these secondary sternal fixation systems are then covered by at least a unilateral or bilateral pectoralis major myocutaneous advancement flaps. Some of these fixation systems require the elevation of the pectoralis major bilaterally to facilitate access to achieve fixation (Fig. 9.2.1 a, b). If, however, at the completion of adequate debridement, whether following a single procedure or a series of procedures, the residual sternum was of significantly diminished volume or was of otherwise poor quality, then bone repair would be ill-​advised, and a subtotal sternectomy should be performed and the mediastinal space obliterated by a vascularized flap. This can be achieved using either pectoralis major flaps based either on the pectoral branch of the acromiothoracic axis, or on internal mammary perforators (Jeevanandam et  al., 1990; Hugo et  al., 1994). The rectus abdominis may be employed either as muscle or vertical rectus abdominis myocutaneous flap (Fleischer, 1993), and may be based on either the superior epigastric artery where the internal mammary artery (IMA) remains in continuity, or on the costomarginal superolateral supply to the rectus where the IMA has been used as a coronary artery graft conduit. Latissimus dorsi flaps have been used for this purpose (Dejesus et al., 2001) as have omental flaps based on either of the gastroepiploic vessels, according to surgeon preference. Where the presentation of the sternotomy infection is more delayed and represents chronic presentation of osteomyelitis, preoperative assessment should include microbiology specimens where available, imaging of the sternum and costal cartilages, and consultation with an infectious diseases physician. Imaging which may delineate the extent of infection prior to surgical intervention includes computed tomography (CT) scanning with bone windows, and radio-​isotope bone scanning in combination with either a white cell scan or gallium scan. Surgical debridement is more likely to require

993

994

SECTION 9  The chest and breast

(a)

(b)

Fig. 9.2.1  Polydioxanone sternal repair (a) sutures through bone (b) all sutures place to tie.

multiple procedures to ensure adequate removal of infected skeletal components, and is less likely to involve the mediastinal contents. It is uncommon with this presentation for secondary sternal repair to be possible, and obliteration of the dead space with muscle or myocutaneous flaps is usually required. Post-​pneumonectomy space infection Post-​pneumonectomy space infection (PPSI) (empyema thoracis) is a morbid condition with a variety of aetiologies. The majority of cases presenting to a plastic surgeon follow previous thoracic surgery, where the patient has often had multiple procedures. There may be other associated complications of previous surgery, including but not limited to, bronchopleural fistula, and possible threatened or leaking vascular or oesophageal anastomoses. Ordinarily, following lobectomy or pneumonectomy the surgical cavity is expected to obliterate by expansion of any residual lung, a degree of mediastinal shift, and elevation of the ipsilateral hemi-​diaphragm. Where infection supervenes, common approaches thereafter include open drainage with or without subsequent Clagett’s procedure (Clagett and Geraci, 1963) in which the cavity is packed with sodium hypochlorite dressing until the cavity is clean with negative wound cultures. This is followed by water-​tight closure of the chest wound again having filled the residual cavity with an antibiotic solution. Some patients will also have had attempted thoracoplasty (Shields, 2005) which is designed to collapse the infected cavity and close fistulae but is a procedure associated with substantial morbidity, mortality, and where successful, a very marked cosmetic deformity and compromise of respiratory function. Thoracoplasty has a reported failure rate of 17–​33%. For the plastic surgeon, management of PPSI involves identification or exclusion of an underlying bronchopleural fistula, decontamination of the space with a combination of systemic antibiotics

and topical irrigation, and ultimately closure either by obliteration of the space or by closure of the fistula where indicated. Fistulae are usually identified on narrow slice CT scan with axial or coronal soft tissue views. If a fistula can be specifically identified, priority should be given at the time of surgical repair to its correction, wherever possible, especially if there is concern that the space will not be readily obliterated. Prior to undertaking surgery, consultation with an infectious diseases physician permits culture-​specific antibiotic management, and the cavity is regularly irrigated with either a povidone-​iodine solution, or where directed by the infectious diseases team, an antibiotic solution. Closure of the fistula can be achieved using a variety of local muscle flap options including pectoralis major, serratus anterior, rectus abdominis, and even the ipsilateral latissimus dorsi depending on the location of the fistula, and where latissimus may have been transected in a thoracotomy or subsequent surgical approach (Pairolero and Arnold, 1989). Free microvascular tissue transfers with the ipsilateral thoracodorsal vessels as recipients have proven to be very effective (Chen et al., 1990; Perkins et al., 1995, 1996b). Any existing wounds on the chest are excised and closed in layers where possible and specific access to the pneumonectomy space is gained via a thoracic window at the medial wall of the axilla created by rib resection in this location. This permits direct visualization of the medial wall of the chest cavity and direct visualization of any larger fistulae. A  series of sutures placed around the fistula will permit the later parachuting of a segment of the transferred free flap directly and securely into the fistula. The remainder of the flap transfer is delivered into the chest cavity via the medial axillary window, to obliterate the space to whatever extent is possible. The flap may be monitored at the medial wall of the axilla, by the preservation of a small skin island.

9.2  Deformities of the chest

Where the residual chest cavity volume is large and the available donor tissue limited, or where it is believed a fistula is present but cannot be specifically identified, consideration is given to the placement of an intrathoracic tissue expander, fully inflated, to obliterate the cavity and block the fistula whilst the expander is fully inflated (Griffin and Stubberfield, 1998). The transferred flap which was adjudged to be insufficient to obliterate the space may then be inset to seal the chest cavity completely.

Radiotherapy Once radiotherapy has been completed to an anatomical field, all of the tissues at all depths within that field will undergo progressive change over time due to the unavoidable damage to the microcirculation. Endarteritis obliterans may occur in any tissue plane. Radio-​ atrophy of soft tissues may then be associated with ulceration and osteoradionecrosis. As the indication for the recommendation of adjuvant radiotherapy following mastectomy have broadened over time, there is a greater population of patients who will have undergone significant doses of radiotherapy to the anterior chest wall, internal mammary chain, or axilla. Patients may also have undergone radiotherapy for the management of lymphoma, primary lung tumour, mesothelioma, or other pathology. As oncological management has improved, patients who have had tumour ablative doses of radiotherapy to the chest may survive for longer periods of time, and therefore, with more progressive radio-​atrophy and the potential for associated wound issues. Ulceration may be precipitated by further surgery required in a zone of existing radiation damage, for example, the management of a skin cancer or even coronary artery grafting. When surgery is undertaken for defects secondary to radiotherapy, the plastic surgeon should attempt to resurface as much of the irradiated field as practicable in order to prevent a similar problem arising at a later date. Therefore, in many circumstances the selected flap for reconstruction may be transferred to the zone of damage initially, its extent mapped out on the anterior chest, and then the radiation-​damaged tissue removed at these predetermined margins. Surgical treatment is ultimately precipitated in most circumstances by patients being unable to cope with the increasing fluid discharge which is usually associated with such wounds. This constant volume of serous and lymphatic discharge may best be managed by the involvement of a stomal therapist until surgery is undertaken. The chest wall defect may involve soft tissue only, or may also involve ribs. Traditionally, such skeletal defects may have been repaired using split rib grafts, or methyl methacrylate sandwiched between two layers of polypropylene mesh. These approaches have been largely supplanted by the use of either Gore-​Tex® (W.L. Gore and Associates, Newark, DE, USA) dual mesh or an acellular dermal matrix, which involves no secondary donor defect, is more readily fixed to the surrounding skeleton, and more flexible with chest movement. Soft tissue cover, whether associated with skeletal replacement or not, requires a vascularized flap. The most versatile reconstruction options include flaps based on the latissimus dorsi, rectus abdominis, pectoralis major, omentum, and any preferred free microvascular tissue transfer. Other muscle flaps employed less frequently include serratus anterior (Arnold et al., 1984) and external oblique (Bogossian et al., 1996). The latissimus dorsi flap may be used where the subscapular vessels are not compromised by the defect (Bostwick et al., 1979). The flap may be transferred as a myocutaneous unit, or muscle only with an overlying split-​thickness skin graft. This latter approach

does afford broad coverage, but yields a stiffer and less flexible outcome for the patient. If the latissimus dorsi is being transferred in a traditional transposition fashion, then its excursion is improved by tunnelling the flap deep to any residual ipsilateral pectoralis major, which will shorten the distance between the pedicle and the defect. Transferred in this fashion the latissimus dorsi flap will readily cross the midline (Fig. 9.2.2 and Fig. 9.2.3). The latissimus dorsi myocutaneous flap may also be designed as a V–​Y advancement flap (Micali and Carramaschi, 2001), a clever modification of design which permits myocutaneous flap coverage of a more extensive area of the anterior chest, without the need for associated split-​thickness skin grafting (9.2.4a–f).

Fig. 9.2.2  Anterior chest wall defect, for Gore-​Tex® and pedicled latissimus dorsi flap repair based on the left thoracodorsal vessels.

Fig. 9.2.3  Anterior chest wall defect, with left pedicled latissimus dorsi myocutaneous flap (note the reach of the flap is nearly to the contralateral axilla).

995

996

SECTION 9  The chest and breast

(a)

(b)

(c)

(d)

(e)

(f)

Fig. 9.2.4  Case of recurrent breast cancer planned for mastectomy (a) pre-operative clinical photograph, (b) anterior planning incisions, (c) planning for V–Y latissimus dorsi advancement flap, (d) excisional defect, (e) completed latissimus dorsi V–Y advancement flap, reaching midline and with no requirement for skin graft on the chest, (f) donor site for the latissimus dorsi V–Y advancement flap.

9.2  Deformities of the chest

Similarly, there are a variety of ways the rectus abdominis muscle may be employed for chest wall reconstruction in the management of radiation-​related defects (Cohen, 1994). Where the internal mammary, and by extension, superior epigastric vessels are in continuity,

the rectus may be used as a muscle-​only flap, vertical rectus abdominis myocutaneous flap (VRAM), or with a transversely orientated skin paddle (TRAM), which may be harvested as a unipedicled or bipedicled flap, and from different horizontal levels of the abdomen

(a)

(b) (i)

(ii) Defect in intercostals between ribs to permit delivery (R) internal mammary vesselsdivided disally pedicle mobilised and delivered between ribs at desred level on chest

Up for orientation

(R) lung deflated Causal

Cranial

Image is taken through chest wall resection before skeletal repair

(c)

(i)

(ii)

ping

Dra

d

d en

hea

(R) anterior chest Orientational

The external aspect of defect created between ribs to allow delivery of recipients pedicle

ts

ien

cip

V

A/

e sr

a

IM

Reflected skin flap to permit delivery of IMA/V pedicle

Edge of Goretex repair Betadine spenge over goretex dual mesh

Fig. 9.2.5  Case of recurrent squamous cell carcinoma after previous right fore quarter amputation (a) pre-operative clinical photograph, (b) chest wall defect defect with ipsilateral internal mammary artery taken down and delivered between ribs (i) intraoperative photograph (ii) explanatory diagram, (c) internal mammary artery and vein readily available adjacent to Gore-Tex® repair as recipient vessels for microvascular flap repair (i) intraoperative photograph (ii) explanatory diagram.

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SECTION 9  The chest and breast

according to requirements. In circumstances where the IMA has either been damaged or used for another purpose, the rectus may be elevated on the costomarginal supply, the most superiorly located thoracoabdominal pedicle. However, this supply enters the muscle at a more lateral position, altering the necessary pivot point of the flap and therefore significantly restricting the range of excursion of the flap. Like the latissimus dorsi flap, where appropriate the rectus abdominis may also be employed as a free microvascular tissue transfer. Pectoralis major muscle flaps may be used for chest wall reconstruction based on either its internal mammary or acromiothoracic supply (Arnold and Pairolero, 1979; Tobin et al., 1983), and is adaptable to many different flap designs. It may be employed as a turn-​over flap based usually on internal mammary perforators, but occasionally on perforators from intercostal vessels. It may be a transposition or a myocutaneous advancement flap based on its pectoral vessel supply. The greater omentum (Dupont and Menard, 1972; Jurkiewicz and Arnold, 1977) can be mobilized from the greater curvature of the stomach vascularized by either the left or right gastroepiploic vessels and delivered to the anterior chest wall through a small defect in the linea alba immediately inferior to the diaphragm. The flap is then covered with a meshed split-​thickness skin graft to achieve soft tissue resurfacing, but may be technically demanding to secure to the anterior chest due to its inherent fluid mobility as a flap. Where available, perforator-​based skin flaps may be used, for example, the thoracodorsal artery perforator (TAP) flap (Schwabegger et al., 2002). Some perforator flaps, however, will have a restricted range of mobility. Free microvascular tissue transfers are frequently employed for more substantial chest wall defects (Netscher and Valkov, 2000; Cordeiro et al., 2001) and their surgical planning then becomes particularly important. It may be necessary for the patient to be repositioned during the course of the procedure to facilitate the surgical sequence whereby a defect is created, free flap elevated, recipient vessels identified, free microvascular tissue transferred, and flap inset. The sequence may vary according to the anatomical location of the donor area and relative ease of surgical access once a chest wall defect has been created. Potential recipient vessels for free tissue transfers include thoracodorsal, internal mammary, subclavian and branches, and vessels such as transverse cervical at the base of the neck. Where feasible, the internal mammary pedicle may be mobilized via the created chest wall defect, and delivered to the external surface of the chest through a window in the intercostal musculature created surgically from within the chest cavity.

Tumour As in other anatomical locations, tumours of the chest wall may be primary or secondary in nature. Primary chest wall tumours are less common than secondary deposits, and the primary tumours may arise from any of the cell types which comprise the chest wall. Primary tumours may be either benign or malignant and broadly may involve bone or soft tissues. The presence of a chest wall mass is the usual presentation but pain may also be a presenting symptom (Figs. 9.2.5a–c). Benign primary chest wall tumours include fibrous dysplasia, osteochondroma, chondroma, lipoma, and haemangioma. Primary

malignant tumours include chondrosarcoma, osteogenic sarcoma, fibrosarcoma, myeloma, and Ewing’s sarcoma. Where the tumour appears to be of soft tissue origin, obtaining a preliminary tissue diagnosis may be useful as some tumours, such as lymphoma, can be radiosensitive and this may indeed be the preferred treatment. However, tissue biopsy whether obtained by needle aspiration, core biopsy, or open incision may yield no diagnostic information. For tumours arising principally in the sternum or costal cartilages the likelihood of malignant disease is very high, biopsies are frequently unhelpful, and planning should be for radical resection.

REFERENCES Arnold PG, Pairolero PC. Use of pectoralis major muscle flaps to repair defects of anterior chest wall. Plast Reconstr Surg 1979;63:205–​13. Arnold PG, Pairolero PC, Waldorf JC. The serratus anterior muscle:  intrathoracic and extrathoracic utilization. Plast Reconstr Surg 1984;73:240–​6. Bogossian N, Chaglassian T, Rosenberg PH, et  al. External oblique myocutaneous flap coverage of large chest-​wall defects following resection of breast tumors. Plast Reconstr Surg 1996;97:97–​103. Bostwick III J, Nahai F, Wallace JG, et al. Sixty latissimus dorsi flaps. Plast Reconstr Surg 1979;63:31–​41. Cabbabe EB, Cabbabe SW. Immediate versus delayed one-​stage sternal debridement and pectoralis muscle flap reconstruction of deep sternal wound infections. Plast Reconstr Surg 2009;123:1490–​4. Chase CW, Franklin JD, Guest DP, et  al. Internal fixation of the sternum in median sternotomy dehiscence. Plast Reconstr Surg 1999;103:1667–​73. Chen H-​C, Tang Y-​B, Noordhoff MS, et al. Microvascular free muscle flaps for chronic empyema with bronchopleural fistula when the major local muscles have been divided-​one-​stage operation with primary wound closure. Ann Plast Surg 1990;24:510–​16. Cicilioni OJ Jr, Stieg FH III, Papanicolaou G. Sternal wound reconstruction with transverse plate fixation. Plast Reconstr Surg 2005;115:1297–​303. Clagett O, Geraci J. A procedure for the management of postpneumonectomy empyema. J Thorac Cardiovasc Surg 45:141–​5. Cohen M. Reconstruction of the chest wall. In:  Cohen M (ed) Mastery of Plastic and Reconstructive Surgery, pp. 1248–​67. Boston, MA: Little, Brown, 1994. Cordeiro PG, Santamaria E, Hidalgo D. The role of microsurgery in reconstruction of oncologic chest wall defects. Plast Reconstr Surg 2001;108:1924–​30. Dejesus R, Paletta J, Dabb R. Reconstruction of the median sternotomy wound dehiscence using the latissimus dorsi myocutaneous flap. J Cardiovasc Surg 2001;42:359–​64. Del Frari B, Schwabegger AH. Clinical results and patient satisfaction after pectus excavatum repair using the MIRPE and MOVARPE technique in adults:  10-​ year experience. Plast Reconstr Surg 2013;132:1591–​602. Dupont C, Menard Y. Transposition of the greater omentum for reconstruction of the chest wall. Plast Reconstr Surg 49:263–​7. Fleischer A. Closure of mediastinal wounds with deepithelialized rectus abdominis musculocutaneous flaps. Ann Plast Surg 1993;31:146–​8. Fox JP, Schnell JL, Adams JR TA, et al. Pectus excavatum: comparison of nonprosthetic repairs using multiple techniques. Plast Reconstr Surg 2007;119:33e–​9e.

9.2  Deformities of the chest

Frey AS, Garcia VF, Brown RL, et  al. Nonoperative management of pectus carinatum. J Pediatr Surg 2006;41:40–​5. Griffin P, Stubberfield J. Tissue deflation for postpneumonectomy empyema. Presentation at Annual Scientific Congress of the Royal Australasian College of Surgeons. Sydney, Australia, 1998. Haller JA Jr, Colombani PM, Humphries CT, et  al. Chest wall constriction after too extensive and too early operations for pectus excavatum. Ann Thorac Surg 1996;61:1618–​25. Hugo NE, Sultan MR, Ascherman JA, et al. Single-​stage management of 74 consecutive sternal wound complications with pectoralis major myocutaneous advancement flaps. Plast Reconstr Surg 1994;93:1433–​41. Jeevanandam V, Smith C, Rose E, et al. Single-​stage management of sternal wound infections. J Thorac Cardiovasc Surg 1990;99:256–​62. Jones G, Jurkiewicz M, Bostwick J, et al. Management of the infected median sternotomy wound with muscle flaps. The Emory 20-​year experience. Ann Surg 1997;225:766–​76. Jurkiewicz M, Arnold P. The omentum: an account of its use in the reconstruction of the chest wall. Ann Surg 1977;185:548–​54. Jurkiewicz M, Bostwick J 3rd, Bishop JB, et  al. Infected median sternotomy wound: successful treatment by muscle flaps. Ann Surg 1980;191:738–​44. Landes G, Harris PG, Sampalis JS, et al. Outcomes in the management of sternal dehiscence by plastic surgery:  a ten-​year review in one university center. Ann Plast Surg 2007;59:659–​66. Lee A Jr, Schimert G, Shaktin S, et al. Total excision of the sternum and thoracic pedicle transposition of the greater omentum; useful strategems in managing severe mediastinal infection following open heart surgery. Surgery 1976;80:433–​6. Levin LS, Miller AS, Gajjar AH, et  al. An innovative approach for sternal closure. Ann Thorac Surg 2010;89:1995–​9. Longaker MT, Glat PM, Colen LB, et  al. Reconstruction of breast asymmetry in Poland’s chest-​wall deformity using microvascular free flaps. Plast Reconstr Surg 1997;99:429–​36. Marks MW, Iacobucci J. Reconstruction of congenital chest wall deformities using solid silicone onlay prostheses. Chest Surg Clin North Am 2000;10:341–​55,  vii. Micali E, Carramaschi FR. Extended VY latissimus dorsi musculocutaneous flap for anterior chest wall reconstruction. Plast Reconstr Surg 2001;107:1382–​90. Molik KA, Engum SA, Rescorla FJ, et al. Pectus excavatum repair: experience with standard and minimal invasive techniques. J Pediatr Surg2001;36:324–​8.

Morshuis W, Folgering H, Barentsz J, et al. Pulmonary function before surgery for pectus excavatum and at long-​term follow-​up. Chest 1994;105:1646–​52. Netscher DT, Valkov PL. Reconstruction of oncologic torso defects: emphasis on microvascular reconstruction. Semin Surg Oncol 2000;19:255–​63. Nuss D, Kelly RE Jr, Croitoru DP, et al. A 10-​year review of a minimally invasive technique for the correction of pectus excavatum. J Pediatr Surg 1998;33:545–​52. Pairolero P, Arnold P. Intrathoracic transfer of flaps for fistulas, exposed prosthetic devices, and reinforcement of suture lines. Surg Clin North Am 1989;69:1047–​59. Perkins D, Hunt J, Pennington D, et al. Secondary sternal repair following median sternotomy using interosseous absorbable sutures and pectoralis major myocutaneous advancement flaps. Br J Plast Surg 1996a;49:214–​19. Perkins D, Lee K, Pennington D, et al. Free flaps in the management of intrathoracic sepsis. Br J Plast Surg 1995;48:546–​50. Perkins D, McCaughan B, Stern H. Microvascular transverse rectus abdominis myocutaneous (TRAM) free flap for the management of a large thoracic empyema. Asia Pacific Heart J 1996b; 5:115–​19. Poland A. Deficiency of the pectoral muscles. Guys Hosp Rep 1841;6:191. Ravitch MM. The operative treatment of pectus excavatum. Ann Surg 1949;129:429–​44. Schaarschmidt K, Kolberg-​Schwerdt A, Dimitrov G, et al. Submuscular bar, multiple pericostal bar fixation, bilateral thoracoscopy:  a modified nuss repair in adolescents. J Pediatr Surg 2002;37: 1276–​80. Schwabegger AH, Ninković M, Piza-​Katzer H, et al. Thoracodorsal artery perforator (TAP) flap: report of our experience and review of the literature. Br J Plast Surg 2002;55:390–​5. Seyfer AE, Fox JP, Hamilton CG. Poland syndrome:  evaluation and treatment of the chest wall in 63 patients. Plast Reconstr Surg 2010;126:902–​11. Shields TW. General Thoracic Surgery. Philadelphia, PA:  Lippincott Williams & Wilkins, 2005. Tobin G, Mavroudis C, Howe WR, et al. Reconstruction of complex thoracic defects with myocutaneous and muscle flaps. Applications of new flap refinements. J Thorac Cardiovasc Surg 85:219–​28. Van Aalst JA, Phillips JD, Sadove AM. Pediatric chest wall and breast deformities. Plast Reconstr Surg 2009;124:38e–​49e.

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9.3

Surgical anatomy of the breast Amy E. Jeeves

Breast anatomy The breast is a remarkable organ. Its brief nutritional and immunological relevance is eclipsed by its role in body image and sexuality in our society. The apparent attractiveness of particular sizes or shapes of breasts as well as their perception as an erotic organ varies between cultures. Breast surgery, in particular cancer treatments and reconstruction, is influenced by our construct of the breast in self-​image and identity. Knowledge of breast anatomy is required in analysis and planning for breast augmentation, breast reduction, congenital anomaly correction, and reconstruction after breast cancer. Most of the literature regarding breast anatomy is derived from applied anatomical concepts, in particular the safety of the neurovascular pedicles in breast reduction and lymphatic drainage in breast cancer. The anatomy of the internal thoracic (mammary) system is also of interest to the plastic surgeon with regard to breast reconstruction.

Gross anatomy The breast is a modified skin appendage. The glandular ducts and alveoli derived from the ectodermal layer grow and branch into the surrounding mesoderm that subsequently becomes the fat and supporting structures of the breast. The breast base in neonates has been shown to closely approximate that of an adult: from the cranial aspect of the second or third rib to caudal edge of the sixth rib, 0.4 cm medial to anterior axillary line to 2.2 cm from sternal edge with a superolateral axillary tail (Rainer et al., 2003). Well-​formed histological elements of lobules, ducts, and dense interlobular stroma are present in subareolar breast biopsies of newborns of either sex with the structure of the infant breast similar to that of the lactating adult (McKiernan et al., 1988). Further development of the female breast consists of proliferation of existing glandular tissue during puberty. Male breast tissue usually comprises fibrous stroma containing a small amount of ductal tissue without lobules. Ductal and stromal tissue hyperplasia occurs in gynaecomastia without lobule formation (Klatt, 2011). Tanner described the changes to the external secondary sexual characteristics that usually occur between the ages of 10 and 15 years

in girls and the scale that bears his name is in common use (Marshall and Tanner, 1969; Tanner, 1969) (Table 9.3.1 and Fig. 9.3.1). The adult breast is generally teardrop shaped but variation is common with age, parity, race, and weight. The upper border of the breast footprint (the borders of the breast as it lies on the chest wall) usually lies at the level of the second or third rib and the inframammary fold usually extends from the fifth rib medially to the sixth intercostal space (Bayati and Seckel, 1995). The deep surface of the breast lies predominantly over the pectoralis major muscle, with some overlap onto serratus anterior superolaterally, rectus abdominus caudally, and the external oblique inferolaterally. Supernumerary breasts or nipples may arise anywhere along the milk line from the axilla to the perineum (Klatt, 2011). Mammary density is related to age and hormonal influence and increased density is associated with breast cancer. Density can be defined by visual or computer-​generated radiological systems (Regini et al., 2014). The visual system is called the Breast Imaging Reporting and Data System (BI-​RADS) and was devised by the American College of Radiology (Table 9.3.2). Macromastia is poorly understood but is presumed to be multifactorial, arising in a milieu of hormonal excess or end-​organ hypersensitivity. Gigantomastia is difficult to define. Dafydd and colleagues (2011) suggest a definition of breast tissue contributing 3% or more to the patient’s total body weight, or breast weight over 1.5 kg per breast. Table 9.3.1  The five breast development stages Stage

Characteristics

1

Pre-​adolescent; elevation of papilla only

2

Breast bud stage; elevation of breast and papilla as a small mound, enlargement of areola diameter

3

Further enlargement of breast and areola, with no separation of their contours

4

Projection of areola and papilla to form a secondary mound above the level of the breast

5

Mature stage; projection of papilla only, due to recession of the areola to the general contour of the breast

Reproduced from Tanner JM, ‘Growth and Endocrinology of the Adolescent,’ in Gardner L. (Ed.), Endocrine and Genetic Diseases of Childhood, Saunders, Philadelphia and London, Copyright © 1969.

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SECTION 9  The chest and breast

to one central larger duct within a lobule. Most lobules open into the lactiferous sinus thence onto the nipple surface (Vorherr, 2012). Sir Astley Cooper’s dissections revealed fewer than 12 patent ducts open onto the nipple (Cooper, 1840). There is no correlation between the amount of glandular tissue and milk production or storage capacity in lactating breasts, and approximately 70% of glandular tissue is located within 30 mm of the nipple (Ramsay et al., 2005). Progesterone and oestrogen are the hormones that most influence growth and apoptosis in the lobules and stroma. The epithelial cells surrounding the lobular acini extrude milk via apocrine secretion under the control of prolactin from the anterior pituitary. The myoepithelial cells surrounding the acinus are sensitive to oxytocin from the posterior pituitary and contract to express milk via the ductal system (Klatt, 2011). Most breast cancers are epithelial in origin, arising either from the ductal or lobular tissues. Paget’s disease of the breast is rare (about 2% of breast cancers) and typically involves the nipple–​areolar complex, presenting with eczema-​like symptoms and is often associated with underlying breast malignancy (Sandoval-​Leon et al., 2013).

Fig. 9.3.1  Tanner classification of breast development. Reproduced from Tanner JM, ‘Growth and Endocrinology of the Adolescent,’ in Gardner L. (Ed.), Endocrine and Genetic Diseases of Childhood, Second Edition, Saunders, Philadelphia and London, Copyright © 1975.

The incidence of unilateral breast hypoplasia is unknown. It is generally accepted that some degree of breast asymmetry naturally occurs in women but there is little literature discussing objective evaluation, aetiology, or incidence. Variation in breast volume, base, projection and inframammary fold position, nipple–​areolar complex size and shape are described (Rohrich et al., 2003). Of 344 patients undergoing breast reduction, 20% had more than 200 g difference between sides (Tenna et al., 2011). Asymmetry was found to vary widely in two different studies of women presenting for mammoplasty. The authors acknowledge the lack of literature regarding the true incidence of breast and chest wall asymmetry and its quantification (Gliosci and Presutti, 1994; Rohrich et al., 2003). Chest wall deformities such as Poland syndrome can also lead to breast asymmetry (Moir and Johnson, 2008).

Histology The breast contains a heterogeneous mix of fat, connective tissue, and glandular elements that change in size and proportion during a lifetime and cyclically under hormonal influence. The lactocytes that secrete and express milk are organized around an alveolus connected to small ducts that are subsequently connected Table 9.3.2  Breast composition Class

Description

A

The breasts are almost entirely fatty

B

There are scattered areas of fibroglandular density

C

The breasts are heterogeneously dense, which may obscure small masses

D

The breasts are extremely dense, which lowers the sensitivity of mammography

Reproduced with permission from D’Orsi CJ et al., 2013 ACR BI-​RADS Atlas: Breast Imaging Reporting and Data System, Table 5, American College of Radiology, USA, Copyright © American College of Radiology 2014.

Aesthetics Many articles have been published on the ideal breast aesthetic. Unfortunately, measurements and algorithms fail to take into account relative volume, symmetry, body proportion, soft tissue density and elasticity, age, race, or the patient’s and surgeon’s own perceptions. Anthropometry and subjective assessment both have limitations and make outcome analysis after breast surgery difficult. Penn’s often quoted article of ‘aesthetically perfect’ breasts, conforming to an equilateral triangle of 21 cm from the sternal notch with a nipple to inframammary distance of 6.9 cm largely concurs with more recent observational studies (Penn, 1955; Westreich, 1997; Liu and Thomson, 2011), though the nipple to inframammary crease distance can vary in young women from 4.5 to 10 cm (Lassus, 1996). The importance of analysis of the breast footprint as well as the breast shape (fullness and ptosis) in aesthetic breast surgery was emphasized by Hall-​Findlay (2010). Mallucci and Branford (2012, 2014) established that topless models from an English tabloid had consistent breast shape and proportions and that the 45:55 ratio of upper to lower pole and a sloped, rather than full upper pole is considered attractive by a variety of observers.

Nipple–​areolar complex The nipple–​areolar complex typically lies over the fourth intercostal space in the non-​ptotic breast. The Montgomery sebaceous glands of the areola open into raised papules called Morgagni tubercles. The nipple is more sensitive to light touch, temperature, vibration, and two-​point discrimination compared with the areola (Kuzbari and Schlenz, 2007). It contains erectile smooth muscle and has a rich subareolar plexus of lymphatics. An increased density of melanocytes is responsible for pigmentation of the nipple and areola; the melanin content of areolar skin has been found to be 2.5 times higher than in breast skin (Dean et al., 2005). The ideal position of the nipple–​areolar complex continues to be debated. No single measurement or relative position can be easily defined. In breast reduction, Wise (1956) described the ideal nipple location at the most prominent portion of the breast. Pitanguy (1960) referred to a point at the level of the projected inframammary fold as the ideal

9.3  Surgical anatomy of the breast

nipple position. In vertical scar reduction, the nipple is usually placed 2 cm below the inframammary crease (Ahmad and Lista, 2008). Hall-​ Findlay (2009) states that as the height of the inframammary fold varies, the nipple is more reliably placed relative to the breast mound, a third to a half way up, slightly below the horizontal meridian, lateral to the vertical meridian and approximately 10 cm below the upper breast border (which can be difficult to accurately define) and 10 cm from the midline. A nipple placed too high with a long nipple-​to-​inframammary fold distance is both unaesthetic and difficult to correct.

Arterial supply The arterial supply of the breast forms a complex network that is variable even in the same individual (Fig. 9.3.2). In particular, slightly different dominant patterns of blood supply to the nipple–​ areolar complex are often described. Traditional dissection studies quote the dominant blood supply to the breast (see Chapter  9.15) as the internal thoracic (internal mammary) artery with significant contributions from the lateral thoracic artery, superficial thoracic artery, axillary artery, as well as

Fig. 9.3.2  Arterial supply of the breast. Reproduced courtesy of David Heinrich.

cutaneous branches from the pectoral branch of the thoracoacromial axis (Anson et al., 1939; Carr et al., 1942; Cormack and Lamberty, 1994). According to Taylor (see Chapter 1.5), the three angiosome territories involved are the thoracoacromial, lateral thoracic, and internal thoracic with the nipple being at the centre of the choke vessel interface (Palmer and Taylor, 1986). There are both superficial and deep arterial systems. The superficial system arises from the internal mammary, highest thoracic, and superior thoracic arteries, whereas the deep system comprises branches of the lateral thoracic, intercostal, and thoracoacromial arteries. The first part of the subclavian artery gives rise to the internal thoracic (mammary) artery, which usually courses 1–​2 cm lateral to the lateral edge of the sternum (O’Dey et al., 2007). Perforators from it pass through the pectoralis major muscle from the second to the sixth space to supply the medial aspect of the breast. The third and fourth perforators are usually dominant here and pass superficially toward the nipple at an average of 1 cm below the skin (le Roux et al., 2010). The first part of the axillary artery has one branch, the superior thoracic artery, supplying some of the uppermost part of the breast. The thoracoacromial axis and lateral thoracic artery arise from the second part of the axillary artery. The pectoral branches of the

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SECTION 9  The chest and breast

thoracoacromial artery axis supply some the more central upper pole. The lateral thoracic artery branches around the lateral aspect of pectoralis major and provides a major contribution to the lateral aspect of the breast. The lateral intercostal perforators pass through serratus anterior along the anterior margin of latissimus dorsi. They arise from the posterior branches of the intercostal artery from the thoracic aorta and reliably supply the inferolateral quadrant. The highest intercostal artery has variable origin coming from the brachiocephalic trunk or less commonly the internal mammary artery and supplies over the first and second intercostal spaces and superior pole.

Venous drainage The veins of the breast run a separate but similarly extensive course from the arteries, joining them to perforate the deep fascia. In vivo studies reveal a subareolar, subcutaneous venous plexus with radiation circumferentially, predominantly via two systems:  superomedially to the second and third intercostal spaces and inferiorly to the fourth or fifth intercostal spaces (Corduff et al., 2010).

Fig. 9.3.3  Lymphatic drainage of the breast. Reproduced courtesy of David Heinrich.

The superficial periareolar ring of communicating vessels connect both to the deep lateral veins and the more superficial coursing medial veins in parallel slings with the lateral veins draining to the subclavian and the medial to the internal mammary system (le Roux et al., 2011). The arterial supply and venous drainage patterns explain the relative reliability of the popular Robbins inferior pedicle (Robbins, 1977) and Hall-​Findlay medial or superomedial pedicle breast reduction techniques (Hall-​Findlay, 1999; le Roux et al., 2010).

Lymphatic drainage The lymphatic drainage of the breast has clinical relevance to sentinel lymph node biopsy, investigations for metastatic breast cancer, and radiotherapy planning. Early mercury injection studies revealed lymphatic drainage of the breast to the ipsilateral axilla. More detailed microsurgical and computed tomography scan studies by Suami and colleagues (2008) and Pan and co-​workers (2009) show high variability in lymphatic drainage. They revealed that the lymphatics course superficially in the parenchyma and do not always coalesce at the nipple.

9.3  Surgical anatomy of the breast

Fig. 9.3.4  Nerve supply of the breast. Reproduced courtesy of David Heinrich.

The breast can drain to the axillary, subpectoral, parasternal, and subscapular nodes as well as the supraclavicular and subclavian lymphatics (Fig. 9.3.3). Axillary lymph node dissections (like the axillary artery) are divided into three levels relative to their relationship to pectoralis minor. Level I is lateral (below) to pectoralis minor, level II deep to it, and level III medial (above) to pectoralis minor.

Nerve supply Anterior and lateral branches from the intercostal nerves supply the breast. Anterior intercostal nerves supply the medial breast from the second to the fifth spaces; the fourth and fifth nerves providing medial contributions to the nipple–​areolar complex (Fig. 9.3.4). The medial nerves become very superficial at the areola, being on average only 2 mm deep to the skin at 3 cm from the nipple–​areolar complex (le Roux et  al., 2010). The predominant nerve supply to the nipple–​areolar complex is a deep branch from the fourth lateral intercostal nerve. Branches from the cervical plexus supply the upper superomedial pole.

Ligamentous support and the inframammary fold The fascial support system is an infrequently studied aspect of breast anatomy, despite its contribution to the aesthetic outcome of breast surgery. Sir Astley Cooper (1840) described the suspensory ligaments which run from the dermis to the deep fascia. The distinct subfascial plane of the breast was described by Jinde and colleagues (2006). The superficial fascial system is more complex with a ring of fascial adhesion zones consisting of the superficial clavicular ligament and deep clavicular ligament superiorly; the medial sternal ligaments, the pectoralis minor suspensory ligament, and lateral fascial confluence laterally; and inferiorly, the triangular fascial condensation (Matousek et al., 2014). The inframammary fold is variously described as dense connective tissue, extending from the inframammary crease to the deep fascia (Jinde et al., 2006), a fusion of the deep and superficial fascia (Muntan et al., 2000), or a ligament from the periosteum of the fifth rib medially and the fifth intercostal space laterally to the dermis of the inframammary crease (Bayati and Seckel, 1995). Some debate the presence of a mesentery-​like

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SECTION 9  The chest and breast

fascial septum, first described by Würinger and colleagues (1998), which contains the neurovascular pedicle to the nipple–​areolar complex.

ACKNOWLEDGEMENTS The author would like to thank David Heinrich, graphic artist, for the production of the figures for this chapter.

REFERENCES Ahmad J, Lista F. Vertical scar reduction mammaplasty:  the fate of nipple-​ areola complex position and inferior pole length. Plast Reconstr Surg 2008;121:1084–​91. Anson BJ, Wright RR, Wolfer JA. Blood supply of the mammary gland. Surg Gynecol Obstet 1939;69:468–​73. Bayati S, Seckel BR. Inframammary crease ligament. Plast Reconstr Surg 1995;95:501–​8. Carr B, Bishop W, Anson B. Mammary arteries. Q Bull Northwest Uni Med School 1942;16:150–​4. Cooper AP. On the Anatomy of the Breast. London: Longman, 1840. Corduff N, Rozen WM, Taylor GI. The superficial venous drainage of the breast: a clinical study and implications for breast reduction surgery. J Plast Reconstr Aesth Surg 2010;63:809–​13. Cormack GC, Lamberty BGH. The Arterial Anatomy of Skin Flaps. Edinburgh: Churchill Livingstone, 1994. D’Orsi CJ, Sickles EA, Mendelson EB, et  al. 2013 ACR BI-​ RADS Atlas: Breast Imaging Reporting and Data System. Reston, VA: American College of Radiology, 2014. Dafydd H, Roehl K, Phillips L, et al. 2011. Redefining gigantomastia. J Plast Reconstr Aesth Surg 2011;64:160–​3. Dean N, Haynes J, Brennan J, et al. Nipple-​areolar pigmentation: histology and potential for reconstitution in breast reconstruction. Br J Plast Surg 2005;58:202–​8. Gliosci A, Presutti F. Asymmetry of the breast: some uncommon cases. Aesthetic Plast Surg 1994;18:399–​403. Hall-​Findlay EJ. A simplified vertical reduction mammaplasty: shortening the learning curve. Plast Reconstr Surg 1999;104:748–​59. Hall-​Findlay EJ. Planning in aesthetic breast surgery. Plastic Surgery Pulse News, Article 13. St Louis, MO: Quality Medical Publishing, 2009. Hall-​Findlay EJ. The three breast dimensions:  analysis and effecting change. Plast Reconstr Surg 2010;125:1632–​42. Jinde L, Jianliang S, Xiaoping C, et al. Anatomy and clinical significance of pectoral fascia. Plast Reconstr Surg 2006;118:1557–​60. Klatt EC. The breast. In:  Klatt EC (ed) Robbins and Cotran Atlas of Pathology, 2nd ed, pp. 363–​80. Philadelphia, PA:  Elsevier Health Sciences, 2011. Kuzbari R, Schlenz I. Reduction mammaplasty and sensitivity of the nipple-​areola complex: sensuality versus sexuality? Ann Plast Surg 2007;58:3–​11. Lassus C. A 30-​year experience with vertical mammaplasty. Plast Reconstr Surg 1996;97:373–​80. le Roux CM, Kiil BJ, Pan W-​R, et  al. Preserving the neurovascular supply in the Hall-​Findlay superomedial pedicle breast reduction: an anatomical study. J Plast Reconstr Aesth Surg 2010;63:655–​62. le Roux CM, Pan, W-​R, Matousek SA, et al. Preventing venous congestion of the nipple-​areola complex: an anatomical guide to preserving essential venous drainage networks. Plast Reconstr Surg 2011;127:1073–​9. Liu Y-​J, Thomson JG. Ideal anthropomorphic values of the female breast: correlation of pluralistic aesthetic evaluations with objective measurements. Ann Plast Surg 2011;67:7–​11.

Mallucci P, Branford O. Concepts in aesthetic breast dimensions: analysis of the ideal breast. J Plast Reconstr Aesth Surg 2012;65:8–​16. Mallucci P, Branford OA. Population analysis of the perfect breast: a morphometric analysis. Plast Reconstr Surg 2014;134:436–​47. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–​303. Matousek SA, Corlett RJ, Ashton MW. Understanding the fascial supporting network of the breast:  key ligamentous structures in breast augmentation and a proposed system of nomenclature. Plast Reconstr Surg 2014;133:273–​81. Mckiernan J, Coyne J, Cahalane S. Histology of breast development in early life. Arch Dis Child 1988;63:136–​9. Moir CR, Johnson CH. Poland’s syndrome. Semin Pediatr Surg 2008;17:161–​6. Muntan CD, Sundine MJ, Rink RD, et al. Inframammary fold: a histologic reappraisal. Plast Reconstr Surg 2000;105:549–​56. O’Dey DM, Prescher A, Pallua N. Vascular reliability of nipple-​areola complex-​bearing pedicles:  an anatomical microdissection study. Plast Reconstr Surg 2007;119:1167–​77. Palmer JH, Taylor GI. The vascular territories of the anterior chest wall. Br J Plast Surg 1986;39:287–​99. Pan WR, Rozen WM, Stella DL, et al. A three-​dimensional analysis of the lymphatics of a bilateral breast specimen: a human cadaveric study. Clin Breast Cancer 2009;9:86–​91. Penn J. Breast reduction. Br J Plast Surg 1955;7:357–​71. Pitanguy I. Breast hypertrophy. In: Wallace A (ed) Transactions of the Second Congress of the International Society of Plastic Surgeons, pp. 509–​22. Edinburgh: Livingstone, 1960. Rainer C, Gardetto A, Frühwirth M, et al. Breast deformity in adolescence as a result of pneumothorax drainage during neonatal intensive care. Pediatrics 2003;111:80–​6. Ramsay D, Kent J, Hartmann R, et al. Anatomy of the lactating human breast redefined with ultrasound imaging. J Anat 2005;206:525–​34. Regini E, Mariscotti G, Durando M, et al. Radiological assessment of breast density by visual classification (BI–​RADS) compared to automated volumetric digital software (Quantra): implications for clinical practice. Radiol Med 2014;119:741–​9. Robbins TH. A reduction mammaplasty with the areola-​ nipple based on an inferior dermal pedicle. Plast Reconstr Surg 1977;59:64–​7. Rohrich RJ, Hartley W, Brown S. Incidence of breast and chest wall asymmetry in breast augmentation: a retrospective analysis of 100 patients. Plast Reconstr Surg 2003;111:1513–​19. Sandoval-​Leon AC, Drews-​Elger K, Gomez-​Fernandez CR, et  al. Paget’s disease of the nipple. Breast Cancer Res Treat 2013;141:1–​12. Suami H, Pan WR, Mann GB, et  al. The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study. Ann Surg Oncol 2008;15:863–​71. Tanner JM. Growth and endocrinology of the adolescent. In: Gardner L (ed) Endocrine and Genetic Diseases of Childhood, pp. 14–​64. Philadelphia, PA: Saunders, 1969. Tenna S, Cogliandro A, Cagli B, et al. Breast hypertrophy and asymmetry: a retrospective study on a sample of 344 consecutive patients. Acta Chir Plast 2011;54:9–​12. Vorherr H. The Breast:  Morphology, Physiology, and Lactation. Philadelphia, PA: Elsevier, 2012. Westreich M. Anthropomorphic breast measurement:  protocol and results in 50 women with aesthetically perfect breasts and clinical application. Plast Reconstr Surg 1997;100:468–​79. Wise RJ. A preliminary report on a method of planning the mammaplasty. Plast Reconstr Surg 1956;17:367–​75. Würinger E, Mader N, Posch E, et al. Nerve and vessel supplying ligamentous suspension of the mammary gland. Plast Reconstr Surg 1998;101:1486–​93.

9.4

Congenital deformities of the breast Michelle L. Lodge

Introduction While congenital anomalies of the breast are unusual in clinical practice, they are a powerful source of anxiety and distress, often go unrecognized until adulthood, and can benefit from early recognition and intervention.

Polythelia and polymastia Polythelia (supernumerary nipples) and polymastia (supernumerary breasts) are relatively common anomalies appearing along the embryonic mammary ridge extending from the axilla to the groin. Less frequently, aberrant breast tissue has been reported to arise in other sites such as face, neck, buttock, hip, back, and perineum (Williams, 1891; Camisa, 1980; Koltuksuz and Aydin, 1997; Basu et al., 2003; Burdick et al., 2003). Most cases of accessory breast tissue are sporadic but familial cases represent 10% of all cases (Loukas et al., 2007). The proposed aetiology of supernumerary breast tissue is failure of regression of tissue along the embryonic mammary ridge, whereas ectopic supernumerary breast tissue may be explained by displacement of the ridge or metaplasia of sweat glands (Pfeifer et al., 1999). Kajava (1915) classified supernumerary breast tissue into eight categories (Table 9.4.1). Table 9.4.1  Kajava classification of supernumerary breast tissue Class

Description

I

Complete breast with nipple, areola, and gland tissue (polymastia)

II

Supernumerary breast without areola, but with nipple and gland tissue

III

Supernumerary breast without nipple, but areolar and gland tissue

IV

Aberrant gland tissue only

V

Nipple and areola only, gland tissue replaced by fat (pseudomammae)

VI

Polythelia, nipples only

VII

Polythelia areolaris, areola only

VIII

Polythelia pilosa, patch of hair only

Reproduced with permission from Kajava Y., The proportion of supernumerary nipples in Finnish population, Duodecim, volume 31, pp.143–​170. Copyright 1915 Duodecim.

Polymastia is seen more commonly in females and presents under the influence of the hormonal changes of menarche, pregnancy, or lactation. The axilla is the most frequent site of occurrence. The ectopic breast tissue may undergo any of the benign and malignant pathology seen in the normal breast. Polymastia requires treatment if there is uncertainty in the diagnosis or if there is pathological change but frequently it is removed for aesthetic and functional concerns. Renal anomalies and renal malignancies can be associated with polymastia. Polythelia is more frequently seen than polymastia. It also may be associated with renal and urinary tract anomalies and cardiac anomalies (Meggyessy and Méhes, 1987). The most common location for polythelia is just below the normal nipple on the left side of the chest. Simple excision may be indicated.

Congenital absence of the breast Complete absence of the breast is a rare disorder. The three variations are athelia (absent nipples), amazia (absent mammary gland but nipple present), and amastia (breast agenesis including nipple and mammary gland). Lin and colleagues described three different groups of congenital absence of the breast including bilateral absence associated with ectodermal defect, unilateral absence as a variant of Poland syndrome, and bilateral absence of breast with or without other congenital anomalies (e.g. cleft palate, high arched palate, hypertelorism, syndactyly) (Lin et al., 2000; Martínez-​ Chéquer et al., 2004). Breast reconstruction can be performed either by tissue expansion and breast implants, or autologous reconstruction. The positioning of the reconstruction on the chest wall needs special consideration and one method is to ask the patient to wear an underwire bra with prosthesis preoperatively and to use the resulting indentations as a guide for placement (Lin et al., 2000).

Tuberous breast deformity The tuberous breast is a developmental deformity initially described by Rees and Aston (1976). It is characterized by a breast with a high

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SECTION 9  The chest and breast

inframammary fold, variable degree of hypoplasia of one or more quadrants, a narrow base, and often herniation of the nipple–​areolar complex. The incidence of tuberous breast is unknown but it is probably underdiagnosed. It frequently occurs bilaterally and often the two sides are asymmetrically affected. The aetiology of tuberous breast is unknown but the suggested cause of the anomaly is an abnormality of the fascial layers of the breast—​either a constricting ring of fascia surrounding the nipple–​ areolar complex (Mandrekas and Zambacos, 2010)  or an abnormally dense connection between the fascial layers in the lower pole of the breast (Grolleau et al., 1999). The breast is encapsulated by a fascial envelope, the superficial fascia, which has a superficial layer covering the breast parenchyma and a deep layer lying on the deep fascia of pectoralis major and serratus anterior. There is an absence of the superficial fascia underneath the areola. It is suggested that abnormal adhesions within the superficial fascia prevents separation of the two layers resulting in restricted growth inferiorly and ‘herniation’ of breast tissue through the nipple–​areolar complex. Some believe the anatomical defect in tuberous breast is a congenital dermal weakness of the nipple–​areolar complex and the dome shape produced is due to attenuated tissues in the nipple–​areolar complex rather than a constricting ring (Pacifico and Kang, 2007; Costagliola et al., 2013).

Classification Rees and Aston initially described two types of tuberous breast in 1976. The first consisted of a breast with proportional vertical and horizontal deficiencies which was small and tuberous shaped, with a large nipple–​areolar complex. The second type was described as a breast more deficient in the vertical dimension with ptosis and down-​pointing nipple (Table 9.4.2). In 1996, von Heimburg and colleagues described a classification depending on the degree of breast hypoplasia and skin deficiency. Type I  has hypoplasia of the lower medial quadrant, type II has hypoplasia of the lower medial and lateral quadrants with sufficient skin in the subareolar region, type III has hypoplasia of the lower and medial quadrants with deficiency of skin in the subareolar region, and type IV has severe breast constriction with minimal breast base (von Heimburg et al., 1996). In 2000, von Heimburg refined the classification by including a description of the breast profile for the four types (von Heimburg, 2000). In 1999, Grolleau and colleagues published a classification system for tuberous breast. Type I is the most minor with only the medial quadrant deficient, type II has both lower quadrants deficient, and type III where all four quadrants are deficient (Grolleau et al., 1999). Costagliola and co-​workers (2013) proposed another type within the classification, type O, defined by isolated nipple–​areolar protrusion with a normal breast base. Yet another classification system describing breast base, inframammary fold, skin envelope, breast volume, and ptosis was published by Meara and colleagues (2000). The authors did not include the areola in their system, as they, like von Heimburg, believed that areolar size and subareolar herniation increases in frequency but not necessarily in severity with increasing stage. Pacifico and Kang (2007) developed the Northwood index which is the ratio of areolar herniation to areolar diameter measured in lateral view. A  ratio of greater than 0.4 of the measured distance

from the edge of the areola to the tip of nipple, divided by the areola diameter, defines tuberous breast (Fig. 9.4.1). The authors believe that this is an objective and reproducible way of diagnosing tuberous breast.

Treatment The aims of surgical treatment of tuberous breast are to lower the inframammary fold, expand the constricted base, increase the skin envelope, augment the breast volume, and reduce the herniated subareolar breast tissue and areolar size when required (Meara et al., 2000). Many different procedures have been described to correct tuberous breast. The options include simple scoring of the breast parenchyma from an areolar or inframammary incision, complex parenchymal flaps with or without breast implants, tissue expansion with or without mastopexy, or dermoglandular flaps. Rees and Aston in their original article described releasing the constricted lower breast by radial parenchymal incisions via an inframammary approach (Rees and Aston, 1976). A laterally based full-​thickness flap to release the constricting ring and advance local tissue described by Dinner and Dowden (1987) has been criticized due to the resulting scarring. Puckett and Concannon (1990) described a technique for the tuberous breast requiring augmentation where, via a periareolar incision, the inferior skin is raised off the breast to the position of the new inframammary fold and then the glandular tissue raised from the posterior aspect. This glandular tissue is then divided from the posterior aspect, retaining a pedicle in the subareolar region and advanced inferiorly to the lowered inframammary fold over a retropectorally placed implant. Scheepers and Quaba (1992) were the first to introduce tissue expansion for treatment of tuberous breast and now this is a well-​ accepted method. This two-​stage approach has many advantages as it allows for lowering of the inframammary fold, expansion of restricted skin, and variable augmentation so that surgery can be performed in a younger population where further breast growth is expected (Fig. 9.4.2). In 1998, Ribeiro published his technique of a circumareolar de-​ epithelialization with horizontal division of the breast below the level of the nipple, undermining of skin to the inframammary fold, and then folding the inferior parenchymal flap over itself to fill the lower part of the breast. A  periareolar suture completed the procedure. He points out in the article that his patients are more concerned with scarring than with size of the breast and hence avoided a prosthesis (Ribeiro et al., 1998). Mandrekas and colleagues (2003) described a similar procedure to Ribiero with a circumareolar de-​epithelialization, elevation of the skin to the inframammary fold, undermining of the inferior aspect of the gland at the level of pectoral fascia, but then a vertical division of the lower parenchyma. This tissue is then approximated centrally and an implant placed if required for volume. In their 10-​year review of the technique, they report few complications and good preservation of lactiferous ducts hence maintaining breast function (Mandrekas and Zambacos, 2010). Muti (1996) describes three different procedures for the severely hypoplastic tuberous breast depending on the volume of the herniated breast tissue in the areolar. Through a circumareolar incision the subareolar glandular tissue was redraped inferiorly either via a

9.4  Congenital deformities of the breast

Table 9.4.2  Comparison of classifications of tuberous breast deformity von Heimburg

Grolleau

Meara

Costaglio et al.

Type 0: nipple–​areolar protrusion with normal breast

Type I hypoplasia lower medial quadrant

Type I hypoplasia lower medial quadrant, lower medial edge shaped like an italic S

Type I minor constriction of base, inframammary fold elevated medially, breast volume not substantially deficient

Type II hypoplasia of lower medial and lateral quadrants

Type II hypoplasia both lower quadrants, down pointing areolar, subareolar cutaneous segment short

Type II moderate constriction base, inframammary fold raised medially and minimally laterally, insufficient skin envelope inferiorly, mild to moderate volume deficiency

Type III hypoplasia of all 4 quadrants, breast base constricted horizontally and vertically

Type III severe constriction of base, substantial elevation of inframammary fold, skin envelope insufficient circumferentially, severe deficiency breast volume

Type III hypoplasia of lower medial and upper quadrants and deficiency of skin in subareolar region

Type IV hypoplasia of all 4 quadrants

Adapted with permission from Costagliola et al., Tuberous breast: revised classification and a new hypothesis for its development, Aesthetic Plastic Surgery, Volume 37, Issue 5, pp.896–​ 903, Copyright © 2013 Springer. Reproduced with permission from Von Heimburg, D, Refined version of the tuberous breast classification, Plastic and Reconstructive Surgery, Volume 105, Issue 6, pp.2269, Copyright © 2000 Wolters Kluwer Health, Inc. Reproduced with permission from Grolleau, J.-​L . et al., Breast base anomalies: treatment strategy for tuberous breasts, minor deformities, and asymmetry, Plastic and Reconstructive Surgery, Volume 104, Issue 7, pp.2040–​2048, Copyright © 1999 Wolters Kluwer Health, Inc. Reproduced with permission from Meara, J. et al., Tuberous breast deformity: principles and practice, Annals of Plastic Surgery, Volume 45, Issue 6, pp.607–​611, Copyright © 2000 Wolters Kluwer Health, Inc.

1009

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SECTION 9  The chest and breast

(a)

(b)

Fig. 9.4.1  Tuberous breasts have a Northwood index of greater than 0.4. (a) Bilateral tuberous breast deformity. (b) In this example the Northwood index is 0.65.

laterally based transposition flap, an inferiorly based triangular flap or quadrangular flap and then an implant inserted. Grolleau and colleagues (1999), in their article outlining a modified three-​part classification, described a procedure for type 1 tuberous breasts. This consisted of a mammoplasty using a superiorly based glandular pedicle flap with a laterally based dermoglandular triangular flap advanced to fill in the defect created by undermining the lower medial quadrant. Recurrence of areolar protrusion after circumareolar reduction is common (Grolleau et  al., 1999)  and areolar revision rates due to expanded areolar or unacceptable scarring of up to 50% have been reported (Bach et al., 2009). Long-​term follow-​up is required as early good results may not be maintained, especially after pregnancy, ageing, and weight changes (Hoffman, 1986). Many different techniques of circumareolar mastopexy have been described for the treatment of tuberous breast deformity. Benelli (1990) described his ‘round block’ cerclage suture in the deep dermis, in a purse-​string fashion (Fig. 9.4.3). Atiyeh and colleagues (1998) argue that a periareolar scar is not inconspicuous and instead performs a peri-​nipple technique concealing the scar between the dome of the nipple and the corrugated areolar skin. A circle is marked around the nipple and then 1.5 cm within the skin–​areolar junction line. The intervening doughnut of areola is de-​epithelialized and a new circle, 4–​4.5 cm in diameter, is marked on the denuded areola. Slow-​absorbing sutures are placed between this marked circle and the areolar–​skin junction

(a)

which inwardly telescopes the redundant areola and takes the tension off the final peri-​nipple non-​absorbable round block suture. Hammond and colleagues (2007) reported reliable long-​term results using an interlocking Gore-​Tex® (W.L. Gore and Associates, Newark, DE, USA) suture after circumareolar mastopexy (Hammond et al., 2007). Fat grafting for treatment of tuberous breast has been described with excellent results (Delay et al., 2013; Derder et al., 2013). The technique described by Delay and colleagues (2013) consists of a fasciotomy of the constricted breast via stab incisions in the inframammary fold and periareolar area with a 14-​gauge trocar followed by transfer of the liposuctioned fat (from abdomen or thighs) to the breast and pectoralis major muscle in one or two sessions. Some patients developed oil cysts diagnosed radiologically but did not require any further investigation. In summary, there are numerous techniques described to correct tuberous breast deformity. The aims of the surgery are to lower the inframammary fold, correct the constricted shape of the breast, and, when required, correct the areolar size and shape and increase breast volume. When selecting the type of procedure one needs to consider the age of the patient, the severity of the deformity noting asymmetry, the current volume of the breast and desired size outcome, and any skin deficiency. Patients need to be carefully counselled regarding the expected outcome of the correction of their tuberous breast and the possible requirement for further surgery.

(b)

Fig. 9.4.2  Surgical treatment of tuberous breast deformity with tissue expansion and exchange to submammary silicone implants. (a) Preoperative photograph and (b) postoperative photograph after removal of tissue expanders and insertion of anatomical implants in a submammary pocket.

9.4  Congenital deformities of the breast

(a)

(b)

Fig. 9.4.3  Treatment of bilateral tuberous breast deformity with two-​stage implant approach and periareolar mastopexy. (a) Preoperative photograph and (b) photograph after exchange of tissue expanders for implants and periareolar mastopexy.

Gynaecomastia Gynaecomastia is the development of breast tissue in males. It may be unilateral or bilateral and its aetiology is varied. True gynaecomastia is enlargement of glandular tissue while pseudo-​gynaecomastia indicates excessive adipose tissue.

Incidence Gynaecomastia is common with reported incidences of 60–​90% of all newborns (Devalia and Layer, 2009), up to 65% of adolescents (Nydick et al., 1961), and 80% of males with a body mass index of 25 kg/​m2 or greater (Niewoehner and Nuttall, 1984).

Aetiology Gynaecomastia is caused by increased oestrogen levels, diminished androgen levels, or a defect in androgen receptors. Physiological gynaecomastia occurs in three age groups. Neonatal gynaecomastia occurs due to the circulation of maternal oestrogens and resolves within weeks to months after delivery (Rohrich et al., 2003). Pubertal gynaecomastia affects up to 65% of teenage males and is thought to be due to an imbalance in plasma oestradiol compared with testosterone (LaFranchi et al., 1975). The severity of the gynaecomastia is variable, commonly not clinically significant, and the majority resolve. The third peak of physiological gynaecomastia, known as senile gynaecomastia, occurs after 65 years of age and is due to decreasing levels of testosterone and peripheral aromatization of testosterone to oestrogen by adipose tissue (Pirke and Doerr, 1975). Pathological gynaecomastia can either be congenital or acquired. Congenital gynaecomastia can be due to decreased androgen production or decreased androgen action at target tissues. The most common cause of congenital gynaecomastia is Klinefelter syndrome, where the primary testicular failure results in low serum testosterone and an increase in the oestradiol/​androgen ratio. The incidence of breast cancer is markedly increased in Klinefelter syndrome (Jackson et al., 1965). Anorchia (vanishing testis syndrome) is a less common cause of gynaecomastia. Congenital defects in the enzymes of testosterone biosynthesis are rare causes but disorders in androgen action are more frequent such as testicular feminization syndrome or Reifenstein syndrome (Glass, 2001). Individuals with true hermaphroditism may develop gynaecomastia due to oestrogen production in ovarian tissues.

Acquired causes of gynaecomastia include infections, such as mumps, orchitis, and leprosy, or testicular damage due to trauma, torsion, chemotherapy, or radiotherapy. Systemic disease such as renal failure, cirrhosis, thyrotoxicosis, or adrenal insufficiency are other aetiologies. Testicular, bronchogenic, adrenal, pituitary, and human chorionic gonadotrophin (hCG)-​secreting tumours may present with gynaecomastia. Pharmaceuticals are implicated in approximately 20% of all cases of gynaecomastia (Table 9.4.3) (Niewoehner and Schorer, 2008). Table 9.4.3  Drugs that may cause gynaecomastia Mechanism of action

Drug

Oestrogens and oestrogen-​ like drugs

Digitalis, diethylstilboestrol, oestrogen-​ containing vaginal creams (via partner), phytoestrogens and oestrogens in food

Drugs which enhance oestrogen formation

Gonadotrophins, e.g. human chorionic gonadotrophin (hCG) Clomiphene withdrawal

Drugs which inhibit testosterone synthesis or action

Spironolactone, ketoconazole, metronidazole, alpha reductase inhibitors (finasteride and dutasteride) Androgen blockers, e.g. bicalutamide H2 blockers and proton pump inhibitors, e.g. ranitidine, cimetidine, esomeprazole

Drugs with an unknown mechanism of action

Marijuana Tricyclic antidepressants Angiotensin-​converting enzyme inhibitors, e.g. captopril, enalapril Heroin Amiodarone Busulfan Methyldopa, reserpine Human growth hormone Antiretroviral drugs Calcium channel antagonists, e.g. verapamil

Anabolic steroids

Isoniazid

Adapted by permission from BMJ Publishing Group Limited. The BMJ, Catherine B Niewoehner, Anna E Schorer, Gynaecomastia and breast cancer in men, volume 336, page 709–​713,  2008.

1011

1012

SECTION 9  The chest and breast

Fig. 9.4.4  Hammond describes a method of controlling areolar size and shape using an interlocking Gore-​Tex® suture (Hammond et al., 2007). (a) The desired areolar size is measured and marked with eight evenly spaced points. (b) The intervening skin between the desired areola and the outer periareolar mark is de-​epithelialized and then incised through dermis 5 mm inside of the outer periareolar incision. Undermining is performed circumferentially in the subdermal plane for 1–​2 cm to minimize bunching. The Gore-​Tex® suture is placed in a wagon-​wheel pattern in the dermis matching the eight pre-​marked points, commencing at the medial border of the areola so that the knot is always accessible if required. The suture is tightened so the dermal shelves overlap hence strengthening the closure. (c) The Gore-​Tex® suture is knotted when the desired size of the areola has been reached. At this stage the periareolar shape is reassessed and further skin is de-​epithelialized as required to attain a perfect circle. Further closure is with a subcuticular 4/​0 absorbable monofilament suture. The areola will be slightly protruding with symmetrical gathering of the periareolar skin.

Mechanisms include direct administration of oestrogen, enhancement of oestrogen formation, and inhibition of testosterone synthesis or action, but the mechanism is unknown in many drugs. Cosmeceuticals and illegal drugs can be implicated as well as antibiotics, hormones, chemotherapeutic agents, proton pump inhibitors, and cardiovascular, psychoactive, and anticonvulsant drugs.

Idiopathic causes of gynaecomastia account for 25% of presentations (Braunstein, 1993).

Histology Three patterns of histological findings are described (Bannayan and Hajdu, 1972): florid, intermediate, and fibrous types. Increased

9.4  Congenital deformities of the breast

numbers of budding ducts in a highly cellular fibroblastic stroma is seen in the florid type, whereas the fibrous type has extensive stromal fibrosis and minimal ductal proliferation, and intermediate lies between these two patterns. It is generally agreed that these histological findings reflect the duration of the gynaecomastia, with the florid pattern seen in breast enlargement less than 4 months’ duration and the fibrous type seen if present greater than a year (Bannayan and Hajdu, 1972).

Evaluation of gynaecomastia History taking identifies the onset and duration of gynaecomastia, symptoms of pain or tenderness, pubertal development, symptoms of hypogonadism, fertility, prescribed or illicit drug use, symptoms of systemic disease (e.g. liver disease, thyrotoxicosis, and renal failure), and malignancies. Clinical examination of the breasts includes evaluation of size, symmetry, nodules, masses, nipple abnormalities, and discharge. Glandular tissue of true gynaecomastia is distinguished from the fatty tissue of pseudo-​gynaecomastia. Simon’s classification of gynaecomastia based on size and skin excess is widely used (Simon et al., 1973). Simon’s classification of gynaecomastia (Fig. 9.4.5): I Minor breast enlargement without skin redundancy. IIa Moderate breast enlargement without skin redundancy. IIb Moderate breast enlargement with skin redundancy. III Large breast enlargement with skin redundancy. (Reproduced with permission from Simon, B., Hoffman, S. & Kahn, S., Classification and surgical correction of gynecomastia, Plastic and Reconstructive Surgery, Volume 51, Issue 1, pp.48–​52, Copyright © 1973 Wolters Kluwer Health, Inc.)

Breast carcinoma in men is rare but there is a 60 times higher incidence in patients with Klinefelter syndrome (Jackson et al., 1965). Signs of possible malignancy include asymmetric hard nodules, skin tethering, nipple retraction, or nipple discharge. Testicular examination should be performed and further investigations are required if the testes are found to be small bilaterally or if asymmetrically enlarged. Testicular cancers have been reported in around 3% of men aged less than 50 years presenting with gynaecomastia (Braunstein, 1993; Daniels and Layer, 2003). Investigations may be warranted after careful history and examination and include liver function tests, renal function tests, and, in some circumstances, thyroid function tests, hCG, luteinizing hormone, testosterone, and oestradiol levels.

Surgical treatment of gynaecomastia The aims of treatment are to symmetrically flatten the thoracic region, eliminate the inframammary fold, remove redundant skin, and correct the position of the nipple–​areolar complex, with the minimum amount of scarring (Cordova and Moschella, 2008). The first description of surgical excision of gynaecomastia was by Paulus Aegineta (690–​625 bc) via an inframammary approach (Aegineta, 1846). Webster (1946) described a semicircular infra-​ areolar incision for gynaecomastia and since then multiple approaches have been proposed using every type of dermal and glandular pedicle for nipple relocation, including transareolar (Pitanguy, 1966), superior dermal pedicle (Fára and Hrivnáková, 1981), vertical bipedicled with horizontal excision (Pers and Bretteville-​ Jensen, 1972), and dermal double areolar pedicle (Cannistra et al., 2009). Nipple grafting techniques have been described, with either the excess skin excised as an ellipse around

(a)

(b)

(c)

(d)

Fig. 9.4.5  Examples of gynaecomastia according to Simon’s classification. (a) Type I, minor breast enlargement without skin redundancy. (b) Type IIa, moderate breast enlargement without skin redundancy. (c) Type IIb, moderate breast enlargement with skin redundancy. (d) Type III, large breast enlargement with skin redundancy.

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SECTION 9  The chest and breast

the nipple (Simon et al., 1973) or at the inframammary fold (Wray et al., 1974). Liposuction has become the mainstay of gynaecomastia treatment, initially suction-​assisted lipectomy, but later, ultrasound-​ assisted liposuction (Teimourian and Perlman, 1983; Rosenberg, 1987; Gingrass and Shermak, 1999; Rohrich et al., 2003). More recently, endoscopic cartilage shaving devices have been used to treat gynaecomastia (Prado and Castillo, 2005; Goh et al., 2010), hence avoiding an areolar incision for excision of the fibrous glandular component. Hammond (2009), in his article on the surgical management of adolescent gynaecomastia, makes the point that the surgical plan needs to address the two issues: how to remove the excess volume and how and when to remove the excess skin. Isolated subareolar bud development is treated by direct excision through a periareolar incision after tumescence. The saucer deformity is avoided by leaving a disc of tissue beneath the areola. Liposuction can then be used to feather the edges of the excision. Patients with bud development and stromal hypertrophy require a combination of removal of the fibrous breast tissue and liposuction of the peripheral fatty tissue. The breast is tumesced through a small periareolar incision and then liposuctioned, preferably using ultrasound-​ assisted liposuction. The remaining fragmented fibrous breast bud is removed piecemeal via a periareolar incision, referred to as the pull-​through technique (Morselli, 1996; Hammond et al., 2003). For adolescents with more marked breast development with excess skin and enlarged areola, Hammond performs the usual volume reduction surgery and allows the skin to retract over the next 6–​12 months. Reassessment after this time often reveals no further skin redundancy or a much lesser amount than previously. Excess skin can be managed through a circumareolar mastopexy, marking a nipple diameter of between 25 and 35  mm and de-​epithelializing a doughnut of surrounding skin, fashioned to result in the nipple placement just above the inframammary fold. A purse-​string suture in the dermis of the outer circle is used to cinch down the outer skin to desired areolar diameter or an interlocking Gore-​Tex® purse-​string is used (Hammond et al., 2007). If this is being performed as a secondary procedure, then it is safe to incise the dermis of the outer periareolar circle and undermine the flaps to decrease the amount of bunching. In patients with large amounts of skin excess, a circumvertical mastopexy is performed, chasing any excess tissue laterally along the inframammary fold. When this is being performed at the same time as the volume reduction, it is advisable only to de-​epithelialize, but if it is a secondary procedure, then the dermis can be incised laterally, leaving the nipple–​areolar complex on a central pedicle (Hammond et al., 2007). Ultrasonic liposuction is far more effective than suction-​assisted liposuction in removing the dense fibrous tissue in gynaecomastia (Rohrich et al., 2003). The technique described by Rohrich and colleagues includes ‘superwet’ tumescence through stab incisions in the lateral inframammary folds bilaterally, ultrasound-​assisted liposuction in a radial fashion, avoiding the area over the upper lateral pectoralis major muscle, with additional passes in the subareolar region, and disruption of the inframammary fold. This is followed by suction-​assisted liposuction to remove emulsified fat and perform final contouring. A  compression garment is worn continuously for 4 weeks postoperatively. With this technique, Rohrich and colleagues (2003) report only 13.1% of patients in their series

required further surgery but of the patients with severe hypertrophy and ptosis 42% required excision of remaining breast tissue and skin after 6–​9 months. Complications from gynaecomastia surgery include haematoma, seroma, scars, infection, nipple necrosis, nipple inversion, under-​resection or over-​resection (saucer deformity), and redundant skin. Courtiss (1987), in his review of 159 patients with gynaecomastia, documented high complication rates for excisional techniques, including over-​resection (18.7%), unattractive scarring (18.7%), haematoma (16.1%), seroma (9.4%), and under-​resection (21.9%). In contrast, his results for liposuction alone showed lower complication rates with no haematomas, an 8.3% under-​resection rate, and unattractive scarring in 13.9%. Liposuction combined with excision decreased the under-​resection rate to 2.8% but increased the unattractive scar rate to 12.5% and haematoma to 5.6% (Courtiss, 1987).

REFERENCES Aegineta P. On male breast resembling the female. In: Adams F (trans) The Seven Books of Paulus Aegineta, pp. 334–​5. London: Sydenham Society, 1846. Atiyeh BS, Hashim HA, El-​Douaihy Y, et al. Perinipple round-​block technique for correction of tuberous/​ tubular breast deformity. Aesthet Plast Surg 1998;22:284–​8. Bach AD, Kneser U, Beier JP, et al. Aesthetic correction of tuberous breast deformity—​lessons learned with a single-​stage procedure. Breast J 2009;15:279–​86. Bannayan GA, Hajdu SI. Gynecomastia: clinicopathologic study of 351 cases. Am J Clin Pathol 1972;57:431–​7. Basu S, Bag T, Saha KS, et al. Accessory breast in the perineum. Trop Doct 2003;33:245. Benelli L. A new periareolar mammaplasty: the “round block” technique. Aesthet Plast Surg 1990;14:93–​100. Braunstein GD. Gynecomastia. N Engl J Med 1993;328:490–​5. Burdick AE, Thomas KA, Welsh E, et  al. Axillary polymastia. J Am Acad Dermatol 2003;49:1154–​6. Camisa C. Accessory breast on the posterior thigh of a man. J Am Acad Dermatol 1980;3:467–​9. Cannistra C, Piedimonte A, Albonico F. Surgical treatment of gynecomastia with severe ptosis: periareolar incision and dermal double areolar pedicle technique. Aesthet Plast Surg 2009;33:834–​7. Cordova A, Moschella F. Algorithm for clinical evaluation and surgical treatment of gynaecomastia. J Plast Reconstr Aesthet Surg 2008;61:41–​9. Costagliola M, Atiyeh B, Rampillon F. Tuberous breast: revised classification and a new hypothesis for its development. Aesthet Plast Surg 2013;37:896–​903. Courtiss EH. Gynecomastia: analysis of 159 patients and current recommendations for treatment. Plast Reconstr Surg 1987;79:740–​53. Daniels IR, Layer GT. Testicular tumours presenting as gynaecomastia. Eur J Surg Oncol 2003;29:437–​9. Delay E, Sinna R, Ho Quoc CH. Tuberous breast correction by fat grafting. Aesthet Surg J 2013;33:522–​8. Derder M, Whitaker IS, Boudana D, et al. The use of lipofilling to treat congenital hypoplastic breast anomalies:  preliminary experiences. Ann Plast Surg 2014;73:371–​7. Devalia HL, Layer GT. Current concepts in gynaecomastia. Surgeon 2009;7:114–​19.

9.4  Congenital deformities of the breast

Dinner MI, Dowden RV. The tubular/​tuberous breast syndrome. Ann Plast Surg 1987;19:414–​20. Fára M, Hrivnáková J. Reduction surgery of the breasts in severe gynecomastia using a surgical flap with a single pedicle at the top. Rozhl Chir Měsíčník Cesk Chir Spol 1981;60:723–​5. Gingrass MK, Shermak MA. The treatment of gynecomastia with ultrasound-​assisted lipoplasty. Perspect Plast Surg 1999;12:101–​12. Glass AR. Gynaecomastia. In: Becker KL (ed.) Principles and Practice of Endocrinology and Metabolism, pp. 1200–​ 6. Philadelphia, PA: Lippincott Williams & Wilkins, 2001. Goh T, Tan BK, Song C. Use of the microdebrider for treatment of fibrous gynaecomastia. J Plast Reconstr Aesthet Surg 2010;63:506–​10. Grolleau JL, Lanfrey E, Lavigne B, et al. Breast base anomalies: treatment strategy for tuberous breasts, minor deformities, and asymmetry. Plast Reconstr Surg 1999;104:2040–​8. Hammond DC. Surgical correction of gynecomastia. Plast Reconstr Surg 2009;124(Suppl.):61e–​8e. Hammond DC, Arnold JF, Simon AM, et al. Combined use of ultrasonic liposuction with the pull-​through technique for the treatment of gynecomastia. Plast Reconstr Surg 2003;112:891–​5. Hammond DC, Khuthaila DK, Kim J. The interlocking Gore-​Tex suture for control of areolar diameter and shape. Plast Reconstr Surg 2007;119:804–​9. Hoffman S. Recurrent deformities following reduction mammaplasty and correction of breast asymmetry. Plast Reconstr Surg 1986;78:55–​62. Jackson AW, Muldal S, Ockey CH, et al. Carcinoma of male breast in association with the Klinefelter syndrome. Br Med J 1965;1:223–​5. Kajava Y. The proportions of supernumerary nipples in the Finnish population. Duodecim 1915;31:70. Koltuksuz U, Aydin E. Supernumerary breast tissue:  a case of pseudomamma on the face. J Pediatr Surg 1997;32:1377–​8. Lafranchi SH, Parlow AF, Lippe BM, et  al. Pubertal gynecomastia and transient elevation of serum estradiol level. Am J Dis Child 1975;129:927–​31. Lin KY, Nguyen DB, Williams RM. Complete breast absence revisited. Plast Reconstr Surg 2000;106:98–​101. Loukas M, Clarke P, Tubbs RS. Accessory breasts: a historical and current perspective. Am Surg 2007;73:525–​8. Mandrekas AD, Zambacos GJ. Aesthetic reconstruction of the tuberous breast deformity:  a 10-​ year experience. Aesthet Surg J 2010;30:680–​92. Mandrekas AD, Zambacos GJ, Anastasopoulos A, et al. Aesthetic reconstruction of the tuberous breast deformity. Plast Reconstr Surg 2003;112:1099–​108. Martínez-​ Chéquer JC, Carranza-​ Lira S, López-​ Silva JD, et  al. Congenital absence of the breasts: a case report. Am J Obstet Gynecol 2004;191:372–​4. Meara JG, Kolker A, Bartlett G, et al. breast deformity: principles and practice. Ann Plast Surg 2000;45:607–​11. Meggyessy V, Méhes K. Association of supernumerary nipples with renal anomalies. J Pediatr 1987;111:412–​13. Morselli PG. ‘Pull-​through’: a new technique for breast reduction in gynecomastia. Plast Reconstr Surg 1996;97:450–​4.

Muti E. Personal approach to surgical correction of the extremely hypoplastic tuberous breast. Aesthet Plast Surg 1996;20:385–​90. Niewoehner CB, Nuttal FQ. Gynecomastia in a hospitalized male population. Am J Med 1984;77:633–​8. Niewoehner CB, Schorer AE. Gynaecomastia and breast cancer in men. BMJ 2008;336:709–​13. Nydick M, Bustos J, Dale JH, et al. Gynecomastia in adolescent boys. JAMA 1961;178:449–​54. Pacifico MD, Kang NV. The tuberous breast revisited. J Plast Reconstr Aesthet Surg 2007;60:455–​64. Pers M, Bretteville-​Jensen G. Reduction mammaplasty based on vertical vascular bipedicle and ‘tennis ball’ assembly. A  different approach. Scand J Plast Reconstr Surg 1972;6:61–​8. Pfeifer JD, Barr RJ, Wick MR. Ectopic breast tissue and breast-​like sweat gland metaplasias: an overlapping spectrum of lesions. J Cutan Pathol 1999;26:190–​6. Pirke KM, Doerr P. Age related changes in free plasma testosterone, dihydrotestosterone and oestradiol. Acta Endocrinol (Copenh) 1975;80:171–​8. Pitanguy I. Transareolar incision for gynecomastia. Plast Reconstr Surg 1966;38:414–​19. Prado AC, Castillo PF. Minimal surgical access to treat gynecomastia with the use of a power-​assisted arthroscopic-​endoscopic cartilage shaver. Plast Reconstr Surg 2005;115:939–​42. Puckett CL, Concannon MJ. Augmenting the narrow-​based breast: the unfurling technique to prevent the double-​bubble deformity. Aesthet Plast Surg 1990;14:15–​19. Rees TD, Aston SJ. The tuberous breast. Clin Plast Surg 1976;3: 339–​47. Ribeiro L, Canzi W, Buss A, et al. Tuberous breast: a new approach. Plast Reconstr Surg 1998;101:42–​50. Rohrich RJ, Ha RY, Kenkel JM, et al. Classification and management of gynecomastia: defining the role of ultrasound-​assisted liposuction. Plast Reconstr Surg 2003;111:909–​23. Rosenberg GJ. Gynecomastia:  suction lipectomy as a contemporary solution. Plast Reconstr Surg 1987;80:379–​86. Scheepers JH, Quaba AA. Tissue expansion in the treatment of tubular breast deformity. Br J Plast Surg 1992;45:529–​32. Simon BE, Hoffman S, Kahn S. Classification and surgical correction of gynecomastia. Plast Reconstr Surg 1973;51:48–​52. Teimourian B, Perlman R. Surgery for gynecomastia. Aesthet Plast Surg 1983;7:155–​7. Von Heimburg D. Refined version of the tuberous breast classification. Plast Reconstr Surg 2000;105:2269–​70. Von Heimburg D, Exner K, Kruft S, et  al. The tuberous breast deformity:  classification and treatment. Br J Plast Surg 1996; 49:339–​45. Webster JP. Mastectomy for gynecomastia through a semicircular intra-​areolar incision. Ann Surg 1946;124:557–​75. Williams WR. Polymastism, with special reference to mammae erraticae and the development of neoplasms from supernumerary mammary structures. J Anat Physiol 1891;25:225–​55. Wray RC, Hoopes JE, Davis GM. Correction of extreme gynaecomastia. Br J Plast Surg 1974;27:39–​41.

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9.5

Preoperative imaging for autologous breast reconstruction Mark Ashton and Iain Whitaker

Introduction In recent years, there has been a progressive refinement in the technique of tissue transfer and widespread integration of perforator flap surgery into the plastic surgery curriculum. No field demonstrates this integration more clearly than the use of the abdomen as a source of donor tissue for breast reconstructive surgery. New developments in vascular imaging, preoperative perforator identification, and an improved understanding of the inter-​relationships between individual perforators were all integral to this advancement and have yielded improved outcomes, decreased donor morbidity, and shorter operative times. An understanding of the latest advances in preoperative imaging and investigations is valuable for surgeons undertaking microsurgical transfers, as is an understanding of perforator anatomy, the methods by which to identify potential perforators and select the ideal perforator, and more importantly, the ability to identify those situations in which there are no suitable perforators and a more traditional myocutaneous flap is a better operative choice.

allows a radial artery free flap to drain via the venae comitantes of the radial artery or the cephalic vein (Timmons, 1986). In the abdomen there is a similar pattern. The primary venous system is a series of craniocaudally orientated superficial veins that sequentially drain different sections of the lower abdomen to the

Basics of vascular anatomy The basic pattern of the vasculature is laid down very early in embryological development, and is remarkably similar across all higher vertebrates (Taylor and Minabe, 1992) (Fig. 9.5.1). The body initially develops a primary vascular framework in which a centrally located arterial system drains to a superficially located venous network. Onto this primary system develops a secondary system of veins and venae comitantes that accompany the central arterial system. In the upper limb, this primary venous system develops into the cephalic and basilic veins. The secondary venous system is the venae comitantes accompanying the radial and ulnar arteries (Woollard, 1922; Caplan and Koutroupas, 1973; Taylor et al., 2001; Bates et al., 2002). This double system of venous drainage

Fig. 9.5.1  Vascular development in the embryo. Copyright Taylor Lab.

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SECTION 9  The chest and breast

saphenous bulb in the groin, and the upper abdomen to the axillae (Lie et al., 2014). The secondary veins are the venae comitantes accompanying the branches of the deep inferior and superior epigastric arteries.

Layers of the superficial integument The integument superficial to the deep fascia can be divided into five separate and discrete layers. While the layers themselves are remarkably consistent, each layer’s tissue composition may change between body regions. As an example, layer 3 or the superficial musculoaponeurotic system (SMAS) in the face becomes galea aponeurotica in the scalp, or Scarpa’s fascia in the abdomen and dartos fascia in the scrotum. Of relevance, vessels only pass from one layer to another at areas of fixation (Taylor et al., 1994) so these areas of fixation can be used to predict perforator location (Taylor et al., 1984, 1991, 2011; Taylor and Palmer, 1987; Itoh and Arai, 1993; Heitmann et al., 2000; Kikuchi et al., 2001; El-​Mrakby and Milner, 2002; Taylor, 2002; Rozen et al., 2007; Wong et al., 2009).

The nervous system in the abdomen and thorax Studies undertaken at the University of Melbourne, Australia (Rozen et al., 2007, 2008a; Rozen and Ashton, 2009) have shown that the nervous system is superimposed onto the pre-​existing vascular frame work, and like the vascular system, the nerves also traverse from a deeper layer to a superficial one at points of stability or fixation. It follows that nerves will invariably accompany perforators as they emerge through the deep fascia (Tansatit et al., 2006). An interesting peculiarity in the abdomen is that the nerves supplying the abdomen form a neurovascular bundle with the most lateral branch of the deep inferior epigastric artery (DIEA), and deep superior epigastric artery (DSEA) (Moon and Taylor, 1988; Rozen and Ashton, 2009) (Fig. 9.5.2). Where there are two main branches of the DIEA (‘type 2’ pattern), this nerve plexus will always be associated with the most lateral branch. The medial branch will always be devoid of intercostal nerves innervating the overlying rectus abdominis musculature, and would therefore be a better choice for a vascular pedicle (Fig. 9.5.3). The identification of a type 2 or 3 DIEA branching pattern and perforators arising from the medial branch is therefore critical where they exist. One advantage of computed tomography angiography (CTA), for example, is that it allows preoperative identification of these perforators. A refinement in imaging and realization of the association of the neural bundles with lateral branches of the DIEA, also explains why early deep inferior epigastric perforator (DIEP) flaps, in which it was advocated that the laterally based perforator should be preferentially targeted, had an incidence of lower abdominal bulge that was not much lower than the traditional muscle sparing transverse rectus abdominis myocutaneous (TRAM) flap. Almost certainly, the process of

Fig. 9.5.2  Cadaver dissection of the posterior aspect of the left rectus abdominus muscle showing the intercostal nerves entering its posterior surface and forming a neurovascular bundle with the most lateral branch of the DIEA. The arrow marks the umbilicus. Copyright Taylor Lab.

raising a DIEP flap on these lateral perforators and associated lateral branches of the DIEA divided the nerves of the intercostal nerve plexus and therefore denervated the remaining rectus muscle medially.

Fig. 9.5.3  Schematic diagrams of the three branching patterns of the DIEA. The DIEA is shown as a single (type I, 29%, left), bifurcating (type II, 57%, centre), or trifurcating (type III, 14%, right) trunk below the umbilicus. The arcuate line is dotted. Reproduced with permission from Harry Moon and G. Taylor, The Vascular Anatomy of Rectus Abdominis Musculocutaneous Flaps Based on the Deep Superior Epigastric System, Plastic and Reconstructive Surgery, Volume 82, Issue 5, pp.815–​32, Copyright © 1988 Wolters Kluwer Health, Inc.

9.5  Preoperative imaging for autologous breast reconstruction

Communication between perforators There is a delicate system of vessels between perforator angiosomes that help to regulate blood flow within the superficial integument (Taylor and Palmer, 1987; Saint-​Cyr et al., 2009; Rozen and Ashton, 2010; Rozen et al., 2010b, 2010c; Wong et al., 2010; Taylor et al., 2011). These interconnecting vessels may be classed as high flow or low flow; they are avalvular and may be termed ‘true’ and ‘choke’ anastomoses, in that the ‘true’ anastomosis is a true connection between the respective perforator angiosome and as such, offers no resistance to flow. If the adjacent angiosome is connected by ‘choke’ anastomoses, this adjacent tissue can usually be captured on a single perforator, but this is not guaranteed. However, if the two angiosomes are connected by true anastomoses, the two territories will effectively function as a single territory and more tissue may be captured safely and reliably. Clearly, preoperative identification of these types of perforator connections is valuable.

The law of equilibrium Numerous studies have documented the ‘dominance’ (Rozen et al., 2010c) or ‘law of reciprocity’ of arterial territories and venous systems. This law states that if one angiosome is large, the territory of the neighbouring angiosome will be small. Similarly, if one venous system is dominant, the corresponding alternative venous system will be diminutive. As an example, if preoperative imaging of one hemi-​ abdomen shows the superficial inferior epigastric artery (SIEA) and superficial inferior epigastric vein (SIEV) to be particularly large, it is likely that the perforators of the corresponding DIEA of the same hemi-​abdomen will be small or inconsequential, irrespective of its classification type. In this situation, the surgeon is advised to abandon a planned DIEP on this side and either use the superficial system as the flap (superficial inferior epigastric artery (SIEA) free flap), revert to a TRAM flap, or if a DIEP is preferred, assess the contralateral hemi-​abdomen. Importantly, it means a surgeon encountering an unusually large SIEV in the initial stages of raising a DIEP flap (irrespective of the preoperative imaging) should be aware that the DIEA system on this side of the abdomen is likely to be small. Additionally, a particularly large SIEV would suggest the primary venous system is the dominant system and that if a lateral abdominal flap is required, the SIEV or superficial circumflex iliac vein should be considered for additional venous anastomosis. With modern imaging, a dominant arterial or venous system can be identified preoperatively (Fig. 9.5.4).

Fig. 9.5.4  CTA showing a dominant SIEA on the right and a correspondingly small right DIEA perforators and a single large DIEA perforator on the left with a small SIEA.

Fig. 9.5.5  An ideal left DIEA perforator. It is single, large, arises from the medial branch of the DIEA, and has no intramuscular course.

The ideal perforator In theory, the ideal perforator is large in calibre with a short intramusculature course, has a large angiosome, and is connected with other perforators by true anastomoses. This perforator should be remote and isolated from neighbouring perforators, and preferably be single. Importantly, these perforators emerge at points of fixation of the deep fascia to the overlying soft tissue. Also, as noted, the lateral perforators are more likely to be accompanied by nerves supplying the adjacent musculature or soft tissue (Fig. 9.5.5 and Fig. 9.5.6). With this information in mind, it is important to choose the most effective preoperative investigations to help find the ideal

Fig. 9.5.6  A CTA showing a medial DIEA perforator winding around the medial border of the rectus muscle.

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SECTION 9  The chest and breast

perforator. Preoperative assessment of the perforator location has been of interest to reconstructive surgeons since the earliest days of microsurgery and there have been several review articles published (Mathes and Neligan, 2010; Smit et al., 2010; Pratt et al., 2012).

Doppler ultrasonography In the first phase of free flap breast reconstruction, the modality most often used for planning was the handheld Doppler probe, using reflected sound waves to detect blood flow through a vessel. The transducer (probe) is applied to the skin with an interface layer of ultrasound gel to facilitate transmission. The transducer sends and receives sound waves that are amplified through a microphone, and emits an audible signal when located over blood vessels, and the pitch alters in relation to the direction of blood flow. This sound is heard loudest if the vessel is perpendicular to and pointing directly at the probe. Handheld units are typically available in 8 and 10 MHz versions, are non-​invasive, cheap, portable, and readily available, and have been advocated in planning microvascular free tissue transfer since the mid-​1970s (Aoyagi et  al., 1975). In addition to its use in identifying donor vessels preoperatively (Taylor et  al., 1990), the handheld Doppler is also widely used for monitoring flow across the anastomoses in the postoperative period (Jallali et al., 2005; Whitaker et al., 2005, 2010). In the early 2000s, Doppler played its part in the emerging field of freestyle perforator flaps (Wei and Mardini, 2004). This concept allows flap harvesting in any anatomical location, where an audible Doppler signal of a perforator is detected adjacent to the soft tissue defect. Several studies have shown the handheld Doppler to be clinically useful in identifying perforators in preparation for various free flap operations (Taylor et al., 1990; Blondeel et al., 1998; Giunta et al., 2000; Xu et al., 2011). However, no well-​designed, controlled studies comparing it to other modalities exist and there is no demonstrable improvement in outcomes in terms of shorter operating time or flap survival. Limitations of the handheld Doppler device include inaccuracies in vessel identification when compared to operative findings, which is more evident with smaller and deeper perforators (Yu and Youssef, 2006); reduced accuracy when compared to newer modalities such as CTA; and high inter-​user variability (Rozen et al., 2008e). Despite these limitations, Doppler continues to be a popular choice for preoperative planning, due to its widespread availability and ease of use.

Colour duplex ultrasonography Duplex ultrasonography uses B-​mode (brightness mode) ultrasound to produce a greyscale, two-​dimensional image on a screen which is augmented by Doppler ultrasound which allows movement, in this case blood flow, to be assigned a colour based upon changes in wavelength. Fast-​and slow-​flowing blood can be distinguished, thus demonstrating arteries and veins. This technology has been shown to be more accurate than Doppler ultrasound in identifying the location of perforators preoperatively in the trunk (Ogawa et al., 2003; De Frene et al., 2006; Seidenstucker et al., 2010), gluteal region (Isken et al., 2009), and in the lower limb (Iida et al., 2003; Ulatowski, 2012; Dorfman and Pu, 2014). However, comparisons with more modern modalities such as CTA, showed colour duplex

ultrasound to be less accurate, slower, and to fail to provide information on other nearby vessels such as the superficial epigastric vessels (Scott et al., 2010). Another limitation of duplex ultrasonography, like that of Doppler ultrasonography, is the inaccuracy of perforator identification when the vessels are small with an intramuscular course (Rozen et al., 2009). Despite studies supporting duplex ultrasonography as a preoperative imaging modality, as with handheld Doppler, there are no controlled studies demonstrating improved outcomes with regard to flap survival or reduced operating times (Pratt et al., 2012).

Computed tomography angiography CTA uses computer-​analysed X-​ray images in combination with a bolus of venous contrast medium to produce high-​resolution reconstructions of vascular structures. In the mid-​1990s, CTA started to replace conventional angiography and has now become the most commonly used modality in angiographic practice (Rubin et al., 1999). Technological advances in CTA, such as an increased number of detector rows, now allow for faster, more detailed images to be produced, often with a lower radiation dose (Rozen et al., 2009). CTA has a number of distinct advantages over traditional imaging modalities. It produces more accurate images than ultrasound (Rozen et  al., 2008e; Scott et  al., 2010), allowing visualization of sub-​millimetre vessels and provides detailed information regarding the intramuscular course of perforating vessels (Phillips et al., 2008; Rozen et al., 2010a). CTA also provides information about other vessels in the scan field that could facilitate preoperatively made back-​ up plans, and may give valuable incidental findings and details of anatomical variants (Whitaker et al., 2009; See et al., 2010). CTA is not without its limitations, and concerns have been raised regarding its high cost and the levels of radiation exposure to the patient. The radiation dose is approximately the same as ten abdominal plain radiographs or 2.5 years of background radiation exposure (Rozen et  al., 2009). Low-​radiation dose protocols (limiting the scanning field), which still offer high-​resolution images, have been described. The radiation dose, however, should be weighed against the benefits in terms of reduced operative time and outcomes (Smit et al., 2009). Although many deem CTA to be non-​invasive, it does require administration of an intravenous dye through a peripheral cannula. However, this is much less invasive than the traditional method of arterial catheterization and avoids the potential risks of pseudoaneurysm and embolism associated with classic catheter angiography. To locate perforators in the abdominal wall, a map of perforator sites as they exit the rectus sheath is produced on a grid system using the umbilicus as the central reference point. This information can then be transposed onto the patient’s abdomen at the time of surgery. In addition to an extremely accurate spatial map, CTA provides information about the intramuscular course of the vessel and about the superficial inferior epigastric system as well as any incidental abdominal wall defects that could pose potential hazards intraoperatively. Numerous series have demonstrated the effectiveness of CTA in accurately predicting the location and calibre of the perforating vessels, particularly in DIEP flaps. This technique is routinely used by high-​volume operators throughout the world (Masia et  al., 2006,

9.5  Preoperative imaging for autologous breast reconstruction

2008a, 2008b, 2010b; Clavero et al., 2008; Rozen et al., 2008c; Acosta et  al., 2010; Grinsell et  al., 2015). Several case–​control studies of preoperative CTA in the setting of abdominal wall based breast reconstruction have demonstrated quantifiable benefits of this investigation including significantly shortened dissection and total operating times (Smit et al., 2009; Uppal et al., 2009; Masia et al., 2010b), reduced cost (Smit et al., 2009; Uppal et al., 2009), reduced complications including flap loss and hernia (Gacto-​Sanchez et al., 2010; Scott et al., 2010), and reduced operator stress levels (Rozen et al., 2008b).

Magnetic resonance angiography Magnetic resonance imaging (MRI) uses large magnets which cause the nuclei of hydrogen atoms in the body to align and resonate, emitting a detectable signal which is processed by computers to produce an image. The technique was developed in the 1970s as an alternative to conventional radiography. Since that time it has become the imaging modality of choice if available, particularly for soft tissue imaging. Despite its widespread use, it remains an expensive technology and scanners are not available in all hospitals. Patient satisfaction is lower than other imaging choices, as scans are generally slow and the machines can be claustrophobic. Metallic implants may be a contraindication. Visualization of vessels is possible using MRI alone; flow-​related enhancement forms images of the vessels by selectively imaging blood that has moved into the receptor plane at the time of capture, thereby distinguishing blood flow from that of static tissue. Images produced using this technique were initially lower-​ resolution images, and studies investigating the potential of MRI for mapping the perforators of abdominal free flaps were promising, although of limited resolution (Ahn et al., 1994). Advances in the field of flow-​related enhancement led to protocol changes and increasingly higher resolution images (Masia et al., 2010a). MRI is now able to resolve detail to a sufficient level to produce acceptable perforator maps and supplementation with non-​ionizing, paramagnetic contrast material such as gadolinium via a peripheral venous cannula, can help to produce even sharper images of arteries (Haider et al., 2009). Commonly referred to as magnetic resonance angiography (MRA), this technique has rapidly found many applications in preoperative imaging in reconstructive surgery. Since 2008 MRA has been used in the field of abdominal-​based breast reconstruction as a way of preoperatively mapping the abdominal perforators. Small case series have now established the accuracy of MRA with gadolinium contrast for identifying the location and calibre of abdominal perforators (Chernyak et al., 2009), although one series reports a 4% false-​negative rate (Newman et al., 2010). One study used a group of controls from the previous year when imaging was not used and demonstrated a lower rate of conversion to transverse rectus abdominis myocutaneous flap in the group that were preoperatively imaged with MRA. Improved outcomes in DIEP flaps associated with the use of MRA preoperatively have been described (Neil-​Dwyer et al., 2009), and there seems to be a role for MRA imaging of the intraflap venous anatomy to identify causes of postoperative venous congestion (Schaverien et al., 2010). Based on the literature demonstrating equivalence of contrast-​enhanced MRA and CTA for arterial perforator imaging, there are groups who believe that due to the superiority in perforator venous imaging, the absence of

ionizing radiation, and the better side effect profile of the contrast agents, contrast-​enhanced MRA is the imaging method of choice for abdominally based perforator flaps (Schaverien et al., 2011).

Thermography Infrared thermography or thermal imaging, is a technique that uses specialized infrared, thermographic cameras to detect radiation emitted from the object being imaged in the infrared range of the electromagnetic spectrum (9000–​14,000  nm) and produce colour images, which vary according to the local temperature (the higher the temperature the brighter the image). This technique of imaging has been used clinically since around 1975, with thermography demonstrating areas of increased skin temperatures in areas of local blood supply. These so-​called ‘hotspots’ correspond to the location of perforators and have been used as a method of preoperatively identifying perforators in flap surgery since the 1990s (Itoh and Arai, 1995; Kalra et al., 2007). More recently, the technique been popularized by de Weerd and colleagues (2006, 2009a; 2009b; 2011; 2012; 2014a; 2014b) and reported by several other groups, with (Itoh and Arai, 1993; Schaverien et al., 2011) and without (Kalra et al., 2007) a cold challenge. In experienced hands, dynamic infrared thermography allows for a qualitative assessment of perforators providing valuable information which helps in planning and designing DIEP flaps (de Weerd et al., 2009b).

Image-​guided stereotactic navigation Stereotactic guidance systems have been used for spatial localization in various surgical specialties for some time, allowing the surgeon accurately to define the location of structures and their own instruments relative to preoperatively captured CT or MRI scans in real time. This is achieved by placing markers on anatomic landmarks which are then registered by an optical sensor on a computer system. The system can then relate the anatomy of the patient and of surgeons’ tools to a pre-​captured CT scan in real time. Although relatively little published data exist regarding the use of these systems in plastic and reconstructive surgery, data exists to support their use in other specialties, demonstrating improved operative safety and lower morbidity (Blomstedt et al., 2007). In a small series of cases, this technology has been used to map out the position of perforators in the preoperative assessment of patients undergoing DIEP flap breast reconstruction (Rozen et al., 2008d). The navigation software was used in conjunction with CTA, and was shown to be feasible and at least as accurate as CTA alone. As the results were not significant, one would have to consider stereotaxy in the context of reconstructive surgery to be in its infancy.

Conclusion Several imaging modalities are currently used to assess patients preoperatively in microvascular reconstructive surgery, with each technique having its proponents. Many surgeons still rely on intraoperative assessment of perforators alone or ‘ad hoc’ usage of adjunctive technologies. Several high-​ volume operators use

1021

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SECTION 9  The chest and breast

Table 9.5.1  Current level of evidence for preoperative imaging techniques Imaging technique

Evidence level

Handheld Doppler probe

4

Colour Doppler/​duplex ultrasound (echo-​colour Doppler)

4

Catheter angiography/​digital subtraction angiography

4

Computed tomographic angiography (CTA): • Abdominal wall flaps • Other body regions

2b 2b

Magnetic resonance angiography (MRA): • Abdominal wall flaps • Other body regions

3b 4

Thermography

4

Image-​guided stereotaxy

4

Source data from Current Level of Evidence for Preoperative Imaging Techniques, by Centre for Evidence-​Based Medicine (CEBM) Criteria.

preoperative imaging routinely, some in specific cases, and others not at all. In all cases where imaging is used it is intuitively felt to reduce the risks associated with surgery, reduce the time taken, relieve operative ‘stress’, and reduce the risk of partial or total flap loss due to anomalous perforator anatomy or absent vessels. As in many aspects of surgery, when assessed objectively, the evidence for most of these forms of imaging is limited. This is further complicated by the fact that most studies differ either in modality or in their application, making this field full of heterogeneous studies from which it is difficult to draw concrete conclusions. There is a large body of evidence to suggest that traditional methods such as the handheld Doppler (which will, however, always remain a useful adjunct) and duplex ultrasound have been superseded. Modern modalities such as CTA and MRA have been shown to be more accurate with less inter-​observer variation. Unlike other modalities, evidence exists showing improved outcomes when preoperative imaging with CTA and MRA are used. This is particularly so for CTA, in which a number of cohort studies have shown statistically significant reductions in operative time (Smit et al., 2009; Uppal et  al., 2009)  surgeons’ stress levels, and improvements in flap outcomes. Although the evidence for CTA is compelling, there is little doubt that the non-​invasive and non-​ionizing options are tempting. The potential superiority in perforator venous imaging alongside the absence of ionizing radiation and promising early results, show there is a significant role for contrast-​enhanced MRA as more groups gain experience in the technique. Table 9.5.1 shows current level of evidence for preoperative imaging techniques.

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Rozen W, Ashton M. Avoiding denervation of rectus abdominis in DIEP flap harvest: the importance of paraneural perforators reply. Plast Reconstr Surg 2009;123:1397–​8. Rozen WM, Tran TM, Ashton MW, et al. Refining the course of the thoracolumbar nerves: a new understanding of the innervation of the anterior abdominal wall. Clin Anat 2008a;21:325–​33. Rozen WM, Anavekar NS, Ashton MW, et al. Does the preoperative imaging of perforators with CT angiography improve operative outcomes in breast reconstruction? Microsurgery 2008b;28:516–​23. Rozen WM, Ashton MW. Re: the perforasome theory: vascular anatomy and clinical implications. Plast Reconstr Surg 2010;125:1845–​6. Rozen WM, Ashton MW, Grinsell D. The branching pattern of the deep inferior epigastric artery revisited in-​vivo: a new classification based on CT angiography. Clin Anat 2010a;23:87–​92. Rozen WM, Ashton MW, Grinsell D, et al. Establishing the case for CT angiography in the preoperative imaging of abdominal wall perforators. Microsurgery 2008c;28:306–​13. Rozen WM, Ashton MW, Le Roux CM, et  al. The perforator angiosome:  a new concept in the design of deep inferior epigastric artery perforator flaps for breast reconstruction. Microsurgery 2010b;30:1–​7. Rozen WM, Ashton MW, Pan WR, et al. Raising perforator flaps for breast reconstruction:  the intramuscular anatomy of the deep inferior epigastric artery. Plast Reconstr Surg 2007;120:1443–​9. Rozen WM, Ashton MW, Stella DL, et al. Stereotactic image-​guided navigation in the preoperative imaging of perforators for DIEP flap breast reconstruction. Microsurgery 2008d;28:417–​23. Rozen WM, Grinsell D, Koshima I, et  al. Dominance between angiosome and perforator territories: a new anatomical model for the design of perforator flaps. J Reconstr Microsurg 2010c;26:539–​45. Rozen WM, Phillips TJ, Ashton MW, et al. Preoperative imaging for DIEA perforator flaps:  a comparative study of computed tomographic angiography and Doppler ultrasound. Plast Reconstr Surg 2008e;12:1–​8. Rozen WM, Whitaker IS, Stella DL, et al. The radiation exposure of computed tomographic angiography (CTA) in DIEP flap planning:  low dose but high impact. J Plast Reconstr Aesthet Surg 2009;62:e654–​5. Rubin GD, Shiau MC, Schmidt AJ, et al. Computed tomographic angiography: historical perspective and new state-​of-​the-​art using multi detector-​row helical computed tomography. J Comput Assist Tomogr 1999;23(Suppl. 1):S83–​90. Saint-​ Cyr M, Wong C, Schaverien M, et  al. The perforasome theory:  vascular anatomy and clinical implications. Plast Reconstr Surg 2009;124:1529–​44. Schaverien MV, Ludman CN, Neil-​Dwyer J, et al. Contrast-​enhanced magnetic resonance angiography for preoperative imaging of deep inferior epigastric artery perforator flaps: advantages and disadvantages compared with computed tomography angiography: a United Kingdom perspective. Ann Plast Surg 2011;67:671–​4. Schaverien MV, Ludman CN, Neil-​Dwyer J, et  al. Relationship between venous congestion and intraflap venous anatomy in DIEP flaps using contrast-​enhanced magnetic resonance angiography. Plast Reconstr Surg 2010;126:385–​92. Scott JR, Liu D, Said H, Neligan PC, et  al. Computed tomographic angiography in planning abdomen-​based microsurgical breast reconstruction:  a comparison with color duplex ultrasound. Plast Reconstr Surg 2010;125:446–​53. See MS, Pacifico MD, Harley OJ, et al. Incidence of “incidentalomas” in over 100 consecutive CT angiograms for preoperative DIEP flap planning. J Plast Reconstr Aesthet Surg 2010;63:106–​10.

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Seidenstucker K, Munder B, Richrath P, et  al. A prospective study using color flow duplex ultrasonography for abdominal perforator mapping in microvascular breast reconstruction. Med Sci Monit 2010;16:MT65–​70. Smit JM, Dimopoulou A, Liss AG, et  al. Preoperative CT angiography reduces surgery time in perforator flap reconstruction. J Plast Reconstr Aesthet Surg 2009;62:1112–​17. Smit JM, Klein S, Werker PM. An overview of methods for vascular mapping in the planning of free flaps. J Plast Reconstr Aesthet Surg 2010;63:e674–​82. Tansatit T, Chokrungvaranont P, Sanguansit P, et  al. Neurovascular anatomy of the deep inferior epigastric perforator flap for breast reconstruction. J Med Assoc Thai 2006;89:1630–​40. Taylor GI, Bates D, Newgreen DF. The developing neurovascular anatomy of the embryo:  a technique of simultaneous evaluation using fluorescent labeling, confocal microscopy, and three-​ dimensional reconstruction. Plast Reconstr Surg 2001;108:597–​604. Taylor GI, Corlett RJ, Boyd JB. The versatile deep inferior epigastric (inferior rectus abdominis) flap. Br J Plast Surg 1984;37:330–​50. Taylor GI, Corlett RJ, Dhar SC, et  al. The anatomical (angiosome) and clinical territories of cutaneous perforating arteries:  development of the concept and designing safe flaps. Plast Reconstr Surg 2011;127:1447–​59. Taylor GI, Doyle M, McCarten G. The Doppler probe for planning flaps:  anatomical study and clinical applications. Br J Plast Surg 1990;43:1–​16. Taylor GI, Gianoutsos MP, Morris SF. The neurovascular territories of the skin and muscles: anatomic study and clinical implications. Plast Reconstr Surg 1994;94:1–​36. Taylor GI, Minabe T. The angiosomes of the mammals and other vertebrates. Plast Reconstr Surg 1992;89:181–​215. Taylor GI, Palmer JH. The vascular territories (angiosomes) of the body: experimental study and clinical applications. Br J Plast Surg 1987;40:113–​41. Taylor GI, Watterson PA, Zelt RG. The vascular anatomy of the anterior abdominal wall: the basis for flap design. Perspect Plast Surg 1991;5:1–​28.

Timmons MJ. The vascular basis of the radial forearm flap. Plast Reconstr Surg 1986;77:80–​92. Ulatowski Ł. Colour Doppler assessment of the perforators of anterolateral thigh flap and its usefulness in preoperative planning. Pol J Surg 2012;84:119–​25. Uppal RS, Casaer B, Van Landuyt K, et al. The efficacy of preoperative mapping of perforators in reducing operative times and complications in perforator flap breast reconstruction. J Plast Reconstr Aesthet Surg 2009;62:859–​64. Wei FC, Mardini S. Free-​ style free flaps. Plast Reconstr Surg 2004;114:910–​16. Whitaker IS, Karoo ROS, Oliver DW, et al. Current techniques in the post-​operative monitoring of microvascular free-​tissue transfers. Eur J Plast Surg 2005;27:315–​21. Whitaker IS, Rozen WM, Chubb D, et al. Postoperative monitoring of free flaps in autologous breast reconstruction: a multicenter comparison of 398 flaps using clinical monitoring, microdialysis, and the implantable Doppler probe. J Reconstr Microsurg 2010;26:409–​16. Whitaker IS, Rozen WM, Smit JM, et al. Peritoneo-​cutaneous perforators in deep inferior epigastric perforator flaps: a cadaveric dissection and computed tomographic angiography study. Microsurgery 2009;29:124–​7. Wong C, Saint-​Cyr M, Arbique G, et al. Three-​and four-​dimensional computed tomography angiographic studies of commonly used abdominal flaps in breast reconstruction. Plast Reconstr Surg 2009;124:18–​27. Wong C, Saint-​Cyr M, Mojallal A, et  al. Perforasomes of the DIEP flap: vascular anatomy of the lateral versus medial row perforators and clinical implications. Plast Reconstr Surg 2010;125:772–​82. Woollard HH. The development of the principal arterial stems in the forelimb of the pig. Contrib Embryol 1922;14:139–​54. Xu ZF, Duan WY, Shang DH, et  al. [Preoperative Doppler evaluation of vascular perforators in the anterolateral thigh flap harvest]. Zhonghua Kou Qiang Yi Xue Za Zhi 2011;46:290–​2. Yu P, Youssef A. Efficacy of the handheld Doppler in preoperative identification of the cutaneous perforators in the anterolateral thigh flap. Plast Reconstr Surg 2006;118:928–​33.

9.6

Breast malignancy Diagnosis and management Kieran Horgan, Barbara Dall, Rebecca Millican-​Slater, Russell Bramhall, Fiona MacNeill, David Dodwell, Indu Chaudhuri, and Sebastian Trainor

Background Breast cancer is the commonest cancer to affect women in developed countries and is increasing in frequency in the Western world. Approximately 50,000 women and 400 men are diagnosed with breast cancer in the United Kingdom each year. Eighty per cent of these individuals will survive for at least 5 years after diagnosis (De Angelis et al., 2014; Saadatmand et al., 2015). In 2012, 11,762 women died of breast cancer in the United Kingdom. Age-​standardized rates of new invasive breast cancer diagnosis have increased from 75 to 126 per 100,000 population in the United Kingdom between 1977 and 2010.

Predisposing factors Age The incidence of breast cancer increases with age, as with the majority of cancers. Peaks in incidence can be seen in many countries for women aged between 50 and 65 years related to the presence of breast screening programmes.

Previous breast cancer The largest predictor of a new breast cancer is a past personal history of breast cancer. The risk of a new primary breast cancer occurring in a previously treated, conserved breast with modern breast cancer management is of the order of 0.5% per year. The risk of a new primary breast cancer developing in the contralateral breast is approximately 0.3% per year (Langlands et al., 2016). It is rare for cancer to spread from one breast to the contralateral breast.

Family history A strong family history of breast or ovarian cancer is an increasingly recognized and publicized risk factor. In this context, it is noted that approximately 5% of all breast cancers are thought to have a proven familial predisposition. The frequency of breast cancer in the general population means many women will have a person within the

extended family who has had breast cancer, but most of these cases are so-​called sporadic or random in nature and do not confer significant increased future risk to other family members. The United Kingdom National Institute for Health and Care Excellence (NICE), has published guidelines on the management of individuals thought to be at increased risk of familial breast cancer (NICE, 2013). There is awareness within the medical community of the importance of enquiring about a woman’s family history of breast and ovarian cancer when they present with any breast symptoms. The guidelines’ protocols allow determination of those who might be at increased risk of familial breast cancer and who require further assessment. After such assessment, many individuals will be designated as having the same risk as the general population and require no further attention. Some individuals will be assigned to a moderate increased risk category. Others will be categorized as high or very high risk for future breast cancer due to their family history. If a patient is in an increased risk group, they are offered programmes of mammographic surveillance and chemoprevention. Genetic testing is frequently offered to these latter groups. In the United Kingdom, NICE permits genetic testing if the history suggests the likelihood of a BRCA gene mutation is 10% or greater. Patients designated as high or very high risk may wish to undergo risk-​reducing surgery. Genetic testing should only be undertaken when an individual has been fully counselled by a trained geneticist and understands all the possible results and their implications. Genetic testing where there is a known specific mutation in that person’s family can be particularly informative as to the estimation of future risk. However, the information base in this area is rapidly increasing. Carriers of the most comprehensively investigated genetic mutations in BRCA1, BRCA2, and p53 have up to an 80% lifetime risk of developing a breast cancer (Antoniou et al., 2003). Ashkenazi Jewish heritage is associated with increased presence of mutations in both BRCA1 and BRCA2 genes. Patients already diagnosed with a breast cancer where the cancer occurs at a particularly young age or is ‘triple negative’ (negative for oestrogen (ER) and progesterone receptors (PR) and negative for human epidermal

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growth factor receptor (HER2) over-​amplification) have an increased likelihood of having a genetic mutation and are frequently offered a test.

Genetic mutation tumour characteristics Breast cancers in individuals who have a genetic mutation share some characteristics less commonly seen in the general breast cancer population. For example, carriers of BRCA1 gene mutations are more likely to present with high-​grade (grade 3) cancers which are ER negative. Carriers of the p53 gene mutation have an increased risk of developing breast cancers which are positive for HER2 over-​amplification.

Contralateral breast risk Any individual already diagnosed with breast cancer is likely to have a greater future risk to their survival from progression of already established systemic occult metastases from the known and treated cancer than from a new primary breast cancer. Such individuals, however, may seek preventative risk-​reducing surgery to the opposite breast and possibly ovaries in the hope of diminishing the risk of development of a new primary breast cancer. These relative risks need to be carefully explained to such patients (Murphy et al., 2013; Narod, 2014).

Hormone replacement therapy Women who have taken hormone replacement therapy have an increased risk of developing breast cancer, which increases with a longer duration of exposure (Million Women Study Collaborators, 2003).

Prior chest wall irradiation Individuals who are exposed to significant ionizing radiation to their chest wall such as supra-​diaphragmatic (mantle) radiotherapy for haematological malignancy at a young age have an increased risk of future breast cancer and are usually part of mammographic screening programmes.

Other factors Relative protective factors for the development of breast cancer include parity, late age at menarche, breastfeeding, and early menopause (including bilateral oophorectomy in premenopausal women). Obesity with a raised body mass index and excessive alcohol intake increase the individual risk for development of a breast cancer (Morimoto et al., 2002).

The diagnostic pathway—​triple assessment As the presentation of breast cancer can be subtle and the associated symptomatology can be non-​specific, a diagnostic process called triple assessment has evolved in order to minimize the potential for a missed breast cancer diagnosis. Triple assessment consists of the modalities of clinical assessment, including history taking and physical examination; appropriate breast imaging; and cytopathology. The application of three independent diagnostic modalities helps to ensure that a cancer is not missed. If a contrasting approach was taken where, for example, mammography was used alone as a single modality, many mammographically invisible cancers would be missed.

Clinical history and examination Patients may present to a breast clinic with symptoms or they may be referred from screening programmes (usually employing mammography). The commonest symptom is the finding of a new focal, visible or palpable change within a breast. Often this will be a lump or localized lumpiness. Occasionally patients will describe a distortion or an abnormality to the normally smooth contour of the breast, which cannot be explained by any previous injury or surgery. The duration of these symptoms will vary greatly and is not a very reliable diagnostic criterion. Other symptoms to suggest a possible breast cancer are a spontaneous bloodstained discharge from one duct of a nipple. Less common presentations are focal pain within a breast, the finding of a new axillary lump, or the manifestations of more advanced or metastatic breast cancer. Many patients will present to their general practitioner or secondary care with pain or tenderness within the breast. It is important when taking a breast history to ensure that a patient who describes having a breast lump means a breast lump rather than an area of focal tenderness. The significance of the presence of any definite breast lump is that it greatly increases the possibility of a breast cancer compared to other symptoms, even though many breast lumps will be benign. Most pain and tenderness within the breast has a hormonal background. Many of the symptoms are cyclical in nature and related to the menstrual cycle. They reach a peak in severity prior to menstruation and are less severe in the 10 days following menstruation. This type of hormonal breast pain is not linked with the presence of a breast cancer. Many breast cancers that present as lumps will be discovered accidentally by patients and will not have given rise to symptoms such as pain or tenderness. Some breast cancers, however, can be both painful and tender and therefore these qualities are not an absolute discriminant. Previously described risk factors should also be assessed as part of the history. Breast examination Clinical examination of the breast is best done in a systematic, reproducible manner as such a discipline is likely to ensure a comprehensive physical assessment and avoid missing important physical signs. The patient should remove all clothing to the waist level and a chaperone should be in attendance. One routine of breast physical examination is to commence with the patient sitting on the couch facing the examiner. Inspection is carried out with the patient’s hands at the hips and also with both arms elevated superiorly. Any indentation or indrawing of the skin of the breast is noted, particularly in an older patient where, in the majority of instances, if there is no other explanation for such skin contour alteration it is likely to indicate an underlying carcinoma (Fig. 9.6.1). The breast tissue is palpated using the flat of the hand rather than a pinching movement. All areas of both breasts are palpated including behind the nipple and the axillary tail of the breast. The axillae are palpated bilaterally. The process is then repeated with the patient lying supine. This meticulous examination routine, done in a repetitive manner, should allow the examiner to conclude whether there are any focal, visible or palpable abnormalities within the breast in the area indicated by the patient or indeed elsewhere in either breast or axilla. Without the knowledge of any further investigations the clinician

9.6  Breast malignancy: diagnosis and management

Fig. 9.6.2  Cyst. Features of a cyst on ultrasound are that it is anechoic and it has posterior enhancement.

Fig. 9.6.1  Right breast cancer displaying visible indentation on the lower inner quadrant of breast.

should then indicate the degree of suspicion for the presence of a malignancy. Summary of assessment nomenclature Traditionally, assessment findings were often descriptive and did not allow easy, accurate communication of the conclusions between different specialists. A method was developed by breast radiologists with the advent of breast screening, in which a numerical value was given to the investigation conclusion. The values range between 1 and 5; 1 = normal, 2 = benign, 3 = abnormal, probably benign, 4 = suspicious of malignancy, and 5 = malignant. The letter P placed in front of one of these numbers signifies the findings are from palpation, for example, P4 signifies that the physical findings were suspicious for malignancy. This scoring system is also used throughout triple assessment with a different preceding letter of R for radiology, B for biopsy, and C for cytology. Physical examination of the patient should also include palpation of other body sites such as the neck and abdomen but these would usually only be relevant for a presentation with more advanced breast cancer.

abnormal clinical or mammographic findings. Ultrasound differentiates reliably between cystic and solid lesions and can also give an accurate assessment of the likelihood of malignancy for solid lesions (Fig. 9.6.2). Ultrasound is painless and does not involve any exposure to radiation and therefore has a high acceptance rating by patients. Ultrasound findings are only reliable when performed by a trained breast ultrasonographer. It is a dynamic test and therefore the copies of the images are of value as an archive but the findings at the time of the examination as visualized and described by the ultrasonographer are particularly important in the absence of a mass lesion. Ultrasound of benign lesions shows that these are often orientated with their long axis horizontal on the chest wall. They displace rather than disrupt the overlying breast tissue (Fig. 9.6.3). In contrast, ultrasound of a malignant lesion shows a mass irregular in shape with its long axis tangential to the chest wall. In appearance the abnormality is taller than it is wide. The normal breast parenchyma is disrupted. There is posterior shadowing (Fig. 9.6.4).

Breast imaging Breast imaging is the second component of the diagnostic triple assessment process. Breast imaging consists of the use of ultrasound, mammography, and magnetic resonance imaging (MRI). Ultrasound Ultrasound is the most frequently employed imaging modality in the symptomatic breast clinic. It is applicable to women of all ages. It is most informative when it is targeted to the area of symptoms, or

Fig. 9.6.3  Fibroadenoma. Features of a benign lesion on ultrasound are an ovoid shape with one or two gentle lobulations, a thin white pseudocapsule, uniform internal echoes, and it sits within breast tissue without disrupting it.

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Fig. 9.6.4  Carcinoma. Features of a malignant lesion on ultrasound are an irregular mass with a thick echogenic corona which disrupts the normal tissue.

Ultrasound allows quick and accurate guided biopsy procedures, which are well tolerated by patients. Mammography Mammography is a method of radiological examination of the breast using specific equipment and involves a low dose of radiation. It is offered to symptomatic women over the age of 40 years. It is also performed for clinically uncertain lumps with a normal ultrasound examination over the age of 35  years or when a malignant breast diagnosis has been made in a younger patient. Mammography is associated with an increased rate of false-​negative diagnoses as the patient’s age decreases under the age of 40  years. Important abnormalities seen on mammography are described as a mass, an

(a)

asymmetry, parenchymal deformity, or calcification. Benign masses are usually well defined and show a clear margin. Malignant masses are ill-​defined with an irregular or spiculated outline (Fig. 9.6.5). Asymmetries are areas of increased density, which are not seen in the other breast or were not present on the previous mammogram. The findings on mammography can at times be non-​specific and comparison with previous mammographic images is an important part of the reporting process. Asymmetry is a less specific sign than a mass but it can indicate malignancy and would prompt a targeted ultrasound of that area. Parenchymal deformities are areas of disrupted breast tissue, which look like an asterisk (Fig. 9.6.6). They can represent a carcinoma which is often low grade in nature or they are associated with a radio-​pathological entity known as a ‘radial scar’—​a sclerosing breast abnormality characterized by an irregular stellate pattern of epithelial proliferation around a fibroelastic core. Twenty per cent of radial scars will have areas of in situ malignancy associated with them. Calcification within the breast is common and is usually benign. Benign calcifications have a coarse appearance, are often widely scattered and sometimes bilateral. Calcification with a central lucency is almost always benign; if coarse it is usually due to post-​traumatic fat necrosis (Fig. 9.6.7). Finer calcification can be associated with benign skin lesions. So-​called ‘milk of calcium’ is also a representation of benign calcification within terminal ducts and has the appearance of ‘layers within a teacup’ on a lateral mammogram. Calcification associated with malignancy is fine and requires magnification of the mammographic image for full assessment. Classically, it is fine casting calcification as it lies within the lining of the ducts. It is described as pleomorphic because the size and shape of the individual calcification is very variable (Fig. 9.6.8). Mammography allows assessment of the area of clinical concern within a breast and can give an indication as to whether it is likely to represent a malignancy. Mammography can also give further information as to whether that malignancy is a focal change within

(b)

Fig. 9.6.5  Carcinoma. (a) Mammogram; (b) magnification view. Features of a malignant lesion on mammography are a mass lesion with an ill-​defined or a spiculated margin.

9.6  Breast malignancy: diagnosis and management

(a)

(b)

Fig. 9.6.6  Parenchymal deformity. (a) Mammogram; (b) magnification view. A radial scar with no atypia seen on the mammogram as an area of disrupted breast tissue which looks like an asterisk.

the breast or if there is evidence of other more diffuse, often in situ, cancer associated with the malignant mass. Mammography will also examine the rest of the ipsilateral breast and the contralateral breast. It is a more accurate examination with increasing patient age, since in the older patient the relative ratio of glandular breast component to fat within the breast decreases. Breast tissue in younger women frequently appears very dense on mammography making the examination less reliable. This is the main reason mammography is not

(a)

performed routinely in symptomatic women under 40  years. The younger breast is also more vulnerable to harmful side effects from irradiation and because of the increased density; a higher radiation dose is required. Breast MRI MRI of the breast is not used routinely in the diagnostic process. Although experience with the use and interpretation of breast MRI

(b)

Fig. 9.6.7  Benign microcalcification. (a) Mammogram; (b) magnification view. This is a postsurgical breast with deformity of the outline of the breast, surgical clips, and coarse benign dystrophic calcification.

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(a)

(b)

Fig. 9.6.8  Malignant microcalcification. (a) Mammogram; (b) magnification view. This is an inflammatory carcinoma with skin thickening, nipple retraction, an ill-​defined mass, and pleomorphic microcalcifiction (variable shapes and sizes and requires magnification to visualize properly).

has improved greatly in recent years, it has a high sensitivity yet lower specificity, which may give rise to diagnostic problems. It is best employed when there are clear diagnostic questions. MRI of the breast can be a very helpful adjunct in providing further information on the extent of malignancy within a breast known to contain a cancer. It is also frequently helpful where there is diagnostic difficulty or concern regarding the possibility of a breast cancer diagnosis which is not supported by the other imaging investigations. MRI of the breast should only be requested after discussion at a multidisciplinary team (MDT) meeting. A specific question should be posed. In practice, MRI scanning of the breast is used primarily to assess the extent of cancer within the breast for certain patients who are considering BCS. It can be particularly helpful in that setting for patients who have invasive lobular carcinoma subtype. It is also used to locate a mammographically occult breast cancer in women who present with metastatic axillary lymph nodes and to monitor the breast cancer response in patients receiving neoadjuvant chemotherapy (NACT) (Fig. 9.6.9 and Fig. 9.6.10). MRI is frequently helpful in trying to assess a reconstructed breast, particularly for the possibility of cancer recurrence or implant integrity. MRI is offered as a screening test for some women with a very high risk of future breast cancer development due to their family history (NICE, 2013).

Cytopathology The third component of triple assessment is cytopathology, using fine-​needle aspiration for cytology or core biopsy for histology. Cytology is now much less frequently used and is confined to the sampling of very small lesions, which are detected only on clinical examination without an imaging abnormality. It is also used in the sampling of lymph nodes. Core biopsy has become the standard diagnostic tool for breast tissue sampling and can be performed either under clinical or imaging guidance, usually ultrasound. Core biopsy, performed with a 14-​gauge needle and taking four samples, will allow a breast cancer diagnosis to be reliably made and also to provide sufficient tissue for the determination of molecular

markers such as ER and HER2 over-​amplification. Many pathologists will also provide an estimation of the cancer grade based on the appearances of the core biopsy. In recent years, the technique of vacuum biopsy has gained popularity, whereby large volumes of tissue can be sampled with mammographic, ultrasound, or MRI guidance. This technique can greatly increase the sensitivity of diagnosis for lesions which previously proved difficult to diagnose non-​operatively such as areas of calcification or mammographic deformity. Vacuum biopsy has decreased the need for a diagnostic open biopsy to obtain a breast cancer diagnosis. In fact, the latter is now a very uncommon procedure in an experienced breast practice.

Breast screening Screening involves the use of a diagnostically effective investigation or test for an identified population subgroup at an increased risk of a specific disease with the expectation that earlier diagnosis will improve outcomes and survival. Mammography is used for breast screening and is offered at regular intervals (3-​yearly in the United Kingdom) to women from the age of 47–​50 years to 70–​73 years. The purpose is to detect asymptomatic malignancy. Patients who experience breast symptoms are a different group and are directed to symptomatic breast clinics. Screening is not offered to younger women as their breasts are too dense to satisfactorily evaluate with mammography and both false-​positive and false-​negative diagnoses may result. The balance of potentially improved breast cancer-​related survival, compared to the increased risk of morbidity for benign pathologies, and the economic, social, and emotional costs of breast screening remain under constant media attention. The concept of lead time bias should be understood when evaluating outcomes of patients diagnosed at screening. Screening will result in earlier diagnosis of a cancer but will only reduce mortality if the date of death

9.6  Breast malignancy: diagnosis and management

(a)

(b)

(a)

(b) (c)

(d)

(c)

(e)

(f)

Fig. 9.6.9  MRI is used to delineate tumours accurately and monitor the response to neoadjuvant chemotherapy. Panels (a), (c), and (e) are high-​ resolution T2-​weighted sequences which demonstrate morphology. Panels (b), (d), and (f) are post-​contrast subtraction images which demonstrate tumour enhancement. Panels (a) and (b) are pre-​treatment and show a large, well-​circumscribed unifocal tumour with central ischaemia which is bright on T2. Panels (c) and (d) are post two cycles of chemotherapy. The tumour has responded very well by shrinking concentrically. Panels (e) and (f) are post four cycles of chemotherapy. A marker clip, which shows as a signal void with a surrounding bright signal, is now in place immediately anterior to the residual tumour. This has been positioned under ultrasound control and will be used to guide conservative surgery.

from the cancer is later than it would otherwise have been. Survival will be inherently elongated with an earlier time of diagnosis but unless the date of death is delayed, mortality remains unaffected. A summary of the advantages and disadvantages of breast screening is contained in the Marmot report (Independent UK Panel on Breast Cancer Screening, 2012). The advent of breast screening

Fig. 9.6.10  Diffuse and multifocal tumours respond with fragmentation of the tumour which is visualized well on the three-​dimensional subtraction maximum intensity projection images. (a) Pre-​treatment—​ hypervascular left breast with extensive diffuse infiltrating tumour. Diffuse hormonal enhancement noted in normal contralateral breast. (b) Post two cycles—​the tumour shows some response with fragmentation of the tumour. The background hormonal enhancement in the contralateral breast is no longer present. (c) Post four cycles—​the tumour shows a partial response with fragmentation of the tumour but no reduction of the overall extent. This patient will have a mastectomy at the end of chemotherapy.

was a major stimulus to institute specialized breast services in the United Kingdom. Breast screening is associated with a much higher incidence of in situ malignancy and with surgery for impalpable breast cancer with a much greater demand for image guidance in these patients.

Pathology of breast cancer Morphological subtype Historically, breast cancer has been classified by its histological appearance. The majority of tumours (~75%) are classified as invasive

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ductal carcinomas of no special type (ductal NST). These are tumours that show special type characteristics in less than half of the tumour. This is a large and heterogeneous group of cancers, which show wide variation in morphology. A minority of breast cancers can be classified as either pure special type (>90% of the tumour shows special type characteristics) or mixed special type (between 50% and 90% of the tumour shows special type characteristics). There are a number of different special types including lobular, mucinous, tubular, micropapillary, and metaplastic. Some of these are associated with specific prognostic features, for example, pure mucinous carcinomas are rarely associated with nodal metastasis and have a better disease-​specific survival than ductal NST carcinomas (Di Saverio et al., 2008), whereas micropapillary carcinomas appear to have a greater propensity for lymphovascular invasion and are associated with nodal metastasis more frequently than ductal NST carcinomas (Zekioglu et al., 2004). In practical terms, the most relevant subtype to identify preoperatively on diagnostic core biopsy is invasive lobular carcinoma. The full extent of invasive lobular carcinomas is frequently underestimated clinically and radiologically. Preoperative awareness of this subtype may suggest different evaluations for tumour extent such as MRI if breast conservation is under consideration (Mann, 2010).

Fig. 9.6.12  An example of a grade 3 invasive carcinoma showing no tubule formation, marked nuclear pleomorphism, and plentiful mitotic figures.

survival, with higher grade linked to a shorter survival time (Rakha et al., 2008).

Grade

Oestrogen receptor status

Histological grading of invasive breast carcinomas provides a powerful prognostic tool if performed correctly. In the United Kingdom, tumour grade is determined using the Nottingham criteria, which allows assessment of three components of tumour morphology—​ tubule/​ glandular formation, nuclear pleomorphism, and mitotic count (NHS Breast Screening Programme, 2005). A score of 1, 2, or 3 is given to each of these components depending on how much or how little of the tumour displays the feature assessed (Fig. 9.6.11 and Fig. 9.6.12). The scores are combined to give a single score (between 3 and 9), which is converted into the appropriate grade (score 3, 4, or 5 = grade 1; score 6 or 7 = grade 2; score 8 or 9 = grade 3). The histological grade is associated with disease-​specific survival and with disease-​free

It is known that oestrogen plays a key role in the development of breast cancer and that it also stimulates the growth of tumours that express ER (ER-​positive breast cancer). Endocrine therapy is designed to remove this stimulatory effect and all breast cancers are tested to determine whether they are ER positive to decide whether endocrine therapy may have utility. Approximately 80% of breast cancers are ER positive (Weigel and Dowsett, 2010). Immunohistochemistry is used to test whether a tumour expresses ER and a score, currently the Allred score (NHS Breast Screening Programme, 2005), is given which reflects the proportion of tumour cell nuclei that are ER positive and the intensity of the positive staining (Fig. 9.6.13). The role of PR status is less clear in determining therapeutic strategies and is not always measured in breast cancer units.

Fig. 9.6.11  A typical grade 1 invasive carcinoma showing obvious tubule formation, minimal nuclear pleomorphism, and very low mitotic activity.

Fig. 9.6.13  An ER-​positive stained section showing diffuse strong nuclear positivity (brown staining) of the tumour cells.

9.6  Breast malignancy: diagnosis and management

HER2 status Trastuzumab is a monoclonal antibody that targets one of the human epidermal growth factor receptors—​HER2 (also known as Neu or ErbB-​2). The gene for this receptor is amplified in approximately 15% of breast cancers and amplification predicts poorer prognosis (Ross et al., 2004). Treatment with trastuzumab significantly improves prognosis in these patients (Yin et al., 2011). As with ER status, all breast cancers are tested to determine whether they overexpress HER2. This is initially done by immunohistochemistry with assessment of the degree of positive staining of the cell membranes (Fig. 9.6.14). A  small proportion of cases are categorized as borderline or uncertain on immunohistochemistry assessment and require further testing with an in situ hybridization technique (Bartlett et al., 2011). Tumours which do not express ER, PR, or HER2 activity are commonly described as triple-​negative breast cancers. These tumours tend to be more commonly associated with a genetic mutation if the cancer is diagnosed in younger patients. They have more aggressive features at diagnosis and consequently a worse overall prognosis (Foulkes et al., 2010). Gene expression profiling has allowed the classification of breast cancer into six different subtypes. These include luminal A, luminal B, HER2 overexpression, basal-​like, claudin-​low, and normal breast tissue-​like (Eroles et al., 2012). This concept of the subdivision of the totality of breast cancers through molecular criteria is thought to be increasingly important in the understanding of individual breast cancer behaviour and treatment response. It may replace more traditional descriptive histopathology and is an area of significant research.

Triple assessment conclusions The findings of the different triple assessment components are combined to allow clinicians to discuss a particular patient’s presentation and decide if a secure diagnosis has been made. An example of this would be a young woman who presents with a discrete firm lump within the breast, which is mobile on clinical examination, consistent with a benign lump such as a fibroadenoma, and summarized with the clinical code P2. The patient proceeds to ultrasound

and the findings again are consistent with a benign lump such as a fibroadenoma and designated R2. Ultrasound-​guided core biopsies were performed and these also show the findings of fibroadenoma, B2. The summary for this patient is presentation with a breast lump in which triple assessment shows the findings of P2, R2, B2, and all of these assessments are in agreement with no discordance. A diagnosis of fibroadenoma is confidently made and the patient can be discharged. Similarly, one can look at the example of a 60-​year-​old woman who presents to clinic with a breast lump with visible overlying skin indentation. The lump has an irregular border, is firm, and not freely mobile. It receives a clinical code of P5. Mammography shows a spiculated mass at the site of the palpable lump. Ultrasound shows that the mass is irregular and taller than it is wide. The combined radiological code is R5. A core biopsy is performed and shows invasive ductal carcinoma B5b. (B5 denotes histological confirmation of malignancy and is subdivided into B5a for in situ carcinoma only and B5b for invasive carcinoma.) The triple assessment summary was P5, R5, B5b. Triple assessment has conclusively diagnosed that this 60-​year-​old woman’s breast lump is an invasive breast cancer and she can safely be offered all treatment modalities without a need for further confirmation of the diagnosis. Though all components of triple assessment are important, cytopathology is the most influential. P4 and R4 breast lumps will proceed directly to treatment if core biopsy histology is B5. If there is discordance between the different elements of the triple assessment then further consideration, investigation, and assessment is required. A P2 R2 lump with a B5 histology requires careful discussion at the MDT meeting and often a repeat confirmatory biopsy will be advised. Similarly, if assessment showed P5 R3 B2, the components of the assessment need re-​evaluation.

Preoperative axillary assessment As described in the section on clinical examination, the axillae are routinely palpated as part of a breast physical examination to detect abnormal or enlarged axillary lymph nodes. In recent decades it is less common to detect palpably malignant axillary nodes in patients with early breast cancer (EBC) at the time of diagnosis. Over the last 15 years there has been a significant increase in expertise of ultrasonic axillary examination, which has been allied to improved sophistication of the available equipment. Ultrasound of the ipsilateral axilla is now performed as an integral component of the preoperative evaluation for a patient with EBC. Ultrasound-​guided biopsy of any abnormal node is often conducted at the same examination as imaging of the axilla. The sensitivity of ultrasound and subsequent needle biopsy to provide a preoperative diagnosis of any axillary nodal metastasis varies with the size of metastasis, whether the patient’s cancer was symptomatic or screen-​detected, the patient’s body habitus, and the experience and skill of the ultrasonographer (Joh et al., 2012). A detection rate of 30–​50% of axillary metastases is commonly reported. Newer refinements which would allow ultrasonic identification and needling of the specific sentinel node are being evaluated across a broader range of patients (Cox et al., 2013).

Preoperative screening for metastases Fig. 9.6.14  Tumour cells showing strong circumferential membranous positivity with HER2 immunohistochemistry.

Most patients with EBC do not require, or benefit from investigations to detect clinically occult systemic metastases (Association of Breast

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Surgery at BASO, 2009; NICE, 2009). Bone scans and computed tomography are not routinely employed. Blood tumour marker assessment is not indicated in this setting. There is also doubt as to the clinical utility of routine measurement of liver function tests and serum calcium levels in the absence of suggestive metastatic symptoms or signs. If there are symptoms or signs suggestive of distant metastases patients should be investigated accordingly.

Multidisciplinary team meetings MDT meetings are an essential and integral component of satisfactory provision of care for all cancer patients including those with breast cancer. The meetings should include representatives of all involved disciplines. In many breast units the breast cancer MDT meetings are separated into a diagnostic MDT and a therapeutic MDT to allow maximum efficiency and use of clinician time. There is a relatively greater oncologist contribution to the therapeutic MDT. However, this system must allow oncological input into the decision-​making at the time of diagnosis particularly in those instances where it may be thought preferable that the patient proceeds with chemotherapy as their first treatment or to allow a prediction as to whether radiotherapy may be required after a mastectomy which would influence reconstructive surgery planning. All patients who have a breast or axillary tissue biopsy performed in the clinic should be discussed at a MDT meeting as should patients where the diagnosis is uncertain. Patients should have their investigations fully discussed by the MDT at the time of diagnosis, ideally before any therapy is offered or any management plan finalized. This allows patients to, for example, benefit from a recommendation that initial NACT followed by surgery may be more advantageous than proceeding straight to surgery. Clear management plans should be agreed and recorded for all patients discussed during the MDT meeting. An electronic patient record system is highly desirable and the members of the MDT should be able to see and confirm the record of the agreed outcome.

Specialist breast care nurses Specialist breast care nurses (BCNs) are an essential component of the modern breast cancer MDT which became formalized in the United Kingdom in the late 1980s with the introduction of national breast screening. It is now an essential requirement to satisfy national peer review that all breast cancer units in the United Kingdom are sufficiently staffed with BCNs. Specialist BCNs are particularly influential and helpful when they are present at the time of initial diagnosis. They will frequently see a patient outside of the patient’s consultations with the medical staff and ensure that the patient fully understands the diagnosis and what the management considerations involve. This allows the BCN to develop a relationship with the patient and to understand better the patient’s viewpoint. This aspect is particularly important, for example, when a patient has an open choice between proceeding with breast-​conserving surgery (BCS) or a mastectomy. It is also valuable when patients are considering aspects of immediate breast reconstruction. The BCN plays a pivotal role within the clinical team, acting as the patient’s advocate. As numbers of patients referred to diagnostic breast clinics have increased in recent years, many breast clinics now include BCNs or Advanced Nurse Practitioners who will triage these referrals, see and

examine the patients, and request appropriate imaging. Specialist nurses also frequently coordinate family history services.

Oncoplastic multidisciplinary team There is an increasing tendency to have an oncoplastic surgery component to the MDT. This allows particularly close discussion between breast radiologists and surgeons, both excisional and reconstructive, to determine tumour extent and distribution within the breast and to allow discussion and agreement on the preferred surgical approach. This collaborative operative planning approach maximizes the potential for optimal excision and restoration of the aesthetic form of the breast. Oncologists also contribute opinions at this MDT meeting, especially as to the likely need for radiotherapy after mastectomy. The BCN will inform the MDT of the patient-​ related factors and the patient’s initial thinking, viewpoint, and preferences.

Breast cancer treatment Breast cancer is arbitrarily divided for management protocols into operable (also known as EBC) or advanced/​metastatic breast cancer. This separation is based on the potential in EBC for curative therapy and in particular the possibility for margin-​free excision of the cancer within the breast and axilla (R0 excision). Using the TNM staging classification, operable breast cancers are T1–​3, N1–​2, Mx and M0 (Brierley et al., 2016, pp. 151–​8). Although an apparent contradiction, the categorization of cancers as early or operable recognizes that a percentage of these cancers will already have distant occult micrometastases. The potential existence of distant metastatic spread in EBC is further recognized by the inclusion of systemic therapies to treat these potential metastases as part of EBC management (NICE, 2009). The management of EBC is coordinated and supervised by the MDT, and meeting attendance is a requirement for all clinicians involved in the management of breast cancer. The different components of the treatment process include surgery to the breast and axilla, radiotherapy to the breast, axilla, and other nodal regions, and systemic treatment using anti-​hormonal approaches, systemic chemotherapy, and specific targeted drugs such as trastuzumab.

Surgery for operable breast cancer The purpose of a surgical approach for cancer within the breast is to remove all of the malignant area. Complete excision is confirmed by pathological assessment of the margins of the excised tissue, which should not show any malignancy. Because of the inability of any pathological assessment to look at all margins in a complete and comprehensive manner, a minimum clear margin has been used to confirm complete excision. This aspect remains under constant debate and review. A recent guideline has suggested ‘that no tumour at the ink’ on the margins of the resected specimen is sufficient but this is controversial and is discussed further in this section (Buchholz et al., 2014). Mastectomy All patients can be offered complete removal of the breast as a mastectomy but it is not necessary for most. As there is no definite separation between breast tissue and subcutaneous fat, despite the most

9.6  Breast malignancy: diagnosis and management

careful of dissection techniques, there will remain a small amount of residual breast tissue after mastectomy (